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Drug & Type (e.g. ACh agonist)

Clinical Use

Pharmacodynamics (mechanism of action)

PILOCARPINE (alkaloid)- (Partial Muscarinic AChR agonist)

In ophthalmology as a treatment for glaucoma (^ ocular pressure).

Causes constriction of sphincter pupillae (circular muscle) (i.e. pupil constricts) for aqueous humour drainage via canals of Schlemm.

BETHANECHOL (choline ester)(M3 AChR selective agonist)

To assist bladder emptying and gastric motility.

NEOSTIGMINE/ PHYSOSTIGMINE (reversible anticholinesterases, competitive inhibitor of AChE against ACh, thus preventing ACh degradation)

Treatment of glaucoma, aiding intraocular fluid drainage. Treatment of ATROPINE (potent Muscarinic antagonist) poisoning esp. in children.

Compete with ACh for active site of acetylcholinesterase (AChE). Donate a carbamyl group to the enzyme which prevents ACh from binding. Carbamyl gp is removed by slow hydrolysis (lasting minutes not ms), leading to an ^ duration of ACh activity in the synapse.

Pharmacokineti cs (passage throughout the body) T ½ = 3 to 4 hrs.

Side effects

Blurred vision, sweating, GI disturbance & pain, hypotension, respiratory distress.

Not a substrate for acetylcholinestera se, PHARM S3 L6.

T ½ = 3 to 4 hrs.

Sweating, impaired vision, nausea, bradycardia (M2), hypotension, respiratory difficulty.

T ½ = 30 mins.

Low doses: excitation with possibility of convulsions. High doses: unconsciousness, respiratory depression, death. NB: at high doses all anticholinesterases can cause increased transmission of ACh at ALL (PNS & SNS) autonomic ganglia.

Resistant to degradation, orally active, limited access to brain. PHARM S3 L6. Only non-polar organophosphate s (e.g. PHYSOSTIGMINE) can cross the Blood-Brain Barrier (BBB). PHARM S3 L6.



Extra Information (e.g. similar drugs)

ECOTHIOPATE (irreversible anticholinesterase)

Treatment (longterm) of glaucoma for ^ intraocular fluid drainage with prolonged action.

A potent inhibitor of AChE, it rapidly reacts with AChE active site, leaving a large blocking group.

T ½ = several days/ weeks. Administered by eye drops.

Blurred vision, sweating, GI pain, bradycardia, hypotension, respiratory distress. Organophosphate poisoning can lead to: S: salivation. L: lacrimation U: urination D: diaphoresis G: GI motility E: emesis B: bronchorrhoea B:bronchconstriction B: bradycardia.

HEXAMETHONIUM (Irreversible Nicotinic ACh antagonistganglion (ionchannel) blocker) TRIMETAPHAN (Nicotinic ACh antagonistganglion blocker)

1st anti-hypertensive (not in use nowadays)

Used to induce hypotension during surgery to reduce bleeding.

When ECOTHIOPATE binds to AChE, it becomes very stable and resistant to hydrolysisrecovery requires the production of new enzymes (i.e. weeks). PRALIDOXIME, if used quickly, can reverse the binding of ECOTHIOPATE to AChE. PHARM S3 L6.


ACh can bind to its postsynaptic nicotinic receptor, but the ion channel, which is blocked won’t let most K+ ions out, preventing



postsynaptic depolarisation.

ATROPINE (Reversible Muscarinic AChR antagonists)

HYOSCINE (Muscarinic AChR antagonists)

TROPICAMIDE (Muscarinic AChR antagonist)

Anaesthetic premedication before operations. It is not an anaesthetic! It merely helps you to control the patient more when they are sedated in operations. Also, may treat Irritable Bowel Syndrome (IBS) by decreasing GI motility & tone. Treatment of motion sickness. Treatment of Parkinson’s disease.

Examination of the retina- prevents the constriction of sphincter pupillae.

Blocks ACh binding site & action on M3 receptors on bronchial smooth muscle to prevent bronchial constriction= patent airway to aerate lungs better. Blocks ACh action on M2R on heart muscle= HR and contractility not decreased. Motion sickness: Input (using ACh) from the labyrinth to the vestibular nucleus is blocked. Parkinson’s: cholinergic/ dopaminergic balance in basal ganglia. Binds to circular muscle’s (sphincter pupillae) Muscarinic receptors.

Orally, peak effects in 1-2 hours.

CNS effects: mild restlessness-> agitation. May be to do with M1 subtype.  Hot as hell (decreased sweating)  Dry as a bone (decreased secretions)  Blind as a bat (cycloplegia: paralysis of the ciliary muscle of the eye and is always in the relaxed state so inability of lens to focus i.e. fatten to look at things closer to you. Mydriasis (constant pupil dilation) may also occur due to paralysis of sphincter pupillae).  Mad as a hatter (CNS disturbance).

ATROPINE poisoning (build up) can be treated with the anticholinesterase PHYSOSTIGMINE. PHARM S4 L7.

CNS effects: sedation. Typical antimuscarinic effects e.g. drowsiness, dry mouth, cycloplegia, mydriasis, constipation.

PHARM S4 L7 & S15 L23.



IPRATROPIUM BROMIDE (Muscarinic AChR antagonists) Ahad’s bro has asthma.

Used in asthma or obstructive airway disease for bronchodilation.

ADRENALINE (direct sympathomimeticbeta dominant)

Treatment of 1) Allergic reactions, anaphylactic shock (i.v.); 2) COPD & asthma (inh?), 3) Heart block (i.v.); 4) Glaucoma; in 5) spinal anaesthesia (i.v.); to prolong 6) local anaesthetic duration.

PHENYLEPHRINE (direct sympathomimeticalpha 1 dominant)

1) Vasoconstriction (topically administered) to stop superficial bleeding from skin and mucous membranes;

M3 AChR on bronchial smooth muscle respond to ACh by muscle contraction. Inhibition of this induces bronchodilation. All adrenoreceptors are G-protein linked but differ in their mechanisms: a1) activate the phospholipase C, inositol triphosphate & diacyl glycerol pathways= muscular contraction; a2) adenylyl cyclase pathways to decrease cAMP for NA –ve feedback; b1/2) adenylyl cyclase to ^ cAMP causing either contraction or relaxation. Longer T ½ than ADRENALINE and resistant to COMT.


IPRATROPIUM has not got many side effects as it can’t really diffuse well from alveoli into blood because it is a quarternary amide and highly charged. CVS: tachycardia, arrhythmias, hypertension, cerebral haemorrhage, pulmonary oedema. Secretions: reduced and thickened mucous -> dry mouth. Skeletal muscle: tremors.




Mode of administration governs the net effect of Adrenaline on blood pressure. PHARM S5 L8.

CLONIDINE (direct sympathomimeticalpha 2 dominant)

ISOPRENALINE (direct sympathomimeticbeta dominant)

DOBUTAMINE (direct sympathomimeticbeta 1 (& 2) dominant) SALBUTAMOL aka Ventolin (direct sympathomimeticbeta 2 (& 1) dominant)

2) Mydriatic eye drops; 3) Nasal decongestant (nose drops/ oral admin). Treatment of hypertension and migraine (oral or i.v. administration)

Treatment of 1) heart block (i.v.) and 2) asthma (but discontinued due to unwanted actions of reflex tachycardia and dysrhythmias). Treatment of heart block (i.v.) or acute heart failure.

Treatment of 1) asthma (inh/oral) by relaxation of bronchial smooth muscle & inhibition of the release of

Reduces sympathetic tone by: 1) alpha 2 adrenoreceptor mediated presynaptic inhibition of NA release & 2) central action in brainstem within baroreceptor pathway to reduce sympathetic outflow.

Stimulates cardiac contraction without a major effect on heart rate.

Oral or i.v. administration.


Plasma T ½ = 2hrs. Less susceptible to uptake 1 and MAO than ADRENALINE.


Plasma T ½ = 2mins; rapidly metabolised by COMT.

No reflex tachycardia like with ISOPRENALINE.

Inhalation/oral admin. Relative resistance to MAO and COMT.

Reflex tachycardia, tremor.



Caution with cardiac, hyperthyroid and diabetic patients (i.v. use).


COCAINE (indirect sympathomimetic)

TYRAMINE (indirect sympathomimetic)

bronchoconstrictor substances from mast cells; 2) threatened uncomplicated premature labour (i.v.). Rare local anaesthetic MOA for in ophthalmology. sympathomimetic effects: prevents the NA reuptake 1 mechanism presynaptically. THIS IS NOT THE MOA FOR ITS LOCAL ANAESTHETIC EFFECTS!

1) Some weak NA agonist function post-synaptically on adrenoreceptors, 2) competes with catecholamines for Uptake 1, displaces NA from intracellular storage vesicles, 3) NA and TYRAMINE compete for sites on MAO.

Plasma T ½ = 30 mins. Degraded by plasma esterases and hepatic enzymes. Well absorbed from all sites; readily crosses BBB (unlike ADRENALINE & NA) T ½ = short, 1st pass metabolism is extensive and does not enter CNS.


Psychological dependence syndrome, tachycardia, vasoconstriction, raise BP, tremors and convulsions, activation of vomiting centres in CNS, depression of medullar respiratory centre, respiratory failure, death.

Do not co-administer with ADRENALINE.


When MAO inhibitors e.g PHENELZINE are administered as antidepressant drugs, ingestion of foods containing TYRAMINE may cause a hypertensive crisis.

PHARM S5 L8. “The cheese reaction”.

PROPANOLOL (beta 1 & 2 antagonist) Pro pain, no gainsaid when exersizing.

ATENOLOL (beta 1 (cardio-) selective antagonist) Atenolol-Angina, Ten ol’ ladies have angina. I give it ten out of ten for being a cardio-selective agonist. LABETALOL (mainly beta 1 (& alpha 1) antagonist) ‘a’ and ‘b’ next to each other in labetalol = alphaand beta antagonist.

Reduces the effect of exercise or stress on heart (HR, CO, or arterial pressure). Useful in reducing SNS activity on the heart after an MI by decreasing the refractory period of the AV node. Sympathetic stimulation can cause arrhythmias after MI. Angina, cardiac dysrhythmias, chronic heart failure, hypertension.


Competitive antagonist of beta adrenoceptors. Bblockers do not reduce peripheral resistance. Mainly antagonises the effects of NA on the heart but will affect any tissue with beta 1 receptors. NB: it is the antagonising action on alpha 1 receptors that has clinical relevance here. Lowers blood pressure by a reduction in peripheral resistance

Fatigue, cold extremities, bad dreams.

1) Asthmatics: bronchoconstriction. 2) Patients with heart disease: cardiac failure. 3) Diabetics: hypoglycaemia (glucose release from the liver is controlled by beta 2 receptors).


Worsening of cardiac failure, bradycardia (heart block), bronchoconstriction, hypoglycaemia (in diabetic on insulin), cold extremities, fatigue, nightmares, impotence.

Less effect on airways than non selective (B1/2) drugs, but still not safe with asthmatic patients.

B-blockers have some common effects: 1) reduce CO, 2) reduce renin release by the kidney. PHARM S6 L9.



but unusually there is no change in HR or CO. PHENTOLAMINE (non-selective alpha antagonist)

No longer clinically used.

PRAZOSIN (highly selective alpha 1 antagonist)

Treatment for hypertension.

Causes vasodilation and a fall in blood pressure due to a blockade of alpha 1 receptors. But concomitant (occurring at the same time) blockade of alpha 2 receptors tends to increase NA release, enhancing the reflex tachycardia that occurs with any blood pressure lowering agent. Causes vasodilation and a fall in arterial blood pressure. CO decreases due to lower venous return & therefore lower preload. Causes an increase in HDL and decrease in LDL cholesterol.

Increased GI motility, and diarrhoea is a common problem. Reflex tachycardia.

Less tachycardia than non-selective alpha antagonists such as PHENTOLAMINE as PRAZOSIN does not block the –ve feedback (alpha 2 receptor) system, preventing increased NA release from the end of nerve terminals. Postural 8


hypotension is troublesome. METHYLDOPA (false transmitter) Dope-her (a pregnant woman) with methyl.

Treatment for hypertension. Can be used in hypertensive pregnant women despite drug crossing blood-placenta barrier.

TUBOCURARINE (competitive Neuromuscular antagonist)

Used in the relaxation of skeletal muscles in surgical operations (= less anaesthetic). It also permits artificial ventilation.


Used in brief surgical procedures such as dislocations and tracheal intubation. It is NOT used in heart surgery as its duration of action is much too short.

Less active than NA on alpha 1 receptors so less effective at causing vasoconstriction. Also, more active than NA on alpha 2 receptors, ^ -ve feedback and decreasing the amount of NA released from the presynaptic nerve terminal. METHYLDOPA is taken up by NA neurons, decarboxylated and hydroxylated to form a-methyl-NA. This is not deaminated by MAO and so builds up in large concentrations within the cell, eventually displacing NA within synaptic vesicles. Causes flaccid Onset of action paralysis = 2/3 mins, and (administered i.v.). It duration of is not metabolised! It paralysis if 40 to is a competitive 60 mins long. nAChR antagonist. Excretion is 70% in the urine and 30% in the bile. Binds to ACh receptor (and remains bound) keeping the channel open and reducing the electrical excitability of the endplate.

Duration of action is 3 to 7 minutes and the block occurs within 30 to 60s of administration i.v. 9

Dry mouth, sedation, orthostatic hypotension (low blood pressure found in some patients when they stand upright), male sexual dysfunction.


Does not affect consciousness, pain sensation and you must always assist respiration. It will cause double vision (due to paralysis of extrinsic eye muscles) and the small muscles of the face, limbs and pharynx to be paralysed. Causes ganglion block; HISTAMINE release causing hypotension (due to a decrease in TPR) and bronchospasm. Post-operative If the patient has a muscle pain due to Plasma the fasciculation Cholinesterase (muscle twitch) (PChE) deficiency the caused during the depolarising block onset of the block. may last for hours. Hyperkalaemia (due to constant outflux

Does not cross BBB or placenta. Actions of TUBOCURARINE can be reversed by the administration of anticholinesterase s. PHARM S7 L10. PHARM S7 L10 & NEURO S8 L.

VERAPAMIL (rate slowing Ca2+ antagonist) Ve-rate-a-milk: it is rate slowing and calcium is found in milk.

To treat paroxysmal (sudden) Supra Ventricular Tachycardias and atrial fibrillations.

DILTIAZEM (rate slowing Ca2+ antagonist)

To treat angina, paroxysmal (sudden) Supra Ventricular Tachyarrhythmias (SVT) and atrial fibrillations.

AMLODIPINE (a DIHYDROPYRIDINEnon-rate slowing Ca2+ antagonists)

To treat hypertension.

of K+ ions trying to repolarise the membrane) that may cause dysrhythmias. 1) Bradycardia and AV block. 2) Worsening of heart failure. 3) Constipation (due to effect of decrease Ca2+ entry to smooth muscle of gut).

Reduce calcium entry into cardiac and smooth muscle cells. It has a strong negative inotropic effect. An important component of contractility is Ca2+ influx into myocytes. It also inhibits AV node conduction. If can ^ Ca2+ influx in SAN you can increase the rate of SAN depolarisation and thus heart rate. Reduce calcium entry into cardiac and smooth muscle cells. It has a weak negative inotropic effect. MOA: Ca2+ antagonists bind to and inhibit L-type Ca2+ channels! Inhibit Ca2+ entry into ONLY smooth muscle cells causing vascular (smooth



1) Headache/ flushing, 2) Ankle oedema 3) Palpitations. 10


muscle) dilation.

ADENOSINE (a metabolite of ATP indicating that cell is working quite hard. Adenosine therefore ‘negatively feeds’ back to hinder a myocyte from depolarising).

To terminate SVT.

Acts on Adenosine (A1) receptors to hyperpolarise cardiac tissue and slow conduction through AV node.

i.v. admin. Actions are short lived (2030s) as it is rapidly metabolised (as it is a natural metabolite of the body) and so safer than VERAPAMIL. T ½ = 10-100 days. Accumulates in the body and therefore causes many side effects!

AMIODARONE (amiodare sounds like “a milliardare”= lots of money = lots of side effects, and sticks around for a long time as well)

Used to treat SVT and VTs.

Multiple ion channel block.

DIGOXIN (cardiac glycoside) A glycoside is a molecule bound to a sugar group.

Used to treat atrial fibrillation by slowing down the ventricular rate and relieves symptoms in chronic heart failure by increasing contractility.

1) Binds to extracellular aspect of alpha subunit of Na+/K+ ATPase, preventing Na+ going out. Leads to ^ [Na+]i slowing the extrusion of Ca2+ via Na+/Ca2+ antiporter. This Na+/Ca2+ exchange transporter normally would let Na+ come into the cell down its conc. grad, concomitantly extruding Ca2+ to 11

Chest pain, SOB, dizziness and nausea. No major S/Es as it is a major metabolite of the body.


1) photosensitive skin rashes 2) hypo- or hyperthyroidism 3) pulmonary fibrosis 4) corneal deposits 5) neurological and gastrointestinal disturbances


Dysrythmias e.g. AV conduction block.

Coadministration of some diuretics that are not K+ sparing i.e. that will decrease plasma [K+]. This will increase DIGOXIN’s actions, increasing the risk of

The effect of DIGOXIN (and cardiac glycosides in general) are increased if plasma [K+] decreases, because of

IVABRADINE (sounds like a funny (channels) old lady). Bradi-cardia is a S/E also.

To treat angina in patients with normal sinus rhythm.

MILRINONE (cardiac inotrope, phosphodiesterase inhibitor)

To treat angina, paroxysmal (sudden) Super Ventricular Tachyarrhythmias (SVT) and atrial fibrillations.

outside the cell. But if [Na+]i is ^ then not much Na+ will enter the cell. This leads to an ^ in [Ca2+]i which is stored in the sarcoplasmic reticulum, thus increasing the amount of Ca2+ released by each action potentional. 2) Stimulates Vagus nerve causing reduced rate of conduction through AV node. Admin: PO/i.v., T ½ = 36 hrs. Blocks If channel (f is for "funny“) – a Na/K channel important in the sinoatrial node. The If channel is weird because it is a voltage –gated ion channel that opens when the SA-nodal cell has repolarised, allowing a steady influx of Na+ ions in (and K+ ions out) which slowly depolarises the cell getting it up to the threshold potential. If at least some of these are blocked, this will reduce the gradient of the slope of the pacemaker potential causing a slower rate of pulse generation and decreasing HR. Inhibits the breakdown of cAMP by phosphodiesterases. cAMP is needed within the myocyte to activate cAMP – dependent protein kinase which does the following via phosphorylation: (1) activates DHP (L-type Ca2+ channels) in the plasma membrane, (2) activates the ryanodine receptor and associated proteins in the sarcoplasmic reticulum 12

1) Bradycardia, 2) 1st degree heart block, 3) Ventricular and supraventricular arrhythmias.


reduced competition for at the K+ binding site on Na+/K+ ATPase. PHARM S9 L11.

1) Severe bradycardia, 2) 2nd/3rd degree heart block, 3) Cardiogenic shock? 4) MI.



ENALAPRIL (ACE inhibitor)

Used to treat hypertension, heart failure, diabetic neuropathy, post-MI, those at high risk of cardiovascular disease.

LOSARTAN (Angiotension receptor blocker): Angio sound like a little boy in a science fiction movie and Losartan is the wizard shields him against badies. Losartan is so strong, he is insurmountable. Although losartan is trying to protect the boy, fetal injury is highly likely.


membrane, (3) activates thin filament proteins esp. troponin, (4) activates thick filament protein ass. with crossbridges etc. (VANDERS p.381). Prevent the conversion of AT1 to AT2 by ACE.

Acts as a noncompetitive, insurmountable AT2 receptor blocker preventing the renal and vascular actions of AT2


Cough, hypotension, hyperkalaemia (can overcome this S/E with K+ sparing diuretics), angiodema/urticaria (rare), fetal injury, renal failure in patients with renal artery stenosis. Generally well tolerated but still some: Hypotension, fetal injury, renal failure in patients with renal artery stenosis.




Used in chronic heart failure in patients who cannot tolerate ACEI. PHARMS9 L12.

ALISKERIN (RASrenin angiotensin system inhibitor)aliskiRENIN! GLYCERYL TRINITRATE (GTN spray)


PHENOXYBENZAMI NE (irreversible a1 adrenoceptor antagonist) – “PHE” is in the drug and the disease. DOXAZOSIN (competitive a1 adrenoceptor blockers). MOXONIDINE (imadazoline agonist)

To provide longlasting alpha blockade in a patient with a phaeochromocytoma





Inhibits sympathetic outflow from the brain.

SUMITRIPTAN (agonist at 5Hydroxy Tryptamine receptors)

Migraine attacks.

Vasocontrictor: constricts some large arteries and inhibits trigeminal nerve transmission. 5 HT1D agonist. All sensory

Angina, acute & chronic heart failure, BP control during anaesthesia.

Inhibits the action of renin in converting angiotensinogen to AT1. Release NO in smooth muscle cells (nitrates) or stimulate guanylyl cyclase (nicorandil) to cause vasodilation. Reduces venous return and TPR.


Nitrates undergo extensive first pass metabolism. Admin: sublingual, T ½ = 5mins.

Hypotension, headaches, flushing due to vasodilation.

Can develop tolerance. PHARM S9 L12.


Coronary vasoconstriction, dysrhythmias


Coronary disease.


branches of CN5 are sensory from the dura mater. WARFARIN (anticoagulant) WOK: W-warfaring O-oral K-Vitamin K

Chronic treatment for venous thrombus.

MOA: prevents activation of Vitamin K.

Oral, absorbed quickly from GI tract, peak blood concentration within 1h, however pharmacological effects are delayed 12 – 16h, peak after 48h and last 4-5 days, due to slow turnover of clotting factors. Binds strongly to albumin, metab by cyt P450.

1) Haemorrhage esp into brain or bowel, 2) teratogenicity- not given to pregnant mothers. Reverse effects: Give low doses of Vit K, or fresh frozen plasma or prothrombin complex concentrate can be infused if a rapid reversal of the warfarin effect is needed.

HEPARIN (anti coagulant) “HAV”: heparin, antithrombin, intravenous.

Acute treatment for venous thrombus.

MOA: activates antithrombin (clotting factor III) which inhibits factor Xa and thrombin by binding to the active serine sites. Low Molecular

Admin- subcut (onset 1 hr later) or i.v. (immediate onset).

Bleeding, thrombocytopenia, osteoporosis (in therapy lasting over 3 months), hypersensitivity (chills, fever, urticaria, rash).


Pregnancy. Drug interactions: 1) ASPIRIN- inhibits platelet function & displaces WARFARIN from albumin (which will ^ plasma [WARF] leading to easy haemorrhaging. 2) ERYTHROMYCIN/ FLUCONAZOLEinhibit cyt P450 so will ^ plasma [WARF] 3) PHENOBARBITALinduces cyt P450 so will decrease plasma [WARF].

Anti-coagulant activity monitored by International Normalised Ratio (INR); a measure of prothrombin time. PHARM S9 L13.


Weight Heparin (LMWH) same effect on Xa but less on thrombin.

ASPIRIN (antiplatelet) The ‘A’ drug: A-aspirin A-arterial thrombus A-asthma A-albumin A-anitplatelet A-analgesic A-anti-pyretic A-antiinflammatory

Arterial thrombus in patients with MI.

MOA: irreversibly inhibits COX-1 which will leads to inhibition of TXA2 formation from platelets.

Oral admin. It is highly plasma protein bound and so will displace WARFARIN from albumin (or other plasma proteins.

CLOPIDOGREL (anti-platelet)

Arterial thrombus in patients with MI.

A pro-drug which inhibits fibrinogen binding to the glycoprotein IIb/IIIa receptors.

Oral admin. Peak plasma conc 4hrs after a single dose but inhibitory effect on platelet not seen until after 4 days of regular dosing.


Reverse effects: stop i.v. HEPARIN & give i.v. PROTAMINE (binds to heparin to produce an inactive complex). GI sensitivity.

Bleeding –GI haemorrhage, diarrhea, rash In some patients neutropenia

Contraindicated in asthmatics as blocking COX-1 can lead to a shift & ^ in production of other AA pathway end products such as an ^ in leukotrienes (potent vasoconstrictor substance) via 5-lipooxygenase enzyme (5-LOX).


Used as a drug of choice in ASPIRIN sensitive patients. Patients should stop the drug 10 days before surgery. PHARM S9 L13.

ABCIXIMAB (antiplatelet) Lots of ‘a’s and ‘b’s in the drug name and an ‘x’, indicating blocking of 2b/3a receptor.

Acute coronary Antagonist of the syndromes used in glycoprotein IIb/IIIa combination with receptor. heparin and aspirinto prevent ischemia in patients with unstable angina.

Admin: i.v. Binds rapidly to platelets. Cleared with platelets. Antiplatelet effect persists for 24-48hrs

Bleeding. May potentially be immunogenic.


STREPTOKINASE (fibrinolytic(thromb olytic)) “strepl-v” = streptokinase, plasminogen, i.v.

Acute MI (perhaps caused by thombus) (give within 12 hrs). Acute thrombotic stroke (give within 3 hrs). DVT/ pulmonary embolus, acute arterial thromboembolism.

MOA: Nonenzymatic protein. Derived from culture of b-hemolytic streptococci. Binds to plasminogen causing a conformational change exposing the active site, causing plasmin activity. Activated plasmin degrades fibrin.

Admin: 30-60 min i.v. infusion. T ½ = 1618mins.

Bleeding. May potentially be antigenic.


ALTEPLASE (fibrinolytic (thrombolytic)) “PLASEminogen ALTivator”.

Acute MI (perhaps caused by thombus) (give within 12 hrs). Acute thrombotic stroke (give within 3 hrs). DVT/ pulmonary embolus, acute arterial thromboembolism.

Is recombinant (synthetic) tPA. It works better on plasminogen bound to fibrin than to soluble plasminogen in the plasma and is therefore said to be clot sensitive. It activates plasmin

Admin: 30 min infusion. Rapidly cleared (T ½ 1218 mins).



that then degrades fibrin and dissolving the clot. HEROIN (is an opiate and is a narcotic/painkiller)

CANNABIS (depressant/miscell aneous)

Cannabinoids are the active constituents in CANNABIS causing a euphoric feeling, the most active cannabinoid being TETRAHYDROCANNA BINOL (THC).

Opiates bind to Mu (µ) (opioid) receptors on the cell body GABA neurones, inhibiting release of GABA onto VTA. This means the VTA is not inhibited allowing release of DOPAMINE at the NAcc = Reward (end point of drugs of abuse). THC (cannabis) binds to CB1 receptors on the cell body of GABA neurones projecting to the cell bodies of the VTA neurones. Like HEROIN, it causes disinhibition, preventing GABA release and facilitating dopamine release at the NAcc. CB1 receptors are Gprotein coupled and act to inhibit

PHARM S11 L14.

Inhalation: only 50% of the dose has a pharmacological effect (some is lost to env or swallowed. THC is metabolised to produce a very reactive metabolite called 11hydroxy THC. T ½ = 7 days. Its effect takes 1 hour or so to 18

1) Worsens psychosis and schizophrenia and 6 fold increase in developing these diseases. 2) Hallucinations 3) Increase appetite – CB1 at hypothalamus (people eat cannabis cakes). 4) Memory loss – CB1 at limbic regions 5) Psychomotor effects – CB1 in the

NABILONE (CB1 agonist) has been developed for its anti-emetic properties. PHARM S11 L14.

COCAINE (stimulant: “upper”)

Local anaesthetic (anaesthetic= reduce or take away sensation).

Adenylate cyclase & Ca2+ channels  decreased neurotransmitter (GABA) release from GABA neurone to VTA.

develop fully and lasts for 2 to 3 hours.

MOA: 1) In local anaesthetic: blocks Na+ channels preventing nerve conduction along those cells. 2) As drug of abuse: Prevents reuptake 1 of monoamines (e.g. dopamine, NA) causing hyperexcitation along with euphoria. This causes euphoria as the dopamine uptake 1 transporter at the NAcc is inhibited, increasing the conc of dopamine in the synapse.

Cocaine HCL: intranasal. Crack/freebase: Inhalation. Smoking it increases the euphoric effect due to ^ blood [COCAINE]. Has a v.quick euphoric effect and 75-90% is rapidly metabolised (T ½ = 20-90 mins) by liver to ecgonine methyl ester (Janine and ester make cocaine) & benzoylecgonin e.


cerebral cortex, substantia nigra, & cerebellum. 6) Peripheral effects e.g. tachycardia, vasodilation (esp of sclera causing blood shot appearance). Mild: Hyperactive, euphoria, ^ libido, anger/ verbal aggression. Severe: Total insomnia, extreme energy or exhaustion. Sudden death effects due to MIs/strokes as a result of ^ sympathetic stimulation (due to build up of monoamines in the SNS synapses of the body.

PHARM S11 L15. A stimulant stimulates the VTA directly.

NICOTINE (stimulant: “upper”) “kNitting COTton”

ALCOHOL (depressant: “downer”) depressant means it depresses certain inhibitory pathways causing disinhibition.

MOA: activation of Onset: seconds. nAChR causing: T ½ = 2-3hrs. 1) Euphoria (stim 70-80% nAChR on cell body undergoes of VTA neurones hepatic causing release of metabolism by dopamine to NAcc). CYP2A6 to 2) Cardiovascular COTININE. disease (as ^ nAChR activation will ^ stim of SNS post-synaptic neurones) 3) ^ lipolysis caused by ^ sympathetic stimulation (B1 rec) ^ free fatty acids ^ VLDL & decreased HDL. 4) ^ TXA2 due to ^ sympathetic stimulation. 5) ^ metabolic rate and appetite. MOA: it is mainly a depressant but paradoxically causes increased impulse activity in some parts of the CNS notably in the mesolimbic dopaminergic neurones involved in the reward pathway. Ethanol causes: 1) enhancement of GABA-mediated inhibition 2) inhibition of Ca2+ entry through 20

1) Cardiovascular disease, 2) atherosclerosis, 3) inappropriate thrombus formation.

Can be protective of Parkinson’s disease (^ brain CYPs) & Alzheimers disease (decrease beta amyloid toxicity and amyloid precursor protein (APP). PHARM S11 L15.

Acute effects: 1) Decreased Ca2+ entry causes cutaneous vasodilation = red faced. 2) Diuresis due to reduced ADH secretion. Chronic effects:

1 unit = 8g of ethanol and max for males= 21 units/wk, and for females= 14 units/wk. DISULFIRAM is a drug that inhibits Aldehyde dehydrogenase



In chronic inflammatory disease e.g. osteoarthritis/rheum atoid arthritis.

voltage-gated Ca2+ channels so inhibiting NT release in response to nerve terminal depolarisation. 3) inhibition of NMDA rec function. (NMDAR=N-methyl D-aspartate rec. Is an ionotropic receptor for glutamate) Acetaldehyde is a reactive and toxic intermediate metabolite which may contribute to hepatotoxicity. Alcohol dehydrogenase oxidises ethanol to aldehyde whilst at the same time reducing NAD+ to NADH. This depletes NAD+ stores within liver cells and may slow down the krebs cycle etc). Inhibit HMG CoA reductase. Activate PPAR alpha receptors. Inhibits cholesterol Absorbed then absorption from GI activated as tract. glucuronide*.

1) Dementia due to cortical atrophy 2) Ataxia due to cerebellar cortex degeneration. 3) Liver cirrhosis. 4) Cushing’s syndrome.

It reversibly inhibits COX-1 and COX-2 (so its effects are short lasting). It is COX-2 that has the primary pro-inflammatory action.

Chronic administration of NSAIDs increases susceptibility to gastric irritation and renal side effects.


causing a build up of ACETALDEHYDE which is toxic. PHARM S11 L16.

PHARM S13 L17. PHARM S13 L17. PHARM S13 L17. *Glucuronide= a substance produced by linking glucuronic acid to another substance. PHARM S13 L18.


In chronic inflammatory disease e.g. osteoarthritis/rheum atoid arthritis in those at risk of gastric and renal disturbance.


Arterial thrombus in patients with MI.

COX-2 has a wider active site allowing for selective inhibition. COX-2 is has several important physiological functions e.g. 1) regulation of ovulation, 2) regulation of parturition, 3) renal blood flow, 4) regulation of blood pressure, 5) proinflammatory actions. Binds and irreversibly inhibits COX-1 much more than COX-2. ASPIRIN has as (1)analgesic, (2)anti-pyretic, (3)anti-inflammatory and (4)anti-platelet actions. ASPIRIN acetylates an amino acid in the COX active site.

Oral admin. The effects of ASPIRIN can only be reversed by de novo synthesis of new COX-1 enzymes.


They have a good GI safety profile, are well tolerated by (but not recommended for) asthmatics, BUT have unwanted cardiovascular effects: COX-2 derived prostaglandins stimulate thrombomodulin which catalyses the following reaction: Thrombin + protein C ďƒ thrombin/protein C, which reduces coagulation. Therefore preventing thrombomodulin activation by inhibiting COX-2 derived prostaglandins may lead to enhanced coagulation.

PHARM S13 L18.

1) Bronchospasm/ bronchoconstriction in sensitive asthmatics. 2) Reduced glomerular filtrate rate and risk of nephrotoxicity. 3) ^ gastric HCL and decreased mucus and bicarbonate gastric secretion may lead to peptic ulcers. 4) Prolonged bleeding times.

PHARM S13 L18.

PARACETAMOL (not an NSAID as exerts no antiinflammatory effects)

Analgesic for mildmoderate pain e.g. headache, toothache.

MOA: unclear. May or may not involve COX inhibition. Main theory: NSAIDS inhibit oxidation of AA  PGG2, but PARACETAMOL inhibits peroxidation of PGG2  PGH2.

FLUTICASONE (glucocorticoid (GC) with high therapeutic index) Anti-inflammatory & immunosuppressive drug. A FLUTe was found in a bow(e)l. There was a FLUTe CORT CASe. Who OWNs the FLUTe, no one knows.

Treats symptoms of inflammatory bowel disease (IBD) active disease.

Derived from cortisol. Admin: suppository or foam enemas. MOA: activate intracellular glucocorticoid receptors which can then act as +ve or -ve transcription factors. It is antiinflammatory, working to (1) reduce influx & activation of some inflammatory cells (2) reduce adhesion molecules on endothelial cells and leucocytes), & (3) reduce the production of certain mediators e.g. IL1, TNF-a, elastase, COX, eicosanoids (e.g. protaglandins and leukotrienes), & NO. It is also immunosuppressive: Causes reduced cell proliferation, clonal expansion, antigen presentation & cytokines. Admin: start with high dose and taper down. BUDESONIDE is a similar drug that is orally/topically administered as 23

Overdose may cause irreversible liver failure due to high levels of a minor PARACETAMOL metabolite (: N-acetyl-pbenzoquinonamine). This is normally safely conjugated with glutathione but if lots of paracetamol is taken glutathione will be depleted. The metabolite oxidises thiol groups of key hepatic enzymes causing cell death  organ failure  death a few days after overdose. If administered quickly, i.v. ACETYLCYSTEINE (or oral METHIONINE) can reverse the effects of overdose. 1) FLUTICASONE has a high therapeutic index so hard to overdose. 2) normal effects of excess GC e.g. osteoporosis, HPA axis suppression, T2DM, hypertension, symptoms ass with Cushing’s syndrome.

PHARM S13 L18.

MESALAZINE (aminosalycylate) Anti-inflammatory drug.

Treatment of symptoms of IBD in prevention of relapse or remission.

AZOTHIOPRINE Immunosuppressan t and an antimetabolite.

An immunosuppressant drug used mainly to aid the survival of organ or tissue implants. Also used to treat (maintain remission in) inflammatory bowel disease, RhA and myasthenia gravis.

has low 1st pass metab and is degraded locally. 1) Reduce synthesis SULFASALAZINE of eicosanoids was initially 2) Reduce free used & was radical levels broken down 3) Reduce (by colonic inflammatory flora) into 5cytokine production aminosalycylic 4) Reduce leukocyte acid (5-ASA) infiltration (caused Ther/E) 5) No & Sulfapyridine immunosuppressive (caused S/E). effects MESALAZINE is 5-ASA. Absorbed from small bowel and colon. Admin: suppositories MOA: interferes with It is a prodrug purines biosynthesis activated by gut and thus DNA flora to 6synthesis and cell MERCAPTOPUR replication. INE (puts a It impairs: “cap” on mononuclear cell “purines”). It is infiltration, also a lymphocyte fraudulent DNA proliferation, base. antibody synthesis, & causes T-cell apoptosis.


Bone marrow suppression: may damage bone marrow causing blood disorders (i.e. macrocytic anaemia). May also causing muscle wasting and skin rashes.

Don’t coadminister with ALLOPURINOL (inhibits Xanthine oxidase) used to treat gout, as will cause 6MERCAPTOPURINE levels to rise causing blood dyscrasias (abnormal state of blood).

Xanthine oxidase normally breaks down 6 MERCAPPTOPUPU RINE but when inhibited by ALLOPURINOL, ALLOPURINOL can say “hALLO” to the large amount of “6mercaptoPURINE” within the blood. PHARM S13 L19.

HAEM 2 b12 def. INFLIXIMAB (Anti-TNFa) The X= 10= T ½ 10 days

Possible curative therapy for IBD (mainly in CD).

1) Anti- TNFa reduces activation of TNFa receptors in the gut. 2) Production of other cytokines, infiltration and activation of leukocytes is reduced. 3) Induces cytolysis of cells expressing TNFa. 4) promotes T-cell apoptosis.

Admin: i.v. T ½ = 10 days. Repeat infusion every 8 weeks. Benefits can last up to 30 wks with a single infusion.

1) 4x incidence in TB & other infections. 2) ^ risk of septicaemia & malignancy. 3) Worsening of heart failure.

Taking with AZOTHIOPRINE ^ number of patients in steroid-free remission after 1 yr. PHARM S13 L19.

MANNITOL Osmotic diuretic “almost OLL of MANN is water”.

To treat acute renal failure (by ^ H2O excretion ,as not enough H2O flowing through the kidney so other parts of the kidney will dry up). To decrease intracranial/ocular pressure (as ^ plasma osmolarity draws water out of tissues).

MOA: filtered by the glomerulus, it is a version of glucose that is not reabsorbed anywhere in the body, esp kidney. It increases the osmolarity of tubular fluid (& plasma) causing decreased reabsorption of H2O into the interstitium where the nephron is freely permeable


1) Water/ electrolyte imbalance (dehydration/ hypernatraemia???) 2) ^ ECF volume (hyponatraemia causing nausea vomiting and pulmonary oedema).



ACETAZOLAMIDE Carbonic anhydrase inhibitors “CarbonZETA jones”

Not used as a diuretic as such as they are weak diuretics. Used to treat glaucoma (by decreasing intraocular pressure), metabolic alkalosis (by ^ HCO3loss), renal stones.

FRUSEMIDE Loop diuretic “Fruit loops sweats”.

1) Oedema – Heart failure, pulmonary, renal, hepatic, cerebral 2) Moderate Hypertension Piretanide 3) Hypercalcaemia 4) Hyperkalaemia

to water e.g. prox tubule, desc LOH and coll duct. MOA: inhibit the Oral. action of carbonic anhydrase thus preventing the reabsorption of HCO3- and Na+, thus H2O reabsorption is reduced. Leads to ^ H2O/Na+/K+/HCO3excretion MOA: Blocks NKCC Oral. thus inhibits 15-30% of all Na+ and Clreabsorption in ascending limb. This decreases the osmolarity of the medullary interstitium and ^ osmolarity (i.e. [K+ and Na+] of filtrate. More Na+ gets to the distal conv tubule and so is reabsorbed through Na+ channel (due to gradient caused by the Na+/K+ ATPase in tubular cell basal 26

1) Metabolic acidosis 2) K+ loss.


Hypovolaemia & Hypotension K+ loss (Ca2+/Mg2+), Metabolic Alkalosis.

Massive K+ loss. Most Potent diuretic. PHARM S14 L22


1) Cardiac failure, hypertension, 2) severe resistant oedema, 3) idiopathic 4) hypercalciuria, 5) nephrogenic diabetes insipidus.


Coadminister with K+ losing diuretic, Primary and secondary hyperaldosteronism (SPIRONOLACTONE)

surface). Leads to overall ^ tubular osmolarity and decreased H2O reabsorption at collecting duct. MOA: inhibits the Na+/Clcotransporter in early distal convoluted tubule.  tubular fluid osmolarity =  H2O reabsorption in the collecting duct.


MOA: SPIRONOLACTONE is an aldosterone receptor antagonist. This will decrease the production of both Na+/K+ ATPases on basal membrane and Na+ channels on apical membrane. AMILORIDE is an inhibitor of aldosterone-sensitive Na+ channels on apical (luminal) membrane. This will 1) Inhibit Na+ reabsorption and K+ excretion in early distal conv tubule. 2)  tubular fluid osmolarity =  H2O reabsorption in the collecting duct. 3)  reabsorption of Na+ to distal tubule  H+ retention ( Na+/H+ exchange) 4)  uric acid loss 27

1) K+ loss ( delivery of Na+ to distal tubule  K+ loss (due to  Na+/K+ ATPase function). 2) Metabolic alkalosis 3) Diabetes mellitusinhibits Insulin secretion.


Hyperkalaemia, Metabolic Acidosis (due to H+ retention) SPIRONOLACTONE – Gynaecomastia, Menstrual Disorders, Testicular Atrophy.


PROMETHAZINE Antiemetic “Promet (an Indian guy) HAD (histaminergic, cholinergic, dopaminergic) some bad curry and wanted to vomit.”

Motion sickness (as a prophylactic), Meniere’s disease (disorder of the labyrinth), hyperemesis gravidarium (pregnancy sickness)


To treat nausea and vomiting associated with: 1) uraemia (severe renal failure) 2) radiation sickness 3) GI disorders 4) cancer chemotherapy intractable vomiting (high doses) e.g. CISPLATIN.

Onset: SPIRONOLACTONE days; AMILORIDE 6 hours. MOA: Acts as a Admin: oral, competitive onset 1-2hrs antagonist at and duration 24 histaminergic (type hrs. H1), cholinergic (muscarinic, M) and dopaminergic (type D2) receptors. Order of potency of antagonistic activity: H1> M > D2 receptors Acts centrally (labyrinth, Nucleus of the solitary tract (NTS)), vomiting centre) to block activation of vomiting centre. MOA: Order of antagonistic potency: D2 >> H1 >>> Muscarinic receptors 1) Acts centrally, especially at Chemoreceptor trigger zone (CTZ) 2) Acts in the gastrointestinal tract- increases

Admin: oral, rapidly absorbed, extensive 1st pass metab. Crosses BBB & placenta.


Dizziness, tinnitus (ringing in the ear), sedation (do not operate machinery), excitation in excess (paradoxical??), antimuscarinic S/Es.

PHARM S15 L23.

In CNS: Drowsiness, Parkinson-like syndrome: rigidity, tremor, motor restlessness. In Endocrine system: Hyperprolactinaemia , galactorrhoae, disorders of menstruation.

Care must be taken with the bioavailability of coadministered drugs- absorption and hence effectiveness of digoxin may be reduced. Nutrient supply may be compromised, so caution with

Intractable vomiting can be so severe that the patient has to stop chemotherapy, so METOCLOPROMIDE must be used here.

smooth muscle motility (from oesophagus to small intestine accelerated gastric emptying 3) accelerates transit of intestinal contents (from duodenum to ileo-coecal valve)

ONDASENTRON Antiemetic “ON DA SErotonin init”.

As an anti-emetic in 1) anti-cancer drug induced vomiting (esp with CISPLATIN). 2) radiotherapy induced sickness.


Triple therapy with CLARITHROMYCIN and a PPI in treating peptic ulcer. Triple therapy with CLARITHROMYCIN and a PPI in treating peptic ulcer. Triple therapy with METRONIDAZOLE and a PPI in treating peptic ulcer.

A 5Hydroxytryptaphan (aka 5-HT or Serotonin) antagonist. Acts to block transmission in visceral afferents and in the chemoreceptor trigger zone (CTZ). Active against anaerobic bacteria and protozoa.

AMOXYCILLIN Broad spectrum antibiotic CLARITHROMYCIN Antibiotic

diabetics. PHARM S15 L23.

Admin: orally, well absorbed, excreted in urine.

Headache, increased bowel transit time, sensation of flushing

PHARM S15 L23.

PHARM S17 L24.

Broad spectrum antibiotic.

PHARM S17 L24.

It is an antibiotic with a macrolide structure inhibiting the translocation of

PHARM S17 L24.


tRNA. OMEPRAZOLE Proton pump inhibitor “two O’s in both the name and the class”.

1) Component of triple therapy in peptic ulcer disease. 2) Peptic ulcers resistant to H2 antagonists e.g. RANITIDINE/ CIMETIDINE.

RANITIDINE Histamine (H2) receptor antagonist SUCRALFATE Cytoprotective ALuminium hydroxide and octasulFATE.

Peptic ulcer disease.

Peptic ulcer disease.

MOA: Irreversible inhibition of H+/K+ ATPase. Inhibits basal and stimulated secretion of gastric acid by the parietal cells by 90%.

Admin: oral. Inactive at a neutral pH. Duration of action is 2-3 days as it accumulates in the canaliculi of parietal cells, minimising its effects on ion pumps elsewhere in the body. Admin: oral.

SUCRALFATE is a polymer containing Aluminium hydroxide and sucrose octasulphate. MOA: it acquires a strong – ve charge in an acid environment and bind to +vely charged groups in large molecules (e.g. in glycoproteins) resulting in gel-like 30


PHARM S17 L24.

Relapses after withdrawal of treatment. Most of orally administered drug remains in the GIT so it may cause constipation and reduce the absorption of some other drugs such as antibiotics and DIGOXIN. Remember, reducing absorption will affect antibiotics and digoxin.

PHARM S17 L24.

BISMUTH CHELATE acts like SUCRALFATE and can be used in triple therapy. PHARM S17 L24.

MISOPROSTOL Prostaglandin analogue

Co-prescribed with oral NSAIDs when used chronically.

ANTACIDS (Al3+, Mg2+).

Non-ulcer dyspepsia.

SODIUM VALPROATE Anti-convulsant.

Epilepsy, bipolar disorder. 1st line for general epilepsy.

VIGABATRIN (suicide inhibitor) Anti-convulsant.

complexes. This coats and protects the ulcer, limits H+ diffusion and pepsin degradation of mucus. It ^ PG, mucus and HCO3secretion and reduces the number of H.pylori. Mimics the action of locally produced PG to maintain the Gastro-duodenal mucosal barrier.

MOA: Neutralises acid, raises gastric pH, and reduces pepsin activity. Acts by slowing down the breakdown of GABA since it is a GABA transaminase inhibitor. Also blocks the voltage gated Na+ channels. MOA: It is an analogue of GABA. Inhibits GABA

Diarrhoea, abdominal cramps, uterine contractions.


PHARM S17 L24. Prostaglandins (PG) stimulate mucus and bicarbonate production and inhibit gastric acid secretion. PHARM S17 L24.

PHARM S18 L25. PHARM S19 L30.


ďƒ Succinic semialdehyde GABA-T


May worsen general epilepsy (e.g. absence and

PHARM S18 L25.

MUSCIMOL Anti-convulsant

BICUCULLINE Convulsant Bi-cu-cu-cu-cu-line= convulsant.

Experimental use.


Experimental use.

BACLOFEN Spasmolytic (antispastic)

Muscle relaxant (sp.cord)

breakdown. It is a selective GABA-T inhibitor by irreversible covalent binding. This increases the concentration of GABA in the synapse. MOA: It is a GABA-A receptor agonist allowing Cl- influx  hyperpolarisation (inhibitory postsynaptic potential, IPSP)  inhibition of firing. MOA: Binds to the same site as GABA on the GABA-A receptor acting as a competitive GABA-A receptor antagonist. MOA: Noncompetitive GABA-A antagonist. Binds inside Cl- ion channels and blocks the flow of CL- ions into the postsynaptic neurone. MOA: GABA-B receptor agonist, acting via G-protein

myoclonic seizures.

PHARM S18 L25.

PHARM S18 L25.

PHARM S18 L25.

PHARM S18 L25.


Goes BAC to the GABA-B receptor.

linked receptors, decreasing Ca2+ conductance  decreasing NT release but somehow this increases GABA conc to inhibit firing of motor neurones to skeletal muscle fibres. MOA: GABA-B receptor competitive antagonist. BARBs don’t just act on BARB receptor of GABA-A receptor complex. They have other receptors too.




General short acting anaesthetics.

PHENOBARBITAL (BARB) Anti-convulsant

To treat seizure.


To treat severe, intractable (hard to

PHARM S18 L25.

Small margin of safety, tolerance, dependence etc.

PHARM S18 L26.

MOA: Acts at BARB site as a BARB

Excreted by kidneys.

Dizziness, nystagmus, ataxia. Specifically induces CYP450 2B6.

T ½ = 20-25 mins.

Not drug of choice – low safety margins,


Caution in children.

PHARM S18 L26.

PHARM S18 L26.


BENZODIAZEPINES (BZD) Bull dozers (BDZ) should not be operated as BZDs can cause sedation. Examples of BZD... DOT: D-diazepam O-oxazepam T-temazepam

control/deal with) insomnia.

agonist causing enhanced GABA binding to GABA-A receptor and increased duration of opening of Clchannels.

MOA: Benzodiazepines bind to the benzodiazepine receptor on the GABA-A receptor complex and: 1) ^ frequency of Clchannel opening, 2) enhances GABA binding. NB: Benzodiazepines (BDZ) and barbiturates (BARB) have no effects on Cl- channels or on the postsynaptic neurone on their own! GABA must be bound to its GABA rec domain on the

Oral, peak plasma 1hr. OXAZEPAM slower. BZD bind strongly to plasma proteins. Excretion: urine, glucuronide conjugates.

depresses respiration, overdose is lethal (use forced alkaline dieresis to counter), alters natural sleep, hangovers, enzyme inducers, Potentiate CNS depressants, dependence, withdrawal syndrome. Contrast the following with BARBs: Advantages Wide margin of safety, therefore overdose ďƒ prolonged sleep ďƒ  can be woken up. FLUMAZENIL is a BDZ competitive antagonist that can be i.v. administered if patient has a BZD overdose. BZDs do not induce liver enzymes. Mild effect on REM sleep. Disadvantages


PHARM S18 L26.

GABA receptor complex for BDZs or BARBs to have any effect at all. BARBs ^ the duration of Clchannel opening (contrast with BZDs).


A treatment for a BENZODIAZEPINE overdose.

DIAZEPAM Anti-convulsant/ Anti-spastic

Anti-convulsant and anxiolytic (long acting). Can’t be used as sedative as T ½ far too long.

Sedation, confusion, ataxia (lack of coordination of movements). Increased [plasma] by aspirin/heparin etc. Dependence (withdraw slowly), tolerance, potentiate other depressants e.g. alcohol.

MOA: competitive benzodiazepine receptor antagonist.

Long acting! T ½ = 32hrs. Converted to either 1-Nordiazepam  oxazepam  gluc. 2-Temazepam  oxazepam  glucuronide.


PHARM S18 L26.

PHARM S18 L26.

PHARM S18 L26.



PHARM S18 L26.

CHLORALHYDRATE Sedative/hypnotic

PHARM S18 L26.

BUSPIRONE Anxiolytic

PHARM S18 L26.


Dopamine replacement therapy.

PHARM S18 L27.


PHARM S18 L27.

DEPRENYL MAO inhibitor

PHARM S18 L27.



PHARM S18 L27.


PHARM S18 L27.


PHARM S18 L27.

NITROUS OXIDE General anaesthetic

PHARM S19 L28.

ISOFLURANE General anaesthetic

PHARM S19 L28.



PHARM S19 L28.


PHARM S19 L28.

LIDOCAINE Local anaesthetic

PHARM S19 L29.

COCAINE Local anaesthetic

PHARM S19 L29.










PHARM S21 L31.


PHARM S21 L31.























To treat iron poisoning (iron overload) – including that resulting from prolonged or constant blood transfusions as in thalassaemia.

It is an iron-chelating agent that combines with iron in body tissues and fluids.


To treat only mild disorders of vWFFactor 8 haemophilia (coagulation/ secondary haemostasis disorder)

Releases endogenous stores of vWF/ F8 so only useful in mild disorders.


Used to treat haemophilia by stabilising a fibrin clot.

Inhibits fibrinolysis.

Administered by subcutaneous infusion (injection) (over several hours, several times a week) as it is not orally active. Dose 0.3 micrograms per kg i.v. gives a peak response at 30 to 60 mins. Dose 300 micrograms i.n. gives a peak response at 6090mins. Intravenous: 0.5g tds. Oral: 1.5g tds, Mouthwash: 1g qds. Widely distributed – crosses placenta. Low concentration in breast milk.



HAEM 3 haemthal.



Human Recombinant GH (Somatotrophin)

To treat GH deficiency to (1) improve muscle strength and exercise capacity, (2) normalise HDL cholesterol levels (bring them up), (3) increase bone mineral content.

OCTREOTIDE (Somatostatin analogue)

Used in the long-term treatment of acromegaly. Shortterm treatment before pituitary surgery in those with Acromegaly.

BROMOCRIPTINE (Dopamine Type 2 receptor agonist)

Treatment of hyperprolactinaemia. Treatment of acromegaly.

Binds to GH receptor on liver cells causing the production of Insulin-Like Growth Factors (IGF-1 & 2).

Binds to Dopamine receptors on lactotroph cells in the adenohypysis, causing the decrease in secretion of prolactin from lactotroph cells.

Injected subcutaneously or intramuscularly. T ½ = 20 mins but peak IGF-1 levels are 20 hrs after administration. Evening administration, 4 to 5 times weekly. Injected 3xa day subcutaneously or intramuscularly. The drug is retained in ECF, with a T ½ = 2 to 4 hrs, metabolised hepatic/renal. Administered 1x a day orally. T ½ = 7 hrs. Hepatic metabolism.


(1) Lipoatrophy at site of injection, (2) Headaches, intracranial pressure, (3) increased risk of Cardiovasc. Accidents, (4) Increase in soft tissue growth resulting in cardiomegaly, (5) increased susceptibility to cancer. (1) GI tract disturbances, (2) Gall stones, (3) initial reduction in insulin secretion (transient hyperglycaemia).


(1) nausea, vomiting, abdominal cramps, (2) dyskinesia, (3) postural hypotension, (4) vasospasm in fingers and toes.



CABERGOLINE (Dopamine Type 2 receptor agonist)

Treatment of hyperprolactinaemia.

Same as above.

LITHIUM/Dimethyl-chlortetracycline (DMCT) – V2 receptor antagonist

To treat Syndrome of Inappropriate ADH (SIADH).

DESMOPRESSIN (V2 receptor agonist)

To treat (1) central (cranial) diabetes insipidus (DI), (2) haemophilia, (3) nocturnal enuresis.

Binds to vasopressin 2 receptors on the plasma surface of the collecting duct cells in order to BLOCK the action of VP. This leads to less water reabsorption & so diuresis. Selectively binds to V2 receptors on the plasma surface of the collecting duct cells causing AQ2, 3 and 4 synthesis.

THIAZIDES (Bendroflumethazi de)

To treat nephrogenic DI.

Administered 1 or 2 x per week. T ½ = 40h+

Like BROMOCRIPTINE but less pronounced.



Oral admin, retained in ECF with a T ½ = 5hrs. Metabolism is hepatic/renal.

Depletes Na+ in ECF leading to a compensatory increase in Na+ reabsorption in the proximal tubule. This leads to a reduction of fluid travelling to the distal tubule (& collecting duct) & a 45

Fluid retention & hyponatraemia. Plasma [Na+] < 120 = poor mental function & nausea. Plasma [Na+] < 110mM = confusion, coma, death. More fluid retention dilutes bld solutes! K+ loss (hypokalaemia), hypercalcaemia.

The beneficial effects of THIAZIDES are enhanced by reduced Na+ intake in the diet. ENDO S2 L3

reduction in urine volume.

TERLIPRESSIN/ FELIPRESSIN (V1a receptor agonists)


To treat varicose veins (veins that are distended, lengthened and tortuous). To prolong the actions of local anaesthetics (mainly FELYPRESSIN). To treat primary hypothyroidism. LIOTHYRONINE is T3 and so can be used to treat myxoedema coma for more rapid action.

Bind to V1a receptors on vascular smooth muscle.

Bind to thyroid receptors on cell membranes.


Both can be taken orally but for fast effect take LIOTHYRONINE intravenously. T4: T ½ = 6 days, T3: T ½ = 2-5 days. Both accumulate if given daily = DON’T. Distribution: almost 100% bound to plasma protein Thyroid Binding Globulin (TBG) made in liver. Hepatic metabolism, 46

Signs and symptoms of hyperthyroidism and enhanced activity in the SNS.

Begin with a low dose and build up gradually. ENDO S2 L5.

biliary & urinary excretion.

PROTIRELIN (TRH analogue).

To treat secondary hypothyroidism. This is a condition in which the activity of the thyroid gland is decreased due to failure of the pituitary gland or hypothalamus.


To treat mainly (1) diffuse hyperthyroid toxic goitre/ Graves’ disease/ exophthalmic goitre. (2) treatment prior to surgery, (3) reduction of symptoms while waiting for radioiodine to act.

Binds to TRH receptors on thyrotroph cells causing release of thyrotrophin (TSH). If TSH levels increase due to PROTIRELIN it indicates that hypothalamus not secreting TRH. Inhibits thyroperoxidase (during iodination of thyroxine phenolic ring) and hence decreases formation of T3/T4 from thyroid gland. Other: may suppress antibody production in Graves’ and [PROPYLTHIOURACIL ] reduce T4 conversion to T3 in peripheral tissues.

Cardiac insufficiency & pregnancy.

Biochemical effect occurs within hrs; clinical effectweeks. Take orally, CARBIMAZOLE is a pro-drug (it must first be converted to METHIMAZOLE) , plasma T ½ = 6 to 15hrs, crosses placenta and is secreted in milk, hepatic metabolism, urine excretion.


(1) Agranulcytosis/ granulocytopenia (reduction or absence of granular leukocytes). (2) rashes, headaches, nausea, jaundice, joint pain.


PROPANOLOL may be included in the treatment to reduce treatment such as tremor and tachycardia. ENDO S2 L5 pharmthyroid.


To treat (1) hyperthyroid storm and to (2) prepare hyperthyroid patient for surgery.

Inhibits H2O2 production (a chemical needed for thyroperoxidase to function correctly), so no iodination of thyroglobulin (TG) occurs.


To treat (1) hyperthyroidism, thyroid tumours (cytotoxic concentration), (2) test for thyroid function (low concs).

The iodine isotope is taken up mainly by the thyroid gland and releases betaparticles which are toxic to the thyroid follicular cells.


To treat Cushings’ syndrome (excess glucocorticoid production). Differentiates between pituitary adenoma and ectopic tumour secretion as the source of high

Inhibits 11-B hydroxylase preventing the conversion of 11deoxycortisol & 11deoxycorticosterone to cortisol & aldosterone respectively.

Hyperthyroid symptoms reduce within 2 days & vascularity & size of gland reduces in 2 wks. Take orally & maximum effect is after 10 days treatment. Single dose (orally in capsule for Graves’ disease or orally/i.v. as a tracer in tests of thyroid function. T ½ = 8 days. Max effect 2 to 3 months, radioactivilty negligible after 2 months. Orally, 250-750 mg TDS.


(1) Allergic reaction e.g. rashes, fever, angioedema.

(1) Avoid children & pregnant patients, (2) hypothyroidism may arise due to too much destruction of thyroid follicular cells. (3) sore throat.

Nausea, vomiting, dizziness, sedation, hypoadrenalism, hypertension on long-term admin (deoxycorticosterone accumulates in ZG and has aldosteronelike

ENDO S2 L5 pharmthyroid.

Pregnancy or breastfeeding women.

Many blood tests will have to be carried out in the weeks and months after the treatment. Technecium can be used instead of Radioiodine for thyroid function tests. ENDO S2 L5

Usually use this 6 weeks prior to surgery to prevent wound infection. ENDO S3 L6 pharmadrenal.

ACTH (& thus cortisol) plasma levels.


To treat Cushingâ&#x20AC;&#x2122;s syndrome, primary hyperaldosteronism, & to reduce sex steroid hormone production.


To treat Cushingâ&#x20AC;&#x2122;s syndrome or control its symptoms prior to surgery.

Inhibits 3-B HSD (hydroxysteroid dehydrogenase). This prevents the conversion of Pregnenolone & 17aOH Pregnenolone to Progesterone and 17a- OH progesterone respectively. Non-specific Orally, 200 to inhibition of 400 mg bd. Cytochrome P450 enzymes such as the one which converts cholesterol into pregnenolone in the ZG.


mineralocorticoid activity, leading to salt retention and hypertension). Nausea, vomiting, diarrhoea, flushing.

Nausea, vomiting, abdominal pain, alopecia, gynaecomastia (due to reduced testosterone production in ZR but mainly the lack of androstenedione which is the main substrate produced by the adrenal cortex used by the gonads to produce androgen (testosterone).

ENDO S3 L6 pharmadrenal.

Usually use this 6 weeks prior to surgery to prevent wound infection. ENDO S3 L6 pharmadrenal.


SPIRONOLACTONE (aldosterone receptor antagonist).

HYDROCORTISONE (pharmacological name for cortisol)

To treat (1) adrenocortical carcinoma (malignant) & (2) prostatic cancer (malignant). To treat primary hyperaldosteronism (conn’s syndrome). Also used in treatment of oedema, congestive heart failure, nephritic syndrome and cirrhosis of the liver.

To treat addison’s disease.

Inhibits conversion of cholesterol to Pregnenolone (v. Toxic).

Orally active

It is a pro-drug rapidly converted to CANRENONE (an active metabolite). Competes with aldosterone for mineralocorticoid receptor (MCR). Competitive antagonism of aldosterone causes less Na+ reabsorption and less K+ excretion (potassium sparing). Binds to intracellular Glucocorticoid Receptors (GR) in most cells of the body.

Orally active, OD (can be in split dose), hepatic metabolism, highly protein bound.

Menstrual irregularities, gynaecomastia (androgen receptor binding), GI tract irritation.

Orally & parenterally active. T ½ = 1.5 hrs. Duration of action of 8 hrs. Distribution: 95% CBG bound. Hepatic metab: reduction of the A ring.

At high doses can cause unwanted ALDOSTERONE-like effects e.g. hypertension, sodium retention, hypokalaemia.


ENDO S3 L6 pharmadrenal.

Renal or hepatic disease.


Patients with adrenocortical insufficiency are unable to produce cortisol in conditions of stress (like in illnesses or before surgery) so provide additional exogenous steroid to protect them.


PREDNISOLONE (glucocorticoid agonist)

To treat addison’s disease.

Binds to intracellular Glucocorticoid Receptors (GR) in most cells of the body.

DEXAMETHASONE (glucocorticoid agonist)

To treat addison’s disease.

Binds to intracellular Glucocorticoid Receptors (GR) in most cells of the body.

FLUDROCORTISON E (mineralocorticoid agonist)

To treat addison’s disease.

Binds to Mineralocorticoid receptors (MR) in the brain and kidney.

Orally & parenterally active. Duration of action 12 hrs. Distribution: CBG bound. Hepatic metab: reduction of the A ring. Orally & parenterally active. Duration of action 40 hrs. Distribution: binds weakly to albumin. Hepatic metab: reduction of the A ring. Orally active. T ½ = hrs. Duration of action of 8 hrs. NB: the neonatal kidney is relatively insensitive to FLUDROCORTIS SONE so higher 51


DEXAMETHASONE is not recommended for children as it impairs growth.


Made as an alternative to ALDOSTERONE as ALDOSTERONE cannot be administered by mouth. ENDO S5 L9.

doses are needed in infants. OESTROGEN (maintains fertility)

Actions: 1) negatively feeds back on Hypothalamo-pituitary gonadal axis (HPG) and at high levels causes LH surge, 2) causes endometrial proliferation (as well as some other tissues), 3) reduces viscosity of cervical mucous favouring penetration of sperm, 4) reduce bone resorption, 5) increase levels of HDLs and low LDLs contributing to low risk of atheromatous disease in premenopausal women, 6) increased uterine contractility (pushing sperm in uterus into fallopian tubes perhaps)- increases myometrial sensitivity to oxytocin towards the end of gestation, 7) promotes salt and water reabsorption from the kidney, 8) increases plasma protein production from the liver (e.g. SHBG and Albumin) which can cause increased blood clotting factors and therefore coagulability -> risk of VTE (esp. in pregnant women). The purpose of increasing blood clotting factors is to prepare for the loss of blood suffered by the mother at parturition. Site of production: mainly ovaries (from developing follicles and main graffian follicle), & corpus luteum.

ENDO S5 L10.


Used in the combined oral contraceptives (COCs). It is a semisynthetic oestrogen. Used in combination with NORETHISTERONE.

ENDO S5 L10.

Upregulates progesterone receptors enhancing sensitivity to progesterone. It contributes to a negative feedback of the HPG axis. It thins cervical mucus, stimulates prolif of endometrium and increases circulating tri-glycerides and HDLs.

Resistant to metabolism and orally active. Can be administered via transdermal skin patches (oestrogens readily cross membranes; avoids 1st pass metabolism). Mainly bound to Sex Hormone Binding Globulin (SHBG) and albumin. 52

(1) Blood clotting factors (increased incidence of thromboembolic disease), (2) endometrial cancer (reduced by coadmin of progestogens e.g. progesterone/ testosterone analogues), (3) breast cancer & discomfort, (4) Salt retention= hypertension, oedema + weight gain due to

increased water reab, (5) nausea etc.

PROGESTERONE (maintains the condition of preganancy)

Actions: 1) Thickens cervical mucus (hostile to sperm preventing subsequent fertilization & pregnancy), 2) causes secretion of nutritious fluid in fallopian tubes for fertilised ovum, 3) decreases contractility of uterus (favours implantation and development of the embryo in the uterus wall)- reduces myometrial sensitivity to oxytocin but progesterone decreases at end of gestation anyway, 4) causes the development of lobules and alveoli in mammary tissue & prepares breast for lactation, 5) suppresses menstrual cycling through negative feedback to HPG axis so no new follicles can develop. Site of Production: Corpus luteum, Placenta, adrenal glands (small amounts, both sexes).

ENDO S5 L10.

NORETHISTERONE (testosterone analogue)

Used in the combined oral contraceptives (COCs). Used in combination with OETHINYL OESTRADIOL.

It is not one of the principle components for the emergency pill. ENDO S5 L10.


Long-lasting PROGESTERONE ONLY contraception. Provides 3 months contraception.

POST-COITAL PILL (morning after pill)

Combined E & P (prescription only) or P (only at higher doses than used in COCs).

Thickens cervical mucus and suppresses menstrual cycling through negative feedback to HPG axis.

Orally active.

Intramuscular injection. Circulating progesterone is bound to albumin, not so much SHBG. 2 doses 12 hours apart beginning WITHIN 72 hours of intercourse! 53

Transient infertility and irregular cycles may occur on discontinuation. May exacerbate depression. Nausea and vomiting- if happens repeat dose. May require coadmin of antiemetic.

Used when OESTROGENS are contraindicated. They are not contraindicated in nursing mothers.

Progestogen only contraceptives may be taken orally. ENDO S5 L10.

Ineffective in terminating an established pregnancy. ENDO S5 L10.

LEVONELLE is an over the counter drug. HRT (hormone replacement therapy)

To reduce the symptoms experienced by postmenopausal women: (1) decreases vasomotor symptoms (hot flushes) and (2) slows down the decreasing bone density.

TIBOLONE (designer HRT, synthetic prohormone).

Relief of vasomotor symptoms of menopause.

SERMs (Selective Estrogen Receptor Modulating drugs)

Menopause treatment.

Oestrogen and progesterone analogues bind to their respective receptors within the body mimicking the normal menstrual cycle. Oestrogen analogues bind to receptors (1) on the endometrium, (2) in the breasts, (3) on bone osteoblasts, and (4) in the hypothalamus and pituitary. Oestrogenic, progestogenic and weak androgenic actions.

Routes of admin: oral, transdermal (patch/gel), percutaneous (through the skin, drugs like ointments), intravaginal, intranasal spray.

Never give unopposed oestrogen to a woman with a uterus as this could lead the endometrial cancer. (1) breast cancer, (2) endometrial carcinoma, (3) Gall stones, (4) Venous thromboembolism, (5) cerebrovascular accident (CVA), (6) cardiovascular disease. No bleeds. When progesterone is constantly given in combination with oestrogen, no menstruation (bleeding) occurs.

SERMS do not have a classical steroid structure and are tissue selective. They have a high affinity for oestrogen

(1) Previous breast cancer diagnosis. (2) if have a high risk of Venous Thromboembolism (VTE) e.g. overweight, previous VTE.

Normal menopausal women can be treated for 5 to 7 years, and premature menopausal women can be treated up to the normal age of menopause. ENDO S6 L11.

ENDO S6 L11.

ENDO S6 L11.


(1) TAMOXIFEN (= an anti-cancer drug)

Used to treat oestrogen-dependent breast tumours and metastatic breast cancers. Prevents osteoporosis. Overall: BREAST- antagonist. ENDOMET- agonist. BONE- agonist.

(2) CLOMIPHENE (= fertility drug, oestrogen receptor antagonist at the hypothalamic level)

Used to treat female infertility due to anovulation (e.g. due to polycystic ovarian syndrome, PCOS).

receptors and displace oestradiol. They activate oestrogen metabolic pathways or block oestrogen receptors. TAMOXIFEN competitively binds to oestrogen receptors on breast tumours leading to decreased DNA synthesis and decreased oestrogen effects. It prevents (pre)cancerous cells from dividing but does not kill them, so it is a cytostatic drug not cytocidal one. Even though it is an oestrogen antagonist in breast tissue, it is an agonist for endometrial and bone tissue. Binds to oestrogen receptors in hypothalamus so blocks the normal negative feedback. Oestrogen can no longer feedback to

Only taken for first 5 days of menstrual cyle to induce ovulation.


Endometrial proliferation (carcinoma), hot flushes, GI disturbances, Menstrual irregularities, Bone pain with metastases.

Acts on the Liver to lower cholesterol (up HDL down LDL); acts on bone to increase density (is an agonist for oestrogen receptors preventing bone loss by inhibiting osteoclasts). ENDO S6 L11.

(1) Multiple pregnancies may occur due to stimulation of mature growth of more than one follicle. Patients


the hypothalamus, GnRH release becomes more pulsatile so more FSH & LH pituitary hormone release. Increased Gn levels cause growth of the ovarian follicle followed by follicular rupture (ovulation). Oestrogenic in bone, anti-oestrogenic in breast and uterus.

need follicle tracking by ultrasound. (2) ovarian hyperstimulation, (3) endometriosis, (4) hot flushes, (5) nausea vomiting headache.


To prevent osteoporosis in postmenopausal women.

Pregnant/lactating women. History of VTE events


Actions: 1)development of male genital tract, 2) maintains fertility (spermatogenesis & trophic support of male genitalia), 3) controls secondary sexual characteristics (hair growth and enlargement of larynx), 4) anabolic effect (increases cell proliferation, stimulates erythropoiesis, causes epiphyses of long bones to unite, increase protein formation), 5) stimulation secretion from sebaceous gland, 6) libido, 7) aldosterone-like effects at high concs, 8) increases liver synthesis of clotting factors and reduces HDL levels, 9)anti-oestrogen effects, 10) potentiates actions of GH during puberty. Site of production: testes (leydig cells), zona reticularis, ovaries (as a precursor for oestrogen), placenta, tumours. 98% binds to SHBG or albumin so the amount of free testosterone will increase by other drugs that bind to plasma proteins e.g. aspirin. 56

ADs= decrease breast cancer, decrease vertebral fractures, no increase in MI. DISADs= increase VTE, does not reduce vasomotor symptoms (hot flushes), increase in fatal stroke. ENDO S6 L11. ENDO S7 L12.

TESTOSTERONE (androgen receptor (AR) agonist)

Used to treat male primary or secondary hypogonadism.

Absorbed rapidly & subject to substantial first pass metabolism.

MESTEROLONE (methyltestosteron e DHT derivative: AR agonist)

Used to treat male primary or secondary hypogonadism.

UNDECANOATE (testosterone ester: AR agonist)

Used to treat male primary or secondary hypogonadism.

Orally active but DOES NOT undergo extensive first pass metabolism. Orally active. More prolonged absorption time.


1) Virilisation, 2) salt and water retention, weight gain and oedema (ALDOSTERONE activity at high doses), 3) acne (stimulation of sebaceous glands). 5) jaundice (as a result of more red cell production and thus breakdown), 6) prostate hypertrophy, 7) low plasma HDL, 8) premature bone fusion in children (stunted growth), 9) testicular atrophy at chronic admin of high doses. Same as above.

Same as above.

CVS or renal failure due to ALDOSTERONE effects.

ENDO S7 L12.

Contraindicated for use in infants and young children.

ENDO S7 L12.

ENDO S7 L12.


Used to treat male primary or secondary hypogonadism.

NANDROLONE (nortestosterone)

Used to treat male primary or secondary hypogonadism and some aplastic anaemias as androgens increase erythropoiesis). Illegal use in sport to increase performance. Used in PCOS (to treat acne and hirsutism), prostate cancer, excessive male sexuality, precocious puberty.

CYPROTERONE ACETATE & FLUTAMIDE (androgen receptor antagonist)

Anabolic/ virilising actions.

Derivative of PROGESTERONE that has high affinity but low efficacy for AR.

Parenteral administration (i.m. in an oily vehicle). Long acting! NB: PROPIONATE is short/medium acting. 1 injection every 2 to 4 weeks. Admin by deep i.m. injection (depot).

Same as above.

ENDO S7 L12.

Same as above. May also cause physical and psychological dependence.

ENDO S7 L12.

Effective orally, rapidly metabolised in the liver, excreted in faeces and urine.

Fluid retention, weight changes, gynaecomastia, inhibition of spermatogenesis (due to AR antagonism on sertoli cells and PROGESTERONE-like actions which reduce LH secretion.

ENDO S7 L12.


FINASTERIDE (5a reductase antagonist)

Used in treatment of benign prostatic hyperplasia.

METOCLOPRAMIDE Used as an anti(Dopamine emetic but also antagonist) clinically relevant as an iatrogenic cause of hyperprolactinaemia. PHENOTHIAZINES Used as an anti(Dopamine psychotic but also antagonist) clinically relevant as an iatrogenic cause of hyperprolactinaemia. CALCIUM SALTS Used to treat (e.g. Calcium osteoporosis in (1) chloride/ postmenopausal glucuronate) oestrogen deficiency (2) age-related deficiency in bone homeostasis (e.g. raised PTH levels and decreased osteoblast activity with aging), and (3) raised glucocorticoid levels e.g. iatrogenic, cushingâ&#x20AC;&#x2122;s syndrome.

Orally active.

Decreases libido, impotence, decreased ejaculation volume, breast tenderness and enlargement, hypersensitivity reactions (angiodema).

Never use in women at child-bearing age to treat PCOS as this is teratogenic.

Prostate size decreases, improved urinary flow rate. ENDO S7 L12.

ENDO S7 L13.

ENDO S7 L13.

CALCIUM CHLORIDE: only intravenously! Orally will cause gastric irritation and injection into tissue may cause tissue necrosis. CALCIUM GLUCONATE: administer orally (no 59

CALCIUM CHLORIDE: may cause peripheral vasodilation, decrease in bld pressure and cutaneous burning.

Osteoporosis is a condition of reduced bone mass and a distortion of bone microarchitecture which predisposes to bone fracture after minimal trauma. ENDO S8 L15.

BISPHOSPHONATE S (e.g. Na+ etindronate & alendronate)


Also osteoblasts turnover to become osteoclasts with age. Also used to treat hypocalcaemias and heart dysrhythmias due to severe hyperkalaemia. Used to treat paget’s disease, to delay bone metastases in cancer patients, hypercalcaemia (associated with malignancy).

Used to treat paget’s disease,postmenopa usal/ GC induced osteoporosis and hypercalcaemia.

gastric irritation) or i.v. for severe hypocalcaemic tetany.

Directly inhibit the recruitment & promote apoptosis of osteoclasts and indirectly increase the activity of osteoblasts (lays down bone matrix). IMPORTANT: osteoid is being formed here not hydroxyapatite.

Administer orally on an empty stomach – milk esp reduces absorption. Accumulates at site of bone mineralisation and remains part of the bone until it is resorbed. Excreted in urine unmetabolised! Administer s.c. or i.m. or intranasally. Resistance due to antibody formation may develop after a few months.


(1) Increased chance of bone fracture due to increase in nonmineral osteoid. (2) gastric pain and GI upsets. (3) oesophagitis. (4) bone pain.

(1) Inflammation at the site of injection, (2) bad taste in mouth, (3) facial flushing, (4) nausea and vomiting, (5) tingling sensation in hands.

Particular care should be taken with patients who have renal insufficiency.

ENDO S8 L15.

ENDO S8 L15.

VITAMIN D (ergocalciferol and calcitriol)

ERGOCALCIFEROL: Used to treat osteomalacia, rickets and hypocalcaemia with associated hypoparathyroidism. CALCITRIOL: To treat osteodystrophy due to chronic renal failure.


1) Induction of labour at term, 2) prevention of post-partum haemorrhage and uterine atony, 3) facilitation of milk letdown.


1) prevention of postpartum haemorrhage and 2) uterine atony,3) routine management of 3rd stage of labour.

Binds to intracellular receptors. Causes increased transcription of calcium transporters in the gut (causing increased Ca2+/PO4abs) and causes increased reab or Ca2+/PO4- in the kidneys. In bone, stimulates osteoclast activity and synergises with PTH. Causes cervical dilation, and uterine contractions from the fundus to the cervix.

Vitamin D is a prehormone and is fat soluble. ENDO S8 L15.

1) Slow i.v. infusion, 2) slow i.v. injection, 3) intranasal spray (for mild letdown). Stays in ECF and limited access to CNS. Liver, kidney, & plasma metabolism â&#x20AC;&#x201C; T ½ = 5mins. 1) i.v, (haemorrhage), 2) orally, 3) i.m.


1) antidiuresis (VPlike effects) with hyponatraemi, 2) compromising placental exchange of foetal oxygen and nutrients, 3) lacerations/ trauma of cervix, 4) uterine rupture, 5) tachycardia. Abdominal, pain, hypertension, nausea, angina pain.

ENDO S8 L16.

1) Pregnancy prior to the 3rd stage of labour, 2) preeclampsia and other vascular diseases.

ENDO S8 L16.

PROSTAGLANDINS (Dinoprostone PGE2, Geneprost PGE1, Carboprost PGF2a)

MIFEPRISTONE (progesterone receptore (PR) antagonist)

1) induction of abortion (dino), 2) induction of cervical ripening (dino), 3) Post-partum haemorrhage in those with OXYTOCIN and ERGOMETRINE resistance) (carbo). 1) early (up to 63 days) abortion (softening and dilation of cervix, followed by gemeprost admin 3648 hrs later.

TOCOLYTICS (Badrenoreceptor agonists)

Delay premature labour.

ORLISTAT (GI lipase inhibitor)

Diet regulation in T2DM.

Blockade of uterine progesterone receptors (PR)  Blastocyst detachment  Decrease in hCG release  Decreased PROGESTERONE secretion from corpus luteum  Decidual breakdown. Receptor activation increases intracellular cAMP causing relaxation of uterine muscle so contractions don’t occur). Inhibits the enzyme lipase in the GI tract causing reduced fat absorption.

1) intravaginally as gel or tablet, 2) gemeprost can be used for cervical ripening in abortion by vaginal pessaries, 3) i.m. injection. Oral, good bioavailability, limited distribution by plasma proteins, enters cells readily, T ½ = 20 to 40 hrs, hepatic, excreted in faeces.

Hypertansion (with carboprost PGF2a), hypotension (with dinoprostone PGE2), nausea, vomiting, potentiation of OXYTOCIN, pyrexia.

ENDO S8 L16.

Vaginal bleed and headaches.

ENDO S8 L16.

ENDO S8 L16.

If eat fatty food staetorrheoa may result.


ENDO S10 L18.

a-GLUCOSIDASE inhibitor



Treatment of obesity in T2DM.

RIMONABANT (CB1? Antagonist)



To reduce weight gain in T2DM.

THIAZOLIDINEDION T2DM. ES (PPAR gamma agonist) GLIBENCLAMIDE (a sulphonylurea, insulin secretagogue) & METAGLINIDES

To treat lean T2DM patients where diet alone has not succeeded.

Delays oligosaccharide absorption from the gut. Acts on the hypothalamus: less re-uptake of Noradrenaline causing more satiety i.e. they feel fuller. Central fat loss and central satiety.

ENDO S10 L18.

Increased blood pressure.

ENDO S10 L18.

ENDO S10 L18.

Increases hepatic insulin sensitivity, and inhibits hepatic insulin gluconeogenesis in the liver. Increases muscle insulin sensitivity, and is associated with less omental fat. Increases insulin output from B-cells. GLEBENCLAMIDE binds to B-cells and causes intracellular ATP to rise, causing K+ (ATP sensitive) channel to stop working. This causes an influx of Ca2+ ions (from voltage dependent Ca2+ channels) leading to vesicles containing insulin being exocytosed. 63

GI side-effects.

Severe liver, cardiac or mild renal failure.

ENDO S10 L18.

ENDO S10 L18.

Hypoglycaemia, weight gain.

ENDO S10 L18.





CAPTOPRIL (ACE inhibitor)

Used for treating diabetics at risk of nephropathy (microvascular complication of diabetes)

GLEBENCLAMIDE bypasses the need for a glucose stimulus to promote release of insulin. Normally glucose enters the B-cell, and is metabolised to produce ATP which works on the K+ ATP sensitive channel causing the rest of the mechanism to occur as above. Messenger that tells your pancreas to secrete more insulin. Increases insulin secretion, suppresses pancreatic release of glucagon, and promotes satiety.

Suncutaneous injection 30 to 60 mins before first and last meal of day.

ENDO S10 L18.

Nausea, vomiting, diarrhoea, headaches, dizziness etc.

GI disease.

ENDO S10 L18.

ENDO S10 L19.


Drug List 1  
Drug List 1  

Drug List 1