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Acetylcholine Bethanechol

Direct –acting cholinergic Carbachol

Pilocarpine

Clolinergic Agonist

Reactivation of acetylcholinesterase

Indirect-acting cholinergic Edrophonium

Irreversible

Physostigmi ne.

Reversible

Neostigmine

Pralidoxime

Insectside

Echotiophate.

Pyridostigmine and ambenonium

Tacrine ,donepezil, Rivastigmine and rivastigmine Rivastigmine and rivastigmine.


Direct–acting cholinergic agonists: Drug class Acetylcholine

MOA

SE

ACh has both muscarinic and nicotinic activity .

USES into the anterior chamber of the eye to produce miosis during ophthalmic surgery

Its actions include the following: 1-dec in heart rate and cardiac output. 2-Dec in BP. 3-In GI and intestinal : Ach increase the secretions of them.

Bethanechol

4-In Genitourinary tract : Ach increase the tone of detrusor muscle, causing urination. 5-In eye, Ach causing miosis. It has directly stimulates muscarinic receptors. e.x: increase intestinal motility and urination. It lacks nicotinic actions.

Carbachol (carbamylcholine)

It has both muscarinic and nicotinic actions. It can release of epinephrine from the adrenal medulla by its nicotinic actions.

Pilocarpine

It exhibits muscarinic activity and is used primarily in ophthalmology.

Bethanechol causes the effects of generalized cholinergic stimulation. These include sweating ,salivation ,flushing ,decrease blood pressure, nausea, abdominal pain, diarrhea, and bronchospasm.

1-In urologic treatment ,it is used to stimulate the atonic bladder. 2- treat neurogenic atony as well as megacolon.

At doses used ophthalmologically , little or no side effects occur due to lack of systemic penetration(quaternary amine).

rarely used therapeutically except in the eye as a miotic agent to treat glaucoma.

blurred vision ,night blindness, and brow ache.

Pilocarpine is used to treat glaucoma and is the drug of choice for emergency lowering of intraocular pressure

Pilocarpine poisoning characterized by exaggeration of various parasympathetic effects including salivation and sweating. Note: Atropine is administered to counteract the toxicity of Pilocarpine.


Agents(reversible)): Drug class

MOA

SE

USES

Edrophonium

short-acting AChE inhibitor. preventing hydrolysis of Ach

Excess Edrophonium may provoke a cholinergic crisis (atropine is the antidote).

diagnosis of myasthenia gravis

Physostigmine

It is reversibly inhibits AChE.

1-In high doses used will lead to convulsions ,bradycardia and fall in cardiac output.

1-The drug increases intestinal and bladder motility, which serves as its therapeutic action in atony of either organ.

2-Inhibition of AChE at the skeletal NMJ causes accumulation of Ach and results in paralysis of skeletal muscle .

2-It is also used in the treatment of overdoses of drugs with anticholinergic actions, such as atropine.

include those of generalized cholinergic simulation, such as, salivation,flushing,dec in BP,bronchospasm and diarrhea.

1-It is used to stimulate the bladder and GIT.

Neostigmine

It is reversibly inhibits AChE in a manner similar to physostigmine.

2-It is also antidote for competitive neuromuscular-blocking agents. 3-Used to manage symptoms of myasthenia gravis.

Pyridostigmine And Ambenonium

It is cholinesterase inhibitor.

SE is Similar to neostigmine.

Used in chronic management of myasthenia gravis.

Tacrine,donepezil, Rivastigmine and rivastigmine.

It is cholinesterase inhibitor.

GI distress is their primary adverse effects.

Used in Alzheimer treatment.


Indirect-Acting Cholinergic Agonists:(Anticholinesterase Agents (Irreversible)). Drug class

MOA

SE

USES

Echotiophate. (Organophosphate compound).

Irreversible AChE inhibitors.

Cholinergic crisis.

open angle glaucoma

Insectside . (Organophosphate compound).

Irreversible AChE inhibitors.

Cholinergic crisis.

Used in agricultural insecticides

Reactivation of acetylcholinesterase: Drug class Pralidoxime.

MOA It can reactivate inhibited AChE.

SE Its SE similar to other AChE inhibitors.

USES ___


Questions ‌ Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------------------------------------------------DOC for emergency lowering of intraocular pressure

-------------------------------------------short-acting AChE inhibitor --------------------------------------------

--------------------------------------------------------------------------------------Used in agricultural insecticides


Answers : A-Pilocarpine It exhibits muscarinic activity and is used primarily in ophthalmology. emergency lowering of intraocular pressure

B-Edrophonium short-acting AChE inhibitor diagnosis of myasthenia gravis

C-Insectside . Irreversible AChE inhibitors. Used in agricultural insecticides


Cholinergic Antagonists

Neuromuscular blocking agents.

Ganglionic blockers.

Nicotine

cisatracurium, Pancuronium, rocuronium, Vecuronium

Antimuscarinic agents.

Tropicamide and Cyclopentolate Ipratropium and tiotropium. Atropine

Darifenacin ,fesoterodine, oxybutynin, solifenacin, tolterodine, and trospiumchloride

Benztropine and trihexyphenidyl

Scopolamine


Antimuscarinic agents: Drug class Atropine

MOA It binds competitively with muscarinic receptors and prevents Ach from binding to those sites.

SE dry mouth, blurred vision ,sandy eyes, tachycardia, urinary retention, and constipation. Effects on CNS include: Restlessness, confusion ,hallucination , and delirium ,which may progress to depression ,collapse of the circulatory and respiratory system, and death

Scopolamine

Ipratropium And tiotropium Tropicamide And Cyclopentolate Benztropine And trihexyphenidyl

Darifenacin fesoterodine, oxybutynin, solifenacin, tolterodine, and trospiumchloride

It blocks the muscarinic receptor by prevents Ach from binding to those sites. Note: It produces peripheral effects similar to those of atropine. However, scopolamine has greater action on the CNS (unlike atropine). It blocks the muscarinic receptors. It blocks the muscarinic receptors.

It blocks the muscarinic receptors.

It blocks the muscarinic receptors.

Blurred vision ,confusion ,mydriasis, constipation, urinary retention

USES 1-In Ophthalmic: Topical atropine exerts both mydriatic and cycloplegic effects. 2- As antispasmodic agent to relax the GI tract. 3- In Cardiovascular: to treat bradycardia . 4-As antisecretory agent to block secretions in the upper and lower respiratory tract prior to surgery. 5-Antidote for cholinergic agonists. -prevention of motion sickness -postoperative nausea and vomiting.

Blurred vision ,confusion ,mydriasis, constipation, urinary retention. Blurred vision ,confusion ,mydriasis, constipation, urinary retention. Blurred vision ,confusion ,mydriasis, constipation, urinary retention

Blurred vision ,confusion ,mydriasis, constipation, urinary retention Note: limit tolerability.

Treatment of (COPD) In ophthalmology, to produce mydriasis and cycloplegia prior to refraction. -Treatment of Parkinson disease.

-overactive urinary bladder.


Ganglionic blocker: Drug class Nicotine.

MOA

SE

USES

Ganglionic blockers act on the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia.

___

___

SE

USES

a-At low dose: Nondepolarizing agents competitively block Ach at the nicotinic receptors on the skeletal muscle. b-At high dose: Nodepolarizing agents can block the ion channels of the motor endplate.

Postoperative muscle pain is common; hyperkalemia and increased intraocular and intragastric pressure may occur.

1-Used in anesthesia

Succinylcholine attaches to the nicotinic receptors and acts like Ach to depolarize the junction of the muscle.

1-Hyperthermia. 2-Apnea. 3-Hyperkalemia.

1-Because of its rapid onset of action , succinylcholine is useful when rapid endotracheal intubation is required during the induction of anesthesia. 2-It is also used during electroconvulsive shock treatment.

Neuromuscular blocking agents: Drug class nondepolarizing (competitive) blockers.

Depolarizing agents

MOA


Questions ‌ Complete First line Drug name or class Second line M.O.A Third line use

----------------------------------------------------------------------------------------Treatment of (COPD)

Scopolamine --------------------------------------------prevention of motion sickness

Succinylcholine -----------------------------------------------------------------------------------------


Answers: A-Ipratropium And tiotropium It blocks the muscarinic receptors. Treatment of (COPD)

B-Scopolamine It blocks the muscarinic receptor by prevents Ach from binding to those sites. prevention of motion sickness

C-Succinylcholine attaches to the nicotinic receptors and acts like Ach to depolarize the junction of the muscle. In induction of anesthesia and electroconvulsive shock


Adrenergic agonist

(sympathomimetics) neurotransmitter

Noradrenaline (Norepinephrine)

Adrenaline (epinephrine)

Characteristics of adrenergic agonist

Chatecholamine

Epinephrine, norepinephrine, isoproterenol and dopamine.

Non cathecholamine

Phenylpherine, Ephedrine, Amphetamine.


Mechanism of action of adrenergic agonist

Direct-acting agonists

Indirect-acting agonists

Mixed-action agonists


DIRECT ACTING AGONIST: Drug name

MOA 1.Cardiovascular:

Epinephrine (alpha &beta ) 1-At low doses, β effects (vasodilation) 2- high doses, α effects (vasoconstriction)

- Increase HR , contractility and cardiac output  potent vasoconstrictor. - Epinephrine constricts arterioles in the skin, mucous membranes, and viscera (α effects), and it dilates vessels going to the liver and skeletal muscle (β2 effects). Renal blood flow is decreased. -the effect of alpha agonist is different from beta agonist. 2.Respiratory: Bronchodilation By acting directly on bronchial smooth muscle (β2 action). 3.Hyperglycemia: Epinephrine has a significant hyperglycemic effect because of increased glycogenolysis in the liver (β2 effect). 4.has Lipolysis activity.

SE -Adverse CNS effects that include anxiety, fear, tension, headache, and tremor. - cardiac arrhythmias, particularly if the patient is receiving digoxin. - pulmonary edema. -tachucardia. - Epinephrine increases the release of endogenous stores of glucose. In diabetic patients, dosages of insulin may have to be increased. - Nonselective β blockers prevent vasodilatory effects of epinephrine on β2 receptors, leaving α receptor stimulation unopposed. This may lead to increased peripheral resistance and increased blood pressure.

USES 1-Bronchospasm. 2-Anaphylactic shock. 3-cardiac arrest. 4- Anesthetics.


Drug name Isoproterenol ( beta agonist)

MOA -stimulate the heart, increasing heart rate, contractility, and cardiac output

SE similar to those of epinephrine .

-direct-acting synthetic catecholamine that stimulates both β1 - and β2 -adrenergic receptors.

Dopamine

Cardiovascular:

1-a1 at high doses.

Has a stimulatory effect on the β1 receptors of the heart, having both positive inotropic and chronotropic effects.

2-B1 at small doses.

Norepinephrine ( alpha & beta) in therapeutic doses, the α -adrenergic receptor is most affected.

Baroreceptor reflex: Norepinephrine increases blood pressure, and this stimulates the baroreceptors, inducing a rise in vagal activity. The increased vagal activity produces a reflex bradycardia,.

-potent bronchodilator (β2 effect). -atrioventricular (AV) block.

-nausea, -hypertension -arrhythmias

-drug of choice for cardiogenic and septic shock -Increase cardiac output , BP and peripheral resistance  use to treat hypotension and severe HF.

-At very high doses, activates α1 receptors on the vasculature, resulting in vasoconstriction. Renal and visceral: dilates renal and splanchnic arterioles by activating dopaminergic receptors, thereby increasing blood flow to the kidneys and other viscera. Cardiovascular actions: Vasoconstriction: Norepinephrine causes a rise in peripheral Resistance. Both systolic and diastolic blood pressures increase. Note: Norepinephrine causes greater vasoconstriction than epinephrine.

USES

- Increased blood flow to the kidney enhances the glomerular filtration rate and causes diuresis  treat oliguria.

-similar to epinephrine

-shock,

In addition, is a potent vasoconstrictor and may cause blanching and sloughing of skin along an injected vein.

Because it increases vascular resistance and, therefore, increases blood pressure.

- If extravasation (leakage of drug from the vessel into tissues surrounding the injection site) occurs, it can cause tissue necrosis.


Drug name

MOA

Fenoldopam

-agonist of peripheral dopamine D1 receptors.

Dobutamine

-β1 receptor agonist.

Oxymetazoline

-stimulates both α1 - and α2 -adrenergic receptors.

Phenylephrine

Clonidine

-direct-acting, binds primarily to α1 receptors.

It is direct acting α2 agonist.

SE Headache, flushing, dizziness, nausea, vomiting, and tachycardia.

it increases AV conduction. Other adverse effects are similar to epinephrine . nervousness, headaches, and trouble sleeping. Local irritation and sneezing may occur with intranasal administration. Rebound congestion and dependence are observed with long-term use. Large doses can cause -hypertensive -headache -cardiac irregularities.

lethargy, sedation, constipation, and xerostomia.

USES treat severe hypertension in hospitalized patients, acting on coronary arteries, kidney arterioles, and mesenteric arteries. used to increase cardiac output in acute heart failure.

-nasal spray decongestants. -ophthalmic drops for the relief of redness of the eyes.

used to treat hypotension in hospitalized or surgical patients (especially those with a rapid heart rate). Phenylephrine acts as a nasal decongestant also used in ophthalmic solutions for mydriasis. used for the treatment of hypertension. It can also be used to minimize the symptoms that accompany withdrawal from opiates, tobacco smoking, and benzodiazepines.


Drug name

MOA

Salmeterol and formoterol

Long acting β agonists (LABAs) that are β2 selective.

Mirabegron

β3 agonist

SE LABAs have been shown to increase the risk of asthma-related deaths. It increase blood pressure and should not be used in patients with uncontrolled hypertension.

USES Used in nocturnal asthma in symptomatic patients taking other asthma medications. It is used for patients with overactive bladder.

INDIRECT-ACTING ADRENERGIC AGONISTS: Drug name Amphetamine

MOA - increase blood pressure significantly by α1 agonist action on the vasculature

SE

USES - discussed under stimulants of the CNS.

___

-as well as β1 -stimulatory effects on the heart.

Tyramine

Cocaine

- enter the nerve terminal and displace stored norepinephrine.

- Its an anesthetics in having the ability to block ( / )dependent norepinephrine Transporter norepinephrine accumulates in the synaptic space  resulting in enhanced sympathetic activity and potentiation of the actions of epinephrine and norepinephrine.

___

- is not a clinically useful drug, but it is important because it is found in fermented foods, such as aged cheese.

- Used In Anesthesia.


MIXED-ACTION ADRENERGIC AGONISTS: MOA Ephedrine

--mixed-action adrenergic agents. They not only release stored norepinephrine from nerve endings but also directly stimulate both α and β receptors.

SE Headache Tremor Hyperactivity Insomnia Nausea Arrhythmias

USES -hypotension. -asthma


Questions ‌ Complete

First line Drug name or class Second line M.O.A Third line use

Isoproterenol

----------------------------------------potent bronchodilator

--------------------------------------------------------------------------------not a clinically useful drug

----------------------------------------block (đ?‘ đ?‘Ž /đ??śđ?‘™ )-dependent norepinephrineTransporter -----------------------------------------

Ephedrine ---------------------------------------------------------------------------------


Answers

A-Isoproterenol ( beta agonist) potent bronchodilator

B-Tyramine displace stored norepinephrine. not a clinically useful drug

C-Cocaine block (

/

)-dependent norepinephrineTransporter

Used In Anesthesia

D-Ephedrine mixed-action adrenergic agents Hypotension and asthma


α-blockers

selective αblockers

α-1 blockers: praosin, teraosin, doxaosin ,tamsulosin.

α-2 blockers: Yohimbine.

Non selective α-blockers

phenoxybenaami ne and phntolamine.


α-ADRENERGIC BLOCKING AGENTS ( alpha antagonist ): Drug name phenoxybenzamine

MOA - Nonselective both α1 and α2 blocker Cardiovascular effects: By blocking α receptors,

SE

USES

postural hypotension, nasal stuffiness, nausea, , vomiting and Reflex tachycardia.

1-Pheochromocytoma. 2-hypertensive crisis.

Postural hypotension.

1-Pheochromocytoma. 2-hypertensive crisis. 3- used locally to prevent dermal necrosis following extravasation of norepinephrine.

Prevents vasoconstriction of peripheral blood vessels by endogenous catecholamines. The decreased peripheral resistance provokes a reflex tachycardia. Epinephrine reversal.

Phentolamine

Nonselective Epinephrine reversal.

Reflex tachycardia.

Selective blockers of the α1 receptor.

Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin

1- Orthostatic hypotension cused by the “first-dose” effect, may be minimized by adjusting the first dose to one-third or one-fourth of the normal dose and by giving the drug at bedtime. 2- Tachycardia 3- Dizziness and headache. 4-sexual dysfunction.

1-alternative to surgery in patients with symptomatic BPH. 2- HTN

Ends in (osin) selective competitive α2 –blocker.

Yohimbine

BPH = Benign prostatic hyperplasia

It is contraindicated in cardiovascular disease, psychiatric conditions, and renal dysfunction.

used as a sexual stimulant and in the treatment of erectile dysfunction.


β-blockers

Selective βblockers

Non selective βblockers

β-1 blockers with partial β-2 agonist

β-1 blockers: Atenolol, Metoprolol and Esmolol

propranolol , timolol , nadolol.

Acebutolol and pindolol.

alpha and beta blockers

labetalol and carvidilol


β-ADRENERGIC BLOCKING AGENTS ( beta antagonist): Ends in (olol) Drug name

MOA

SE

USES

Nonselective β antagonist. -Bronchoconstriction Propranolol

Cardiovascular: -Decrease Cardiac output and oxygen consumption. -Have Negative inotropic and chronotropic effects. -Antiarrhythmic effect. Peripheral vasoconstriction: The reduction in cardiac output produced by all β -blockers leads to decreased blood pressure, which triggers a reflex peripheral V.C that is reflected in reduced blood flow to the periphery. Bronchoconstriction: Blocking β2 receptors in the lungs with COPD or asthma. Disturbances in glucose metabolism: β blockade leads to decreased glycogenolysis and decreased glucagon secretion. Use with caution for insulin diabetic pt. Blocked action of isoproterenol.

-Arrhythmias -Fatigue

-HTN. -Angina pectoris. -MI. -Margrine. -hyperthirodisim.

-Sexual impairment -Metabolic disturbances. -CNS effects.

Nadolol And Timolol

- Nonselective β antagonists.

-glaucoma

Acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, and nebivolol

-Selective β1 antagonists

- cardioselective β blockers in hypertensive patients with impaired pulmonary function.

Acebutolol and pindolol

Antagonists with partial agonist activity. they have intrinsic sympathomimetic activity (ISA).

Labetalol and carvedilol

Antagonists of both α and β Adrenoceptors.

-first-line therapy for chronic stable angina. hypertensive patients with moderate bradycardia. 1-orthostatic hypotension. 2-dizziness.

1-Hypertension. 2-Heart failure.


   

V.C = vasoconstriction COPD = Chronic obstructive pulmonary disease HTN = hypertension MI = myocardial infarction

DRUGS AFFECTING NEUROTRANSMITTER RELEASE OR UPTAKE

Drug name Reserpine

MOA - interfere with neurotransmitter release from storage vesicles This causes the ultimate depletion of biogenic amines. Sympathetic function, in general, is impaired because of decreased release of norepinephrine.

SE has largely been replaced with newer agents with better side effect profiles and fewer drug interactions

USES - hypertension


Questions ‌ Complete First line Drug name or class Second line M.O.A Third line use

Phenoxybenzamine -------------------------------------------------------------------------------------------

---------------------------------------------Selective Îą1 blocker ----------------------------------------------

Propranolol -------------------------------------------------------------------------------------------

---------------------------------------------Antagonists with partial agonist activity they have (ISA). ----------------------------------------------


Answers A-phenoxybenzamine Nonselective α blocker Pheochromocytoma and HTN crisis

B-Prazosin Selective α1 blocker alternative to surgery in patients with symptomatic BPH and HTN

C-Propranolol Nonselective β antagonist Margrine.

D-Acebutolol and pindolol Antagonists with partial agonist activity they have (ISA). hypertensive patients with moderate bradycardia


Drugs Used in Parkinson’s Disease 1-Levodopa and carbidopa Drug class

Levodopa

MOA

- transported into the CNS and converted to dopamine

-a dopamine decarboxylase inhibitor,

Carbidopa

-diminishes the metabolism of levodopa in the periphery, thereby -increasing the availability of levodopa to the CNS

SE -Peripheral effects: Anorexia, nausea, and vomiting, Tachycardia and ventricular extrasystoles, Hypotension, mydriasis, Saliva and urine are a brownish color -CNS effects: Visual and auditory hallucinations and abnormal involuntary movements (dyskinesias), Levodopa can also Cause mood changes, depression, psychosis, and anxiety.

USES

-levodopa–carbidopa substantially reduces the severity of symptoms for the first few years of treatment

Contraindication With Antipsychotic drugs concomitant administration of The vitamin pyridoxine (B 6) and monoamine oxidase inhibitors (MAOIs)

2-Selegiline and rasagiline Drug class

MOA

SE

Selegiline

-selectively inhibits monoamine oxidase (MAO) type B (metabolizes dopamine)

-selegiline at recommended doses has little potential for causing hypertensive crises.

Rasagiline

-an irreversible and selective inhibitor of brain MAO type B

___

USES Parkinson’s Disease

Parkinson’s Disease


3-Catechol-O-methyltransferase inhibitors Drug class

MOA -Selectively and reversibly inhibit COMT.

Entacapone and tolcapone

- central uptake of levodopa

SE dyskinesias, hallucinations, and sleep disorders. Most seriously, fulminating hepatic necrosis is associated with tolcapone use.

USES

-Both of these agents reduce the symptoms of “wearing-off” phenomena seen in patients on levodopa−carbidopa

Entacapone does not exhibit this toxicity and has largely replaced tolcapone.

4-Dopamine receptor agonists Drug class

MOA

SE

USES

-similar to levodopa (ergot derivative)

-orthostatic hypotension are more common,

-are effective in Patients exhibiting fluctuations in response to levodopa.

Bromocriptine -whereas dyskinesia is less prominent. -bromocriptine may cause the mental condition to worsen.

Apomorphine.

Rotigotine pramipexole ropinirole

-These are nonergot dopamine agonists.

-hallucinations, -insomnia, -and orthostatic hypotension - but dyskinesias are less frequent than with levodopa

-acute management of the hypomobility “off” phenomenon -once-daily transdermal patch ___ ___

Bromocriptine It should be used with caution in patients with a history of myocardial infarction or peripheral vascular disease. Because bromocriptine is an ergot derivative, it has the potential to cause pulmonary and retroperitoneal fibrosis.


5-Amantadine Drug class

MOA - ď‚­ the release of dopamine, -blocking cholinergic receptors,

Amantadine

- and inhibiting the Nmethyldaspartate (NMDA).

SE -restlessness, agitation, and hallucinations,

USES -Parkinson’s Disease

-and, at high doses, it may Induce acute toxic psychosis. Orthostatic hypotension,

Current evidence supports action at NMDA receptors as the primary action at therapeutic concentrations.

urinary retention.

6-Antimuscarinic agents Drug class Benztropine, Trihexyphenidyl, Procyclidine, Biperiden

MOA

SE

-Blockage of cholinergic receptor

- These agents can induce mood changes

-it helps to correct the imbalance in the dopamine/acetylcholine ratio

-and produce xerostomia (dryness of the mouth),

USES - much less efficacious than levodopa and play only an adjuvant role in antiparkinsonism therapy

-constipation, and visual problems typical

Antimuscarinic agents CI in patients with glaucoma,prostatic hyperplasia, or pyloric stenosis.


DRUGS USED IN ALZHEIMER’S DISEASE 1-Acetylcholinesterase inhibitors Drug class donepezil galantamine rivastigmine

MOA - inhibition of acetylcholinesterase (AChE)

SE - anorexia, tremors, bradycardia, and muscle cramps

- have some selectivity for AChE in the CNS, as compared to the periphery

USES

-mild to moderate Alzheimer’s disease. - Rivastigmine management of dementia associated with Parkinson’s disease

2-NMDA receptor antagonist Drug class Memantine

MOA - block the NMDA receptor and limiting Ca2+ influx into the neuron

SE - are indistinguishable from the symptoms of Alzheimer’s disease

USES

- moderate to severe Alzheimer’s disease.


DRUGS USED IN MULTIPLE SCLEROSIS 1-Disease-modifying therapies Drug class

Interferon β1a and interferon β1b

Glatiramer

Fingolimod

Teriflunomide

MOA - help to diminish the inflammatory responses that lead to demyelination of the axon sheaths.

-resembles myelin protein and may act as a decoy to T-cell attack. -alters lymphocyte migration, resulting in fewer lymphocytes in the CNS. - pyrimidine synthesis inhibitor that leads to a lower concentration of active lymphocytes in the CNS.

SE

USES

- depression, -MS -local injection site reactions, -hepatic enzyme increases, -and flulike symptoms. - a postinjection reaction Usually self-limiting. -first-dose bradycardia and is associated with an increased risk of infection and macular edema. -elevated liver enzymes.

-MS

-MS

-MS

- Flushing and abdominal pain Dimethyl fumarate

Natalizumab

Mitoxantrone

-alter the cellular response to oxidative stress to reduce disease progression

-MS

- is a monoclonal antibody indicated for MS in patients who have failed first-line therapies.

-MS

- is a cytotoxic anthracycline analog that kills T cells and may also be used for MS.

-MS

Teriflunomide It should be avoided in pregnancy.


2-Symptomatic treatment Drug class

Dalfampridine

MOA - potassium channel blocker, improves walking speeds in patients with MS.

SE

USES - It is the first drug approved for manage symptoms of MS such as spasticity, constipation, bladder dysfunction, and depression.

___

DRUGS USED IN AMYOTROPHIC LATERAL SCLEROSIS Drug class

MOA

SE

USES

- an NMDA receptor antagonist. It is believed to act by

Riluzole

-it is the only drug indicated for the management of ALS. ___

inhibiting glutamate release and blocking sodium channels

Drug-Drug interaction Drug name pramipexole

Interaction -Cimetidine inhibits renal tubular secretion increase the half-life of pramipexole

-with (CYP450) inhibitors ropinirole inhibit the metabolism of ropinirole, requiring an adjustment in ropinirole dosage.


Questions …

First line Drug name or class

Complete

Second line M.O.A Third line use

__________________________________ Natalizumab dopamine decarboxylase inhibitor __________________________________

__________________________________ __________________________________

__________________________________ __________________________________ acute management of the hypomobility “off” phenomenon

__________________________________ inhibition of (AChE) management of dementia associated with Parkinson’s disease __________________________________ potassium channel blocker __________________________________


Answers A-Carbidopa dopamine decarboxylase inhibitor Parkinson’s Disease

B-Apomorphine. These are nonergot dopamine agonists acute management of the hypomobility “off” phenomenon

C-rivastigmine inhibition of acetylcholinesterase (AChE) management of dementia associated with Parkinson’s disease

D-Natalizumab a monoclonal antibody MS

E-Dalfampridine potassium channel blocker manage symptoms of MS


Benzodiazepines Zolpidem Zaleplon Eszopiclone

BARBITURATES

Anxiolytic and Hypntic Drugs

Ramelteon

Antidepressants

Buspirone


anxiolytic drugs

I.Benzodiazepines MOA 1-the targets for benzodiazepine actions are (GABA-A) receptors 2- Benzodiazepines modulate GABA effects by binding to (BZ) receptors -Binding of GABA to its receptor triggers an opening of the central - BZ increase the frequency of channel openings produced by GABA ion channel chloride influx hyperpolarization decreases neurotransmission by (action potential inhibition ) Therapeutic use Anxiety disorders Sleep disorders Amnesia Seizures Muscular disorders anxiety related to Panic disorder insomnia cause a form of adjunctive status -Spasticity depression and conscious sedation therapy epilepticus -multiple sclerosis schizophrenia prior to anesthesia -cerebral palsy prolonged shortand longTemazepam Midazolam Clonazepam lorazepam Diazepam Drug example treatment term treatment Triazolam diazepam Flurazepam clonazepam , alprazolam Estazolam lorazepam , Quazepam diazepam Adverse effect Drowsiness , confusion , Ataxia ( high doses ) , Cognitive impairment.

II.BARBITURATES MOA -potentiate GABA action on chloride entry (by prolonging the duration of the Cl-channel openings) . -block excitatory glutamate receptors Therapeutic use Anesthesia Anticonvulsant Sedative/hypnotic -tonic–clonic seizures -anxiety, nervous tension, -refractory status epilepticus -Insomnia ( not accepted -tolerance-) Thiopental (IV) Phenobarbital Butalbital + acetaminophen or aspirin + caffeine Drug example (for migraine headahes) Adverse effect drowsiness, impaired concentration, mental and physical sluggishness , hangover effect , nausea and dizziness . Abrupt withdrawal : nausea , vomiting, seizures, delirium, and cardiac arrest , death . Why BZ have replaced barbiturates ?


1-Less tolerance & physical dependence 2- BZ are Safe in overdose 3-They cause less disturbance in sleep patterns 4-BZs produce minimal sedation and motor impairment 5- Barbiturates causes drug interaction because they are enzyme inducers 6-A Benzodiazepine antagonist is available (Flumazenil)

Drug example

Note :

1.Antidepressants first-line agents for chronic anxiety disorders and GAD Selective serotonin serotonin/norepinephrine reuptake inhibitors reuptake inhibitors (SNRIs) (SSRIs) -escitalopram -venlafaxine -paroxetine -duloxetine Use alone

Therapeutic use MOA

Combination With

OTHER ANXIOLYTIC AGENTS

benzodiazepines

Long-term use of antidepressants and benzodiazepines for anxiety disorders is often required to maintain ongoing benefit and prevent relapse

2-Buspirone chronic treatment of GAD mediated by serotonin (5-HT1A) receptors, although it also displays some affinity for D2 and 5-HT2A receptors SE: headaches, dizziness, nervousness, nausea, and light-headedness - has an efficacy comparable to that of the benzodiazepines -not effective in acute anxiety states

OTHER HYPNOTIC AGENTS MOA Therapeutic use

Zolpidem selectively binds to the subtype of BZ receptor middle-of-the-night awakening

Adverse effect

nightmares, agitation, anterograde amnesia, headache, GI upset, dizziness, and daytime drowsiness

Note :

-shows few withdrawal effects -exhibits minimal rebound insomnia -little tolerance occurs with prolonged use

Zaleplon Oral nonbenzodiazepine hypnotic similar to zolpidem

Eszopiclone Acts on the BZ1 receptor Effective for insomnia for up to 6 months anxiety, dry mouth, headache, peripheral edema, somnolence, and unpleasant taste

-fewer residual effects on psychomotor and cognitive function compared to zolpidem

These drugs do not alter sleep stages and hence are often the preferred hypnotics. This may be due to their relative selectivity for the BZ1 receptor. All three agents are controlled substances .

Ramelteon selective agonist at the MT1 and MT2 subtypes of melatonin receptors. insomnia characterized by difficulty falling asleep (increased sleep latency) dizziness, fatigue, and somnolence. Ramelteon may also increase prolactin levels. -minimal potential for abuse -no evidence of dependence or withdrawal effects -can be administered long term.


SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs): Citalopram , Escitalopram , Fluoxetine , Fluvoxamine, Paroxetine, Sertraline

SEROTONIN/NOREPINEPH RINE REUPTAKE INHIBITORS (SNRIs): Desvenlafaxine Duloxetine, Levomilnacipran, Venlafaxine

Antidepressants

ATYPICAL ANTIDEPRESSANTS :

Bupropion, Mirtazapine Nefazodone Trazodone

TRICYCLIC ANTIDEPRESSANTS (TCAs): Amitriptyline, Amoxapine, Clomipramine ,Desipramine, Doxepin Imipramine, Maprotiline ,Nortriptyline Protriptyline, Trimipramine

Vilazodone ,Vortioxetine

MONOAMINE OXIDASE INHIBITORS (MAOIs): Isocarboxazid ,Phenelzine Selegiline , Tranylcypromine


Drug class Selective serotonin reuptake inhibitors (SSRIs)

SEROTONIN / NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) A. Venlafaxine and desvenlafaxine

B. Duloxetine

C.Levomilnacipran

MOA - block the reuptake of serotonin, leading to increased concentrations of the neurotransmitter in the synaptic cleft

- SNRIs, may be effective in treating depression in patients in whom SSRIs are ineffective.

-Venlafaxine is a potent inhibitor of serotonin reuptake and, at medium to higher doses, is an inhibitor of norepinephrine reuptake. Venlafaxine has minimal inhibition of the CYP450 isoenzymes and is a substrate of the CYP2D6 isoenzyme. Desvenlafaxine is the active, demethylated metabolite of venlafaxine - inhibits serotonin and norepinephrine reuptake at all doses.

- older SNRI

atypical antidepressants:

SE headache, sweating, anxiety and agitation, gastrointestinal (GI) effects (nausea, vomiting, diarrhea), weakness and fatigue, sexual dysfunction, changes in weight, sleep disturbances (insomnia and somnolence

USES 1-The primary indication for SSRIs is depression. 2- A number of other psychiatric disorders, including obsessive– compulsive disorder, panic disorder, generalized anxiety disorder, posttraumatic stress disorder, social anxiety disorder, premenstrual dysphoric disorder.

___

___

The most common side effects of venlafaxine are nausea, headache, sexual dysfunction, dizziness, insomnia, sedation, and constipation. At high doses, there may be an increase in blood pressure and heart rate

___

GI side effects are common with Insomnia, dizziness, somnolence, sweating, and sexual dysfunction are also seen. may increase blood pressure or heart rate. -similar to other SNRIs.

___

treatment of depression in Europe and fibromyalgia in the United States).


Drug class A. Bupropion

MOA

SE

- is a weak dopamine and norepinephrine reuptake inhibitor ___

B. Mirtazapine

C. Nefazodone and trazodone

D. Vilazodone

E. Vortioxetine

-enhances serotonin and norepinephrine neurotransmission by serving as an antagonist at presynaptic Îą2 receptors. - Additionally, some of the antidepressant activity may be related to antagonism at 5-HT2 receptors. -It is sedating because of its potent antihistaminic activity -These drugs are weak inhibitors of serotonin reuptake. -Their therapeutic benefit appears to be related to their ability to block postsynaptic 5-HT2a receptors. -Both agents are sedating, probably because of their potent histamine H1 -blocking activity - is a serotonin reuptake inhibitor and a 5-HT1a partial agonist. -Although the extent to which the 5HT1a receptor activity contributes to its therapeutic effects is unknown, this possible mechanism of action renders it unique from that of the SSRIs. - a combination of serotonin reuptake inhibition, 5-HT1a agonism, and 5-HT3 and 5-HT7 antagonism as its suggested mechanisms of action to treat depression

___

contributing to orthostasis and dizziness

- similar to the SSRIs, including a risk for discontinuation syndrome if abruptly stopped.

nausea, vomiting, and constipation, which may be expected due to its serotonergic mechanisms

USES used to alleviate the symptoms of depression. Bupropion is also useful for decreasing cravings and attenuating withdrawal markedly sedating, which may be an advantage in depressed patients having difficulty sleeping.

used off-label for the management of insomnia.

___

___


Drug class

MOA

TRICYCLIC ANTIDEPRESSANTS

-Inhibition of neurotransmitter reuptake -Blocking of receptors

MONOAMINE OXIDASE INHIBITORS

-form stable complexes with the enzyme, causing irreversible inactivation. This results in increased stores of norepinephrine, serotonin, and dopamine within the neuron and subsequent diffusion of excess neurotransmitter into the synaptic space

SE

USES

blurred vision, xerostomia (dry mouth), urinary retention, sinus tachycardia, constipation, and aggravation of angleclosure glaucoma

The TCAs are effective in treating moderate to severe depression. Some patients with panic disorder also respond to TCAs. used to help prevent migraine headache and treat chronic pain syndromes

occipital headache, stiff neck, tachycardia, nausea, hypertension, cardiac arrhythmias, seizures

for depressed patients who are unresponsive or allergic to TCAs and SSRIs or who experience strong anxiety. A special subcategory of depression


FIRST-GENERATION ANTIPSYCHOTIC (high potency) :

FIRST-GENERATION ANTIPSYCHOTIC (low potency) Chlorpromazine Prochlorperazine

Fluphenazine Haloperidol , Loxapine Perphenazine , Pimozide

Thioridazine

Prochlorperazine Thiothixene Triuoperazine

Antipsychotic Drugs

SECOND-GENERATION ANTIPSYCHOTIC: Aripiprazole, Asenapine , Clozapine , Iloperidone, Lurasidone, Olanzapine , Quetiapine , Paliperidone , Risperidone , Ziprasidone


Drug class

MOA

SE

USES

A. Firstgeneration antipsychotics

-The first-generation antipsychotic drugs (also called conventional, typical, or traditional antipsychotics) are competitive inhibitors at a variety of receptors, but their antipsychotic effects reflect competitive blocking of dopamine D2 receptors. -particularly drugs that bind tightly to dopaminergic neuroreceptors, such as haloperidol

- First-generation antipsychotics are more likely to be associated with movement disorders known as extrapyramidal symptoms (EPS),

-Antipsychotic

B. Secondgeneration antipsychotic drugs

-Dopamine antagonism -Serotonin receptor–blocking activity inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

1- All antipsychotic drugs can reduce hallucinations and delusions associated with schizophrenia. 2-: Dystonias (sustained contraction of muscles leading to twisting, distorted postures), Parkinson-like symptoms, akathisia (motor restlessness). 3-blurred vision, dry mouth confusion, and inhibition of gastrointestinal and urinary tract smooth muscle, leading to constipation and urinary retention.

(Second-generation agents are generally used as first-line therapy for schizophrenia) 1-. Treatment of schizophrenia. 2- Prevention of nausea and vomiting


Drug name

MOA -Binds to GABA inhibitory receptor

Benzodiazepines

SE Hypornatremia, drowsiness, fatigue, Stevens-Johnson syndrome.Blood dyscrasias.

USES -Acute-seizures (emergency). -Lonazepam and clobazam may be prescribed as adjunctive therapy for particular types of seizures. -Diazepam for prolonged generalized tonic–clonic seizures

-Blocks sodium

-Hyponatremia in elderly.

-Focal seizures,

channels Carbamazepine

-generalized tonic-clonic seizures, -trigeminal neuralgia -bipolar disorder. -Voltage-gated sodium

Dizziness, somnolence, diplopia,

-Partial-onset seizures in

channel blocker

and headache.

adults.

Eslicarbazepine Serious AE: rash, psychiatric

-Inhibiting T-type calcium channels.

Drowsiness, hyperactivity, nausea, sedation, GI upset,

-Open voltage-gated M-

Urinary retention,QT interval

type potassium

prolongation,blue skin

channels

discoloration,and retinal

-Absence seizures.

Ethosuximide Ezogabine

abnormalities.

___


Drug name Felbamate

MOA

SE

-Multiple proposed mechanisms

Irritability, Aplastic anemia and hepatic failure.

USES -Refractory epilepsies (particularly LennoxGastaut syndrome)

Gabapentin

-Unknown

-Mild drowsiness, dizziness, ataxia, weight gain, and diarrhea

Adjunct therapy for focal seizures and treatment of postherpetic neuralgia.

Lacosamide

-Blocks sodium channels

Dizziness, headache, and fatigue

Lamotrigine

-Blocks sodium channels and high voltage-dependent calcium channels.

Rash (Stevens-Johnson syndrome—potentially life threatening).

Adjunctive treatment of focal seizures

-Focal, generalized, absence seizures, Lennox-Gastaut syndrome, and bipolar disorders

Levetiracetam

-Unknown

-Mood alterations, Sedation, dizziness, headache

-Adjunct therapy of focal onset, myoclonic, primary generalized tonic–clonic seizures

Oxcarbazepine

-Blocks sodium channels

Hyponatremia, Vertigo,

-Partial-onset seizures.

ataxia, and diplopia.

Perampanel

Phenobarbital and primidone

-Blocks AMPA glutamate receptors

-Enhancement of the inhibitory effects of GABA-mediated neurons

Serious psychiatric and behavioral reactions, dizziness

Adjunctive treatment of partial-onset seizures

-Status epilepticus ___


Drug name Phenytoin

MOA

USES

-Blocks voltage-gated sodium

Depression of the CNS

Focal and generalized

channels

(nystagmus and ataxia)

tonic– clonic seizures

And

Gingival hyperplasia , peripheral neuropathies

fosphenytoin Rufimamide

- Blocks Sodium channel

Tiagabine

-Blocks GABA uptake.

Topiramate

SE

-Multiple mechanisms of action

Potential for shortened QT intervals.

and status epilepticus. Adjunctive treatment of seizures associated with Lennox- Gastaut syndrome

Seizures have occurred in patients using tiagabine

Adjunctive treatment

who did not have epilepsy.

seizures

weight loss, and

Partial and primary

paresthesias. Renal

generalized epilepsy.

stones, glaucoma,

Prevention of

oligohidrosis (decreased

migraine.

in partial-onset

sweating), and hyperthermia Valproic acid

-Sodium channel blockade,

and divalproex

blockade of GABA-T, and at the

Weight gain, easy bruising, nausea, tremor.

T-type calcium channels

Focal and primary generalized epilepsies

Vigabatrin

- Irreversible binding of GABA-T

Visual field loss,anemia, somnolence

Zonisamide

- Blockade of both voltage-gated

CNS adverse effects,

sodium channels and T-type

kidney stones.

calcium currents

Oligohidrosis increased body temperature and decreased sweating

Focal epilepsy


Questions ‌ Complete First line Drug name or class Second line M.O.A Third line use

------------------------------------------Blocks GABA uptake. -------------------------------------------

------------------------------------------Inhibiting T-type calcium channels. Absence seizures.

Oxcarbazepine ------------------------------------------Partial-onset seizures

Zonisamide ------------------------------------------Focal epilepsy


Answers A-Tiagabine Blocks GABA uptake. Adjunctive treatment in partial-onset seizures

B-Ethosuximide Inhibiting T-type calcium channels. Absence seizures.

C-Oxcarbazepine Blocks sodium channels Partial-onset seizures

D-Zonisamide Blockade of both voltage-gated sodium channels and T-type calcium currents Focal epilepsy


I. Inhaled anesthetics - Inhalation anesthetics are volatile liquids except nitrous oxide which is a volatile gas.     

Halothane Isoflurane Desflurane Sevoflurane Nitrous oxide (N2O)

1. Halothane:

Advantages

Disadvantages

- It has a sweet odor

- Inadequate muscle relaxation

- It is highly potent

- Poor analgesic (supplemented with No

- Non-irritant to the respiratory system

piates)

- Rapid induction and fast recovery

- May produce respiratory failure

- Useful in plastic surgery to produce

- Marked arterial hypotension due to

“bloodless area” through inducing controlled

myocardial depression & vasodilatation

hypotension

- Sensitization of the heart to adrenaline which may cause cardiac dysrhythmias, particularly ventricular extrasystoles -Hepatotoxic (life-threatening hepatic necrosis)

Halothane is not hepatotoxic in children. Also, it has a pleasant odor. This makes it the agent of choice for children. SE:.Malignant hyperthermia


2. Isoflurane - It is a halogenated anesthetic that has low biotransformation and low organ toxicity. - Isoflurane is a very stable molecule that undergoes little metabolism - Unlike the other halogenated anesthetic gases, it does not induce cardiac arrhythmias nor sensitize the heart to the action of catecholamines.

3. Desflurane:

4. Sevoflurane:

- Induction & recovery are faster than halothane.

- It resembles desflurane but it is more potent.

- Its potency is lower than the above mentioned halogenated anesthetics.

-It is less likely to cause respiratory irritation suitable for children.

- causes some respiratory tract irritation which can lead to cough & bronchospasm.

- It is metabolized to fluoride nephrotoxic.

- It causes a concentrationdependent hypotension (due to peripheral and coronary v.d.).

5. Nitrous Oxide (laughing gas) N2O Advantages

Disadvantages

- Non-irritant to the respiratory tract

- Weak general anesthetic

- Rapid induction and recovery

- Inadequate muscle relaxation

- No serious effects on circulation, respiration

- Prolonged exposure ( 6 h)  inactivation of

- Good ANALGESIA, useful for production of

methionine synthase, an enzyme required

analgesia during child birth (during delivery)

for DNA and protein synthesis,  bone marrow depression  aplastic anemia & leucopenia It should be avoided in anemic patients - May cause abortion & fetal abnormality (teratogenic) if given during pregnancy


II. Intravenous Anesthetics

Ultrashort-Acting Barbiturates - They are ultrashort-acting, because of the rapid entry to the CNS, which is followed by a relatively quick redistribution of the drug to different body tissues. - Examples: thiopental sodium, methohexital sodium and thiamylal sodium Therapeutic Uses: 1. Brief general anesthesia for minor operations 2. Induction of anesthesia which is then completed by another anesthetic agent, e.g.,N2O 3. Anticonvulsant 4. For basal anesthesia, the drug is given rectally in doses less than those required to produce full anesthesia.

Etomidate - It is a potent ultrashort-acting non-barbiturate hypnotic agent lacking analgesic properties. - Its pharmacological properties are similar to those of barbiturates. - It is used for induction and supplement to maintain anesthesia.

Benzodiazepines - They are useful as pre-anesthetic medication and for induction and maintenance of anesthesia.  Examples: - Diazepam, lorazepam and midazolam (midazolam has a slower in onset of action than all drugs but lacks the tendency to cause respiratory & CVS depression)  Uses in anesthesia - Diazepam for preanesthetic medication - Lorazepam is used extensively in cardiac surgery. It produces amnesia and is particularly useful during cardiopulmonary bypass to ensure unawareness of the procedure.


ketamine 1.produces analgesia, amnesia and paralysis of movement without actual loss of consciousness. 2.It blocks NMDA-receptors

III.LOCAL ANESTHETICS (LAs) - Mechanism of action: Na+ channel blockade - They abolish sensation in certain area of the body without producing unconsciousness. Adverse effects:.   

Seizures Cardiovascular collapse Allergy


Drug class

MOA -Interaction with opioid receptors on CNS and other anatomic structures,

1-Morphine

-also acts at κ receptors in spinal cord.

SE -Respiratory depression -addiction -Hypotension -Dysphoria -Sedation -Constipation -Urinary retention

uses -Analgesia -Anesthesia -Antitussive -relieves diarrhea -in acute pulmonary edema

- the release of substance P, which modulates pain perception in the spinal cord.

2-Codeine

-Its conversion to morphine by the CYP450 2D6 enzyme system

3-Oxycodone and oxymorphone

Same MOA of morphine

4Hydromorphone and hydrocodone

Same MOA of morphine

5-Fentanyl

6-Sufentanil, alfentanil, and remifentan

7-Methadone

8-Meperidine

Same side effect

Same side effect

Same MOA of morphine also has 100-fold the analgesic potency of morphine and is used for anesthesia.

three synthetic opioid agonists related to fentanyl. Sufentanil is even more potent than fentanyl, -mediated by μ receptors. - In addition, methadone is an antagonist of -(NMDA) receptor - and a norepinephrine -and serotonin reuptake inhibitor. - κ agonist, - some μ agonist activity -and has anticholinergic effect

CNS SE in patients with renal insufficiency

-Less histamine release, sedation, -and constipation in comparison to morphine

___ -cause torsades de pointes -interacting with cardiac potassium channels.

-delirium - hyperreflexia - Myoclonus - seizures. Naloxone does not antagonize the effects of normeperidine could worsen seizure activity

-good antitussive activity at doses that do not cause analgesia -only for mild to moderate pain. -higher-dosage used only by patients who tolerant to opioids -it is preferred over morphine in patients with renal dysfunction -treatment of cancer patients who are tolerant to opioids -combined with local anesthetics for labor and postoperative pain. -analgesic - and sedative properties during surgical procedures requiring anesthesia. the controlled withdrawal of dependent abusers from opioids and heroin

Not recommended as first-line opioid choice.


PIOID AGONISTS

(NMDA) receptor = N-methyl-d-aspartate receptor

Drug interaction – caution Morphine  

in patients with asthma, because it is releases histamine depressant actions by phenothiazines, (MAOIs), and TCA

Codeine  

Do not use in patients with renal dysfunction. inhibitors of CYP2D6

Fentanyl    

in transdermal patch because death resulting from hypoventilation. in opioid-naïve patients, patches should not be used in managing acute and postoperative pain drug interaction by the CYP450 3A4 system

Methadone 

in patients with a family or personal history of QT prolongation or those taking other medications that can prolong the QT interval.

Meperidine  

should only be used for short-term (≤48 hours) management of pain elderly patients or those with renal insufficiency, hepatic insufficiency, preexisting respiratory compromise or recent administration of MAOIs. Serotonin syndrome has also been reported in patients receiving both meperidine and (SSRIs).


PARTIAL AGONISTS AND MIXED AGONIST–ANTAGONISTS Drug class

1-Buprenorphine

MOA

-partial agonist, acting at the μ receptor.

SE It causes little -sedation, -respiratory depression

uses

opioid detoxification or maintenance or dependence

- hypotension,

-agonist on κ receptors

2- Pentazocine

-and is a weak antagonist at μ and δ receptors.

-respiratory depression -  the activity of the GIT. -High doses  BP

- relieve moderate pain

and can cause -hallucinations, -nightmares, -dysphoria, -tachycardia, -dizziness

Like pentazocine

-Abuse -psychotomimetic effects

-treatment of chronic pain

3- Nalbuphine and butorphanol

-butorphanol is available in a nasal formulation that has been used for severe headaches

caution Pentazocine  When use in patients with angina or coronary artery disease, since it can increase systemic and pulmonary arterial pressure and, thus, increase the work of the heart.


ANTAGONISTS Drug class

MOA

SE

-antagonist at μ, κ, and δ receptors, 1-Naloxone - with a 10-fold higher affinity for μ than for κ receptors.

2-Naltrexone

-similar to those of naloxone. It has a longer duration of action

___

hepatotoxicity

uses -reverse the coma and respiratory depression of opioid overdose.

-combination with clonidine (or with buprenorphine) for rapid opioid detoxification -alcoholism

OTHER ANALGESICS Drug class

MOA

SE

-agonist at the μ receptor 1- Tapentadol

-and an inhibitor of norepinephrine reuptake

- binds to the μ opioid receptor. 2- Tramadol

uses moderate to severe pain, both chronic and acute.

___

- Anaphylactoid reactions

-moderate to moderately severe pain

-weakly inhibits reuptake of norepinephrine and serotonin

Tapentadol should be avoided in patients who have received MAOIs within the last 14 days Drug – Drug intraction with Tramadol such as SSRIs, MAOIs, and tricyclic antidepressants,


Questions ‌ 1- Complete

First line Drug name or class Second line M.O.A Third line use

Pentazocine ---------------------------------------------------------------------------

--------------------------------------------------------------------------good antitussive activity

-------------------------------------partial agonist, acting at the Îź receptor. --------------------------------------

--------------------------------------------------------------------------For both chronic and acute. pain

-------------------------------------has anticholinergic effect Not recommended as first-line opioid choice.


Answers 1- Complete A- Pentazocine -agonist on κ receptors and is a weak antagonist at μ and δ receptors. relieve moderate pain

B- Codeine Its conversion to morphine good antitussive activity

C- Buprenorphine partial agonist, acting at the μ receptor. opioid detoxification or maintenance or dependence

D- Meperidine has anticholinergic effect Not recommended as first-line opioid choice.

E- Tapentadol -agonist at the μ receptor and an inhibitor of norepinephrine reuptake For both chronic and acute. pain


Drugs of Abuse

HALLUCINOGENS

Synthetic Cannabinoids

Marijuana

Lysergic acid diethylamide

SYMPATHOMIMETICS

Synthetic Cathinones

Methylenedioxymethamphetamine (MDMA),

ETHANOL

drugs used in the treatment of alcohol dependence:

Acamprosate

Amphetamines

Naltrexone

Cocaine

Disulfiram


HALLUCINOGENS Drug class

MOA - LSD produces its psychedelic effects through serving as a potent partial agonist at 5-HT2A receptors.

SE 1-mood alterations, sleep disturbances, and anxiety. 2-tachycardia, increased blood pressure and body temperature, dizziness, decreased appetite, and sweating 3-most troubling side effects are the loss of judgment and impaired reasoning = bad trip

Marijuana

Synthetic Cannabinoids

-CB1 receptors are activated by marijuana, Marijuana stimulates the amygdala, causing the user to have a sense of novelty to anything the user encounters through an enhancement of sensory activity. For this same reason, heavy users have a down-regulation in their CB1 receptors, leaving them with a feeling of boredom when not taking the drug. The effects of marijuana on Îł-aminobutyric acid (GABA) in the hippocampus diminish the capacity for shortterm memory in users

1- Tachycardia 2- Impaired memory 3- Hallucinations 4- Conjunctivitis 5- increased appetite 6- Impaired coordination

- similar to marijuana

1-tachycardia 2-hypertension. 3-extreme hallucinations

Marijuana help in the treatment of chemotherapy-induced nausea and vomiting, cachexia secondary to cancer and AIDS, epilepsy, chronic pain, MS, glaucoma, and anxiety


SYMPATHOMIMETICS Drug class

Cocaine

MOA -(CNS) stimulation by inhibiting the reuptake of norepinephrine into the adrenergic neuron,thus increasing the amount of catecholamines available at the synapse.

SE

Management the toxicity

-Euphoria ,Tachycardia

cocaine toxicity is treated with:

-Agitation, Hypertension

-short-acting antihypertensive, -anticonvulsants, -and symptomatic supportive care.

-Seizure Arrhythmias and Respiratory failure

-stimulate the pleasure center result from inhibition of reuptake of dopamine and serotonin

Amphetamine

Synthetic Cathinones

- very similar to those of cocaine. In many cases, these effects may last longer and be associated with more stimulation and less euphoria

- similar to cocaine

- similar to that of cocaine toxicity.

- similar to cocaine

-dehydration and renal failure -water intoxication and hyponatremia -ruxism (teeth grinding) and trismus (jaw clenching) serotonin syndrome

-similar to that of cocaine toxicity -Cyproheptadine is a serotonin antagonist that has been used to treat serotonin syndrome.

- increase the release and inhibit the reuptake of catecholamines (norepinephrine, epinephrine, and dopamine)

- similar to cocaine

- similar to the emergent treatment of cocaine


ETHANOL MOA Ethanol (EtOH)

SE

ethanol exerts its desired and toxic effects through several mechanisms, -enhancing the effects of the inhibitory neurotransmitter GABA, -inducing the release of endogenous opioids, -and altering levels of serotonin and dopamine. Ethanol is a selective CNS depressant at low doses resulting in decreased inhibitions and the characteristic loquaciousness or drunken behavior.

-profound hepatic, cardiovascular, pulmonary, hematologic, endocrine, metabolic, and CNS damage

At high doses, it is a general CNS depressant, which can result in coma and respiratory depression

Management the toxicity 1- symptomatic supportive care 2- administration of thiamine and folic acid to prevent/treat Wernicke encephalopathy and macrocytic anemia.

3- Extremely high levels can be dialyzed,

The following are drugs used in the treatment of alcohol dependence Drug name

Disulfiram

MOA -blocks the oxidation of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase

Note - seriously desiring to stop alcohol ingestion

This results in the accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea.

-stop alcohol ingestion in conjunction with supportive psychotherapy Naltrexone

- long-acting opioid antagonist -better tolerated than disulfiram and does not produce the aversive reaction that disulfiram does.

Acamprosate

- poorly understood MOA

- used in alcohol dependence treatment programs in conjunction with supportive psychotherapy


CNS Stimulants CNS Stimulants

PSYCHOMOTOR STIMULANTS

HALLUCINOGENS

Methylxanthines

These agents are discussed in detail in Chapter 15

Nicotine

Amphetamine

Methylphenidate

Varenicline

Cocaine


Drug name

MOA Several mechanisms: -including translocation of extracellular , increase in cAMP and cGMP

Methylxanthines

caused by: -inhibition of phosphodiesterase,

Nicotine

-relax the smooth muscles of the bronchioles.

-A high dosage is required for toxicity, which is manifested by emesis and convulsions.

-Caffeine used in combination with the acetaminophen and aspirin for the management of headaches.

-The lethal dose is induces cardiac arrhythmias.

-In low doses, nicotine causes ganglionic Stimulation by depolarization.

-Irritability and tremors. -Intestinal cramps. -Diarrhea. -Increase heart rate and blood pressure. In addition, cigarette smoking increases the rate of metabolism for a number of drugs.

The effects of amphetamine is indirect. It Depend upon  level of catecholamine in synaptic spaces. -by releasing intracellular stores of catecholamine,

USES

-Moderate doses of cause insomnia,Anxiety and agitation.

-and blockade of adenosine receptors.

-At high doses, nicotine causes ganglionic blockade.

Amphetamine

SE

may cause addiction, leading to dependence, tolerance, and drugseeking behavior. In addition, they have undesirable effects on CNS , CVS , and GIT

The transdermal patch and chewing gum containing nicotine have been shown to reduce nicotine withdrawal Symptoms and to help smokers stop smoking. - (ADHD). -Narcolepsy. -Appetite suppression.

- also inhibits (MAO) and is a weak reuptake transport inhibitor, high levels of catecholamine are readily released into synaptic spaces.

Methylxanthines stimulate secretion of gastric acid,CI in individuals with peptic ulcers.

  

cAMP = cyclic adenosine monophosphate cGMP = cyclic guanosine monophosphate ADHD = Attention deficit hyperactivity disorder


Drug name

MOA

- is a dopamine and norepinephrine transport inhibitor

SE

-GI adverse effects are the most common and include:

USES

- ADHD

-Other reactions include anorexia, insomnia, nervousness, and fever.

Methylphenidate

-In seizure patients, methylphenidate may increase seizure frequency, especially if the patient is taking antidepressants.

Varenicline

Cocaine

-partial agonist at neuronal nicotinic Acetylcholine receptors in the CNS.

- blockade of reuptake of the monoamines (norepinephrine, serotonin, and dopamine) into the presynaptic terminals.

____

-management of smoking cessation in patients with nicotine withdrawal symptoms.

- severe depression. ____

Methylphenidate CI in patients With glaucoma. Patients taking varenicline should be monitored for suicidal thoughts, vivid nightmares, and mood changes.


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

Nicotine ------------------------------------------------------------------------------------------------------------------------------------partial agonist at neuronal nicotinic Acetylcholine receptors in the CNS.

--------------------------------------------Cocaine --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(ADHD),Narcolepsy and Appetite suppression.


Answers 1- Complete A-Nicotine In low dosesnicotine causes ganglionic Stimulation At high doses causes ganglionic blockade.

Reduce withdrawal Symptoms and to help smokers stop smoking

B-Varenicline partial agonist at neuronal nicotinic Acetylcholine receptors in the CNS. management of smoking cessation

C-Cocaine blockade of reuptake of the monoamines into the presynaptic terminals. ____

D-Amphetamine ď‚­ level of catecholamine in synaptic spaces and inhibits (MAO) and is a weak reuptake transport inhibitor (ADHD),Narcolepsy and Appetite suppression


.


1- Diuretics … Drug class

MOA

SE

- and water reabsorption. -  blood volume -  COP and RBF

Thiazide diuretics

Special indication In patient who has Osteoporosis

Hyperuricemia Hyperglycemia

Loop diuretics

Act on the thick ascending loop of henle - / / cotransport -  renal vascular resistance -  RBF

Potassium-sparing diuretics

-inhibit DCT

/

-

Patients with poor renal function or not responded to thiazide diuretic

-

__

exchange in

combination with other diuretics to  loss of

Thiazide diuretics in Patients with inadequate kidney function Thiazide diuretics antagonized by probenecid

2-  Blocker … Ends in (OLOL) Drug class  Blocker

MOA Block  receptor -  sympathetic activity from(CNS) - inhibit the release of renin -  the secretion of aldosterone

Nonselective  Blocker

SE - Bradycardia

- CNS SE fatigue, lethargy, and insomnia.

in patients with asthma.

  

COP = cardiac output RBF = renal blood flow And CI = contraindication

 

DCT = distal convoluted tubules (CNS) = central nervous system

Special indication HTN patients with concomitant heart disease.


MOA 3-Renin inhibitor

Acts earlier in the renin–angiotensin– aldosterone system than ACE inhibitors or ARBs Block ACE enzyme and  B.P by - PVR

4-ACE inhibitor

Ends in (pril)

SE Diarrhea, especially at higher doses, and can also cause cough and angioedema Dry cough ,

Ends in(Sartan)

Block the AT1 receptors

__

- HTN with diabetic nephropathy

Altered taste , Angioedema and

5-ARBs blockers

Special indication

- Patients with systolic dysfunction

Hyperkalemia

- hypertensive patients with chronic kidney disease

similar to those of ACE inhibitors, but the risks of dry cough significantly decreased.

in patients with a compelling indication of diabetes, heart failure, or chronic kidney disease

ACE inhibitor , ARBs and Renin inhibitor CI in pregnant women ARBs should not be combined with an ACE inhibitor for the treatment of hypertension due to similar mechanisms and adverse effects. Aliskiren is metabolized by CYP 3A4 and is subject to many drug interactions

    

ACE = Angiotensin-converting enzyme B.P = blood pressure PVR = peripheral vascular resistance First line treatment ARBs = Angiotensin II Receptor Blockers

AT1

= Angiotensin II Receptor


Drug class 6- Ca2+ Channel blocker

MOA

SE

Block the inward movement of calcium by binding to Ltype calcium channels in the heart and in smooth muscle. smooth muscle relaxation V.D

-First-degree atrioventricular block -constipation - headache and dizziness

Special indication Hypertensive patients who also have asthma, diabetes, and/or peripheral vascular disease, angina.

-Peripheral edema 7- α adrenoceptor blocking agents

8- Clonidine

block of α1adrenoceptors, relaxation of both arterial and venous smooth muscle. Acts centrally as an α2 agonist to produce inhibition of sympathetic vasomotor centers , reduced total peripheral resistance and decreased blood pressure

9- Methyldopa

10- Vasodilator

α2 agonist that is converted to methylnorepinephrine centrally to diminish adrenergic outflow from the CNS. act by producing relaxation of vascular smooth muscle

-lack of energy -headache and dizziness -postural hypotension and first dose hypotension -sedation, -dry mouth, -constipation

-Hypertension refractory cases. -Benign prostatic hyperplasia -Hypertension that has not responded adequately to treatment with two or more drugs. -hypertension complicated by renal disease.

-sedation

-

-drowsiness.

-increase plasma renin concentration, resulting in sodium and water retention. -Headache tachycardia nausea, sweating, arrhythmia, and precipitation of angina.

__

-Hypertrichosis

Ca2+ Channel blocker C I in patients with heart failure or with atrioventricular block 

V.D = Vasodilation


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

-----------------------------

-----------------------------

Block ACE enzyme

-----------------------------

-----------------------------

combination with other diuretics to ď‚Ż loss of đ??ž

Methyldopa ----------------------------HTN in pregnancy

-------------------------------------------------------HTN patients with concomitant heart disease.

--------------------------------------------------------in patient who has Osteoporosis

2- True and false ? A. One of side effect of Ca2+ Channel blocker is rebound HTN ( B. M.O.A of ACE inhibitor is Block the AT1 receptors ( ) C. D. E. F.

)

ď ˘ Blocker decrease the secretion of aldosterone ( ) Loop diuretics can be use in Patients with poor renal function ( ) Îą adrenoceptor blocking agents cause Hypertrichosis ( ) M.O.A of Renin inhibitor Acts earlier in the renin–angiotensin–aldosterone system than ACE inhibitors or ARBs ( )


Answers 1- Complete A-

ACE inhibitors (Captopril,Lisinopril…….pril) Block ACE enzyme HTN with diabetic nephropathy or Patients with systolic dysfunction or HTN pt. with chronic kidney disease

B-

Potassium-sparing diuretics inhibit / exchange in DCT combination with other diuretics to  loss of

C- Methyldopa α2 agonist that is converted to methylnorepinephrine HTN in pregnancy

D-  Blocker Block  receptor HTN patients with concomitant heart disease.

E-

Thiazide diuretics - and water reabsorption. -  blood volume -  COP and RBF

in patient who has Osteoporosis

2-True and false ? A. B.

(F) because rebound HTN SE of Clonidine (F) because ARBs inhibitor is Block the AT1 receptors

C. D. E. F.

(T) (T) (F) because Vasodilator cause Hypertrichosis (T)


Drug class

MOA

SE

Special indication

Thiazides Act mainly in the cortical region of the ascending loop of Henle and the distal convoluted tubule to decrease the reabsorption of Na+, by inhibition of a Na+/Cl− cotransporter

-Hypokalemia -Hyponatremia -Hyperuricemia -Volume depletion -Hypercalcemia -Hyperglycemia

1- Hypertension 2- Heart failure 3- Hypercalciuria 4- Diabetes insipidus

-Hyperuricemia -Acute hypovolemia -Potassium depletion -Hypomagnesemia -Ototoxicity

1. Acute pulmonary edema 
 2. Acute/chronic peripheralEde ma caused from heart Failure or renal impairment 3. Hypercalcemia 
 4. Hyperkalemia 


 excretion of Na+ and Cl− 
  excretion of K+
  excretion of Ca2+ 
  peripheral vascular resistance

Loop diuretics

Inhibit the cotransport of Na+/K+/2Cl− in the luminal membrane in the ascending limb of the loop of Henle. Therefore, reabsorption of these ions is decreased 
  excretion of Na+  excretion of K+  excretion of Ca2+

Antagonizes aldosterone receptor sites rendering the spironolactone–receptor complex inactive. It prevents translocation of the receptor complex into the nucleus of the target cell, resulting in a failure to produce mediator proteins that normally stimulate the Na+/K+-exchange sites of the collecting tubule. Thus, a lack of mediator proteins prevents Na+ reabsorption and, therefore, K+ and H+ secretion  excretion of Na+  excretion of K+

-Gastric upset -Hyperkalemia -Nausea -Lethargy -Mental confusion

1- Hypertension 2- Heart failure 3- Diuretic of choice in patients with hepatic cirrhosis 
 4- Secondary hyperaldosteronism 5- Heart failure 
 6- Resistant hypertension 
 7- Ascites 
 8- Polycystic ovary syndrome 



Potassium sparing diuretic CI in patients with renal dysfunction because of the increased risk of hyperkalemia

Drug class Carbonic anhydrase inhibitor

MOA

SE

Special indication

- Inhibits carbonic anhydrase located intracellularly and on the apical membrane of the proximal tubular epithelium . The decreased ability to exchange Na+ for H+ in the

-Metabolic acidosis -Potassium depletion -Renal stone Drowsiness -Paresthesia

1. Glaucoma 
 2. Mountain sickness 


-Extracellular water expansion -Dehydration -Hypo- or hypernatremia

-They are used to maintain urine flow following acute toxic ingestion of substances capable of producing acute renal failure.

presence of acetazolamide results in a mild diuresis.  excretion of Na+  excretion of K+  excretion of HCO3− Osmotic diuretics

Used to increase water excretion rather than Na+ excretion, they are not useful for treating conditions in which Na+ retention occurs.

-In patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities, and trauma.

Carbonic anhydrase inhibitor CI In Patients with hepatic cirrhosis, because it could lead to a decreased excretion of NH4+.


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

------------------------------------------------------------------------------------Diabetes insipidus

------------------------------------------------------------------------------------Diuretic of choice in patients with hepatic cirrhosis 


------------------------------------------Inhibits carbonic anhydrase -------------------------------------------


Answers 1- Complete A-Thiazides inhibition of a Na+/Cl− cotransporter Diabetes insipidus

B- Potassium sparing diuretic Antagonizes aldosterone receptor Diuretic of choice in patients with hepatic cirrhosis

C-Carbonic anhydrase inhibitor Inhibits carbonic anhydrase Glaucoma and Mountain sickness


Drug class ACEIs: Ends in( pril) Captopril Enalapril Fosinopril Lisinopril Quinapril Ramipril

MOA

SE

ProduceV.D by inhibiting formation of angiotensin II.

-postural hypotension

-symptomatic and asymtomatic HFrEF.

 secretion of aldosterone

- renal insufficiency,

-All stages of left ventricular failure.

-hyperkalemia

-Patients with the lowest EF

- persistent dry coug - angioedema(rare)

ARBs: Ends in (sartan) Candesartan Losartan Telmisartan Valsartan

competitive antagonists of

Aldosterone antagonists: Eplerenone Spironolactone

B-blockers:

Uses

Spironolactone : is a direct antagonist of aldosterone, thereby preventing salt retention, myocardial hypertrophy.

similar to that of ACE inhibitors. However, the ARBs have a lower incidence of dry cough and angioedema.

eplerenone has a lower incidence of endocrine-related side effects

 Eplerenone: is a competitive antagonist of aldosterone at mineralocorticoid receptors thereby preventing salt retention, myocardial hypertrophy.  sympathetic stimulation of heart and circulation

Bisoprolol Carvedilol Metoprolol tartrate Metoprolol succinate

-Recent MI or are at high risk for a cardiovascular event -Hypertension -Hypertension -As a substitute for ACE inhibitors in those patients with severe cough or angioedema -severe stages of HFrEF or HFrEF -recent MI

-chronic, stable HF. ___

-reduce morbidity and mortality associated with HFrEF

ACE inhibitors and ARBs are should not be used in pregnant women. The potential for symptomatic hypotension if use concomitantly with a diuretic.

B-BLOCKERS: 1-Carvedilol and metoprolol are metabolized by the cytochrome P450 2D6 isoenzyme, drugs and increase the risk of adverse effects. 2-carvedilol is a substrate of P-glycoprotein (P-gp). Increased effects of carvedilol may occur if it is coadministered with P-gp inhibitors. β-Blockers should also be used with caution with other drugs that slow AV conduction, such as amiodarone, verapamil, and diltiazem

 

MI = myocardial infarction. = angiotensin II type 1 receptor.


Drug class

MOA 

Diuretics: Bumetanide Furosemide Torsemide Metolazone

Vasodilators: Hydralazine Isosorbide dinitrate

 Plasma volume and edema and relieve symptoms of circulatory congestion

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance.

SE

Uses

Overdoses of loop diuretics can lead to profound hypovolemia.

-Patients who require extensive diuresis and those with renal insufficiency.

Headache, hypotension, and tachycardia (combination)

{ they should only be used to treat signs and symptoms of volume excess} a combination of hydralazine and isosorbide dinitrate: 1- intolerant of ACE inhibitors or β-blockers, or if additional vasodilator response is required

drug-induced lupus (hydralazine)

2- black patients with HFrEF 

Inotropic agent: Digitalis glycosides

enhance cardiac contractility and  cardiac output.

digoxin toxicity(Anorexi a, nausea, and vomiting). blurred vision, yellowish vision (xanthopsia), arrhythmias, hypokalemia

severe HFrEF after initiation of ACE inhibitor, β-blocker, and diuretic therapy.

DIGOXIN: Digoxin is a substrate of P-gp, and inhibitors of P-gp, such as clarithromycin, verapamil, and amiodarone, can significantly increase digoxin levels, necessitating a reduced dose of digoxin. Digoxin should also be used with caution with other drugs that slow AV conduction, such as β-blockers, verapamil, and diltiazem Drug class Inotropic agent: β-Adrenergic agonists, such as dobutamine and dopamine

Inotropic agent: Phosphodiesterase inhibitors )Milrinone)

MOA

SE

 intracellular (cAMP) activation of protein kinase. Protein kinase then phosphorylates slow calcium channels  entry of calcium ions into the myocardial cells and enhancing contraction  intracellular conc. of cAMP  intracellular and, therefore, cardiac contractility.

Uses short-term treatment of acute HF in the hospital setting.

___

Long-term, milrinone therapy may be associated with a substantial increased risk of mortality.

___


Questions … Choose the one best answer. 1.which drug decrease secretion of aldosterone? A. B. C. D.

Bisoprolol Dopamine Quinapril Hydralazine

2.which is important to monitor in patients taking digoxin? A. B. C. D.

Potassium Magnesium Chloride Iron

3. after long time use of HF medication patient have lupus what patient use of HF medication ? A. B. C. D.

Milrinone Isosorbide dinitrate Furosemide Hydralazine

4. which of this drugs use in short-term treatment of acute HF in the hospital setting? A. B. C. D.

Dobutamine Digitalis glycosides Eplerenone Captopril

5. Long-term use of …………….. may be associated with a substantial increased risk of mortality? A. B. C. D.

Metolazone Carvedilol Milrinone tartrate


Answers

1. 2. 3. 4. 5.

C Quinapri A Potassium D Hydralazine A Dobutamine C Milrinone


CLASS I (Na+-channel blockers):

CLASS II (Ã&#x;adrenoreceptor blockers):

Disopyramide (IA) ,Flecainide (IC)

Atenolol

, Lidocaine (IB), Mexiletine (IB), Procainamide (IA), Propafenone (IC), Quinidine (IA).

Esmolol Metoprolol

Antiarrhythmics

CLASS IV (Ca2+ channel blockers):

CLASS III (K+ channel blockers):

Diltiazem,

Amiodarone,

Verapamil

Dofetilide Dronedarone OTHER ANTIARRHYTHMIC DRUGS : Adenosine Digoxin Magnesium sulfate

Ibutilide, Sotalol .


CLASS I ANTIARRHYTHMIC DRUGS Drug class 1.Class IA antiarrhythmic drugs: Quinidine, procainamide, and disopyramide

2. Class IB antiarrhythmic drugs: Lidocaine and mexiletine

3. Class IC antiarrhythmic drugs: Flecainide and propafenone

MOA

SE

USES

- prevents sodium influx , inhibits potassium channels, and blocks calcium channels

- Large doses of quinidine may induce the symptoms of cinchonism (for example, blurred vision, tinnitus, headache, disorientation, and psychosis).

-Quinidine is used in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias.

- In addition to sodium channel blockade, lidocaine and mexiletine shorten phase 3 repolarization and decrease the duration of the action potential

- Lidocaine has a fairly wide therapeutic index. It shows little impairment of left ventricular function and has no negative inotropic effect. Central nervous system (CNS) effects include nystagmus (early indicator of toxicity), drowsiness, slurred speech, paresthesia, agitation, confusion, and convulsions, which often limit the duration of continuous infusions.

Although amiodarone has supplanted lidocaine for use in ventricular fibrillation or pulseless ventricular tachycardia (VT), lidocaine may be useful as an alternative. Lidocaine may also be used in polymorphic VT or in combination with amiodarone for VT storm

-suppresses phase 0 upstroke in Purkinje and myocardial fibers. This causes marked slowing of conduction in all cardiac tissue, Automaticity is reduced by an increase in the threshold potential, rather than a decrease in slope of phase 4 depolarization.

- Flecainide is generally well tolerated, with blurred vision, dizziness, and nausea occurring most frequently.

- Flecainide is useful in the maintenance of sinus rhythm in atrial flutter or fibrillation in patients without structural heart disease (left ventricular hypertrophy, heart failure, atherosclerotic heart disease) and in treating refractory ventricular arrhythmias.


CLASS II ANTIARRHYTHMIC DRUGS  

These drugs diminish phase 4 depolarization and, thus, depress automaticity, prolong AV conduction, and decrease heart rate and contractility useful in treating tachyarrhythmias caused by increased sympathetic activity. They are also used for atrial flutter and fibrillation and for AV nodal reentrant tachycardia

CLASS III ANTIARRHYTHMIC DRUGS Drug class

MOA

SE

Amiodarone contains iodine and is related structurally to thyroxine. It has complex effects, showing class I, II, III, and IV actions, as well as αblocking activity. Its dominant effect is prolongation of the action potential duration and the refractory period by blocking K+ channels

shows a variety of toxic effects, including pulmonary fibrosis, neuropathy, hepatotoxicity, corneal deposits, optic neuritis, bluegray skin discoloration, and hypo- or hyperthyroidism

Dronedarone is a benzofuran amiodarone derivative, which is less lipophilic, has lower tissue accumulation, and has a shorter serum half-life than amiodarone. It does not have the iodine moieties that are responsible for thyroid dysfunction associated with amiodarone. Like amiodarone, it has class I, II, III, and IV actions.

liver failure.

3. Sotalol

although a class III antiarrhythmic agent, also has potent nonselective βblocker activity.

This drug can cause the typical adverse effects associated with β-blockers but has a low rate of adverse effects when compared to other antiarrhythmic agents

4. Dofetilide

pure potassium channel blocker

1. Amiodarone

2. Dronedarone

- is a potassium channel blocker that also activates the inward sodium current (mixed class III and IA action

severe refractory supraventricular and ventricular tachyarrhythmias. management of atrial fibrillation or flutter

used to maintain sinus rhythm in atrial fibrillation or flutter, but it is less effective than amiodarone.

___

5. Ibutilide

USES

QT prolongation and proarrhythmia

maintenance of normal sinus rhythm in patients with atrial fibrillation, atrial flutter, or refractory paroxysmal supraventricular tachycardia and in the treatment of ventricular arrhythmias. first-line antiarrhythmic agent in patients with persistent atrial fibrillation and heart failure or in those with coronary artery disease ___


Type of angina 1- Angina of Effort (Exertional, Stable, Classic) 2- Variant (Prinzmetal, Vaso-spastic) Angina: Avoid Non-selective -Blockers 3- Unstable angona (pre-infraction, crecendo)


A) Anti-Anginal Drugs Drug class

MOA

Nitrates

- Release NO Arterio-venodilator

SE

USES

-Postural hypotension & tachycardia -Tolerance & crosstolerance between nitrites &

1-all type of angina

b- Isosorbid Dinitrate.

- Met-Hb and cyanosis especially by Nitrites >Nitrates

2-Acut MI 3-CHF 4- Cyanide poisoning

C- Isosorbid Mononitrate.

- Hypersensitivity reaction as skin rash.

Organic nitrates a-Glyceryl Trinitrate (GTN, Nitroglycerin).

Organic nitrite: Amylnitrite

- Dangerous interaction with sildenafil (viagra)? severe hypotension.

Inorganic nitrite: Sodium nitrite



a- Acute attacks b- In Long Term Prophylaxis

No = nitric oxide

Never Stop nitrate therapy Suddenly? Rebound ischemia & infarction


Drug class

Phenylalkaylamines (Verapamil). CCBs

Benzothiazepines (Diltiazem)

MOA 1-They block Voltagedependent L-type calcium channels present in Heart, Blood vessels and Smooth muscles.

SE -Bradycardia -Heart block -Heart failure -Hypotension -constipation -Headache -dizziness -flushing

2- They decrease Ca2+ influx into lead to: cardiac muscles inhibition &VD artery

USES -Prophylactic treatment of all types of angina. -Antiarrhythmic in supraventricular arrhythmia (class IV) - Hypertension - Hypertrophic cardiomyopathy, cerebrovascular accidents and premature labour.

- Is similar to verapamil but less potent less effect on contraction.

-ankle edema -Hypotension -headache -flushing -nausea -vomiting -Steal phenomenon

-Hypertension. -Migraine headache Hypertrophic -cardiomyopathy -Raynaud’s disease

Dihydropyridines (Nifedipine)

- CCB

Niterndipion

- it is similar to nifedipin but more potent and has longer duration

Nimodipoin -C.C.B

B-Blockers

- Block B receptor



-Bradycardia -Long diastole lead to: increase EDV increase preload increase O2 needs

EDV = End-Diastolic Volume

B-Blockers CI in Variant (Prinzmetal) angina

-reduce morbidity following subarachnoid haemorrage probably by preventing vasospasm. -Decrease HR -Decrease contractility -long use anti hypertension and decrease afterload lead to decrease cardiac work and O2 Consumption -Prophylaxis of Angina Pectoris (stable & unstable)


Drug class

MOA 1-Nitrate-like Release NO = Arteriovenodilator.

SE - Headache.

USES -Angina -Heart failure

Nicorandil 2-Opens ATPdependent K+Channel.

B) Adjuvant Drugs 

Aspirin antiplatelet inhibit Thromboxane-A2 formation

Dipyridamol -antiplatelet , +ve Inotropic effect, Blood vessels V.D and decrease B.P

 

Ticlopidine & Clopidogrel ADP-Receptors Blockers Abciximab & Tirofiban GP IIb/IIIa-Receptors Blockers


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------------------------------------------------Cyanide poisoning

Verapamil -------------------------------------------Antiarrhythmic in supraventricular arrhythmia

-------------------------------------------Nitrate-like Release NO --------------------------------------------------------------------------------------ADP-Receptors Blockers --------------------------------------------


Answers 1- Complete A-Nitrates Release NO Cyanide poisoning

B-Verapamil CCBs Antiarrhythmic in supraventricular arrhythmia

C-Nicorandil Nitrate-like Release NO -Angina and Heart failure

D-Ticlopidine & Clopidogrel ADP-Receptors Blockers Adjuvant Drugs


Anticoagulant: Drug class

MOA

SE

USES

-Accelerates the antithrombin III reaction.

-Toxicity (Hemorrhage , heparin-induced thrombocytopenia)

-Treatment and prevent thromboembolic diseases

-Hypersensitivity to heparin

-prevent clotting during blood transfusion.

-Reversible alopecia

-prevent embolism in patients with long standing A.F ..(Atrial Fibrillation)

-Osteoporosis

Fondaparinux Hirudin e.g lepirudin

Argatropan

Ximelagatran Warfarin (orally)

- inhibits activated factor X. - Direct thrombin inhibitor (Potent competitive) - Direct thrombin inhibitor (week competitive) - Direct thrombin inhibitor - Inhibit synthesis of vitamin K Dependent coagulate factor

- Anticoagulant. - heparin-induced thrombocytopenia

- Anticoagulant.

- heparin-induced thrombocytopenia

- Anticoagulant.

- heparin-induced thrombocytopenia - Hemorrhage

- Anticoagulant.

Warfarin CI in pregnancy but Heparin can use in pregnancy

- Anticoagulant.


Platelet inhibitors: Drug class 1-Abciximab 2-Asprin 3-Cilostazol 4-Clopidogrel 5-Dipyridamole 6-Eptifibatide 7-Prasugrel 8-Ticagrelor 9-Ticlopidine 10-Tirofban

MOA preventing platelet aggregation by: COX-1 (asprin) or ADP or GP IIb/IIIa

SE oral: -Angioedema -Reye syndrome SJS (Asprin) -Bleeding -Bronchospasm -GI disturbances IV: -Hypotension -Nausea -Vomiting -Thrombocytopenia

USES -Aspirin is used in the prophylactic treatment in cardiac event

Thrombolytic agents: Drug class 1-Alteplase (tPA) 2- Reteplase 3-Tenecteplase 4-Streptokinase 5-Urokinase   

MOA - Directly or indirectly to convert plasminogen to plasmin.

SE - hemorrhage

USES Treatment of DVT and serious PE Treating acute peripheral arterial thrombosis or MI.

DVT = Deep vein thrombosis PE = pulmonary embolism MI = myocardial infarction

ttt for bleeding: Drug class 1-Aminocaproic 2-Protamine sulfate 3-Tranexamic acid 4-Vit K1

MOA - Fibrinolytic

CVA = cerebrovascular accident

SE -Muscle necrosis -Thrombosis -CVA -Seizures -Flushing

USES -for bleeding disorder


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

----------------------------------------inhibits activated factor X ------------------------------------------------------------------------------------------------------------------------Treatment of DVT and serious PE

Asprin -----------------------------------------

----------------------------------------Tranexamic acid ---------------------------------------------------------------------------------


Answers 1- Complete A-Fondaparinux inhibits activated factor X. Anticoagulant.

B-Asprin COX-1 inhibitor prophylactic treatment in cardiac event

C-Thrombolytic agents convert plasminogen to plasmin. Treatment of DVT and serious PE

D-Tranexamic acid Fibrinolytic bleeding disorder


MOA

SE - liver enzymes

1-Statins

2-Niacin (nicotinic acid)

3-Fibrates

-Competitive inhibitors of HMG CoA reductase, the rate limiting step in cholesterol synthesis. -  TAG levels and may  HDL cholesterol levels.

-Myopathy and rhabdomyolysis

-Strongly inhibits lipolysis in adipose tissue.

-Intense cutaneous flush and pruritus.

-  liver TAG levels and  hepatic VLDL production, which in turn  LDL-C plasma concentrations

- increased expression of lipoprotein lipase and decreasing apolipoprotein (apo) CII concentration.

USES -First-line treatment for patients with elevated risk of ASCVD. -All types of hyperlipidemias

-Most effective agent for increasing HDL-C. -Familial Hyperlipidemias.

-Predisposes to Hyperuricemia and gout.

-Severe hypercholesterolemias,

- Predisposition to form gallstones Myositis.

-Hypertriglyceridemias.

-GI disturbances

-Useful (in combination with diet or niacin) for treating type IIA and type IIB Hyperlipidemias.

-type III hyperlipidemia.

-Increase the level of HDL cholesterol by increasing the expression of apo AI and apo AII.

-Anion-exchange resins that bind negatively charged bile acids and bile salts in the small intestine.

4-Bile Acid binding Resins

-The resin/bile acid complex is excreted in the feces thus lowering the bile acid concentration. -This causes hepatocytes to increase conversion of cholesterol to bile acids.

-impair the absorption of the fatsoluble vitamins (A, D, E, and K)

-Cholestyramine can also relieve pruritus caused by accumulation of bile acids in patients with biliary stasis. -Colesevelam is also indicated for type 2 diabetes due to its glucose-lowering effects.


Drug class 5-Cholesterol absorption inhibitor

6-Omega-3 fatty acids

MOA

SE

- Selectively inhibits absorption of dietary and biliary cholesterol in the small intestine.

- Adverse effects are uncommon

- Inhibit VLDL and triglyceride synthesis in the liver.

-GI effects -Fishy aftertaste

USES - Often used as an adjunct to statin therapy or in statinintolerant patients. - Predominately used for TAG lowering.

Administration of aspirin prior to taking niacin decreases the flush. Bile Acid binding Resins CI in patients with significant hypertriglyceridemia (≥400 mg/dL).

  

TAG = triglyceride HDL = high density lipoprotein ASCVD = Arteriosclerotic cardiovascular disease


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

-------------------------------ď‚­expression of lipoprotein lipase --------------------------------

Statins ---------------------------------------------------------------

--------------------------------

-------------------------------Familial Hyperlipidemias


Answers 1- Complete A-Fibrates increased expression of lipoprotein lipase Hypertriglyceridemias and type III hyperlipidemia

B-Statins HMG CoA reductase inhibitors All types of hyperlipidemias

C-Niacin Inhibits lipolysis in adipose tissue Familial Hyperlipidemias


.


HYPOTHALAMIC AND ANTERIOR PITUITARY HORMONE Name of the hormone

1.Adrenocorticotropic hormone (corticotropin)

2.Growth hormone (somatotropin) growth hormone–releasing hormone (GHRH)

MOA

Activates G protein by binding to surface of adrenal cortex receptors then synthetic and release of adrenocorticosteroids and adrenal androgen

- stimulate GH synthesis and secretion, its mediated through the somatomedins —insulin-like growth factors 1 and 2.

SE

USES

Only when longer use, such as hypertension, peripheral edema, Hypokalemia, emotional disturbances, and increased risk of infection.

-Diagnostic tool to differentiate between primary and secondary adrenal insufficiently

-Injected site pain -edema, -arthralgias -myalgia’s -flu-like symptoms -increased risk of diabetes

-treatment of growth hormone deficiency or failure in children.

-treatment of infantile spasm

-Growth failure due to Prader-Willi syndrome. -AIDS wasting syndrome management. -GH replacement in adults with GH deficiency.


Name of the hormone

3.Somatostatin

(Growth hormone-inhibiting hormone)

MOA

- Suppressing growth hormone and thyroidstimulating hormone release by binding to receptors in pituitary. -inhibit release of insulin, glucagon, and gastrin

SE

-Diarrhea -abdominal pain -flatulence -nausea -steatorrhea

USES

-Acromegaly -flushing associated with carcinoid tumors -bleeding esophageal varices

4.Gonadotropin-releasing hormone

It is important for releasing of (FSH) and (LH) by secretion of gonadotropinreleasing hormone (GnRH) from the Hypothalamus in anterior pituitary. administration of GnRH continuously will inhibits gonadotropin release through down-regulation of the GnRH receptors On the pituitary then leads to reduced production of gonadal steroid hormones.

In women: -hot flushes -sweating -diminished libido -depression -ovarian cysts In men: -Hot flushes -Edema -Gynecomastia -diminished libido

-Prostate cancer -endometriosis -precocious Puberty


Name of the hormone

MOA

SE

USES

5.Gonadotropins: -Menotropins -Urofollitropin -Follitropina alfa+beta -Human chorionic -choriogonadotropin

6.Prolactin

- Regulation of gonadal steroid hormones.

-ovarian enlargement

- Infertility treatment

-ovarian hyperstimulation syndrome

- Responsible for stimulating and maintaining lactation by secreting it from the anterior Pituitary and lead to Decreases sexual drive and reproductive function.

bromocriptine cabergoline SE:

-Nausea -Headache -Sometimes psychiatric problems.

bromocriptine and cabergoline are prolactin antagonist used in -treatment of pituitary microadenomas -type 2 diabetes


HORMONES OF THE POSTERIOR PITUITARY Name of the hormone

1.Oxytocin

2.Vasopressin

MOA

SE

- Making the myoepithelial cells contracting around the mammary alveoli then

- Uncommon toxicities when used properly.

-stimulate uterine contraction and induce labor -and stimulate milk ejection

-Hypertension -uterine rupture -water retention -fetal death

antidiuretic and vasopressor effects

Major : -water intoxication -hyponatremia

Works by increasing water permeability and reabsorption in the collecting tubules by binding to the V2 receptor in kidney.

3.Desmopressin

-Labor inducing

-Milk ejections

- The major use of is to treat diabetes

insipidus -management of cardiac arrest -control bleeding Of esophageal varices.

It effects are Mediated by the V1 receptor, which is found in liver, vascular smooth muscle And other tissues.

- Vasopressor analog has minimal activity at the V1 receptor, making it largely free of pressor effects

USES

- Local irritation

- Longer acting than vasopressin and is preferred for the -treatment of diabetes Insipid -nocturnal enuresis


thyroid hormones: Name of the hormone 1.Triiodothyronine ( T3) ( Most active form)

Thioamides Propylthiouracil PTU methimazole

MOA Inhibition of thyroid hormone synthesis Inhibit both the oxidative processes required for iodination of tyrosyl groups And the condensation (coupling) of iodotyrosines to form T3 and T4.

SE

USES

-hepatotoxicity and, rarely, -agranulocytosis

- hyperthyroidism

-Nervousness -palpitations -tachycardia -heat intolerance -Unexplained weight loss.

- hyperthyroidism

PTU blocks the peripheral conversion of T4 to T3.

2.thyroxine (T4) Levothyroxine

___


Name of the hormone Iodide

MOA

- Blockade of hormone release by iodination of tyrosines inhibiting.

SE

sore mouth and throat

USES

-thyroid storm -hyperthyroidism -prior to surgery

swelling of the tongue + larynx rashes ulcerations of mucous membranes metallic taste in the mouth

β-blockers:

Block B receptors

___ -metoprolol -propranolol

- Thyroid storm


Questions ‌ Complete First line Drug name or class Second line M.O.A Third line use Urofollitropin -----------------------------------------------------------------------------------------------------

---------------------------------------------------

Gonadotropin-releasing hormone

---------------------------------------------------

---------------------------------------------------

Diagnostic tool to differentiate between primary and secondary adrenal insufficiently.

Prostate cancer

--------------------------------------------------Oxytocin

---------------------------------------------------

---------------------------------------------------

---------------------------------------------------

Vasopressor analog

prior to surgery

---------------------------------------------------

nocturnal enuresis


Answers A-.Adrenocorticotropic hormone Activates G protein Diagnostic tool to differentiate between primary and secondary adrenal insufficiently

B-Gonadotropin-releasing hormone It is important for releasing of (FSH) and (LH) Prostate cancer

C-Urofollitropin Regulation of gonadal steroid hormones. Infertility treatment


D-Oxytocin stimulate uterine contraction and induce labor and stimulate milk ejection Labor inducing and Milk ejections

E-Desmopressin Vasopressor analog nocturnal enuresis

F-Iodide Blockade of hormone release by iodination of tyrosines inhibiting prior to surgery


Drug class

MOA

USES

SE

Elevated glucose level Type 1,2 diabetic.

-

A)

in type 1 diabetes: Replaces the absent insulin secretion

Injectable agent

1.Insulin and insulin analogs. Rapid-acting: lispro,aspart,glulisine. Intermediate-acting: NPH. Long-acting: glargine.

2. Amylin analog

In type 2 diabetes: to supplement insufficient insulin secretion.

-

-

Analog of amylin Amylin receptors activating

Type 2 Type 1

-

Activating GLP-1 receptors + Analog of glucagon-like Peptide-1 (GLP-1)

Exenatide

Type 2

-

-

Degrades GLP-1 and other Incretins By Inhibiting of the dipeptidyl Peptidase4(DPP-4)

liraglutide

Hypoglycemia (serious and common.) weight gain. local injection site reactions. Lipodystrophy.

Diabetics patients with renal insufficiency requires a decrease in insulin dose.

Gl disturbances Hypoglycemia Headache nausea Anorexia Vomiting Gl disturbances Headache pancreatitis

diabetic gastroparesis

Insulin receptor activation

Pramlintide

3.incretin mimetics

CI

Increases glucosedependent insulin release; decreases secretion of glucagon; slows gastric emptying; increases satiety

-

Rhinitis upper respiratory infections rare allergic reaction

cresol hypersensitivity hypoglycemic unawareness. thyroid carcinoma


Drug class

A)

Oral agent

1.insuline seretagogues - Sulfonylureas 1)Glipizide 2)Glyburide 3)glimepiride

MOA USES closing ATP-sensitive K" channels Type 2 diabetes to Increases insulin secretion From pancreatic beta cells

Same as Sulfonylureas

-

-

-

Type 2 diabetes

-

SE Hypoglycemia weight gain hyperinsulinemia,

Used in caution with hepatic impairment patient

- Glinides

-biguanides.

Stimulates insulin secretion Endogenous glucose production decreasing

-

1)metformin

-

Decreases hepatic production of glucose

-Thiazolidinediones

1)pioglitazone

2)rosiglitazone

-

Binds to peroxisome proliferator–activated receptor-_ in muscle, fat and liver to decrease insulin resistance

Gastrointestinal disturbances, Lactic Acidosis (rate)

acute myocardial infarction exacerbation of heart failure sepsis

Type 2 diabetes binds to PPAR-y to Regulates gene expression

CI Should be cautioned with hepatic or renal insufficiency

Fluid retention, Edema Anemia weight gain Bone fractures in women May worsen heart disease increase risk of Myocardial infarction

acute renal failure. bladder cancer heart failure Avoid in liver disease


Drug class

MOA

USES

SE

CI

- Îą-Glucosidase inhibitors

cc-glucosidasestid intestinal Inhibiting

Type 2 diabetes

Gl disturbances

bowel disease, colonic ulceration, intestinal obstruction

1) Acarbose 2) miglitol

Decreases glucose absorption

- Dipeptidyl peptidase-4 inhibitors

enzyme DPP-4 inhibiting type which is responsible for 2 diabetes. the inactivation of incretin hormones suchas GLP-1

nasopharyngitis headache.

reabsorbing filtered glucose in the tubular lumen. By inhibiting SGLT2 of the kidney

urinary tract infections, and urinary frequency. Hypotension

1)Alogliptin 2) linagliptin 3) linagliptin 4) sitagliptin

- Sodium–glucose cotransporter 2 inhibitors 1)Canagliflozin 2)dapagliflozin

Increases urinary glucose excretion

type 2 diabetes.

severe renal impairment.


Questions ‌ Complete

First line Drug name or class Second line M.O.A Third line use

A --------------------------------------------Amylin receptors activating ---------------------------------------------

B Glyburide -----------------------------------------------------------------------------------------

c --------------------------------------------cc-glucosidasestid intestinal Inhibiting

---------------------------------------------


Answers Complete A-Pramlintide Amylin receptors activating Type 2 Type 1 B-Glyburide closing ATP-sensitive K" channels to Increases insulin secretion Type 2 diabetes C-miglitol cc-glucosidasestid intestinal Inhibiting Type 2 diabetes


Drug class Estradiol

MOA

SE

USES

- Estradiol is a nuclear hormone, meaning it acts on receptors present inside the cell, that can activate or deactivate transcription in the nucleus. Estradiol interacts with a target cell receptor (Erι or Erβ) within the cytoplasm of the cell.

1-Thromboembolism

1-contraception. 2- postmenopausal hormone therapy (HT) 3-premenopausal patients who are deficient in estrogen hormone. (hypogonadism) 4- prevention of osteoporosis (previously)

2- Peripheral edema 3- Myocardial Infarction

4- Hypertension 5- Breast tenderness

Tamoxifen

raloxifene

- compete with estrogen for binding to the estrogen receptor in breast tissue

- raloxifene acts as an estrogen agonist in bone, leading to decreased bone resorption, increased bone density, and decreased vertebral fractures

6- Nausea 1-hot flashes 2- nausea 3- endometrial hyperplasia 4-Malignancies Hot flashes and leg cramps

- metastatic breast cancer

- approved for the prevention and treatment of osteoporosis in postmenopausal women


Drug class

MOA

SE

USES

Clomiphene

-acts as a partial estrogen agonist and interferes with the negative feedback of estrogens on the hypothalamus. This effect increases the secretion of gonadotropin-releasing hormone and gonadotropins, thereby leading to stimulation of ovulation .

headache, nausea, vasomotor flushes, visual disturbances, and ovarian enlargement. Use of clomiphene increases the risk of multiple births (twins or triplets).

-treatment of infertility associated with anovulatory cycles.

Finasteride

- inhibit 5Îą-reductase resulting in decreased formation of dihydrotestosterone

Impotence And Headache

- benign prostatic hyperplasia

Mifepristone

- is aprogesterone antagonist with partial agonist activity.

Uterine bleeding and the possibility of an incomplete abortion.

Mifepristone is often combined with the prostaglandin analog misoprostol (administered orally or intravaginally) to induce uterine contractions


Drug class

MOA

SE

USES

testosterone

testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass , growth of body hair and the prevention of osteoporosis.

Weight gain, acne, decreased breast size, deepening voice, increased libido, and increased hair growth

1-Androgenic steroids are used for males with primary hypogonadism or secondary hypogonadism.

progesterone

- progesterone promotes headache, depression, weight gain, the development of a secretory endometrium that can changes in libido, acne and hirsutism accommodate implantation of a newly forming embryo. inhibit the production of gonadotropin and, therefore, prevent further ovulation. maintaining the endometrium in a favorable state for the continuation of the pregnancy and reducing uterine contractions.

2- Anabolic steroids can be used to treat chronic wasting associated with human immunodeficiency virus or cancer.

- used in combination with estrogens for contraception or the treatment of hormone deficiency


Drug name

MOA

SE

USES

*Short acting:

1.Cortisone

Making gluconeogenesis in the liver and kidney by increasing amino acid uptake,

Its dose related Most common SE: Osteoporosis

-Elevating gluconeogenic Enzymes activity Promote normal intermediary metabolism -Increase resistance to stress By increasing the level of plasma glucose.

-Promote normal intermediary metabolism -Increase resistance to stress

sex hormone synthesis decreasing Cushing-like syndrome when using it with excessive treatment Cataracts with long term use Hyperglycemia with DM

2.Hydrocortisone Identical to natural cortisol

Decreased Growth in children Glaucoma Centripetal distribution of body fat

Fluticasone *long acting: betamethasone or

-Replacement therapy for primary adrenocortical insufficiency (Addison disease)

Increased risk of infection

-Replacement therapy for secondary or tertiary adrenocortical Insufficiency

Increased appetite

-inflammatory disorders

Emotional disturbances

Treatment of allergies Acceleration of lung maturation

Hypokalemia


dexamethasone *intermediate acting: alter blood cell levels in plasma

1.Methylprednisolone 2.Prednisolone

Peripheral edema Makes decrease in eosinophil’s, basophils, monocytes, and lymphocytes By redistributing them to lymphoid tissue.

3.Prednisone

increase hemoglobin, erythrocytes, platelets, And polymorphonuclear leukocytes.

4.Triamcinolone

Lowering of circulating lymphocytes. Decrease proinflammatory cytokines.

-Arthritis -Bronchial inflammation

Hypertension

-Asthma -Rheumatoid arthritis -Ulcerative -Crhon’s disease -It minimizes steroid effects on the fetus, so preferred to pregnant. -asthma -Eczema -diabetic retinopathy - anti inflammatory -Replacement therapy for congenital adrenal hyperplasia (CAH)

Inhibits phospholipase A2 then blocks the arachidonic acid release. Decreased prostaglandins and leukotriene’s production Decreased histamine release by stabilizing mast cell and basophil membranes. Fludrocortisone Binds to the mineralocorticoid receptor to Reabsorption of sodium, bicarbonate, and water by making Aldosterone acts on distal tubules and collecting ducts in the kidney

- treat low glucocorticoid levels caused by disease of the adrenal gland, for example : Addison disease


Drug name

MOA

Eplerenone

Aldosterone antagonist acts on mineralocorticoid receptor

Spironolactone

antagonize aldosterone and testosterone synthesis.

Ketoconazole

inhibiting the synthesis of all gonadal and adrenal steroid hormones. Anti-fungal agent

SE

USES

ejection fraction reduce

-hypertension -heart failure

hyperkalemia, gynecomastia, menstrual irregularities, And skin rashes.

-Antihypertensive -Hyperaldosteronism -hirsutism in women

-Cushing syndrome. ___


Questions ‌ 1- Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------------------------------------------------------------Crhon’s disease

-------------------------------------------------Binds to the mineralocorticoid receptor to Reabsorption of sodium, bicarbonate, and water

--------------------------------------------------

-------------------------------------------------Identical to natural cortisol --------------------------------------------------

Ketoconazole ---------------------------------------------------------------------------------------------------


Answers 1- Complete A-Prednisolone alter blood cell levels in plasma Crhon’s disease

B-Fludrocortisone Binds to the mineralocorticoid receptor to Reabsorption of sodium, bicarbonate, and water Addison disease

C-Hydrocortisone

Identical to natural cortisol

Replacement therapy for primary adrenocortical insufficiency (Addison disease) Replacement therapy for secondary or tertiary adrenocortical Insufficiency inflammatory disorders

D-Ketoconazole inhibiting the synthesis of all gonadal and adrenal steroid hormones Cushing syndrome.


Drug class

ANOREXIANTS: Diethylpropion Phentermine

MOA Phentermine exerts its pharmacologic action by increasing the release of norepinephrine and dopamine from the nerve terminals and by inhibiting reuptake of these neurotransmitters, thereby increasing levels of neurotransmitters in the brain. The increase in norepinephrine signals a“fight-or-flight� response by the body, which, in turn, decreases appetite.

SE

USES

-Dry mouth, -headache, -insomnia, -constipation

-antiobesity

- gastrointestinal symptoms

- Antiobesity

nausea, headache, dry mouth, dizziness, constipation, and lethargy

antiobesity drug

-paresthesias, -suicidal ideation -cognitive dysfunction

-antiobesity drug

Diethylpropion has similar effects on norepinephrine. LIPASE INHIBITORS: Orlistat

SEROTONIN AGONISTS: Lorcaserin

COMBINATION DRUGS: Phentermine/Topiramate

- inhibits gastric and pancreatic lipases -Lorcaserin selectively activates 5-HT2C receptors, which are almost exclusively found in the CNS. This activation, in turn, stimulates proopiomelanocortin neurons, which activate melanocortin receptors, thereby causing a decrease in appetite - topiramate is anticonvulsant , it was observed that patients lost weight while taking the medication. -Because of the sedating effects of topiramate, the stimulant phentermine was added to counteract the sedation and promote additional weight loss.

chronic weight management.

long-term use in the treatment of obesity.


corticosteroids

LABAs

SABAs

methylprednisolone predinsolon

formetrol salmetrol

albuterol levalboter

asthma cholinergic antagonists ALTERNATIVE DRUGS USED TO TREAT ASTHMA

Leukotriene modifiers

cromolyn

Theophylline

Omalizumab

 

LABAs = Long Acting B² Adrenergic Agonist SABAs = Short Acting B²-Adrenergic Agonist

Ipratroium aclidinium bromide tiotropium zileuton Zafirlukast Montelukast


Drug class Corticosteroids: Methylprednisolone predinsolon

LABAs: Formetrol salmetrol SABAs: albuterol levalboter

MOA

SE

Uses

-inhibition of phospholipase A2 PG and leukotrienes  No. of inflammatory cells in airway -mast cell stabilization histamine release capillary premeability and mucosal edema Tolerance -Long Acting B² Adrenergic Agonist

-hoarseness -adrenal suppression -osteoporosis -oropharyngeal candidiasis

Asthma

similar to quick relief B² agonists

providing bronchodilation

-Short Acting Adrenergic Agonist

-tachycardia -hyperglycemia -hypokalemia

-bronchospasm -acute bronchoconstriction -not-anti inflammatory -not use for persistent asthma

corticosteroids Their most important action is inhibition of airway mucosal inflammation LABAs   

long duration of action (12hr) Neither should be used for quick relief of an acute asthma use of LABAs monotherapy is contraindicated

SABAs quik relief asthma symptoms(4-6 hr)


ALTERNATIVE DRUGS USED TO TREAT ASTHMA These drugs should be used in conjunction with ICS therapy for most patients, not as monotherapy Drug class cholinergic antagonists: Ipratroium Long -action – Anticholinergic: . aclidinium bromide . tiotropium

MOA

SE

Antimuscarinic agent

Uses Ipratroium: 1-instead of inhaled Bagonists in asthmatics

___

2-in addition to inhaled Bagonists in asthmatics for treatment of acute asthma exacerbations in the emergency department 3-in COPD patient aclidinium bromide and tiotropium: 1-COPD

Leukotriene modifiers: 1-Zileuton 2-Zafirlukast 3-Montelukast

1-it is 5 lipoxygenase inh. that is prevent leukotriene (LTD4)synthesis

-elevation of liver enzymes -headache -dyspepsia

all 3 drug prophylaxis

-cough

-for mild persistant asthma -Allergic rhinitis

2and3- LTD4-receptor antagonist Cromolyn

inhibits mast cell degranulation and release of histamine

Theophylline

is unclear

___

Omalizumab



inhibits the binding of IgE to mast cells

ICS = Inhaled corticosteroids

-anaphylactic reaction -arthralgias -fever -rash -Secondary malignancies

-most effective bronchodilator -relieve airflow obstruction in chronic asthma -decreases its symptoms -anti-inflammatory for treatment of moderate to severe persistent asthma in patients who are poorly controlled with conventional therapy


Food impairs the absorption of zafirlukast Ipratroium  not recommended for the routine treatment of acute bronchospasm in asthma  slower than inhaled SABAs cromolyn is a prophylactic anti-inflammatory agent theophylline:  narrow therapeutic window  nomerous drug interaction  mointoring of theophylline blood level is necessary uses of Omalizumab limited by the high cost


A low risk Less symptoms B Low risk More symptoms C high risk

COPD

less symptoms D High risk More symptoms ď‚­airflow, alleviate symptoms, and decrease exacerbation rates

Inhaled bronchodilators

FIRST Short-acting anticholinergic Short-acting B2 agonist ALTERNATIVE Long-acting anticholinergic

FIRST Long-acting anticholinergic Long-acting B2 agonist ALTERNATIVE

Long-acting B2 agonist Short-acting B2 agonist and shortacting anticholinergic

Long-acting anticholinergic and long-acting B2 agonist

FIRST

FIRST

Inhaled corticosteroid + long-acting B2 agonist or Long-acting anticholinergic

ICS + long-acting B2 agonist and/or Long-acting anticholinergic

ALTERNATIVE

ICS + long-acting B2 agonist and longacting anticholinergic or ICS + long-acting B2 agonist and PDE-4 inhibitor or Long-acting anticholinergic and long-acting B2 agonist or Long-acting anticholinergic and PDE-4 inhibitor

Long-acting anticholinergic and long-acting B2 agonist Long-acting anticholinergic and PDE-4 inhibitor Long-acting B2 agonist and PDE-4 inhibitor

ALTERNATIVE


COPD c.other agents Roflumilast MOA:is a phosphodiesterase-4 inhibitor uses: to reduce exacerbations in patients with severe chronic bronchitis its activity is not well defined ,in COPD it is to reduce inflammation by  levels of intracellular cAMP in lung cells Roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm

B. Corticosteroids

The addition of an ICS to a long-acting bronchodilator may improve symptoms lung function and quality of life in COPD patients with FEV1 of < 60% predicted be restricted to these patients used: for acute exacerbations

SE:  risk of pneumonia ------------oral corticosteroids are not recommended for long-term treatment

SE: nausea, vomiting, diarrhea

 

COPD = chronic obstructive pulmonary disease FEV1 = forced expiratory volume in 1 second (In healthy adults this should be approximately 70–85% )


ALLERGIC RHINITIS

Adrenergic agonists Intranasal corticosteroids First-generation Antihistamines (H1receptor blockers) second-generation

Other Agent

Intranasal cromolyn

LT antagonists

ipratropium


DRUGS USED TO TREAT ALLERGIC RHINITIS

Adrenergic agonists

Intranasal corticosteroids

Short-acting Îą-adrenergic agonis

beclomethasone, budesonide, fluticasone,ciclesonide, mometasone, and triamcinolone

-Phenylephrine Longer-acting -oxymetazoline MOA: constrict dilated arterioles in the nasal mucosa and reduce airway resistance note: the Îą-adrenergic agonist intranasal formulations should be used no longer than 3 days due to the risk of rebound nasal congestion( rhinitis medicamentosa)

are the most effective medications for treatment of allergic rhinitis They improve sneezing ,itching, rhinorrhea, and nasal congestion

Antihistamines (H1receptor blockers) more effective for prevention of symptoms.

First-generation antihistamines (diphenhydramine and chlorpheniramine) SE: sedation, performance impairment, and other anticholinergic effects. second-generation antihistamines

SE: are localized. nasal irritation, nosebleed, sore throat, and, rarely, candidiasis. improvement may not be seen until 1 to 2 weeks after starting therapy

(fexofenadine, loratadine,desloratadine, cetirizine, and intranasal azelastine) are generally better tolerated. Combinations of antihistamines

phenylephrine and pseudoephedrine alone or combination with antihistamines is not recommended

Other Agent 1- Intranasal cromolyn : administered before contact with an allergen 2- LT antagonists :as monotherapy or in combination with other agents 3- ipratropium: is available to treat rhinorrhea associated with allergic rhinitis or the common cold


DRUGS USED TO

TREAT COUGH

Opioids 1- Codeine: selectively suppress cough center in medulla oblongata therapeutic effects occur at doses lower than those required for analgesia SE: constipation, dysphoria, and fatigue , tolerance 2- Dextromethorphan: has no analgesic effects in antitussive doses Dextromethorphan has a significantly safer side effect profile than codeine and is equally effective for cough suppression 3- Guaifenesin: an expectorant single-ingredient formulation and is also a common ingredient in combination products with codeine or dextromethorphan.

Benzonatate MOA: benzonatate suppresses the cough reflex through peripheral action. It anesthetizes the stretch receptors located in the respiratory passages, lungs, and pleura SE: include dizziness, numbness of the tongue, . mouth, and throat


Questions â&#x20AC;Ś 1- Complete

First line Drug name or class Second line M.O.A Third line use

-------------------------------inhibit of phospholipase A2 --------------------------------

SABAs: albuterol and levalboter ---------------------------------------------------------------

-------------------------------inhibits mast cell degranulation and release of histamine --------------------------------

Codeine ---------------------------------------------------------------

-------------------------------phosphodiesterase-4 inhibitor --------------------------------


2-True and false ? A. B. C. D. E.

LABAs Their most important action is inhibition of airway mucosal inflammation ( ) Omalizumab inhibits the binding of IgE to mast cells ( ) Beclomethasone improvement may not be seen until 1 to 2 weeks after starting therapy ( We can use LABAS as monotherapy ( ) Cromolyn use as bronchodilator ( )

)


Answers 1- Complete A-Corticosteroids : Methylprednisolone and

predinsolon

inhibit of phospholipase A2 asthma , COPD and ALLERGIC RHINITIS

B-SABAs: albuterol and Short Acting

levalboter

Adrenergic Agonist

bronchospasm and acute bronchoconstriction

C-Cromolyn inhibits mast cell degranulation and release of histamine for mild persistant asthma and Allergic rhinitis

D-Codeine suppress cough center in medulla oblongata cough

E-Roflumilast phosphodiesterase-4 inhibitor COPD

2-True and false ? A. B. C. D. E.

(F) corticosteroids Their most important action is inhibition of airway mucosal inflammation (T) (T) (F) use of LABAs monotherapy is contraindicated (F) Cromolyn is not bronchodilator


Cause sedation: Brompheniramine Chlorpheniramine Clemastine Cyproheptadine Doxylamine

1st generation

Used for motion sikness: Cyclizine Diphenhydramine Dimenhydrinate Hydroxyzine Meclizine Promethazine

Antihistamines

Older, widely used effective most of them penetrate the CNS and cause sedation

Weak sedation: Acrivastine / Cetirizine Levocetirizine Non-sedation: nd

2 generation

Desloratadine Fexofenadine Loratadine

Specific for peripheral H1 receptors. Polar (made by adding carboxyl groups) not cross BBB > not cause sedation


Drug class

MOA - Blocker -in addition they interact cholinergic, adrenergic, or serotonin receptors

SE

USES

1)

Allergic and inflammatory

-Sedation fatigue,

conditions:

dizziness, lack of

such as azelastine ,

coordination, and

olopatadine,

tremors.

ketotifen)

st

1- 1 generation -anticholinergic effects;

NOT indicated for

Dryness -Topical formulations of diphenhydramine can

bronchial asthma

2)

Motion sickness and nausea:

cause hypersensitivity

Diphenhydramine/ dimenhydrinate/

-specific for receptors.

cyclizine/ meclizine headache Some general side

nd

2- 2

generation

effects of

promethazine,

3)

Somnifacients (Sleep inducer) :

Antihistamines:      

Drowsiness Urinary retention Tachycardia Hypotension Vertigo Dry mouth

first-generation antihistamines, such as diphenhydramine and doxylamine

Increased appetite

Drug-Drug interaction: 

Patients taking (MAOIs) should not take antihistamines because the MAOIs can exacerbate the anticholinergic effects of the antihistamines.

first-generation antihistamines (diphenhydramine and others) with anticholinergic actions may decrease the effectiveness of cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) in the treatment of Alzheimer’s disease

(MAOIs) = monoamine oxidase inhibitors


Dexlansoprazole , Esomeprazole , Lansoprazole , Omeprazole , Pantoprazole , Rabeprazole

PPI: inhibitors of the H+/K+ -ATPase proton pump

Cimitidine , Ranitidine , Famotidine , Nizatidine

H2 receptor antagonists and regulation of gastric acid secretion Misoprostol, Analog of prostaglandine enzyme

Triple therapy: PPI combined with amocicillin + clarithomycine

Antimicrobial agents Antacid Treatment of peptic ulcer disease and astroesophage al reflux disease

Prostaglandins

Mucosal protective agents

Antimotility agents

Aluminum hydroxide, Methylcellulose Bismuth subsalicylate

Gastrointes tinal and Antiemetic drugs

Antidiarrheals

Agents that modify fluid and electrolyte transport

Control chemotherpy induced nausea and vomiting

Stool softeners Docusate sodium, docusate calcium

Senna, Bisacodyl, Castor oil

Saline and osmotic laxative

Bulk laxatives

Chloride channel activators

Emetic actions of chemotherapeutic agents Antiemetic drugs

Laxatives

Irritants and stimulants

Hydrophilic colloids, Methylcellulose, Psyllium seeds, Bran

Sucralfate , Bismuth subsalicylate

Mechanisms that trigger vomiting

Diphenoxylate, Lperamid Adsorbants

Quadruple therapy: bismuth subsalicylate, metronidazole and tetracyclic + PPI

Magnesium citrate, Magnesium hydroxide

1- Phenothiazines (prochlorperazine)

2- 5-HT3 receptor blockers (Ondansetron, granisetron, palonosetron, dolasetron)

3- Substituted benzamides (metocloperamide)

4- Butyrophenones (droperidol and haloperidol )

5- Benzodiazepines (alprazolam and lorazepam)

6- Corticosteroids Lubiprostone

Lubricant laxative Mineral oil, Glycerin

(methylprednisolone and dexamethasone)

7- Substance p/neurokinin-1 receptor blocker (aprepitant)

8- Combination regimens


Antimicrobial agents: Drug

MOA

SE

USES Drug of choice

Triple therapy: ___ PPI combined with amocicillin + clarithomycine

Eradication of H.pylori result in rapid healing of active ulcers and low recurance rates

Quadruple therapy: ___

Eradication of H.pylori

bismuth subsalicylate, metronidazole and tetracyclic + PPI

____________________________________________________________ Drug

MOA

SE

USES

H2 receptor antagonists

histamine H2 receptors antagonist

-Well tolerated -Endocrine effects. These effect include gynecomastia and galactorrhea -CNS effects

-Peptic ulcer -Acute stress ulcers -Gastroesophageal reflux disease (GERD)

PPI: inhibitors of the H+/K+ -ATPase proton pump

PPIs bind to the H+/K+ ATPase and suppress the secretion of hydrogen ions H+ into the gastric lumen

Well tolerated Elevated gasric PH Impaire the absorbtion of calcium carbonate Hypomagnesemia and increased incidence of pneumonia

-Stress ulcer treatment and prophylaxis -Gerd -Erosive esophagitis -Active duodenal ulcer -Pathologic hypersecretory condation -Reduce the risk of bleeding from ulcers caused by asprin and other NSAID-induced ulcer -Used with antimicrobial regimens to eradicated H.pylori


Drug

MOA

SE

Prostaglandins

Inhibit secreation of acid and stimulate secretion of mucus and bicarbonate

Diarrhea and nausea

Antacid

Are weak bases that react with gastric acid to form water and salt to diminish gastric acidity. Because pepsin is activeate PH greater than 4 antacid also reduce pepsin activity

Mucosal protectective agent

Enhance mucosal protective mechanism, thereby preventing mucosal injury, reducing inflammation, and healing existing ulcer

Sucralfate

Bismuth Subsalicylate Mechanisms that trigger vomiting Emetic actions of chemotherapeutic agents Phenothiazines (prochlorperazine) 5-HT3 receptor blockers

Substituted benzamides

Constipation Mg hydroxide cause diarrhea

USES

-Peptic ulcer disease -GERD -Duodenal ulcer cause Al hydroxide

-Well tolerated

Antimicrobial action Motion sickness Pregnancy Hepatitis Chemotherapy

Directly activate the medullary CTZ or vomiting center

Dopamine D2 receptor antagonist

Effective against low or moderately emetogenic chemotherapeutic agents

Selectively block 5-HT3 receptors in the periphery and in the brain Dopamin D2 receptors antagonist

Emesis linked with chemotherapy Extrapyramidal symptoms, limit long term high dose use


Drug

MOA

USES SE

Butyrophenones

A potent dopamine D2 receptor antagonist

Benzodiazepines

Sedative anxiolytic and amnesic Not know, but it may involve blockage of prostaglandins Taregets the neurokinin-1 receptor in the brain and block the actions of the natural substance Antiemetic drugs are often combined to increase antiemetic activity or decrease toxicity Activate presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis Act by adsorbing intestinal toxins or microorganisms or by coating or protecting the intestinal mucosa Decrease fluid secretion in the bowel

Corticosteroids

Substance p/neurokinin-1 receptor blocker

Combination regimens

Antimotility agents

Adsorbent

Agents that modify fluid and electrolyte transport Senna

Bisacodyl

-May prolong the QT interval Lengthed QT interval is a marker for the potential of ventricular tachyarrhythmia

-Sedation in endoscopy and surgery -Combination with opioids or benzodiazpines

Secretion into the bowel water and electrolyte.

Used in treating opioid induced constipation.

Act directly on nerve fibers in the mucosa of colon

Potent stimulant of the colon


Drug

Castor oil

Bulk laxative

Saline and osmotic laxative Stool softeners

Lubricant laxative Chloride channel activators

MOA

Broken down in the small intestine to ricinoleic acid, wich is very irritating to the stomach and promotly. Increase peristalsis. They form gels in the large intestine causing water retention distension, thereby increasing peristaltic activity Non absorbal salt that hold water in the intestine by osmosis Emulsified with the stool produce softer feces and ease passage Act by facilitating the passage of hard stools Activating chloride channels to increase fluid secretion in the intestinal lumen.


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

Ranitidine ------------------------------------------(GERD)

-------------------------------------------------------------------------------------

------------------------------------------Reduce the risk of bleeding from ulcers caused by asprin and other NSAID

Ondansetron -------------------------------------------------------------------------------------

------------------------------------------Combination with opioids or benzodiazpines


Answers 1- Complete A-Ranitidine H2 receptors antagonist (GERD)

B- Dexlansoprazole , Esomeprazole , Lansoprazole , Omeprazole , Pantoprazole , Rabeprazole PPI Reduce the risk of bleeding from ulcers caused by asprin and other NSAID-induced ulcer

C- Ondansetron 5-HT3 receptor blockers Emesis linked with chemotherapy

D-Butyrophenones dopamine D2 receptor antagonist Combination with opioids or benzodiazpines


For Erectile Dysfunction

For Benign Prostatic Hyperplasia.

Phosphodieste rase -5inhibitor

5-alpha reductase inhibitors.

Alpha 1adrenergic antagonists. Phosphodiestrase 5inhibitors. Terazpsin ,doxazosin,

Tadalafil

Finasteride, dutasteride

Tamsulosin, alfuzosin, and

Alprostadil

Sildenafil, vardenafil, tadalafil, avanafil


Phosphodiestrase 5-inhibitors: Drug class

MOA

SE

USES

Sildenafil, vardenafil, tadalafil, avanafil.

It inhibits the breakdown of cGMP so the vasodilatory of effect of NO is enhanced.

1-There is an inherent cardiac risk associated with sexual activity. 2-have the potential to cause priapism.

-treat Erectile dysfunction

Alprostadil

It increases the concentration of cyclic AMP (cAMP).

1-Since alprostadil is not systemically absorbed ,adverse systemic effects are rare. 2Hematoma,ecchymosis, and rash are possible from alprostadil injection. 3-It may leads to priapism.

-treat Erectile dysfunction

Alpha 1-adrenergic antagonists: Drug class Terazpsin, doxazosin, Tamsulosin, alfuzosin, and silodosin.

MOA

SE

USES

They are selective competitive blockers of the alpha1receptors.

1-Orthostati hypotension. 2-Tachycardia. 3-Vertigo. 4-Sexual dysfunction.

-treat Benign Prostatic Hyperplasia

SE

USES

5-alpha reductase inhibitors: Drug class Finasteride, dutasteride

MOA inhibit the enzyme 5-alpha reductase ,which is responsible for converting testosterone to the more active dihydrotestosterone (DHT).

1-Cause sexual side effects, such as decreased ejaculate ,decreased libido, ED, gynecomastia, and oligospermia. 2-have teratogenic potential.

-treat Benign Prostatic Hyperplasia


Phosphodiesterase -5-inhibitor: Drug class Tadalafil

MOA Inhibit of the PDE-5 allows for vasodilation and relaxation of the smooth muscle of the prostate and bladder, which thereby improves symptoms of BPH.

SE

___

USES Tadalafil is the only PDE-5 inhibitor approved for the treatment of BPH.


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------It increases the concentration of (cAMP). ---------------------------------------------

doxazosin, -----------------------------------------------------------------------------------------

--------------------------------------------Inhibit of the PDE-5 ---------------------------------------------


Answers 1- Complete A-Alprostadil It increases the concentration of cyclic AMP (cAMP). Erectile dysfunction

B-doxazosin, They are selective competitive blockers of the alpha1-receptors. treat Benign Prostatic Hyperplasia

C-Tadalafil Inhibit of the PDE-5 BPH.


Agent used to treat Anemias Drug class

MOA

-Dark stools. -GI disturbance (Local irritation). - Fatal hypersensitivity and anaphylactoid reactions can occur in patients receiving parenteral iron.

Iron deficiency anemia

Corrects the folic acid deficiency.

Nontoxic, no substantiated side effects. -Rare hypersensitivity reactions to parenteral injections have been reported.

Folic acid deficiency (Megaloblastic anemia).

Corrects vitamin B12 deficiency.

-Nontoxic even in large doses.

-Deficiencies of vitamin B12.

2-Folic acid (folate)

-Pernicious anemia.

-stimulates stem cells to differentiate into proerythroblasts. 4-Erythropoietin

USES

Corrects The iron deficiency 1-Iron

3-Cyanocobalamin, Hydroxocobalamin (vitamin B12):

SE

-Promotes the release of Reticulocytes from the marrow. -initiation of hemoglobin formation

-Elevation in blood pressure -and arthralgia in some cases.

-Used to treat anemia caused by end-stage renal disease. -Anemia associated with human immunodeficiency virus infection -Anemia in bone marrow Disorders.

Antidote of iron is Deferoxamine Darbepoetin is a long-acting version of Erythropoietin therefore have no value in acute treatment of anemia.


Agent used to treat Neutropenia Drug class

1-Sargramostim

2-Filgrastim 3-Pegfilgrastim

MOA Granulocyte– macrophage colony– stimulating Factors

SE Common: -Bone pain

USES -prophylactically to reduce risk of neutropenia following chemotherapy and bone marrow transplantation.

Myeloid growth factors or granulocyte colony– stimulating factors (GCSF) Both stimulate granulocyte production in the marrow to increase the neutrophil counts

Agent used to treat sickle cell disease

Drug class

MOA

SE

USES

1-Hydroxyurea

- fetal hemoglobin levels, thus diluting the abnormal hemoglobin S (HbS).

-Bone marrow suppression And -cutaneous vasculitis.

-reduce the frequency of painful sickle cell crises

2-Pentoxifylline

- deformability of red blood cells and - viscosity of blood.

-GI side effects that lessen with food.

-treat intermittent claudication in patients with peripheral vascular disease.


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

____________________________ ____________________________ Iron deficiency anemia

Sargramostim ____________________________ ____________________________

____________________________ ____________________________ reduce the frequency of painful sickle cell crises


Answers 1- Complete A-Iron Corrects The iron deficiency Iron deficiency anemia

B-Sargramostim Granulocyte–macrophage colony–stimulating Factors to treat Neutropenia

C-Hydroxyurea - fetal hemoglobin levels, thus diluting the abnormal hemoglobin S (HbS). reduce the frequency of painful sickle cell crises


AGENTS FOR ACNE 1-Retinoids

Vitamin A derivatives Comedolytic Anti-inflammatory

DESCRI PTION

1st generation Tretinoin (topical) Isotretinoin (oral)

MOA

2-Benzoyl Peroxide Topical agent

3rd generation

Adapalene (topical) Tazarotene (topical) *considered first-line therapy

Initiate transcription by binding to nucleic retinoic acid receptors.

Antiseptic against P. acnes.

Photosensitivity Suicide attempt (isotretinoin) Birth defects (isotretinoin*) *contraindicated in pregnancy

ď&#x201A;§

Topical agent Keratolytic Antiinflammatory

P.acne = propionibacterium acne

4-Azelaic Acid

5-Antibiotics

For mild to moderate inflammatory acne

For moderate to severe acne with inflammation

Antiinflammatory Anticomedogenic

First-line for mild to moderate acne with no inflammation

Irritation Dryness Skin peeling

SE

3-Salicylic Acid

Penetrates the pilosebaceous unit and works as an exfoliant to clear comedones.

Antibacterial activity against P. acnes.

Oral Minocycline Doxycycline Erythromycin

Topical Clindamycin Erythromycin

Against the gram + P. acnes

Normalizes keratinization Erythromycin: Infrequent use due to GI side effects


TOPICAL ANTIBACTERIAL AGENTS Gram + Drug name 1-Bacitracin

2- Mupirocin

3- Retapamulin

MOA Cell wall inhibitor

Protein synthesis inhibitor

Protein synthesis inhibitor

SE Systemic use is toxic

USES Used in combination with Neomycin and/or Polymyxin Prevention of skin infections after burns or minor scrapes -Treating impetigo

___

___

-Infections caused by (MRSA) impetigo

Gram – Drug name 1- Polymyxin B

MOA

SE

Disrupts the bacterial cell membrane ___

USES -With neomycin and bacitracin (“triple antibiotic”) -Skin infections after minor skin trauma

2- Neomycin

Skin infections caused by gram-negative organisms such as Pseudomonas, E. coli, and Klebsiella sp.

(MRSA) = methicillin- resistant Staphylococcus aureus

___

Allergic dermatitis


ECTOPARASITIC INFECTIONS MOA USE

1-Lindane

2-Permethrin

Protein synthesis inhibitor Impetigo

 Pediculicide (kills lice) and scabicide  Neurotoxic to lice  Treat scabies  Preferred over lindane for treatment for lice and scabies, since lindane can cause neurotoxicity

3-ivermectin

4-Synergized pyrethrins & piperonyl butoxide

  

5-Crotamiton

Scabicide and has antipruritic functions

Alternative treatment for lice and scabies

Nonprescription Used for head and pubic lice Pyrethrins are pesticides and piperonyl butoxide prevents the lice from metabolizing the pyrethrins, thereby enhancing their effect First-line treatment for pediculosis


AGENTS FOR PIGMENTATION DISORDERS

Hydroquinone

Methoxsalen

•Uses: 1- hyperpigmentation associated with freckles and melasma 2- combination with topical retinoids too treat photoaging •MOA: inhibition of the tyrosinase enzyme required for melanin synthesis. •SE: possible carcinogenicity in higher concentrations or excessive quantities •Monobenzone It is used to even out the skin discoloration associated with vitiligo, it causes permanent depigmentation.

•Use: Vitiligo •MOA: inhibits cell proliferation and promotes cell differentiation of epithelial cells. •Topical: used for small patches. Oral: used for widespread disease •SE: skin aging and possible carcinogenicity


AGENTS FOR PSORIASIS Tazarotene (topical)

USE

Plaque psoriasis

1-Retinoids Acitretin (oral) Second-generation

USE

Pustular forms of psoriasis

CONTRAINDICATIONS

1-ethanol: increase transesterification of acitretin to etretinate 2-pregnancy (teratogenic)

SE

Cheilitis, pruritus, peeling skin, and hyperlipidemia

Calcipotriene, calcitriol

2-Vitamin D analogues

1-Synthetic vitamin D3 derivatives 2-Topical

USE

Plaque psoriasis

MOA

Inhibits keratinocyte proliferation and increase keratinocyte differentiation.

SE

3-Keratolytic agents

Elevation in calcium levels, itching, dryness, burning irritation, and erythema.

Coal tar and salicylic acid Improve corticosteroid penetration USE

Localized psoriasis in scalp

MOA

Inhibits excessive skin cell proliferation and may also have antiinflammatory effects.


TOPICAL CORTICOSTEROIDS Drug class 1-CORTICOSTEROIDS

MOA

SE

USES

-Inhibitory effects on the arachidonic acid cascade, -depression of production of many cytokines, and effects on inflammatory cells. In psoriasis, - they inhibit epidermal cell mitosis.

Skin atrophy, striae, purpura, acneiform eruptions, dermatitis, local infections, and hypopigmentation. In children, systemic toxicity, including depression of the hypothalamic–pituitary– adrenal axis and growth retardation.

-Psoriasis, -eczema, -contact dermatitis, -and other skin conditions manifested by itching and inflammation.

It may cause tachyphylaxis (decrease in response after repetitive use, tolerance) can occur with continuous use.

TRICHOGENIC AGENTS Minoxidil, Finasteride  TOPICAL THERAPY It does not cause systemic hypotension.

USE

Androgenic alopecia (“male pattern baldness”)

MOA 1-Minoxidil

2-Finasteride

Shortening the rest phase of the hair cycle.

5-α reductase inhibitor that blocks conversion of testosterone to the potent androgen 5-α dihydrotestosterone (DHT).

SIDE EFFECTS

Decreased libido, decreased ejaculation, and erectile dysfunction.

CONTRAINDICATIONS

Pregnancy


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

Benzoyl Peroxide ---------------------------------------------------------------------

----------------------------------5-Îą reductase inhibitor -----------------------------------

Retapamulin ----------------------------------impetigo

Hydroquinone ---------------------------------------------------------------------

----------------------------------Disrupts the bacterial cell membrane ----------------------------------


Answers 1- Complete A-Benzoyl Peroxide Antiseptic against P. acnes. FOR ACNE

B-Retapamulin Protein synthesis inhibitor Impetigo

C-Polymyxin B Disrupts the bacterial cell membrane Skin infections after minor skin trauma

D-Hydroquinone inhibition of the tyrosinase enzyme required for melanin synthesis pigmentation disorders

E-Finasteride 5-Îą reductase inhibitor trichogenic agent


DRUGS FOR OSTEOPOROSIS

Alendronate

Calcitonin Denosumab Ibandronate Risedronate Raloxifene Teriparatide Zoledronic acid

Pamidronate Tiludronate

DRUGS FOR DISORDERS OF BONE REMODELING

Etidronate


Post manupause woman

Denosumab ,Teriparatide

No, But at high risk

History of bone fracture Yes (Recent vertebral fracture)

Calcitonin

No

Bisphosphonates


Drug class

MOA

SE

 Osteoclastic bone

-Diarrhea.

resorption mainly through

-Abdominal pain. -musculoskeletal pain.

 Osteoclastic apoptosis and inhibition of the cholesterol biosynthetic pathway.


- Oral bisphosphonates associated with: esophagitis and esophageal ulcers **patients should remain upright after taking them.

USES -Osteoporosis -Paget disease - Bone metastases -Hypercalcemia of malignancy.

-High IV dose Osteonecrosis of the jaw. - Long term use of Etidronate 
 osteomalacia 
 

2- Estrogen replacement:

-Selective estrogen receptor modulator

(Raloxifene )

Rare:

Atypical fractures. -Hot flashes. -Leg cramps.

- It has estrogen-like effects on bone and estrogen antagonist effects on breast and endometrial tissue - Increases bone density without increasing the risk of endometrial cancer. -It decreases the risk of invasive breast cancer and also reduces levels of total and low- density lipoprotein cholesterol.

-Risk of venous thromboembolism similar to estrogen.

Prevention and treatment of osteoporosis


Drug class

MOA Reduces bone resorption, but it is less effective than bisphosphonates.

SE -Intranasal administration include rhinitis and other nasal symptoms. -Resistance to calcitonin.

4- Denosumab

It is a mAB that targets receptor activator of nuclear factor kappa-B ligand and inhibits osteoclast formation and function.

Increased risk of: -Infections -Dermatological reactions -Hypocalcemia

USES -OP in women who are at least 5 years postmenopausal. -A unique property of calcitonin is the relief of pain associated with OP fracture, beneficial in patients with a recent vertebral fracture

- Postmenopausal OP in women at high risk of fracture. - It should be reserved for those who are intolerant of or unresponsive to other OP therapies.

-Osteonecrosis of the jaw -Atypical fractures.

5- Teriparatide

-First approved treatment for OP that stimulates bone formation -Promotes bone formation by stimulating osteoblastic activity

Op = osteoporosis

-Increased risk of osteosarcoma in rats

-For patients at high risk of fractures and those who have failed or cannot tolerate other osteoporosis therapies.


Questions â&#x20AC;Ś 1- Complete

First line Drug name or class Second line M.O.A Third line use

-----------------------------

activator of nuclear factor kappa-B ligand --------------------------------------------------------Reduces bone resorption, but it is less effective than bisphosphonates.

----------------------------Raloxifene

----------------------------Prevention and treatment of osteoporosis ----------------------------stimulating osteoblastic activity ---------------------------------------------------------

----------------------------Paget disease


A-Denosumab activator of nuclear factor kappa-B ligand Postmenopausal OP in women at high risk of fracture. It should be reserved for those who are intolerant of or unresponsive to other OP therapies.

B-(Raloxifene ) Selective estrogen receptor modulator Prevention and treatment of osteoporosis

C-Bisphosphonates: ď&#x201A;Ż Osteoclastic and ď&#x201A;­ Osteoclastic apoptosis Paget disease

D-Calcitonin Reduces bone resorption, but it is less effective than bisphosphonates. OP in women who are at least 5 years postmenopausal.and a unique property of calcitonin is the relief of pain associated with OP fracture

E-Teriparatide stimulating osteoblastic activity For patients at high risk of fractures and those who have failed or cannot tolerate other osteoporosis therapies


NSAIDs

Aspirin celecoxib

acetaminophen Methotrexate Hydroxychloroquine

Disease-Modifying Antirheumatic Drugs

Leflunomide Minocycline Sulfasalazine Glucocorticoids

Antiinflammatory, Biological therapies Antipyretic, In rheumatoid and Analgesic arthritis Agents

Adalimumab Certolizumab pegol Etanercept Golimumab Infliximab Abatacept Rituximab Tocilizumab Tofacitinib Anakinra Colchicine

Drug used for treatment of gout

Allopurinol Febuxostat Probenecid Pegloticase

Drugs to treat migraine headaches

Triptans Ergot alkaloids

Sumatriptan Frovatriptan Zolmitriptan Ergotamine dihydroergotamine


celecoxib

Aspirin

Drug name

MOA

SE

Therapeutic uses

Aspirin irreversibly acetylates (and, thus, inactivates) COX, an enzyme that required for prostaglandins and thromboxane synthesis.

Gastrointestinal side effect ranging from dyspepsia to bleeding, Increased risk of bleeding (antiplatelet effect) and, Sodium and water retention and may cause edema in some patients.

Used to treat pain, and reduce fever or inflammation (for example, osteoarthritis, gout, and RA) or common conditions (for example, headache, arthralgia, myalgia, and dysmenorrhea). It is sometimes used to treat or prevent heart attacks, strokes, and chest pain (angina).

Note: Aspirin exhibit analgesic activity at lower doses and at higher doses show anti-inďŹ&#x201A;ammatory activity.

Note: Aspirin should be avoided in patients less than 20 years old with viral infections, and should be used with caution in patients with asthma.

Note: Aspirin interacts with warfarin, phenytoin, and valproic acid resulting in higher free concentrations of these agents.

Inhibits prostaglandin synthesis by selectively reversible COX-2 inhibition.

Headache, dyspepsia, diarrhea, abdominal pain.

Used to treat RA, osteoarthritis, and acute mild to moderate pain. Note: Patients who are at high risk of ulcers and require aspirin for cardiovascular prevention should avoid the use of celecoxib.

Acetaminophen

ACETAMINOPHEN Inhibits prostaglandin synthesis in the CNS. It has less effect on COX in peripheral tissues (due to peripheral inactivation), which accounts for its weak anti-inďŹ&#x201A;ammatory activity.

At normal therapeutic doses, acetaminophen is virtually free of adverse effects. With large doses of acetaminophen, hepatic necrosis can result.

Acetaminophen is the analgesic/antipyretic of choice for children with viral infections or chickenpox (due to the risk of Reye syndrome with aspirin).


Disease-Modifying Antirheumatic Drugs

Leflunomide

Hydroxychloroq uine

Methotrexate

Drug name

MOA Methotrexate is a folic acid antagonist that inhibits cytokine production and purine nucleotide biosynthesis, leading to immunosuppressive and antiinflammatory effects.

Its mechanism of action in autoimmune disorders is unknown.

Leflunomide is an immunomodulatory agent that preferentially causes cell arrest of the autoimmune lymphocytes through its action on dihydroorotate dehydrogenase (DHODH). Activated proliferating lymphocytes require constant DNA synthesis to proliferate. Pyrimidines and purines are the building blocks of DNA, and DHODH is necessary for pyrimidine synthesis. After biotransformation, leflunomide becomes a reversible inhibitor of DHODH.

SE The most common side effects observed after treatment of RA are mucosal ulceration and nausea. Cytopenias, cirrhosis of the liver, and an acute pneumonia-like syndrome may occur with chronic administration. Note: Taking leucovorin (folinic acid) once daily after methotrexate reduces the severity of adverse effects. Folic acid taken on off-days is widely used. Hydroxychloroquine has less effect on the liver and immune system than other DMARDs; however, it may cause ocular toxicity, including irreversible retinal damage and corneal deposits. It may also cause CNS disturbances, GI upset, and skin discoloration and eruptions. Headache, diarrhea, and nausea. Other untoward effects are weight loss, allergic reactions, including a flu-like syndrome, skin rash, alopecia, and hypokalemia. It is not recommended in patients with liver disease, because of a risk of hepatotoxicity.

Therapeutic uses Methotrexate used alone or in combination therapy, has become a mainstay of treatment in patients with rheumatoid or psoriatic arthritis.

Hydroxychloroquine is used for early, mild RA, often combined with methotrexate. This agent is also used in the treatment of lupus and malaria.

Leflunomide is approved for the treatment of RA. It can be used as monotherapy or in combination with methotrexate.


Glucocort Sulfasalazine icoids

Minocycline

minocycline has been shown to be effective in the treatment of early RA, it is generally not utilized as First-line therapy. Minocycline can be used as monotherapy or in combination with other DMARDs.

Its mechanism of action in treating RA is unclear.

potent anti-inflammatory drugs

Sulfasalazine is used for early, mild RA in combination with methotrexate and/or hydroxychloroquine.

Note: Timely dose reductions and cessation are necessary to avoid adverse effects associated with long-term use

Commonly used in patients with RA to provide symptomatic relief and bridge the time until DMARDs are effective.

MOA

SE

Adalimumab

Adalimumab is a recombinant monoclonal antibody that binds to TNF-α, thereby interfering with endogenous TNF-αactivity by blocking its interaction with cell surface receptors.

Certolizumab pegol

BIOLOGIC THERAPIES IN RHEUMATOID ARTHRITIS Drug name

Certolizumab is a unique TNF-α blocker that contains a Fab fragment of a humanized antibody and is a potent neutralizer of TNF-α biological actions. It is combined with polyethylene glycol (pegylated).

It may cause headache, nausea, agranulocytosis, rash, reaction at the injection site, or increased risk of infections, such as urinary tract infections, upper respiratory tract infections, and sinusitis. Adverse effects are similar to other TNF-α inhibitors.

Therapeutic uses Indicated for treatment of moderate to severe RA, either as monotherapy or in combination with methotrexate. It is also indicated for psoriatic arthritis, ankylosing spondylitis, and Crohn disease.

It has similar indications to adalimumab.


Etanercept Golimumab Infliximab Abatacept

Etanercept is a genetically engineered, soluble, recombinant, fully human receptor fusion protein that binds to TNF-α, thereby blocking its interaction with cell surface TNF-α receptors.

Generally well tolerated. As with all TNF-α inhibitors, it can increase the risk for infections, malignancy, and new or worsening heart failure.

Use in patients with moderate to severe RA, either alone or in combination with methotrexate. It is also use in ankylosing spondylitis and psoriasis.

Golimumab neutralizes the biological activity of TNF-α by binding to it and blocking its interaction with cell surface receptors.

golimumab may increase hepatic enzymes. Reactivation of hepatitis B may occur in chronic carriers, and may increase the risk of malignancies and serious infections. Infusionsite reactions, such as fever, chills, pruritus, and urticaria, may occur. Infections (for example, pneumonia, cellulitis, and activation of latent tuberculosis), leukopenia, and neutropenia have also been reported. headache, upper respiratory infections, nasopharyngitis, and nausea

used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs for patients with moderate to severe RA.

Infliximab is a chimeric monoclonal antibody composed of human and murine regions. The antibody binds specifcally to human TNF-α and inhibits binding with its receptors.

Abatacept is a soluble recombinant fusion protein that competes with CD28 for binding on CD80/CD86 protein, thereby preventing full T-cell activation.

Note: Concurrent use with TNF-α inhibitors is not recommended due to increased risk of serious infections.

Note: The combination of etanercept and methotrexate is more effective than methotrexate or etanercept alone in retarding the RA disease process, improving function, and achieving remission.

Use in combination with methotrexate in patients with RA who have had inadequate response to methotrexate monotherapy, plaque psoriasis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, and Crohn disease.

Note: not indicated for monotherapy, as this leads to the development of anti-infliximab antibodies, resulting in reduced efficacy. Indicated for patients with moderate to severe RA who have had an inadequate response to DMARDs or TNF-α inhibitors.


Rituximab Tocilizumab Tofacitinib Anakinra

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes, resulting in B-cell depletion. Tocilizumab is a monoclonal antibody that inhibits the actions of IL-6 by blocking the IL-6 receptor.

Infusion reactions (urticaria, hypotension, and angioedema) are the most common complaints with this agent and typically occur during the first infusion.

Tofacitinib is an oral inhibitor of Janus kinases.

Hemoglobin concentrations must be monitored during therapy due to the risk for anemia.it may also increase the risk for secondary malignancy, opportunistic infections, renal, or hepatic dysfunction. This agent is associated with neutropenia.

Anakinra is an IL-1 receptor antagonist.

Use in combination with methotrexate for patients with moderate to severe RA who have had an inadequate response to TNF-Îą inhibitors.

Used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs for patients with moderate to severe RA.

Indicated for the treatment of moderate to severe RA in patients who have had an inadequate response or intolerance to methotrexate.

Indicated for the treatment of moderate to severe RA in patients who have failed one or more DMARDs. Note: Infrequently used in the treatment of RA.


DRUGS USED FOR THE TREATMENT OF GOUT

Pegloticase

Probenecid

Febuxostat

Allopurinol

Colchicine

Drug name

MOA Colchicine binds to tubulin, a microtubular protein, causing its depolymerization. This disrupts cellular functions, such as the mobility of granulocytes, thus decreasing their migration into the affected area. Furthermore, colchicine blocks cell division by binding to mitotic spindles. Allopurinol a xanthine oxidase inhibitor, is a purine analog. It reduces the production of uric acid by competitively inhibiting the last two steps in uric acid biosynthesis that are catalyzed by xanthine oxidase Febuxostat a xanthine oxidase inhibitor .

Probenecid promotes renal clearance of uric acid by inhibiting the urateanion exchanger in the proximal tubule that mediates urate reabsorption. At therapeutic doses, it blocks proximal tubular reabsorption of uric acid. Pegloticase acts by converting uric acid to allantoin, a water-soluble nontoxic metabolite that is excreted primarily by the kidneys.

SE

Therapeutic uses

May cause nausea, vomiting, abdominal pain, and diarrhea. Chronic administration may lead to myopathy, neutropenia, aplastic anemia, and alopecia.

Used for the treatment of acute gouty attacks and also used as a prophylactic agent to prevent acute attacks of gout in patients initiating urate-lowering therapy.

Well tolerated by most patients. Hypersensitivity reactions, especially skin rashes, are the most common adverse reactions. Note: Febuxostat does not have the same degree of renal elimination as allopurinol and thus requires less adjustment in those with reduced renal function.

Effective urate-lowering therapy in the treatment of gout and hyperuricemia secondary to otherconditions, such as that associated with certain malignancies or in renal disease.

Note: should not be used in pregnancy, and it should be used with caution in patients with hepatic, renal, or cardiovascular disease

Used for the treatment of gout.

Indicated for patients with gout who fail treatment with standard therapies such as xanthine oxidase inhibitors.


Drugs to treat migraine headaches class

MOA

SE

Triptans

The triptans are serotonin agonists, acting at a subgroup of serotonin receptors found on small peripheral nerves that innervate the intracranial vasculature.

May cause nausea but much less than that occurs with dihydroergotamine and the vasoconstriction caused by ergotamine. Pain and pressure sensations in the chest, neck,

Ergot alkaloids

The action of the ergot alkaloids is complex, with ability to bind to 5-HT1 receptors, α receptors, and dopamine receptors. 5-HT1 receptors located on intracranial blood vessels are targets that cause vasoconstriction with the use of these agents.

Drug example

throat, jaw,d izziness and malaise have also been seen with the use of triptans. Nausea is a common adverse effect.

  

Sumatriptan Frovatriptan Zolmitriptan

 

Ergotamine dihydroergotamine

Note: The use of dihydroergotamine is limited to severe cases of migraines. Ergotamine and dihydroergotamine are contraindicated in patients with angina and peripheral vascular disease because they are significant vasoconstrictors.

Prophylaxis for migraine headache Indicated if the attacks occur two or more times a month and if the headaches are severe or complicated by serious neurologic signs. β-Blockers are the drugs of choice for migraine prophylaxis . Propranolol , metoprolol, atenolol, and nadolol, have been shown to be effective.

The calcium channel blocker verapamil is an alternative.

Anticonvulsants (divalproex).

Antidepressants (tricyclics) have also shown effectiveness in preventing migraine. Antidepressants are especially useful for migraine prophylaxis in patients with comorbid depression.

Drugs for tension and cluster headache Tension headaches

cluster headache

Analgesics such as NSAIDs (for example, naproxen and ibuprofen), acetaminophen, and aspirin are used for symptomatic relief of tension headaches. Acetaminophen and/or aspirin may also be combined with caffeine. Butalbital, a barbiturate, in combination with acetaminophen or aspirin with or without caffeine is also used in tension headaches.

Inhalation of 100% oxygen and triptans (especially sumatriptan) are used as frst-line abortive strategies for cluster headache.


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

----------------------------------------------IL-1 receptor antagonist.

-----------------------------------------------

moderate to severe RA

serotonin agonists -----------------------------------------------

Febuxostat

Methotrexate

-----------------------------------------------

folic acid antagonist

-----------------------------------------------

-----------------------------------------------

Answers


1- Complete A-Anakinra IL-1 receptor antagonist. moderate to severe RA

B-Febuxostat xanthine oxidase inhibitor gout

C-Triptans (Sumatriptan , Frovatriptan and Zolmitriptan) serotonin agonists migraine headaches

D-Methotrexate folic acid antagonist rheumatoid or psoriatic arthritis.


CLASS PENICILLINS Naturally occurring peniciilins

Drug name Penicillin G , Penicillin V

Penicillinase-resistant penicillins

Methicillin , nafcillin , oxacillin and dicloxacillin

Extended spectrum penicillins

Antipseudomonal penicillins

mechanism of action

bactericidal drugs interfere with the synthesis of the bacterial cell wall

(closely related to penicillin)

First generation

bactericidal drugs interfere with the synthesis of the bacterial cell wall

Cefuroxime, cefotetan, cefoxitin, cefotetan, cefaclor, .cefamandole and cefprozil

Side Effect Hypersensitivity  (angioedema and .anaphylaxis) Nephritis  (Methcillin)

Neurotoxicity

(effective against gram-) active against Pseudomonas aeruginosa.

Ticarcillin , piperacillin

CEPHALOSPORINS

Second generation

(No activity aginst gram -) treatment MSSA (Similar to penicillin G but more effective aginst gram -) *Ampicillin is the drug of choice for the Listeriosis *Dentists use Amoxicillin prophylactically for the prevention of bacterial endocarditis .

Ampicillin , Amoxicillin

Cefadroxil, Cephazolin and Cephalexin

Uses (Gram + and few - )Pneumonia , diphtheria , Gonorrhea , syphilis

* against gram + * in patients with penicillin allergy *.cover MSSA *.treatment of pneumonia )Less against + and more against -) Used in-patient allergic to .( gonorrhea(,pinicillins

* Stevens-Johnson syndrome * anaphylactic response * cross sensitivity between penicillin and cephalosporins


Third generation

Cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, cefdniir, ceftibuten .and cefixime

(less active against gram+ and more active against -) *treatment of serious infections by -gram negative bacteria *drugs of choice for treatment of meningitis *.Treatment of gonorrhea

Fourth generation

Cefepime

* broad-spectrum * Empiric use * .it is effective in meningitis

advanced generation

Ceftaroline

* broad-spectrum * effective parentrally against MRSA *treatment of complicated skin infections * community-acquired pneumonia .*.powerful antipseudomonal effect

CARBAPENEMS

Imipenem

Other β-lactam antibiotics that inhibit the cell wall synthysis *broadest spectrum β-lactam antibiotic *used in empiric therapy

*degradation by renal dehydropeptidase forms an inactive metabolite that is potentially nephrotoxic ,.


*Similar to imipenem but is stable to dehydropeptidase

meropenem

*.are used in empiric therapy *used in severe infections of the skin

ertapenem

Monobactams

Aztreonam

parenteral bactericidal antibiotic that inhibits cell .wall synthesis

* )only against gram-) *Treatment of the infection cuased by negative bacteria

*it lacks coverage against P. .aeruginosa It accumulates in patients with renal failure (avoid in .)renal patients

Other agents affecting the cell wall Vancomycin

It inhibits the synthesis of bacterial cell wall

*For serious infections with multidrug resistant gram-positive *.)MRSA or MRSE)

Bacitracin and Telavancin

*-treat life .threatening antibiotic causing colitis *.)Active against MRSA and VRE) *Both are given IV

Fosfomycin

*Telavancin is the last choice for hospital-acquired *)for treatment of UTIs) It is safe for .use in pregnancy

*.)red man syndrome( *ototoxicity and nephrotoxicity( monitored for safety and efficacy)

Telavancin causes renal impairment and it is contraindicated in pregnant .women


Polymyxins

polymyxin-B and polymyxin-E

*clinically used in topical preparations

drops. Systemic (parentaral) use of polymyxins was limited due to their severe nephrotoxicity and ;neurotoxicity


TETRACYCLINES Demeclocycline Doxycycline Minocycline Tetracycline

LINCOSAMIDES Clindamycin

GLYCYLCYCLINES Tigecycline

OTHERS Chloramphenicol Quinupristin/Dalfopristin

MACROCYCLIC Fidaxomicin

MACROLIDES/KETOLIDES Azithromycin clarithromycin Erythromycin Telithromycin

TYGACIL AMINOGLYCOSIDES Amikacin Gentamicin Neomycin Streptomycin Tobramycin

OXAZOLIDINONES Linezolid


drug Tetracyclines Demeclocycline Doxycycline Minocycline Tetracycline Glycylyclines Tigecycline

Aminoglycosides Amikacin Gentamicin Neomycin Streptomycin Tobramycin

Macrolides and ketolides Azithromycin clarithromycin Erythromycin Telithromycin fidaxomicin

chloramphenicol

clindamycin

Quinupristin/dalfopristin

Linezolid Clindamycin

M.O.A Bind reversibly to 30s ribosmal subunit

S.E Tooth discoloration

USE Acne ,endocarditis,meningitis

bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome bind to the 30s ribosomal sub-unit and cause a misreading of the genetic code

photosensitivity, discoloration of growing teeth, and fetal damage.

ONLY TIGECYCLINE

ototoxicity and nephrotoxicity NEUROMUSCULAR PARALYSIS

irreversibly binding to the 50S ribosomal subunits thus inhibiting translocation

cholestatic jaundice

inhibits RNA polymerase sigma subunit

Anemia Neutropenia Hypersensitivity

reversibly binds to a receptor site on the 50S subunit of the bacterial ribosome, inhibiting peptidyl transferase suppresses protein synthesis by interfering with the development of initiation complexes and with aminoacyl translocation reactions. Combination drug bins to separate site on 50 S ribosome Inhibiting the formation of the 70S initiation complex

treat severe or serious bacterial infections

treat respiratory tract infections

gastric distress

treat diarrhea caused by infection with Clostridium difficile life-threatening infections

Gray baby syndrome anemia

Jaundice diarrhea

middle ear infections, bone or joint infections

Hyperbilirubinemia Arthralgia and myalgia

skin structure infections

Thrombocytopenia

pneumonia, skin infections, and infections that are resistant to other antibiotics.


Fluoroquinolones: GENERATION

DRUG NAME Nalidixic acid Cinoxacin Norfloxacin Ciprofloxacin Enoxacin Ofloxacin Levofloxacin Sparfloxacin Moxifloxacin Gemifloxacin

1st 2nd

3rd 4th

Drug name

SPECRUM Gram negative ,but not pseudomonas species. Gram negative some gram positve & some Atypial. Same as 2nd generation with extended gram positeve and a typical coverage. Same as 3rd generation with broad anaerobic coverage.

Trovafloxacin

MOA

SE

Norfloxacin nausea, vomiting, and diarrhea.

Ciprofloxacin

Levofloxacin

Moxifloxacin

enter bacteria through porin channels and exhibit antimicrobial effects on DNA gyrase (bacterial topoisomerase II) and bacterial topoisomerase IV.

Headache and dizziness or lightheadedness,phototoxicity,tendinitis or tendon rupture patients with (CNS) disorders, such as epilepsy, should be treated cautiously with these drugs.

USES Nonsystemic infections urinary tract infections (UTIs), prostatitis, and infectious diarrhea

systemic infections cystic fibrosis Travelerâ&#x20AC;&#x2122;s diarrhea typhoid fever 2nd line in : tuberculosis

Peripheral neuropathy and glucose prostatitis, skin dysregulation infections, CAP, and nosocomial pneumonia (hypoglycemia and hypoglycemia) not indicated for the treatment of UTIs.


Folate antagonist:

Drug name

sulfonamide

Trimethoprim

MOA

USES -Enterobacteriaceae urinary tract Nocardia infections -sulfadiazine+pyrimethamine for toxoplasmosis -Sulfadoxine+pyrimethamine as an antimalarial drug

-inhibit the synthesis of bacterial dihydrofolic acid by compete with substrate(PABA) for the bacterial enzym

Crystalluria,Hypersensitivity, Hematopoietic disturbances,Kernicterus

potent inhibitor of bacterial dihydrofolate reductase

Effects of folic acid deficiency: megaloblastic anemia, leukopenia, and granulocytopenia, especially in pregnant

UTIs bacterial prostatitis

Nausea and vomiting Glossitis and stomatitis Hyperkalemia Megaloblastic anemia, leukopenia, and thrombocytopenia

UTIs respiratory tract infections Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, and ampicillin- or chloramphenicol-resistant salmonella infections activity against MRSA drug of choice for infections caused by susceptible Nocardia species and Stenotrophomonas maltophilia.

Cotrimoxazole combination of trimethoprim with sulfamethoxazole

SE

inhibit two sequential steps in the synthesis of tetrahydrofolic acid

sulfa drugs should be avoided in newborns and infants less than 2 months of age, as well as in pregnant women at term. Sulfonamides should not be given to patients receiving methenamine, since they can crystallize in the presence of formaldehyde .


URINARY TRACT ANTISEPTICS/ANTIMICROBIALS: Drug name

Methenamine

MOA

decomposes at an acidic pH of 5.5 in urine, thus producing formaldehyde,

SE

GIT distress at higher doses, albuminuria, hematuria, and rashes

which acts locally and is toxic to most bacteria.

Nitrofurantoin

inhibits various enzymes and damages bacterial DNA

Hemolytic anemia with G6PD deficiency GIT disturbances, acute pneumonitis,and neurologic problems. Interstitial pulmonary fibrosis with chronic use

USES chronic suppressive therapy to reduce the frequency of UTIs patients with chronic urinary catheterization to reduce catheterassociated bacteriuria or catheterassociated UTI

useful against E.coli, Grampositive cocci


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------potent inhibitor of dihydrofolate reductase ---------------------------------------------

----------------------------------------------------------------------------------------2nd line in : tuberculosis

Nitrofurantoin -----------------------------------------------------------------------------------------


Answers 1- Complete A-Trimethoprim potent inhibitor of dihydrofolate reductase UTIs and bacterial prostatitis

B-Ciprofloxacin Inhibit DNA gyrase and topoisomerase IV. 2nd line in : tuberculosis

C-Nitrofurantoin inhibits various enzymes and damages bacterial DNA useful against E.coli, Grampositive cocci


Drug name

Isoniazid

Rifampin ( never given as a single agent )

MOA

Inhibit mycolic acid leads to a disruption in the bacterial cell wall.

blocks RNA transcription by interacting with the β subunit of mycobacterial DNAdependent RNA polymerase.

SE Hepatitis is the most serious adverse effect Peripheral neuropathy due to pyridoxine deficiency convulsions in patients prone to seizures

Hepatitis flu-like syndrome , with fever, chills, and myalgia acute renal failure, hemolytic anemia, and shock

USES

M. tuberculosis

-intracellular and extracellular mycobacteria including M. tuberculosis, and NTM -effective against many gram-positive and gram-negative organisms -Used as prophylactic in meningococci or Haemophilus influenzae.

Pyrazinamide

Ethambutol

MOA is unclear. Pyrazinamide must be enzymatically hydrolyzed by pyrazinamidase to pyrazinoic acid, which is the active form

liver toxicity

inhibits arabinosyl transferaseâ&#x20AC;&#x201D;an enzyme important for the synthesis of the mycobacterial cell wall.

optic neuritis diminished visual acuity and loss of ability to discriminate between red and green

active against tuberculosis bacilli in acidic lesions and in macrophage

___


2nd line therapy : less effective and more toxic than the first-line agents. Drug name

note

Streptomycin

Greater action against extracellular organisms streptomycin-resistant organisms may be treated with kanamycin or amikacin

Para-aminosalicylic acid

replaced by ethambutol for drug-susceptible TB, PAS remains an important component of many regimens for MDR-TB

Capreomycin

inhibits protein synthesis. Capreomycin is primarily reserved for the treatment of MDR-TB.

Cycloserine

disrupts d-alanine incorporation into the bacterial cell wall Adverse effects involve CNS disturbances and seizures

Ethionamide

analog of isoniazid . Adverse effects include nausea, vomiting, and hepatotoxicity. Hypothyroidism, gynecomastia, alopecia, impotence, and CNS effects

Fluoroquinolones

treatment of multidrug-resistant tuberculosis. Some NTM also are susceptibl

Macrolides

azithromycin and clarithromycin are included in regimens for several NTM infections Azithromycin may be preferred for patients at greater risk for drug interactions

Bedaquiline

active against many types of mycobacteria. an ATP synthase inhibitor may cause QT prolongation, and monitoring of the electrocardiogram is recommended.


Drugs for Leprosy :

Drug name

Dapsone

Clofazimine

MOA

inhibits dihydropteroate synthetase in the folate synthesis pathway.

binding to DNA lead to the generation of cytotoxic oxygen radicals that are toxic to the bacteria.

SE

hemolysis methemoglobinemia, and peripheral neuropathy.

develop a pink to brownish-black discoloration of the skin

USES It is bacteriostatic for M. leprae, and resistant strains may be encountered. Treatment of pneumonia caused by Pneumocystis jirovecii in immunosuppressed patients. is bactericidal to M. leprae and has activity against M. tuberculosis and NTM.


DRUGS FOR SUBCUTANEOUS AND SYSTEMIC MYCOTIC INFECTIONS: Drug name

MOA

SE

USES

-It binds to ergosterol in the plasma membranes of sensitive fungal cells. Amphotericin B

There, it forms pores. The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death. -5-FC enters the fungal cell via a cytosinespecific permease, an enzyme not found in mammalian cells.

Antimetabolite antifungals

It is subsequently converted to a series of compounds, including 5fluorouracil and 5 fluorodeoxyuridine 5â&#x20AC;˛ monophosphate, which disrupt nucleic acid and protein synthesis

-Fever and chill -Renal impairment -Hypotension -Thrombophlebitis

-causes reversible neutropenia, thrombocytopenia, and dose-related bone marrow depression. -Reversible hepatic dysfunction

- life-threatening mycoses.

- treatment of systemic mycoses and for meningitis caused by C. neoformans and C. albicans.

-GIT disturbances (nausea, vomiting, and diarrhea) -severe enterocolitis

- They inhibit C-14 Îą-demethylase (a cytochrome P450 [CYP450] enzyme),

Azole antifungals

thereby blocking the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes. The inhibition of ergosterol biosynthesis disrupts membrane structure and function, which, in turn, inhibits fungal cell growth.

- imidazoles are given topically for cutaneous infections, ___ -triazoles are given systemically for the treatment or prophylaxis of cutaneous and systemic fungal infections.


Drug name

Fluconazole

Itraconazole

Posaconazole

Voriconazole

MOA

___

___

SE

USES

nausea, vomiting, headache, and skin rashes. Hepatotoxicity can also occur

prophylaxis against invasive fungal infections in recipients of bone marrow transplants. It also is the drug of choice for Cryptococcus neoformans after induction therapy with amphotericin B and flucytosine and is used for the treatment of candidemia and coccidioidomycosis

nausea, vomiting, rash (especially in immunocompromised patients), hypokalemia, hypertension, edema, and headache. Hepatotoxicity can also occur

is the drug of choice for the treatment of blastomycosis, porotrichosis, paracoccidioidomycosis, and histoplasmosis.

___

GIT disturbances headaches

___

high trough concentrations are associated with visual and auditory hallucinations and an increased incidence of hepatotoxicity

interfere with the synthesis of the fungal cell wall by inhibiting the Echinocandins synthesis of β(1,3)-dglucan, leading to lysis and cell death.

fever, rash, nausea, and phlebitis at the infusion site

treatment and prophylaxis of invasive Candida and Aspergillus infections in severely immunocompromised patients. the drug of choice for invasive aspergillosis. also approved for treatment of invasive candidiasis, as well as serious infections caused by Scedosporium and Fusarium species. have potent activity against Aspergillus and most Candida species, including those species resistant to azoles


DRUGS FOR CUTANEOUS MYCOTIC INFECTIONS: Drug name

Squalene epoxidase inhibitors (Terbinafine) (Naftifine) (Butenafine)

Griseofulvin

MOA inhibiting squalene epoxidase, thereby blocking the biosynthesis of ergosterol, an essential component of the fungal cell membrane Accumulation of toxic amounts of squalene results in increased membrane permeability and death of the fungal cell.

disruption of the mitotic spindle and inhibition of fungal mitosis.

SE

-GIT disturbances -headache -Rash -Taste and visual disturbances -transient elevations in serum hepatic transaminases.

USES Oral terbinafine is the drug of choice for treating dermatophyte onychomycoses (fungal infections of nails).

Naftifine 1% cream and gel are used for topical treatment of tinea corporis, tinea cruris, and tinea pedis.

butenafine 1% cream is used for topical treatment of tinea infections.

___

treatment of onychomycosis, although it is still used for dermatophytosis of the scalp and hair.

rare after oral administration, Nystatin

Imidazoles

Ciclopirox

Tolnaftate

Resemble those of amphotericin B.

___

inhibits the transport of essential elements in the fungal cell, disrupting the synthesis of DNA, RNA, and proteins. distorts the hyphae and stunts mycelial growth in susceptible fungi.

but Topical and vaginal forms may cause skin irritation

contact dermatitis, vulvar irritation, and edema

___

___

treatment of cutaneous and oral Candida infections.

For tinea corporis, tinea cruris, tinea pedis, and oropharyngeal and vulvovaginal

seborrheic dermatitis. Tinea pedis, tinea corporis, tinea cruris, cutaneous candidiasis, and tinea versicolor

treat tinea pedis, tinea cruris, and tinea orporis


Questions … 1- Complete First line Drug name or class Second line M.O.A Third line use

--------------------------------------------binds to ergosterol in the plasma membranes and it forms pores ---------------------------------------------

Terbinafine -----------------------------------------------------------------------------------------

---------------------------------------------

inhibit C-14 α-demethylase cutaneous infections

--------------------------------------------inhibiting the synthesis of β(1,3)d-glucan ---------------------------------------------


Answers 1- Complete A-Amphotericin B binds to ergosterol in the plasma membranes and it forms pores life-threatening mycoses.

B-imidazoles inhibit C-14 Îą-demethylase cutaneous infections

C-Terbinafine Squalene epoxidase inhibitors drug of choice for treating dermatophyte onychomycoses

D-Echinocandins inhibiting the synthesis of β(1,3)-d-glucan Aspergillus and most Candida species


AMEBIASIS DRUGS: Drug class Chloroquine

Dehydroemetine

Iodoquinol

Paromomycin

MOA

SE

___

___

- inhibits protein synthesis by blocking chain elongation

___

-is directly amebicidal -also exerts its antiamebic actions by reducing the population of intestinal flora

- The nitro group of metronidazole is able to serve as an electron acceptor, Metronidazole

forming reduced cytotoxic compounds that bind to proteins and DNA, resulting in death of the E. histolytica trophozoites

Tinidazole

Same as Metronidazole

- nausea, - cardiotoxicity , -neuromuscular weakness, - dizziness, and rash

Rash, diarrhea, and dose-related peripheral neuropathy, including a rare optic neuritis

USES used in combination with metronidazole to treat amebic liver abscesses.

- is an alternative agent for the treatment of amebiasis -is amebicidal against E. histolytica And -is effective against the luminal trophozoite and cyst forms “ treatment of the asymptomatic colonization state”

against the intestinal (luminal) forms of E. -Gastrointestinal distress histolytica “ treatment of the -diarrhea asymptomatic colonization state”

-epigastric distress -abdominal cramps -oral moniliasis -rarely neurotoxicity

infections caused by: -Giardia lamblia, -Trichomonas vaginalis, -anaerobic cocci, -anaerobic gramnegative bacilli

Same as Metronidazole

-amebiasis, - amebic liver abscess, -giardiasis, - and trichomoniasis


MALARIA DRUGS:

Drug class

Artemether

MOA

SE

production of free radicals resulting from cleavage of the drugâ&#x20AC;&#x2122;s endoperoxide bridge by heme iron in the parasite food vacuole.

-High doses may cause prolongation of the QT interval.

These agents may also covalently bind to and damage specific malarial proteins -inhibits mitochondrial processes such as electron transport, as well as ATP and pyrimidine biosynthesis. Atovaquone-proguanil

-Cycloguanil, the active metabolite of proguanil, inhibits plasmodial dihydrofolate reductase, thereby preventing DNA synthesis.

-Hypersensitivity reactions

nausea, vomiting, abdominal pain, headache, diarrhea, anorexia, and dizziness.

USES

-first-line agents for the treatment of multidrugresistant P. falciparum malaria

-effective for chloroquine-resistant strains of P. falciparum, -prevent and treat of malaria

binds to heme, preventing its polymerization to hemozoin.

Chloroquine

The increased pH and the accumulation of heme result in oxidative damage to the phospholipid membranes,

-blurred vision -Discoloration of the nail beds and mucous membranes

- drug of choice in the treatment of erythrocytic P. falciparum malaria, except in resistant strains

leading to lysis of both the parasite and the red blood cell.

Mefloquine

-undetermined.

-disorientation, hallucinations, and depression -â&#x20AC;&#x153;ECG abnormalities and cardiac arrest are possible â&#x20AC;&#x153;

-in multidrug-resistant forms of P. falciparum


Drug class

MOA - metabolites of primaquine act as oxidants that are responsible for the schizonticidal action

Primaquine as well as for the hemolysis and methemoglobinemia encountered as toxicities.

Pyrimethamine

- inhibits plasmodial dihydrofolate reductase

Quinine

- interferes with heme polymerization, resulting in death of the erythrocytic form of the plasmodial parasite

SE

- drug-induced hemolytic anemia

USES

- used in conjunction with agents to treat the erythrocytic form

- is not used alone for P. falciparum

- cinchonism, a syndrome causing (nausea, vomiting, tinnitus, and vertigo).

-antimalaria

LEISHMANIASIS DRUGs : Drug class

Miltefosine

Sodium stibogluconate

MOA

SE

USES

-appears to interfere with phospholipids in the parasitic cell membrane to induce apoptosis.

- Nausea and vomiting

- dermatitis -peripheral neuropathy -insomnia and anorexia.

- unknown

-pancreatitis -elevated liver enzymes -arthralgias, myalgias -cardiac arrhythmias.

-leishmaniasis


TRYPANOSOMIASIS DRUGs: Drug class

MOA

SE

USES treatment of

-The highly reactive radicals are toxic to T. cruzi. Nifurtimox

hypersensitivity reactions (anaphylaxis,dermatitis) and gastrointestinal , weight loss. Peripheral neuropathy, headache and dizziness .

-T. cruzi infections (Chagas disease), -chronic stage of such infections has led to variable results, -treatment of second-stage T. brucei gambiense

Benznidazole

Eflornithine

Melarsoprol

Pentamidine

Suramin

- similar to nifurtimox

- dermatitis, peripheral neuropathy, insomnia, and anorexia.

- alternative for the treatment of Chagas disease

- irreversible inhibitor of ornithine decarboxylase.

- anemia, seizures, and temporary hearing loss

- first-line treatment for second-stage African trypanosomiasis caused by T. brucei gambiense.

- reacts with sulfhydryl groups of various substances, including enzymes in both the organism and host.

- CNS toxicity -peripheral neuropathy, -and albuminuria. -Hypersensitivity reactions -febrile reactions -Hemolytic anemia .

- treatment of African trypanosomal infections in the second stage

- T. brucei concentrates pentamidine by an energy-dependent, highaffinity uptake system.

-Serious renal dysfunction, -hyperkalemia, -pancreatitis, -and diabetes.

- alternative for prophylaxis or treatment of infections caused by Pneumocystis jirovecii and leishmaniasis

-inhibits many enzymes, especially those involved in energy metabolism lead to trypanocidal activity.

shock and loss of consciousness,acute urticaria, blepharitis, and neurologic problems

- the first stage of African trypanosomiasis

-Inhibition of this enzyme halts the production of polyamines in the parasite, thereby leading to cessation of cell division.


TOXOPLASMOSIS DRUG : Drug class

MOA

Pyrimethamine

____

SE - hypersensitivity

USES -Drug of choice to treat toxoplasmosis

GIARDIASIS DRUGs: Drugs

Metronidazole

treatment of choice is oral metronidazole for 5 days .

Nitazoxanide

administered as a 3-day course of oral therapy .

Tinidazole

An alternative for Metronidazole , administered orally as a single dose .


Questions â&#x20AC;Ś 1- Complete First line Drug name or class Second line M.O.A Third line use

-----------------------------------------is directly amebicidal ------------------------------------------

----------------------------------------------------------------------------------first-line agents for the treatment of multidrug-resistant P. falciparum malaria

----------------------------------------------------------------------------------leishmaniasis

Benznidazole -----------------------------------------------------------------------------------


Answers 1- Complete A-Paromomycin is directly amebicidal against the intestinal (luminal) forms of E. histolytica

B-Artemether production of free radicals and damage specific malarial proteins first-line agents for the treatment of multidrug-resistant P. falciparum malaria

C-Sodium stibogluconate unknown leishmaniasis

D-Benznidazole The highly reactive radicals are toxic to T. cruzi. alternative for the treatment of Chagas disease


Nematodes drugs: Drug name

Diethylcarbamazine

Ivermectin

Mebendazole

MOA - kills the microfilariae and has activity against adult worms.

- targets the glutamate-gated chloride channel receptors. Chloride influx is enhanced, and hyperpolarization occurs, resulting in paralysis and death of the worm

- acts by inhibiting the assembly of the microtubules in the parasite

SE

USES

fever, nausea, vomiting, arthralgia, and headache

- drug of choice for filariasis caused by infection with Wuchereria bancrofti and Brugia malayi

- Mazzotti reaction (fever, headache, dizziness,somnolence, and hypotension)

- drug of choice for the treatment of cutaneous larva migrans, strongyloidiasis, and onchocerciasis caused by Onchocerca volvulus -pediculosis

- abdominal pain and diarrhea

- first-line for the treatment of infections caused by whipworms pinworms hookworms and roundworms.

- mild and include nausea, vomiting, and diarrhea

-infections caused by roundworms, pinworms, and hookworms

- toxic effects

- topical treatment of cutaneous larva migrans (creeping eruption)

- irreversable block glucose uptake. -It acts as a depolarizing, neuromuscular-blocking agent, Pyrantel pamoate

causing release of acetylcholine and inhibition of cholinesterase, leading to paralysis of the worm

Thiabendazole

___


Trematodes drug : Drug name

Praziquantel

MOA -  Permeability of the cell membrane to calcium causing contracture and paralysis of the parasite.

SE

- dizziness, malaise, and headache as well as gastrointestinal upset.

USES all forms of -schistosomiasis, -other trematode infections, -and cestode infections such as taeniasis..

Cestodes drugs : Drug name

Albendazole

MOA - It inhibits the mitochondrial phosphorylation of (ADP) in the parasite, making it lethal for the cestode’s scolex and segments but not for the ova.

SE

___

-Anaerobic metabolism may also be inhibited.

USES

- treatment of -taeniasis, -diphyllobothriasis, -other cestode infections.

- When used in (1 to 3 days) “ headache and nausea” - inhibits microtubule synthesis Niclosamide -inhibit glucose uptake in nematodes

(ADP) = adenosine diphosphate

-And in (3 months) has a risk of hepatotoxicity and, rarely, agranulocytosis or pancytopenia. -treatment of neurocysticercosis including headache, vomiting, fever, and seizures.

- treatment of cestodal infestations, such as cysticercosis and hydatid disease (caused by larval stage of Echinococcus granulosus).


Questions â&#x20AC;Ś 1- Complete

First line Drug name or class Second line M.O.A Third line use

--------------------------------------------------------------------------------drug of choice for filariasis

Mebendazole ------------------------------------------------------------------------------------------------------------------------ď&#x201A;­ Permeability of the cell membrane to calcium

-----------------------------------------

Albendazole --------------------------------------------------------------------------------Niclosamide ----------------------------------------cestodal infestations


Answers 1- Complete A-Diethylcarbamazine kills the microfilariae drug of choice for filariasis

B-Mebendazole inhibiting the assembly of the microtubules in the parasite and irreversable block glucose uptake. first-line for the treatment of infections caused by whipworms pinworms hookworms and roundworms

C-Praziquantel ď&#x201A;­ Permeability of the cell membrane to calcium Schistosomiasis, trematode and cestode infections

D-Albendazole inhibits the mitochondrial phosphorylation of (ADP) and Anaerobic metabolism may also be inhibited. treatment of taeniasis, diphyllobothriasis, and cestode infections.

E-Niclosamide inhibits microtubule synthesis and inhibit glucose uptake cestodal infestations


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Easy Pharmacology  

Summarised form of the lippincott pharmacology book.

Easy Pharmacology  

Summarised form of the lippincott pharmacology book.

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