Dr. S. HIMAGIRI Postgraduate Student
DEPARTMENT OF CONSERVATIVE DENTISTRY & ENDODONTICS SRI RAMACHANDRA DENTAL COLLEGE AND HOSPITAL CHENNAI
1 DEFINITION CLASSIFICATION
TYPES OF DENTAL PAINS
DENTAL PAINS OF PULPAL ORIGIN DENTAL PAINS OF PERIODONTAL ORIGIN MECHANISM OF PAIN
MANAGEMENT OF PAIN
OPIOID AND NON-OPIOID ANALGESICS ANTI-MICROBIAL DRUGS
CLASSIFICATION β - LACTUMS AMINO GLYCOSIDES MACROLIDES METRONIDAZOLE QUINOLONES BROAD SPECTRUM ANTIBIOTICS SULFONAMIDES RATIONALE BEHIND ANTIBIOTICS
PAIN The international association for the study of pain [IASP] has given following definition. DEFINITION Pain
associated with actual or potential tissue damage or described in terms of such damage. SOME OF COMPREHENSIVE LIST OF PAIN RELATED TERMS
Allodynia: It is a pain due to stimulus that does not normally produce pain or pain that occurs with out any noxious stimulus.
Hyperalgesia: It is an increased response to stimulus that is usually painful or increased sensitivity to stimulation evoked pain.
Causalgia: A syndrome of burning pain.
Neuralgia: Pain in the distribution of a nerve.
Paraesthesia: It is an abnormal sensation (But not unpleasant) whether spontaneous or provoked.
Analgesia: Absence of sensitivity to pain
Anesthesia: Absence of all sensation
PAIN CLASSIFICATION Classification of pain is important because to 1. Evaluating, Treating, Assessing the progress of pain symptoms. 2. Comparing the pain experience between individuals. IASP
4 - Classified pain according to a number of parameters AXIS - I - Regions (the body region or site of the reported pain. Axis – II - (Systems) The body system whose abnormal function produces pain Axis – III - (Temporal) temporal characteristics of pain and the pattern of occurrence Axis – IV - Patients statement Time since onset, and intensity of pain. Axis – V – Etiology of pain problem. TYPES OF DENTAL PAINS BEHAVIOR OF DENTAL PAINS It should be recognized that dental pains are extremely versatile and have propensity to mimic nearly any pain disorder. The degree of such pain may vary from mild tenderness to unbearable intensity, dental pain may be spontaneous, it can be intermittent, some times pain can be radiating, or non – radiating. LOCALIZATION The patient very poorly localizes pain arising solely from the dental pulp. It is frequently difficult for him or her to determine whether the offending tooth is mandibular or maxillary, much less which tooth is involved. The pain is felt diffusely in the teeth, jaws and head.
5 Pain arising from the periodontal structures. However, is quietly readily localizable by the patient, especially when offending tooth is touched or pressed. TYPES OF PAINS Dental pains may have their origin in the dental pulps or the periodontal structures. So depends upon their origin classified in to two types. 1. Dental pains of pulps origin. 2. Dental pains of periodontal origin. The visceral character of pulpal pain is displayed particularly in its clinical behavior. The pulpal pain is of threshold type and no response occurs until the threshold level is reached. Pulpal pain is responding to noxious stimulus that is unrelated to ordinary masticatory movements, it responds to impact, shock, thermal and chemical irritants, but not to ordinary masticatory function. The pulpal pain is nearly non localizable by subject. Pulpal pain may be classified as acute, chronic, depends upon duration. Recurrent, mixed with periodontal ligament, and the pulpal pain does not remain the same indefinitely, generally it resolves, becomes chronic, or proceeds to involve the periodontal structures by direct extension through apex of the tooth root. PERIODONTAL ORIGIN Periodontal pain is deep somatic pain of the musculo skeletal type. As such it is more localized than pulpal (visceral pain and it is intimately related to masticatory Bio â€“ mechanical function.
6 The causes of periodontal pain are many and varied. It may occur as a primary periodontal inflammatory condition due to a local cause such as trauma, occlusal overstressing or contact with adjacent embedded tooth. (or) It may occur as a result of dental prophylaxis, endodontic treatment, and orthodontic therapy. But periodontal pain of all types presents no real diagnostic problem because the receptors present in the P.L are capable of precise localization of the stimulus, and this is true that cot can differentiate whether lateral or apical periodontitis by per cussing to the long axis of the tooth or to the long axis of tooth. MECHANISM OF PAIN Odontogenic pain is usually caused by either noxious physical stimuli e.g. (thermal, electrical, mechanical, chemical) or the release of inflammatory mediators that stimulate pain receptors located on the trigeminal nerve ending. There are two major classes of receptors. A - δ Fibers, C – Fibers. In tooth pulp there are at least 3 times to 8 times more unmyelinated “C” fibers as compared with A –δ fibers.
A - δ fibers,
associated with acute pain where as c- fibers associated with dull aching pain After activation of C and A- δ fibers Transmit pain signals via Trigeminal Nerve To the Trigeminal Nucleus Caudalis (Located in medulla) From medullary dorsal horn Pain signals transferred Higher center (Hypothalamus)
7 COMPONENTS OF PAIN Pain sensation has got components 1. Fast pain 2. Slow pain Receptors for both components of pain are the same, these are free nerve endings, but the afferent nerve fibers are different, the fast sensation carried by A - δ fibers, slow sensation carried by C type Nerve fibers.
FAST PAIN by Mechanical
SLOW PAIN and Produced by chemical stimuli
thermal stimuli Primary afferent neuron generally Generally are C fibers. is Aδ fibers Synapse in sub nucleus caudles
Neospino thalamic tract
gelationosa Carried by paleo spinothalamic
tract. to Fibers ascend through reticular
formation where pains modulated. Therefore be influenced by many
modulating inter neurons. are Nerve transmitter are substance P
acetylcholine or nor epinephrine endorphins Pain is easily localized as to exact Difficult locate and is felt as a location of origin is perceived by deep dull aching sensation. the individual sharp pain
PATHWAYS OF PAIN SENSATION
GG- Gassrieon Ganglion, Th- Thalamus, STM – Trigeminal spinal tract nucleus
RECEPTORS Stimuli ↓ Thermal, Chemical etc Free nerve endings (Distributed) through out body. ↓ A-δ, C fibers (afferent) ↓ Transmitting impulses to Substantia gelationosa in the posterior gray horn ↓ In the form of lateral spinothalamic tract ↓ These nerve fibers terminate in thalamus From thalamus pain sensation carried to cerebral cortex some fibers react to hypothalamus. The center for pain sensation is in the post central gyros of parietal cortex.
9 IN ACUTE PAIN Thalamus receive impulses from A-Î´ fibers and send it to the cortex for evaluation and response the motor cortex quickly co-ordinate a response with the basal ganglia and cerebellum, producing descending impulse to a motor neuron creating muscle action. Reticular formation has two areas. 1. Reticular facilitatory area. 2. Reticular Inhibitory area. RETICULAR FACILITATORY AREA Region contains group of neurons that secrete acetylcholine an excitatory transmitter and impulses are carried to the higher center. RETICULAR INHIBITORY AREA Located in the medulla, and reduces the tonic signals transmitted through the spinal cord by secreting serotonin. MANAGEMENT OF PAIN The effective management of pain is a hallmark of clinical excellence, the pain management is an integral part of endodontics and the practice of endodontic requires a thorough under standing of pain mechanisms and management. OPIOID AND NON-OPIOID ANALGESICS Established analgesic strategies using opioid and non-opioid analgesics provide practitioners with an effective means of controlling most patientâ€™s pain.
GENERAL CONSIDERATIONS IN DRUG SELECTION In 1986 an expert committee of the world health organization (WHO) proposed a useful approach to drug selection that has become known as the “analgesic ladder” this ladder can applicable to both. Cancer pains as well as acute, chronic and non-malignant pains. Because
pharmacological management is likely to be comparatively simple, where as the management of chronic pain is much more challenging and places considerably more demands on the practitioner. Analgesics should always be administrated orally when utilization of this route is possible.
Acetaminophen, acetylsalicylic acid, or other NSAID’S are employed first for mild to moderate pain.
If pain is not adequately controlled, if pain is moderate to severe, opioid should be employed along with the non-opioid analgesics, but at this stage use a low potency opioid. E.g. Codeine oxycodine, hydrocodine is used first.
If treatment pain is inadequate (or) patients presents with severe pain, a high potency opioid [morphine, hydromorphine) should be selected and prescribe along with the non-opioid analgesics.
NSAID ANALGESICS NSAIDS constitute a diverse group of compounds that differ in chemical structure however they share a variety of pharmacological properties, clinical actions and side effects.
The common pharmacologic profile is the result of a common mechanism of action for most NSAIDS. This is inhibition of inflammatory mediators, (or) prostaglandin synthesis. Most NSAIDS are derivatives of carboxylic acid and can be subdivide on the basis of chemical structure. Salicylates Indole derivatives Propionic acid derivatives Aryl acetic acid Sulfonamide Para amino phenol derivative
Aspirin Indo methacin Ibuprofen, Ketaprofen Diclofenac sodium Nimesulide. Paracetamol
PARACETAMOL Analgesic and poor anti-inflammatory drug adverse effects are common to NSAID drugs. Those are 1. Anti platelet activity. 2. Minimal gastric irritation. 3. Hepatotoxicity is of concern.
Acute overdose more than 10g/day produce liver injury.
Nausea, vomiting, diarrhea, Abdominal pain, shock, are early manifestations that may occur 4 to 12 hours after ingestion. If these side effects continue for 48 hours hepatic injury becomes apparent.
Mild to moderate pain with little inflammation.
It is often compounded with low – potency opioid for the relief of more severe pain.
It is recommended as an antipyretic and can be used for those sensitive to aspirin.
Oral route 500mg/every 6 hourly.
MECHANISM OF ACTION Most of the available NSAIDS inhibit cyclo-oxygenase, an enzyme that catalyzes the conversion of arachidonic acid to several types of prostaglandins. These prostaglandins usually generated by tissue trauma and mediate several components of the peripheral inflammatory response, including fever, vasodilatation.
Prostaglandins also mediate
nociception (pain) by sensitization of peripheral and central pain receptors in synergy with other chemical mediators, such as bradykinin histamine.
CELL MEMBRANE (Phospholipids) Corticosteriods inhibits ARACHIDONIC ACID NSAID’s inhibits Lipo-oxigenase
5-Hydroperoxyeicosa – tetraenoic acid
Cyclic Endo peroxidases
Thromboxane A2 Prostaglandins E2, I2 Prostocyclin I2 ACTIONS
INHIBITION Analgesia; Prevention of pain nerve ending. Antipyretic Anti inflammatory Anti thrombotic.
SHARED TOXICITIES DUE TO PG SYNTHESIS INHIBITION Gastric mucosal damage. Bleeding. Asthma, anaphylactic reaction in susceptible individuals. NSAIDS also have prostaglandins independent effects. These includes
migration, which contribute to there anti-inflammatory properties. PHARMACOKINETICS NSAIDS are rapidly absorbed from the gastro intestinal tract primary from the stomach. Following oral administration, adequate plasma levels are reached with in 30minutes and peak in approximately 2 hours levels gradually decline there after. Depending on the half- life of the agent. NSAIDS are highly protein bound and all are metabolized in liver and excreted in urine. ADVERSE EFFECTS An understanding of the adverse effects associated with the NSAD’S is vital to their appropriate use.
Three major problems commonly
encounter with the use of NSAIDS drugs.
GASTROPATHY NSAIDS are inhibiting the synthesis of prostaglandin these prostaglandins are participating in gastric mucosal cytoprotection and also help gastric Hco 3- serrations. So inhibition of these prostaglandins results in gastropathy.
14 HOMEOSTATIC DEFECTS Hemostasis is depending on prostaglandins synthesis by both platelets and endothelial cells. Aspirin irreversibly acetylates the active site of platelet cyclo-oxygenase; there by destroying its enzymatic ability, bleeding time will be altered until new platelets can be produced generally in 6 â€“ 10 days. By comparison the other NSAIDS reversibly inhibit platelet cyclo-oxygenase. Enzyme function is restored after the drug is cleared from the body. NEPHROTOXICITY NSAIDS
significant nephrotoxicity. Prostaglandins inhibit tubular reabsorption of sodium, water by antagonizing the effect of ADH hormone; NSAID can thus lead to fluid retention impaired responsiveness to diuretic therapy. DRUG INTERACTIONS / PREGNANCY It is probably best to avoid such medications during pregnancy, particularly during early stages of the first trimesters.
OPIOID ANALGESICS Treatment of pain of moderate to severe intensity generally requires
administration requires a sound understanding of opioid pharmacology as well as the characteristics of the commonly used agents.
15 OPIOID RECEPTORS The effect of exogenous opioid administration is based on interaction with receptors for endogenous opioid. These include met, leu, enkephalin β- endorphine. Interaction with opioid receptors mediates a broad spectrum of pharmacologic effects several receptors types have been identified to date, those are: µ, K, δ. OPIOID RECEPTORS. Receptor type µ1
Prototypic lingams Endogenous Exogenous Morphine β-
Proposed action Supra spinal anaesthesia Respiratory depression
CVS effects DOSAGE Drug Morphine Codeine Heroin OPIOID EFFECTS
10mg 130 mg 1 mg
30 mg 200 mg 10 mg
Duration of action 3 to 4 hours 2 to 4 hours 3 to 4 hours
Depends on the severity of action drugs divided in to week, and strong categories. Week opioids such as propoxyphene, codeine must be given in relatively large doses to have analgesic effects. Strong opioids are such as morphine and fentanyl. ANTIBIOTICS IN DENTISTRY Antimicrobial drugs are the greatest contribution of the present century to therapeutics.
16 DEFINITION OF CHEMOTHERAPY Defined as use of chemical compound in the treatment of infectious disease so as to destroy offending parasites or organisms without damaging the host tissue. ANTIBIOTICS Defined by Walksman Anti
These are chemical substances produced by microorganisms, which suppress the growth of or kill other organisms at very low concentration. SELECTION OF ANTIMICROBIAL AGENT Selection of most appropriate antibiotics requires knowledge of 1. The organism identity and its sensitivity to a particular agent 2. The site of the infection. 3. Safety of the agent. 4. Patient factor 5. The cost of therapy FAILURES OF CHEMOTHERAPY There are several reasons for failures of chemotherapy. Those are as follows:
Improper selection of a drug, dose, root of administration.
If treatment begun too late.
Failure to take necessary adjuvant measures. •
Example: Drainage of abscess
Poor host defence •
Trying to treat untreatable (viral) infections •
CLASSIFICATION OF ANTIMICROBIAL AGENTS Classification based on chemical structure
β - Lactum •
ACCORDING TO THE MECHANISM OF ACTION
Inhibit cell wall synthesis •
Inhibit protein synthesis •
Misreading of M-RNA
Interfere with DNA function •
ACCORDING TO TYPE OF ACTION
β – LACTUM ANTIBIOTICS These antimicrobial agents selectively interfere with the synthesis of bacterial cell wall.
The most important members of the group are
penicillin’s and cephalosporins. B-Lactum agents are the most widely used systemic antibiotic agents in the world. At present, the four β -Lactum antibiotics in use are Penicillin’s Cephalosporins Carbapenems
These are reserved for
Gram negative aerobes
PENCILLINS Discovered in 1928 by Alexander Fleming. Clinically used in 1941 by Chain and Florey. Obtain from fungus P. Notatum presently isolated
19 from mutant P. Chrysogenum. The penicillin’s are the most widely effective antibiotics and are among the least toxic drugs known but the major adverse reaction to penicillin is hypersensitivity. Penicillin is a generic term for a group of antibiotics similar in chemical structure but difference in 1.
Resistance to β-lactamase hydrolysis. Based on these properties, penicillin’s are usefully divided in to
three groups 1.
Extended spectrum penicillin’s
Natural penicillin’s: Penicillin G
Semi-synthetic Acid resistant Phenoxy Methyl Penicillin Phenoxy Ethyl Penicillin Pencillinase Resistant Methicillin, Oxacillin Cloxacillin Nafcillin
Extended spectrum Amino penicillin
Ampicillin, Amoxycillin, Bicampicillin
Carboxy penicillin →
Uriedo penicillin →
20 Amdino penicillin →
β-Lactamase Inhibitors Plus extended spectrum penicillin’s Clavulanic Acid Sulbactam
Anti staphylo coccal penicillin’s Methicillin Oxacillin Cloxacillin
MECHANISM OF ACTION Penicillin’s interfere with last step of bacterial ‘Cell Wall Synthesis’ and thus causes cell lysis. They are therefore bactericidal. The penicillin binding proteins present on the cell membrane, are enzymes involved in the synthesis of cell wall and in the maintainance of the morphological features of the bacteria and these penicillin binding proteins catalyze formation of cross linkages between peptidoglycan chains. Penicillin’s inhibits the trans-peptidase step, thus hindering the formation of cross-linking. This is essential for cell wall synthesis.
gram-positive bacteria cell wall is almost entirely made of peptidoglycan, which is 50 layers thick and extensively cross-linked. bacteria,
lipoprotein. This may be reason for higher susceptibility of the grampositive bacteria to Penicillin – G. Blood, pus, tissue fluids do not interference with the anti bacterial action of β- lactum antibiotics. PENICILLIN ‘G’ ANTIBACTERIAL SPECTRUM Effective against gram-positive cocci, Pneumococci, staphylococcus aureus.
21 Gram-negative cocci, N. gonorrhea, N. meningitides Gram-positive Bacilli, B.anthracis, C.diptheriae, C. Tetani. PHARMACOKINETICS Penicillin G’ is acid labile, destroyed by gastric acid, as such less than1/3rd of an oral dose is absorbed in the active form Plasma t½ is – 30 minutes Excreted through Urine DOSAGE 1.
Sodium, penicillin “G” (Crystalline Penicillin) Inj. 0.5 – 5mu/IM/ I.V, 6-12 Hours
Potassium penicillin G for oral uses 2-8 Lac Units, 1 hr before or, 2 hr after food.
Fortified procaine penicillin G Contain 3 Lac units procaine +1 Lac Units sodium penicillin G
DRAW BACKS ♦
Poor oral efficacy
Susceptibility of Pencillinase Enzyme
Pencillinase is an enzyme produce by some bacteria, which opens β-lactum rings, and inactivate penicillin “G” E.g.
E. Coli H-Influenza
Narrow spectrum of activity
HYPERSENSITIVITY These reactions are the major problem in the use of penicillin’s an incidence of 1-10% reported. Frequent manifestations are
Rash, Itching, Urticaria and fever, Anaphylaxis.
rare but it may be fetal. JARISCH – HERXHEIMER REACTION When penicillin injected in a syphilitic patient, (particularly secondary syphilis) may produce shivering, fever, myalgia, exacerbation of lesion even vascular collapse, this is due to sudden release of spirochetal lytic products and last in 12-72 hours. PHENOXY METHYL PENICILLIN (OR) PENICILLIN (V) Has spectrum similar to penicillin “G” it differ from penicillin G only in that it is acid stable, given orally it dissolves after reaching duodenum and produces higher plasma concentrations than the same amount of Penicillin-G given orally. Dose 250-500 mg given 6 hourly.
PENCILLINASE RESISTANT PENICILLIN These groups of penicillin’s have ability to protect the β-lactum ring from attack by staphylo coccal Pencillinase. There use is restricted to the treatment of infections caused by Pencillinase – producing staphylococci. gram-negative β-lactamase.
But they are not resistant to
23 METHICILLIN It is pencillinase resistant but not acid resistant, must be injected. CLOXACILLIN This drug is pencillinase resistant and acid resistant. DOSE 250mg to 500 mg orally every 6 hours. EXTENDED SPECTRUM PENICILLIN This semi synthetic penicillinâ€™s are active against a variety of gram-negative bacilli. AMPICILLIN It is active against all organisms sensitive to Penicillin-G and in addition to many gram-negative bacilli E.g., H. Influenza E.coli
DOSE E.g. 0.5-2g oral /IV/IM every 6 hours USES Urinary tract infection, Respiratory tract infections, gonorrhea, typhoid, septicemias etc.
24 ADVERSE EFFECTS Diarrhoea is frequent after oral administration.
Because it is
incompletely absorbed, the unabsorbed drug irritates the lower intestine, as well as causes marked alteration of bacterial flora. AMOXYCILLIN
Oral absorption is better,
Food does not interfere
Incidence of diarrhoea is less
DOSE 0.25 to 1g TDS Oral/IV/IM every 6 hours CARBOXY PENICILLIN’S Carbencillin are effective against Pseudomonas and Proteus but penicillin “G” is not effective against above organisms. This drugs neither penicillin resistant nor acid resistant, so given IM, 1-2 g every 4-6 hours. Amoxycillin is combined with Clavulanic acid.
This drug is
commercially available as augmentin. Use in severe infections. DOSE 125 to 250mg + TID (or) 200 to 1000 mg IM /IV CEPHALOSPORINS
These are a group of semi-synthetic antibiotics derived from cephalosporin “C” obtained from fungus “Cephalosporium”.
Chemically related to penicillin’s it contain β- lactum ring.
generation. Based on the 1. Bacterial susceptibility patterns 2. Resistance to β-lactamase FIRST GENERATION These are active against gram-positive bacteria but weaker against gram-negative bacteria. SECOND GENERATION More active against gram-negative organisms with some members active against anaerobes. THIRD GENERATION Very active against gram–negative and gram-positive, but no effect against anaerobes. FOURTH GENERATION Very effective against anaerobes. OTHER β – LACTUM ANTIBIOTICS Carba penems Mono bactums These were developed to deal with B-Lactamase producing gramnegative organisms, which were resistant to broad spectrum and extended spectrum penicillin’s. Carba penems are derived from the streptomyces species E.g. Imipenem
26 ADVERSE EFFECT Nausea, Vomiting,Neuro Toxicity MONO BACTUM This has an unusual spectrum being actively only against gramnegative aerobic rods. E.g. Haemophilus.
But no action against gram-
positive organisms (or) Anaerobes. AMINOGLYCOSIDS These are a group of antibiotics of complex chemical structure, resembling each other in antimicrobial activity; the main agents of this group are Gentamicin, streptomycin, Amikacin, Kanamycin, Neomycin, Fromycetin. MECHANISM OF ACTION Aminoglycoside inhibit bacterial protein synthesis they bind to sites on the 30’s subunit of the bacterial ribosome, causing an alteration in codon; anti-codon recognition.
This result in misreading of the
M-RNA results in the production of defective bacterial proteins. So their effect is bactericidal. ANTIBACTERIAL SPECTRUM ♦
Are effective against many aerobic Gram-negative and some grampositive organisms.
Streptomycin is very active against M. Tuberculosis.
Amino glycosides may be given together with a penicillin in infection caused by streptococcus, pseudomonas.
Gentamicin is the most commonly used aminoglycoside
27 1-1.5mg/kg I.M/I.V 8 hourly Fromycetin are too toxic for parental use and are only used topically. PRECAUTIONS AND INTRACTIONS
Avoid during pregnancy - Risk of fetus toxicity
Avoid concurrent use of other ototoxic drugs E.g.
High cieling diuretics
Avoid concurrent use of other nephro toxic drugs E.g.
Amphotericin B, Vancomycin.
Do not mix it with any drug in same syringe / infusion bottle.
PHARMACOKINETICS The amino glycosides are poly-cations, and highly polar. They are not absorbed in the gastro intestinal tract. So they usually given I.M (or) I.V. binding to plasma proteins are minimal, they do not enter cells, they reach high concentrations in secretions and body fluids. Plasma Half-life is 2-3 hours Elimination virtually by GFR UNWANTED EFFECTS Main hazards being ototoxicity nephro toxicity OTOTOXICITY
Involves progressive damage to and destruction of the sensory cells in the cochlea, vestibular organ of the body, which results in ataxia, loss of balance.
All amino glycosides product vestibular damage most commonly is streptomycin and gentamicin.
Cochlear damage results in deafness associated with Kananycin, Neomycin, and Amikacin.
NIPHRO TOXICITY Consists of damage to the kidney tubules and can be reversed if the use of the drug is stopped. Optic nerve dysfunction has been reported with use of streptomycin. MACROLIDES For the past 40 years erythromycin has been the only macrolide antibiotic.
Azithromycin are the
recent additions in macrolides. ERYTHROMYCIN It was isolated from streptomyces erythreus in 1952. MECHANISM OF ACTION Is inhibition of bacterial protein synthesis their action may be bactericidal
concentration. And the type of microorganism. The drugs are bound to 50â€™s ribosome results in misreading of M-RNA causes improper production of bacterial proteins. ANTI MICROBIAL SPECTRUM Is very similar to that of penicillin and it has proved to be a safe and effective alternative for penicillin sensitive patients, effective against gram-positive and spirochetes but not against most gram-negative organisms exception being Nisseria gonorrhea. PHARMACOKINETICS
29 Erythromycin base is acid labile; to protect it from gastric mucosa it
Erythromycin widely distributed in the body, it is 70-80% plasma protein binding, partially metabolized and excreted primarily in the bile. DOSE 250 â€“ 500 mg 6 hourly NEWER MACROLIDES In an attempts to overcome the limitation of erythromycin like narrow spectrum, Gastric intolerance Gastric acid lability Low oral bioavailability Poor tissue penetration ROXY THROMYCIN Semi-synthetic long
spectrum closely related to erythromycin. Average plasma Â˝ life: 12 hr It is alternative to erythromycin for ENT infections Skin, soft tissues, genital tract infection DOSE (150 mg BID, Adults) 50mG Kid Tab, BID AZITHROMYCIN This new generation of erythromycin has an expanded spectrum, improved pharmacokinetics.
It is more active than other macrolides against H. Influenza but less actives against gram positive cocci
High activity is exerted on respiratory pathogens E.g., Mycoplasma Chlamydia, Campylobacter
Primary indication Pharyngitis Tonsillitis Otitis, and Staphylococci streptococci skin and soft tissue infections.
DOSE 500mg / once daily COMPARISON OF MACROLIDES Erythromycin Clarithromycin Azithromycin GIT Disturbance
Food Affects absorption
I V use
Prolonged Tissue Level
Oral prophylactic regimens for dental procedure PROCEDURE Standard prophylaxis
Dose Adults 2 gm Children Orally
50 mg /kg hr
31 Allergic to penicillin
Children 20 mg, / kg orally or Adult
Children 15 mg / kg orally
procedure Adult 500mg, Children
15 mg / kg orally 1 hr before procedure
METRONIDAZOLE Metronidazole (flazyl) was introduced in to the anti-microbial pharmacopoeia in 1959 for the treatment of “Trichomonas Vulgaris” and was later used for infections caused by many anaerobic bacteria. It is rapidly and almost completely absorbed when given orally and is relatively inexpensive; also it is used as I.V especially for serous anaerobic
Metronidazole is distributed well in to bone, saliva, mucosa, and even brain abscess. It is bactericidal and although its spectrum of activity is confined narrowly to anaerobes of odontogenic infections caused by prevotella, fuso-bacterium porphyromonus, along with β-Lactum (penicillin) is necessary to ensure adequate microbial killing.
Because a most
odontogenic infections are poly-microbial including aerobic of anaerobic species. However, more than 90% of obligate anaerobes are susceptible to metronidazole, but Actinomyces, propionibacterium are not sensitive. The mechanism of action is it kills the organism by damaging DNA. ADVERSE EFFECTS
Side effects are relatively frequent but mostly non-serious.
Anorexia, nausea, metallic taste Headache Glossitis Dryness of mouth (very rarely).
Prolonged administration may cause peripheral neuropathy and central nervous system effects.
INTERACTIONS A disulfiram like intolerance to alcohol occurs among patients taking metronidazole they should be instructed to avoid drinking. USES
200, 400 mg / BID
CLINDAMYCIN Clindamycin is a chemical modification of lincomycin, which was first isolated in 1962. SPECTRUM OF ACTIVITY BACTERIA Gram +ve Aerobes
RESISTANT Methicillin resistant
S. Aureus Gram -ve
Pepto streptococcus Actinomyces
33 Gram -ve
C. Difficile Prevotella
porphyromonus Fusobacterium bacteroides
It is an ideal anti-microbial drug for odontogenic infections.
It is also logical substitute for cephalosporins.
Clindamycins readily absorbed from GI-tract, food des not interfere, half-life is 2-4 hours.
It moves rapidly from serum in to tissues and penetrates well in to bone joints, soft tissue and saliva.
ADVERSE EFFECTS Fever, Rash, Anaphylaxis (rarely), Neutropenia, Thrombocytopenia and Neuropathy. VANCOMYCIN It is a glyco-peptide originally isolated form a soil specimen obtained in borneo. It is used primarily against penicillin resistant staphylococci organisms.
Poorly absorbed by oral route and reaches high concentration in the intestine, which makes it useful in the therapy of C. difficile (Colitis)
Intra muscular is very painful, IV route is preferred
Useful against gram-positive organism seen in oro facial Infections, Including streptococci, Staphylo cocci, Corny bacterium, Actinomyces.
It is drug of choice against Methicillin resistant staphylococci organisms.
It is used as a prophylactic anti microbial agent in High-risk prosthetic valve patients who undergo intraoral procedures.
QUINOLONES They are entirely synthetic antimicrobials primarily against gram – negative bacteria. The first member of quinolone is Nalidaxicacid it is introduced in mid 1960’s. MECHANISM OF ACTION
Quinolones inhibit the enzyme bacterial DNA gyrase.
Bactericidal action probably results from digestion of DNA by exonucleases whose production is signaled by the damaged DNA.
Nalidaxicacid acid Oxalinic acid
E. coli, Klebsiella Proteus
Enterobacteriae P. Aeruginosa
P. Aeruginosa Staphylococcus
Same as above
All of above organisms mentioned.
Nalidaxicacid acid the first oral quinolone was used primarily in urinary tract infections. Serum concentration is low so it could not be used successfully in infection in other body sites. NO ACTIVE AGAINST ♦
Gram +ve, (or) anaerobes, and are no value in the therapy for common odontogenic infections.
Second generation Quinolones contain fluorine, which enhance their antimicrobial activity.
Ciprofloxin is active against staphylococcus and pseudomonas but no activity against anaerobes, so limit usefulness in odontogenic infection they are useful against bacterial dysentery.
streptococci, drawback is causes photosensitivity skin reaction. ♦
Trovafloxacin (Trovan) is the newest and most promising fourth generation
fluoroquinolones is its expended activity against streptococci bacteria. ♦
Which makes it attractive as therapeutic option in odontogenic infections.
It has increased Bioavailability activity is not altered by food ingestion
It is absorbed rapidly after oral dosing its serum half life is 10hrs (make once daily dosing possible)
Dose is 100-200 mg / kg
Drawback is hepatotoxicity.
BROAD SPECTRUM ANTIBIOTICS TETRACYCLINES Tetracyclines are obtained from soil actinomycetes. The first to be introduced was chlortetracycline in 1948 under the name “Aureomycin’. All tetracyclines are slightly bitter solids, which are weakly water soluble, on the basis of chronology of development they may be divided in to 3 groups Group – I
Group – II
Group – III
Tetracycline MECHANISM OF ACTION ♦
Primary bacteriostatic; inhibit protein synthesis by binding to 30s ribosome’s.
When originally introduced tetracyclines inhibited practically all type of pathogenic organisms except fungi and viruses.
37 The older tetracycline’s are incompletely absorbed from G.I.T, Absorption is better if taken in empty stomach, doxycycline and Minocycline are completely absorbed irrespective of food. Tetracycline’s
Tetracyclines along with milk and antacids DOSAGE Widely distributed in body and bind to calcified tissues of bones and teeth oral capsule is the dosage form in which tetracycline are most commonly administered the capsule should be taken 1/2hr before (or) 2 hr after food. DOSE Doxycycline 100mg BID 1st day followed by 100mg 12-24 hrs, tetracycline 250 -500 mg QID. Minocycline 200mg initially followed by 100 mg BID. ADVERSE EFFECTS
Gastric irritation, discoloration of teeth → Chelating properties
Tetracyclines have chelating property and its chelate with calcium and gets deposited in developing teeth and bone, when given mid pregnancy to 5 months of extra uterine life. The Deciduous teeth are affected and result in brown discoloration, these teeth more susceptible to caries.
Kindly damage → fancony syndrome
Should avoid during pregnancy, lactation
Avoid in patients on diuretics
Do not mix injectable tetracycline with penicillin results inactivation.
CHLORAMPHENICOL Initially obtained from streptomyces Venezuelae in1974. MECHANISM OF ACTION
Inhibits bacterial protein syntheses
Antimicrobial spectrum these drugs are bacteriostatic though high concentration has been shown to exert bactericidal effects.
These drugs are effect against salmonella typhus but resistant strains are now rampant.
AVDERSE EFFECTS A plastic anaemia and hemolytic anaemia these mainly due to bone marrow depression.
GRAY BABY SYNDROME Baby stops feeding and vomits become hypotonic and hypothermic it occurs because of inability of newborn to adequately metabolize and excreted chloramphenicol. SULPHONAMIDES Were first antimicrobial effective against pyrogenic bacterial infections.
MECHANISM OF ACTION Many bacteria synthesize their own folic acid of which paminobezoic acid (PABA) is a constituent and is taken up from the medium.
Hypothesis regarding sulfonamide action which is wild
accepted sulfonamides, being structural analogues of PABA, inhibit bacterial folate synthetaze and folic acids is not found and a number of essential metabolic reaction suffer. COTRIMOXAZOLE Combination of trimethoprim sulphamethoxozole PABA Sulfonamide
folate synthetaze ↓ DHFA
Dihydro folate reductase ↓ THFA
Individually, Trimethoprim Sulphamethoxozole is Bacteriostatic DRAW BACKS
RATIONALE BEALIND ANTIBIOTIC USAGE
40 To serve in the best interest of our patients and profession, it is imperative that we not only know which antibiotic has to be employed; but more importantly we should be judicious enough to realize whether there is any needing one et al? Thus the rationale behind the use of antibiotic in endodontics should be based up on the following three core criteriaâ€™s: ď‚§
Whether antibiotics are indicated in a given endodontic infection? The cardinal rule one should remember is that antibiotics are
designed primarily to control active microbial infections, not for preventing the possibility of infections, unless the patient is medically compromised.
The common objective behind prescribing antibiotics
during an endodontic infection is to kill the infection present in the pulp space and / or the peri apical area many of us fail to understand that, for antibioticâ€™s to kill the susceptible bacteria, the systemic antibiotic has to be carried by the blood circulation in to the pulp space to come in direct contact with the bacteria in an infected or necrosed pulp this does not happen as the blood supply in such case is highly constrained and restricted. Thus the role of antibiotics in infections restricted to the pulp space is minimal if any.
In case of periapical pathoses, it is very
important to appreciate that most chronic endodontic periapical lesions are not infected lesions but are inflammatory lesions; in periapical inflammation, bacteria may or may not be present in the periapical tissues, as it is not an infectious process, the inflammation is mostly caused by the bacterial toxins, their harmful metabolic by products or disintegrating pulp tissue from the root canal the periapical tissue also endowed with powerful natural and specific defense mechanisms hence elimination of irritants, especially pathogenic bacteria in the root canal by careful chemo mechanical debridement is for more effective than antibiotics in preventing flare-ups and treating chronic endodontic periapical lesions.
When to advocate prophylactic antibiotic? Active microbial infections with manifestation of local and
systemic signs and symptoms such as diffuse swelling with sinus discharge, fever, malasie lymphadenopathy and elevated white cell count.
Preventing the possibility of any infection following bacteremia
in high-risk patients. Indication for prophylactic coverage
Prosthesis cardiac valves
Pervious bacterial endocarditis
Complex, cyanotic CHF
Rheumatic heart disease
Uncontrolled diabetic mellitus
Mitral value relapse
following the chemo mechanical debridement of pulp space in high-risk patents.
Choosing the right antibiotic? Selecting the right antibiotic dentist should have knowledge about
microbiology because most of the endodontic infections caused by gramnegative anaerobic bacteria, however most infections are usually controlled with appropriate antibiotics in 7 to 10 days. CONCLUSION A thorough understanding of pharmacology of antibiotics is essential for successful use in treating and preventing of infections. Many dentists routinely prescribe antibiotics to prevent the possible
42 development of pain of swelling during endodontic therapy; this is being done more out of tradition rather than with any some scientific knowledge; the future value of antibiotics in treating life threatening infectious disease may be diminished or eliminated if they are used indiscriminately.
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