Drugs in endodontics and operative dentistry

CONTENTSINTRODUCTION

DEFINITIONS

PHARMACODYNAMICS

PHARMACOKINETICS

DRUG NOMENCLATURE

ROUTES OF DRUG ADMINISTRATION

ABSORPTIONKINETICS OF ELIMINATIONFACTORS MODIFYING DRUG ACTIONDRUGS IN ENDODONTICS - ANTIANXIETY DRUGS - ANALGESICS * Opioid Analgesics * Non Opioid Analgesics -ANTIBIOTICS IN ENDODONTICS - LOCAL ANAESTHETICS DRUGS IN OPERATIVE DENTISTRY - ANTI SIALOGOUGES - STYPTICS CONCLUSION REFERENCES

Introduction

What is a drug?

any chemical agent which effects any biological process WHO 1966, Drug is any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipientWhat is Pharmacology?

the study of how drugs effect a biological system

What is Pharmacology ?The study of how drugs effect biological systemsPharmacokinetics Pharmacodynamics What the body does to drug What the drug does to bodyPharmacotherapeutics Pharmacocognosy The study of the use of drugs Identifying crude materials as drugsToxicology

PharmacodynamicsWhat the drug does to the body

Physiological and biochemical effects of drug and their mechanism of action at organ system or subcellular or macromolecular level

Dose response curve

Dose response curve...

PharmacokineticsWhat the body does to the drugMovement of the drug in and alteration of the drug by the body; includes absorption, distribution, binding or localization or storage, biotransformation and excretion of the drug.

Pharmacodynamic agents

Chemotherapeutic agents

t1/2 (Half-Life)- the time required for the plasma concentration of a drug to be reduced by 50%ED50 (effective dose)- The dose of a drug that is effective for 50% of the population exposed to the drugLD50 (lethal dose)- the dose at which death occurs in 50% of subjectsTherapeutic index = Median lethal dose (LD50) Median effective dose (ED50)Clinical set up-bounded by drug producing minimal therapeutic effect and dose producing maximal adverse effect

Drug Nomenclature*Chemical name- Propranolol 1-(isopropylamino)-3-(1-naphthyloxy) propranolol*Nonproprietary name- Competent scientific body- USAN, BANEx-Meperidine (USA) & Pethidine( UK, India)

*Proprietary name ( Brand name)- Accepted by manufacturer & is his property or trademarkEx- Atenolol ALTOL, ATECOR, BETACARD, ATEN, ATCARDIL, , LONOL, TENOLOL, TENORMIN

Routes of Drug Administration I) LOCAL ROUTES 1) Topical 2) Deeper tissues 3) Arterial supply

II) SYSTEMIC ROUTES 1) Oral 2) Sublingual or buccal 3) Rectal 4) Cutaneous 5) Inhalation 6) Nasal 7) Parenteral - subcutaneous - Intramascular - Intravenous - Intradermal injection

Oral absorption (enteral route)Advantages

Disadvantages

Parenteral routeRoutes of administration other than oral route termed as parenteralAdvantagesDisadvantages

Absorption Absorption is the movement of drug from its site of administration into the circulation Oral absorption-

Non ionized lipid soluble drugs-

Acidic drugs-

Basic drugs-

Bioavailability It refers to the rate and extent of absorption of a drug from a dosage form as determined by its concentration time curve in blood or by its excretion in urine IV Bioavailability is 100%, it is frequently lower after oral ingestion bcozThe drug incompletely absorbed First pass metabolism in intestine or liverChemically equivalent but Biologically in equivalent Bioavailability has practical significance in drug with low safety margin

First pass (Presystemic) metabolism This refers to metabolism of a drug during its passage from the site of absorption into the systemic circulation

Attributes of drugs with high first pass metabolismOral higher than S.L/ Parentral dose Individual variation Increased in patients with severe liver diseasesIncreased if another drug competeting with it in first pass metabolism is given concurrently

Ex- Chlorpromazine and Propranolol

Kinetics of eliminationDrug elimination is the sum total of metabolic inactivation and excretionFIRST ORDER KINETICS (Eponential)ZERO ORDER KINETICS ( Linear) PLASM HALF LIFE-

It is the time taken for its plasma concentration to be reduced to half of its original value

Factors modifying drug action1) Body size Individual dose=2) Age child dose=

Child dose=

BW (Kg) 70X Average adult doseAgeAge +12X Adult dose (YOUNGS FORMULA)Age20X Adult dose

(DILLINGS FORMULA)

3) Elderely4) Sex5) Species and race6)Genetics7) Routes of administration8) Environmental factors and time administration 9) Psychological factors Placebo- This is an inert substance which is give in the garb of medicine. It works by Psychological rather than pharmacological means and often produces responses equivalent to the active drug

Anti anxiety drugsAnxiety- it is an emotional state, unpleasant in nature, associated with uneasiness, discomfort and concern or fear about some defined or undefined future threat.

Antianxiety- these are ill defined group of mild CNS depressants which are aimed to control the symptoms of anxiety, produce a restful state of mind without interfering with normal mental or physical functions. Sedatives- the drug that subdues the excitement and calms the subject without inducing sleep though drowsiness may be produced

Hypnotic- a drug that induces and or maintains sleep similar to normal arousable sleep

Oral benzodiazepinesCLASSIFIACTION-Long acting with active metabolites single adult dose (mg) t- half life(Hours) Diazepam 2-10 14-100Chlordiazepoxide 5-10 5-30Halazepam 20-40 14-65Flurazepam 15-30 -Parazepam 5-10 - Clorazepam 7.5-1.5 -

Medium to short acting with no active metabolites

single adult dose Elimination half lifeTriazolam 0.125-0.25 1.5-5.5Temazepam 15-30 9-38Alprazolam 0.25-0.5 12-15Lorazepam 2-3 10-20 Oxazepam 10-15 5-20Estazolam 1-2 10-24Quazepam 7.5-15 30-100

Pharmacological actionsPreparation-1960

Pharmacodynamics-AntianxietySedative-hypnoticAnticonvulsantAmnesic Skeletal muscle relaxantInduce anterograde amnesia Mechanism of action- Facilitates inhibitory action of gamma aminobutyric acid (GABA)

ADVERSE REACTIONS Few n mildExcessive CNS depressionDrowsinessSomnolenceDecreased motor coordination, Impaired intellectual functions other are - CNS depressant synergism - Release of anxiety bound hostility - acute overdosage - excerberation of porphyria

Pharmacology of painTwo components of pain -Pain perception, and Pain reaction Pain perception is the reasonably objective component of the pain phenomenon

Pain reaction is the emotional response to the percieved injury and its painful manifestation

Analgesics- Opiates-

Opioid analgesics-

Narcotic analgesics-

Classification 1.Natural opium alkaloids - Morphine, Codeine

2.Semisynthetic opiates - Diacetylmorphine(Heroin), Pholcodeine many others like- Hydromorphone, Oxymorphone, Hydrocodeine, Oxycodone, are not used in India 3. Synthetic opioids- Pethidine, Fentanyl, Methadone, Dextroprpxyphene, Tramadol, Ethoheptazine

Morphine *Source- natural opium alkaloid milky exudate of unripe capsules of poppy plant, papaver somniferum a) Phenanthrene group- Morphine, Codeine and Thebaine. b) Benzylisoquinoline group- Papaverine, Noscapine, Narcine

Pharmacological actions1) Analgesia-

2) CNS-

3) Respiration-

4) Pupil-

5) Emetic action-

6) Antitussive effect

7) ADH secretion-

8) GIT- 9) Biliary tract-

10) Other smooth muscles-

Absorption, fate and excretion-

Preparation and dose 1. tincture opium 0.3 to 2 ml by mouth 2. morphine sulphate- 3. morphine hydrochloride 8 to 20 mg by mouth or by injectionAdverse reactions 1.Dysphoria, mental clouding 2.Nausea, vomiting, rashes 3. Tremor, delirium, and skin rashes 4. acute morphine poisoning- resp. depression, pin point pupil, cyanosis, reduced body temp, hypotension, shock and coma5. Depression of foetal respiration6. Tolerance and drug dpendenance

Therapeutic uses 1.analgesic 2. sedation and slep 3. pre-anaesthetic medication 4. acute LVF5. Diarrhoeae6. As antitussive

Narcotic Analgesics in Dentistry

Codeine, hydrocodone, oxycodone, and pentazocine. Employed exclusively for pain relief NOT anti-inflammatory

Combinations of opioids such as codeine and aspirin or acetaminophen are commonly employede.g Oxycodone (related to codeine - but 6-fold more potent)(Percocet -- contains acetaminophen) (Percodan -- contains ASA)

Comments related to use of narcotic analgesics in dentistryDRUG INTERACTIONS Other CNS depressants will increase the degree of respiratory depression with opioids Opioids and phenothiazines produce at least additive CNS depression. This combination may also increase orthostatic hypotension, as can opioids and tricyclic antidepressants. Respiratory acidosis caused by large doses of opioid agonists may increase entry of local anaesthetics into the CNS Well documented interaction between meperidine and MAO inhibitors - severe and immediate reactions - include excitation, rigidity, hypertension, and sometimes death.

CLASSIFICATION (Acc. to Tripathi) A. Analgesic and antiinflammatory :Aspirin, Salicylamide, Benorylate, DiflunisalPhenylbutazone, oxyphenbutazonePyrazolone derivatives Indomethacin, sulindacIndole derivatives Ibuprofen,Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen.Propionic acid derivatives Mephenamic acid Anthranilic acid derivativeDiclofenac, Tolmetin Piroxicam, Tenoxicam, Meloxicam.Oxicam derivatives Ketorolac.NImesulideSulfonanilide derivative NabumetoneAlkanones Aryl acetic acid derivativePyrrolo pyrrole derivativeSalicylates

B. Analgesic but poor antiinflammatory:Paracetamol (Acetaminophen)Paraaminophenol derivative Metamizol (Dipyrone), propiphenazone Pyrazolone derivatives NefopamBenzoxazocine derivative Acc. to Goodman and Gillman A. Non selective Cox inhibitor Aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salfasalazine, olsalazine. Salicylic acid derivatives Acetaminophen Para amino derivatives Indomethacin, sulindacIndole & indene acetic acid Tolmetin, diclofenac, ketorolac. Heteroaryl acetic acid

Ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, oxaproxin. Aryl propionic acid Mefenamic acid, meclofenamic acid Anthranilic acid (fenamates) Oxicams (piroxicam, Meloxicam) Enolic acid Nabumetone. Alkanones RofecoxibDiaryl substituted furanones B. Selective cox-2 inhibitor Celecoxib Diaryl substituted Pyrazoles Etodolac Indole acetic acid NimesulideSulfonanilides

MECHANISM OF ACTION Odontogenic pain Acute pain Noxious stimuli Tissue destruction or injury Cellular destruction Release / synthesis of histamine / prostaglandin / bradykininPeripheral nociceptor / free nerve endings PAIN+Disease process +Surgical intervention

Phospholipid of cell membrane

Arachidonic acid

Prostaglandins InflammationCOX-1COX-2

Beneficial actions due to PG Synthesis inhibition Analgesia Antipyresis Antiinflammatory Antithrombotic Closure of ductus arteriosus

Shared toxicities due to PG synthesis inhibition Gastric mucosal damage Bleeding Limitation of renal blood flow Delay / prolongation of labour Asthma & anaphylactoid reactions

COMMON PROPERTIES OF ALL NSAIDS AnalgesiaAntipyresisAnti-inflammatoryDysmenorrhoeaAntiplatelet aggregatory Ductus arteriosus closureParturition Gastric mucosal damageRenal effectsAnaphylactoid reactions

SALICYLATES Aspirin (prototype) Pharmacological actions Analgesic (0.3-1.5 g/day) Antipyretic RespirationGITAntiinflammatory (3-6 g/day or 100mg/kg/day) Immunological effectUricosuric effectCVSBloodEndocrinesMetabolic effectLocal actions

2-5 g/day 5g/day

Pharmacokinetics 80% bound to plasma proteins.Volume distribution 0.17 L/kg. Plasma t = 15-20 min. Release salicylic acid (t ) = 3-5 hrs. Antiinflammatory doses (t ) = 8-12 hrs. (30 hrs in poisoning)

Adverse effects Salicylism : dizziness, tinnitus, vertigo, reversible impairment of hearing imbalance& vision, excitement & mental confusion, hyperventilation & electrolyte Acute salicylate poisoning : fatal dose-15-30g , > 50 mg/dl.

Contraindications :Sensitivity, peptic ulcers, bleeding tendency, chicken pox or influenza. Chronic liver disease Diabetics, low cardiac reserve or frank CHF, juvenile rheumatoid arthritis. Precautions :Stopped 1 week before elective surgery. During pregnancy Avoided by breast feeding mothers. G-6-PD deficient individuals

Interactions : Warfarin, naproxen, sulfonylureas, phenytoin and methotrexate. Oral anticoagulants. Uric acid Probenecid Methotrexate. Furosemide and thiazides Spironolactone. Protein bound iodine levels.

Uses :Analgesic Antipyretic Acute rheumatic fever (4-6 g)Rheumatoid arthritis (3-5 g) Osteoarthritis Postmyocardial infarction & poststroke patientsPregnancy induced hypertension and preeclampsiaDelay labourPatent ductus arteriosus * Aspirin, dispirin, colosprin

PYRAZOLONES Phenylbutazone Pharmacokinetics 98% bound to plasma proteins.Plasma t = 60 hrs. Dose 100-200 mg BD/TDS

Interactions : Sulfonamides, tolbutamide, warfarin, imipramine & methotrexate AnticoagulantsPhenytoin & tolbutamide

OxyphenbutazoneMetamizol (Dipyrone) : 0.5-1.5 gPropiphenazone : 300-600 mg TDSSioril, phenabidAnalgin, novalgin Saridon, anafebrin

Adverse effects

Uses :Rheumatoid arthritis Ankylosing spondylitisPsoriatic arthritisAcute goutAcu. Exa. destructive arthropathiesMalignancy asso. feverPatent ductus arteriosus closure (0.1/0.2 mg/kg/12 hrlyP L Indicin, indocap

PROPIONIC ACID DERIVATIVES Pharmacokinetics 90-99% bound to plasma proteins.

DrugPlasma t Dosage Ibuprofen 2 hr400-800 mg TDSBrufen, emflam Naproxen12-16 hr250 mg BD/TDSXenobid, naxidKetoprofen2-3 hr100 mg BD/TDSKetofen Fenoprofen2-4 hr300-600 mg TDSArflur Flurbiprofen4-6 hr50 mg BD/QIDFlurofen

Adverse effects

Uses :Analgesic Antipyretic Dysmenorrhoea

Adverse effects

ARYL-ACETIC ACID DERIVATIVES Diclofenac sodium :Pharmacokinetics 99% bound to plasma proteins.Plasma t = 2 hrs50 mg TDS/BD, 75 mg i.m.

Uses :Ankylosing spondylitisOsteoarthritisDysmenorrhoea Rheumatoid arthritis Bursitis Post-traumatic / post-op inflammatory conditionTolmetin : 400-600 mg TDSVoveran, diclonac, movonac

OXICAM DERIVATIVES Piroxicam Pharmacokinetics 99% bound to plasma proteins.Plasma t = 2 days20 mg BD / 20 mg OD

Uses :Ankylosing spondylitisOsteoarthritisDysmenorrhoea Rheumatoid arthritis Acute goutMusculoskeletal injuries DentistryEpisiotomy Tenoxicam : 20 mg ODMeloxicam : 7.5-15 mg/day (rheumatoid & osteo-arthritis) Dolonex, pirox, piricam, toldinP L Melflam, Meloxi

PYRROLO-PYRROLE DERIVATIVE Ketorolac :Pharmacokinetics Highly bound to plasma proteins.Plasma t = 5-7 hrs10-20 mg / 6 hrly (orally)

Uses :Post-op / acute musculoskeletal pain (15-30 mg i.m. / 4-6 hrsRenal colicBony metastasis Migraine Ketorol, torolac

Adverse effects

PARA-AMINO PHENOL DERIVATIVESPhenacetin 1887 Paracetamol (acetaminophen) 1950Actions Pharmacokinetics 1/3 bound to plasma proteins.Plasma t = 2-3 hrs3-5 hrs (orally)0.5-1g TDSInfants - 50 mgChildren 1-3 yrs- 80-160 mg 4-8 yrs 240-320 mg 9-12 yrs 300-600 mg

Adverse effects Analgesic nephropathyAcute paracetamol poisoning150 mg/kg Fatality > 250 mg/kgEarly manifestations / 12-18 hrs / 2 days

Mechanism of toxicityTreatment Gastric lavageN-acetylcysteine 150 mg/kg / i.v./ 15 min / 20 hrs75 mg/kg / orally / 4-6 hrs / 2-3 days

BENZOXAZOCINE DERIVATIVE Nefopam 30-60 mg TDS oral20 mg i.m. 6 hrlyNefomax

Exacerbation of rheumatoid arthritis, ankylosing spondylitis, acute gout, acute rheumatic fever aspirin, indomethacin, naproxen, piroxicamAsthma or anaphylactoid reactions to aspirin nimesulide

ADVANCES Selective cox-2 inhibitors : Celecoxib, rofecoxib, valdecoxib, etoricoxib, meloxicam, diisopropyl flurophosphate.Action CelecoxibP L Use-osteoarthritis, rheumatoid arthritis Dose 200 mg / day OD or 100 mg BD. Commercial names Celebrex, Celib, Celfast, Celact etc. Banned July 2001 Rofecoxib P L Dose 12.5 mg OD (max. dose 25 mg) Commercial name Vioxx, Dolib MD, Roff, Rofaday Banned September 2004

Valdecoxib Dose 10-20 mg ODCommercial name Valed, Valus, Vorth, Bextra Banned 7 April 2005.Other drugs banned by FDA BenoxaprofenPhynylbutazoneOxyphenbutazoneSaprofenPiroxicam

PAIN MANAGEMENT STRATEGY 3Diagnosis efinitive Rxrugs Definitive treatment : Pulpotomy, pulpectomyExtractionIncision & drainage

Drug : Pretreat with NSAIDsPrescribe by clock Long acting LAFlexible prescription plan

Flexible analgesic prescription planAspirin like drugs indicated Aspirin like drugs contra indicated Ibuprofen 200 mgAcetaminophen 600-1000mgNSAIDs (alone max.effective dose) OR NSAID + acetaminophen Acetaminophen 600-1000 mg + codine 60 mg Ibuprofen 400 mg/4 hrly and equivalent of acetaminophen 600 mg / codine 60 mg 4 hrly Acetaminophen 1000 mg with equivalent of oxycodone 10 mg NSAID (max. dose) & acetaminophen / oxycodone 10 mg combination Mild painModerate painSevere pain

Analgesics after certain endodontic procedures

ANTIBIOTICS

Antimicrobial agent : substances that will suppress the growth / multiplication of microorganisms. antimicrobial agents may be antibacterial, antiviral / antifungal. Antibacterial agent : substances that destroy or suppress the growth / multiplication of bacteria. They are classified as antibiotic or synthetic agents.

Antibiotic agent : against life (greek-anti means against and biosis means life). Chemical substances produced by microorganisms that have the capacity in dilute solutions, to produce antimicrobial action.

CLASSIFICATION OF ANTIMICROBIAL DRUGS Mechanism of action :Inhibit cell wall synthesisPenicillinsCephalosporinsVancomycinBacitracin Cause leakage from cell membranes Polypeptides Polymyxins, colistin, BacitracinPolyenes Amphotericin B, Nystatin

Inhibit protein synthesis TetracyclinesChloramphenicolErthromycin,ClindamycinLinezolidCause misreading of m-RNA code and affect permeabilityAminoglycosides StreptomycinGentamicin

Inhibit DNA gyrase Fluoroquinolones Ciprofloxacin Interfere with DNA functionRifampinMetronidozoleInterfere with DNA synthesis IdoxuridineAcyclovirZidovudineInterfere with intermediary metabolismSulfonamidesPAS Sulfones Ethambutol

B) Chemical structure Sulfonamides and related drugsSulfadiazine and othersSulfones Dapsone (DDS), Paraaminosalicylic acid (PAS).Diaminopyrimidines TrimethoprimPyrimethamineQuinolonesNalidixic acidNorfloxacinCiprofloxacin etc

-lactam antibiotics PenicillinsCephalosporinsMonobactamsCarbapenemsTetracyclinesOxytetracyclineDoxycycline etcNitrobenzene derivative Chloramphenicol

AminoglycosidesStreptomycinGentamicinNeomycin etcMacrolide antibioticsErythromycinRoxithromycinAzithromycin etcPolypeptide antibioticsPolymyxin-BColistinBacitracinTyrothricin

GlycopeptidesVancomycinTeicoplanin OxazolidinoneLinezolidNitrofuran derivativesNitrofurantoinFurazolidoneNitroimidozoles MetronidozoleTinidazole

Nicotinic acid derivativesIsoniazidPyrazinamideEthionamide Polyene antibioticsNystatinAmphotericin-BHamycin Azole derivatives MiconazoleClotrimazoleKetoconazolefluconazole

Others RifampinLincomycinClindamycinSpectinomycinSod. fusidateCycloserineViomycinEthambutolThiacetazoneClofazimineGriseofulvin

C) Type of organisms against which primarily activeAntibacterial PenicillinsAminoglycosidesErythromycin etcAntifungal GriseofulvinAmphotericin BKetoconazole AntiviralIdoxuridineAcyclovirAmantadineZidovudine etc

AntiprotozoalChloroquinePyrimethamineMetronidazoleDiloxanide etcAnthelminticMebendazolePyrantelNiclosamideDiethyl carbamazine etc

D) Spectrum of activityNarrow spectrumPenicillin GStreptomycinErythromycinBroad spectrumTetracyclinesChloramphenicol

E) Type of actionPrimarily bacteriostatic SulfonamidesTetracyclinesChloramphenicolErythromycinEthambutolPrimarily bactericidal PenicillinsAminoglycosidesPolypeptidesRifampinCotrimoxazoleCephalosporinsVancomycinNalidixic acidCiprofloxacin

F) Antibiotics are obtained from FungiPencillin CephalosporinGriseofulvinBacteriaPolymyxin BColistinBacitracinTyrothricinAztreonam Actinomycetes AminoglycosidesTetracyclinesChloramphenicolMacrolidesPolyenes

Misconception about antibioticsImproper choice- drug, dosage, duration of therapyIgnorance of Microbial biologyAntibiotics- safe & do no harmAntibiotics prophylaxis commonly successfulTo mask poor surgical procedure I dont know what else to do syndromeMalpractice negligence suit

Myths in antibiotic theapyI. Antibiotic cure patientsII. Antibiotics are substitute for surgical drainageIII. The most important decision is which antibiotic use IV. Antibiotic therapy is a science and not an artV. Culture and sensitivity are required VI. Antibiotics increase host defence to infectionVII. Multiple antibiotics are superior to a single antibiotic

VIII. Antibiotic prophylaxis is usually effectiveIX. Bactericidal agents are always superior to bacteriostatic agentX. Antimicrobial are effective in chronic infectious diseases XI. Antibiotics are safe and nontoxicXII. Antibiotic dosage are established for most infectionsXIII. Infection require a complete course of therapy

BETA LACTAM ANTIBIOTICS Pencillins Most important antibiotics first extracted from the mould PENICILLIUM NOTATUM First used in 1941 clinically and was a miracle drug with a least toxic effect.

CLASSIFICATION OF PENICILLINS Natural penicillin Penicillin G (benzyle penicillin)Procaine penicillin GBenzathine penicillin G Acid resistant penicillinPhenoxymethyl penicillin (pencillin V)Phenoxyethylpenicillin (phenethecillin)Penicillianse resistant penicillinsAcid labile methecillin, nafcillin, cloxacillin, dicloxacillinAcid resistant flucloxacillin

Penicillins effective against gram positive and some gram-negative organismsAmpecillinAmpoxycillinTalampicillin Extended spectrum penicillinsCarboxypenicillins carbenicillin, ticarcillinUreidopencillins piperacillin, mezlocillinAmidino pencillins mecillinam, pivmecillinam Penicillins with betalactamase inhibitorsAmoxycillin clavulanic acid (Augmentin)Ticarcillin clavulanic acid (Timentin)

BENZYL PENICILLIN (PENCILLIN G)PnG is a narrow spectrum antibiotic; activity is limited primarily to gram positive bacteria Is available in the form of water soluble sodium and potassium saltsThis salts in a dry state are stable at room temperature for years. The aqueous solution however requires refrigeration and deteriorates considerably with in 72 hours.Antibactrial activity Most potent AMA, inhibits the growth of susceptible organism.Mainly gram +ve, gram ve cocci and some gram +ve bacilli with exception of enterococci.Cocci Highly sensitive Streptococci, Pneumococci, Staph. aureus, N. gonorrhoeae, N. meningitis Bacilli B. anthracis, Corynebacterium diphtheriae, clostridium tetany and spirochetes Actinomyces israelii is moderately sensitive

Mechanism of action :Bactericidal drug effective mainly against multiplying organisms.Pencilline requires cell wall that contains peptidoglycans. Peptidoglycan is heteropolymeric component of cell wall provides rigid mechanical, crosslinked lattice like structure. Penicillin binding to this proteins are bacterial enzymes on the cell wall are responsible for synthesis and cross linkage of peptidoglycans in the cell wall. Penicillins bind to these proteins and inactivate them, thereby preventing the synthesis and cross linkage. This weakens bacterial cell wall and makes organism vulnerable to damage. As the cell wall synthesis occurs during the growth phase the antibiotic is more effective against actively multiplying organisms.

Absorption fate and excretion :About 1/3 of drug is activated on oral administration.Absorbed from the duodenum.Because of the inadequate absorption the oral dose should be 4/5 times larger than the intramuscular dose.As food interferes with its absorption PnG should be given orally atleast 30 min after food or 2 to 3 hours before food. B. Pencillin in aqucous solution is rapidly absorbed after SC or IM administration. Peak plasma level of 8 to 10 units per ml is reached with in 15 to 30 min and drug disappears from plasma with in 3-6 hours.

Widely distributed in the body and significant amounts appear in liver, bile, kidney, jointfluid and interstine.PnG is excreted mainly by the kidney but in small part in the bile and other routes.50% drug is eliminated in urine with in first hour.Preparation and dose :PnG inj 0.5-5 MU i.m or i.v 6-12 hoursProcaine pencillin inj 0.5, 1 MU dry powder in vialPenidure 0.6, 1.2, 2.4 MU as dry powder in vialFortifide PP inj 3+1 lac U vial

ADVERSE REACTIONS :Miscellaneous reactions :Nausea and vomiting on oral PnGSterile inflammatory reaction at the site of IM inj.Prolonged IV administration may cause thrombophlebitisAccidental IV administration of procaine PP cause anxiety, mental disturbances paraesthesia and convulsions Intolerance :Major problem with PnG includes idiosyncratic, anaphylactic and allergic reactions

Other allergic reactions are Skin rashes Serum sicknessRenal disturbance Hemolytic disturbanceAnaphylaxisJarisch herxheimer reactionSuper infectionHyperkalemiaAcute non allergic reaction

Uses :PnG is the drug of choice for infectionsStreptococcal infectionsPneumococcal infectionsMeningococcal infectionsGonorrhoea Syphilis Diphtheria Tetanus and gas gangreneProphylactic uses

SEMI SYNTHETIC PENCILLINS The major drawbacks of benzyl pencillin are :Inactivation by the gastric hydrochloric acidShort duration of actionPoor penetration into CSFActivity mainly against gram +ve organismPossibility of anaphylaxisAttempts therefore have been made to synthesize pencillin free from such drawbacks.P.chrysogenum produces natural penicillins which produce the 6 amino-penicillanic acid (6-APA) nucleus. The attachment of side chains are inhibited and instead various organic radicals can be substituted. Thus a variety of semisynthetic resins are produced.

I) Acid resistant pencillins :1. Potassium phenoxymethyl penicillin (penicillin V)Similar antibacterial spectrum like benzylpenicillin.More active against resistant staphylococciLess inactivated by the gastric acid.Plasma levels achieved is 2 to 5 times higher than benzylpenicillin.50-70% is bond to plasma proteins.25% of drug is eliminated in urineAvailable as 60 & 125 mg tablets.Administered in the dose of 250 500 mg at 4-8 hours intervals, atleast 30 min before food.This can be used in less serious infections (pneumocci and streptococci).

Dose : infants 60 mg, children 125-250 mg given 6 hourlyCRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg tablets125 mg/5 ml dry ser

2. Potassium phenoxyethyl penicillin and 3. Azidocillin Both have similar properties to penicillin V and no difference in the antibacterial effect

II) Pencillinase resistant pencillins :Methicillin Effective in staphylococciIt is given IM or IV (slow) in the dose of 1 gm every 4-6 hours.Haematuria, albuminuria and reversible interstitial nephritis are the special adverse effect of methicillin. Cloxacillin Weaker antibacterial activity.Distrubuted thro out the body, but highest s concentration in kidney and liver. 30% excreted in urine.Oral dose for adults 2-4 gm divided into 4 portions children 50-100mg/kg/day.IM adults 2-12 gm/day, children 100-300 mg/kg/day every 4-6 hours. BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.

Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl penicillins, similar to cloxacillin, but not marketed in India. Nafcillin :More active than methicillin and cloxacillin but less active than PnG80% of drug bonds with plasma proteins excreted by liver in patients with renal failure.Dose is similar to cloxacillin.

III) Extended spectrum pencillins :Amino pencillins Ampicillin Antibacterial activity is similar to that of PnG that is more effective than PnG against a variety of gram-ve bacteria Drug is effective against H.influenzae strep.viridans, N.gonorrhea, Salmonella, shigellae, Klebsilla and enterococci.Absorption, fate and excretion :Oral absorption is incomplete but adequateFood interferes with absorption Partly excreted in bile and partly by kidney

Dose : 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours Children : 25-50 mg/kg/dayAMPILIN, ROSCILLIAN, BIOCILIN 250, 500 mg cap 100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj. USES :Urinary tract infectionsRespiratory tract infectionsMeningitis GonorrhoeaTyphoid feverBacillary dysentrySepticaemiasSBE

Adverse effects :Diarrhoea is frequent Skin rashes is more commonUnabsorbed drug irritates lower interstinesPatient with history of hypersensitivity to PnG should not be given ampicillin.

AMOXYCILLIN :This is a semisynthetic penicillin (amino-p-hydroxy-benzylpencillin)Antibacterial spectrum is similar to ampicillin but less effective than ampicillin for shigellosis.Oral absorption is better; food does not interfere; higher and more sustained blood levels are produced.It is less protein bond and urinary excretion is higher than that of ampicillin.Incidence of diarrhoea is less

Dose : 0.25-1 g TDS oral; AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.

USES :TyphoidBronchitis Urinary infectionSBEGonorrhoea

Carboxy penciillins :The Carboxypenicillins, the Ureidopenicillins and the Amidino penicillins are considered extended spectrum penicillins, because they inhibit a wide variety of aerobic gram-ve bacilliThey are ineffective against most strains of staph. AureusThey have following properties :Highly active against anaerobesMost useful in infections caused by other gram-ve rodsAct synergistically with amino glycoside antibiotics, particularly enterobacteriacea.Much less active than penicillin G against gram+ve organismsThe CNS penetration is about 10% of their serum levels and hence not recommended for the treatment of meningeal infections.

CARBENICILLIN Has similar spectrum as other penicillin Weaker antibacterial activity than ampicillinActive against pseudomonas, proteusInactive against klebsiella and gram ve cocciAcid labile and has to be given by parenteral route onlyPeak plasma level is 2hours and excreted in urine

Dose : 1-2g im/iv 4-6hoursAdverse effects :Cause congestive heart failure Bleeding disorders-impaired platelet functionUses :Pseudomonas ,burns, UTI and septicemiaPYOPEN,CARBELIN 1g,5g per vial

BETA LACTAMASE INHIBITORSCLAVULANIC ACID Obtained from STREPTOMYCES CLAVULIGERUSBetalactam ring no antibacterial activitySuicide inhibitor inactivated after binding to enzymePermeates the outer layers of cell wall of gram-ve bacteria

Pharmacokinetics :Oral absorption- rapidBioavailability-60%Distribution similar that of amoxicillinExcretion-tubular secretionUses :Amoxicillin+clavulanic acid (augmentin)Ticarcillin+clavulanic acid (timentin)Staph aureus,H influenza, gonorrhoea and E coli

Adverse effects :Poor g.i. tolerance HepatotoxicityAUGMENTIN, AMONATE, ENHANCIN250+125mg tab 1-2tab TDS 250+50mg vial im/iv 6-8 hourly

SULBACTAMSemisnythetic betalactamase inhibitorRelated chemically in activity to clavulanic acid Progressive inhibitor ,highly active against betalactamase2-3 times < potentOral absorption- inconsistent,preferably im/ivSulbactam+ ampicillin=DicapenSULBACIN, AMPITUM 1g+ 0.5g per vial im/iv 6-8hourly1g+500mg tab

Adverse effects :Pain-thrombophebitisRashes and diarrhoeaUses :Mixed aerobic-anaerobic infectionsGonorrhoeaSkin/soft tissue infections

CEPHALOSPORINS Cephalosporium acremonium was the first source.They contain 7 amino cephalosporonic acid nucleus. Structurally they contain betalactam and didhydro thiazine rings. Mechanism of action : Act by inhibiting bacterial cell was synthesis and are bactericidal. New derivatives are much more resistant than the older cephalosporins

Classification Classified according to its antibacterial activity. First generation cephalosporin Good activity against gram +ve bacteria. (except enterococci). Most oral cavity anaerobes are sensitive.Parental Oral CEPHALOTHIN CEPHALEXINCEFAZOLINCEPHRADINE CEFADROXIL

Cephalaxin and Cephadroxil : Useful in treating community acquired, respiratory and urinary tract infections and in surgical prophylaxis. Not choice for systemic infections. Cefazolin : For antimicrobial prophylaxis in most surgical procedures. Given only IM / IV. Dose: Oral 0.25 - 1g 6-8 hrly Children : 25-100mg/kg/day IM 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases). Drops cephaxin 125mg/5ml syrup. 100mg /ml ped. drops.SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, DROXYL

Second generation cephalosporins : Increased activity against gram ve organism. More active against anaerobes. Parenteral Oral CEFUROXIME CEFACLOR CEFOXITIN CEFUROXIME AXETIL Cefaclor and cefuroxime axetil retains significant by oral route. More active against H. influenzae, E coli.Dose : 250mg, 125mg, 125mg/5ml syr. and 50 mg /ml ped. drops. KEFLOR, CEFTUM, CEFOGEN, FUROXIL.

Third generation cephalosporin : They highly augmented against gram ve enterobacter and pseudomonas. Highly resistant to -lactamase from gram ve bacteria. Less active on gram +ve cocci Parenteral Oral CEFOTAXIME CEFIXIME CEFTIZOXIME CEFDINIR CEFTRIAXONE CEFTIBUTEN CEFTAZIDIME CEFOPERAZONE Dose : 100, 200 mg tab/cap.100mg/5ml syr., 50mg/ml susp. CESPAN, CEFOPROX, PROCADAX, CEPODEM, ORFIX.

Fourth generation cephalosporins : Developed in 1990 similar to that of 3rd generation.Highly resistant to -lactamases. Active against many bacteria resistant to earlier drugs. It has high potency and extended spectrum. Effective in many serious infections.Parenteral CEFEPINE, CEFPIROME USES : Serious and resistant hospital acquired infections. Septicaemia, Lower respiratory tract infection.Dose : 1-2g IM / IV 12 hrly. CEFROM, CEFORTH 1g inj.

Guiding principle for the use of cephalosporins : Cephalosporins are expensive and should not be used where an equally effective, alternative antibiotic is available. None of them is effective against infections by enterococci. None of them is agent of choice of anaerobic infections. Except for cefotaxine, ceftriazone, the CNS penetration of cephalosporins is poor. General features of cephalosporins Most of them given by oral route IM can cause pain so IV is given. Mainly excreted by kidney.Dosage is altered in patients with renal insufficiency. Most cephalosporins penetrate CSF so useful for the treatment of meningitis.

Adverse reactions : Local reactions cause pain (IM) and cause thrombophlebitis (IV) Allergy skin rashes Super infection Nephrotoxicity CNS toxicity Blood toxicity Intolerance to alcohol Cross reactivity with penicillin

Uses : Alternatives to pencicillins. RTI, UTI and soft tissue infection Penicillinase producing staph infection. Septicaemias. Surgical prophylaxis Meningitis, gonorrhoea Typhoid Mixed aerobic and anaerobic infections Infection by odd organism or hospital infections Prophylactic treatment in neutropenic patients.

MACROLIDESThey are called macrolides because they contain a many membered lactone ring to which are attached one or more deoxy sugars. Clarithromycin differs from erythromycin only by methylation of the hydroxyl group at the 6 position, and Azithromycin by the addition of a methyl substituted nitrogen atom into the lactone ring.

Antibacterial activity :Narrow spectrum antibioticBacteriostatic but bactericidal at higher concEffective against penicillin resistant staphylococciActive against gram+ve cocci and bacilliPharmacokinetics :Erythromycin base - acid labileGiven with enteric coated - incomplete absorptionIts acid stable esters are better absorbedWidely distributed in body Metabolised in liverExcreted through kidney and bile

Dose :Adults 250 - 500mg 6hrlyChildren 30 60mg/kg/dayErythromycin base - ERYSAFE 250 mg tabEROMED - 333mg tab, 125/5ml suspErythromycin stearate ERYTHROCIN 250,500mg tab 100mg/5ml susp100mg/ml ped drops

Adverse effects :GIT epigastric pain On high doses hearing impairmentHypersensitivity reactions rareUses :Substitute for penicillinWhooping cough ChancroidPenicillin resistant infections

CLINDAMYCINIt is lincosamide antibiotic having similar action (macrolide 50s)Semisynthetic derivative of Lincomycin Bacteriostatic low concBacteriocidal high conc Most active against gram+ve cocci, C.diphtheriae, Actinomyces Highly active against anaerobes (B fragilis)Pharmacokinetics :Oral absorption goodDistribution skeletal and soft tissuesExcreted in urine

Adverse effects :Rashes UrticariaAbdominal pain SuperinfectionEnterocolitis DiarrhoeaUses :Anaerobic and mixed infectionsDoses : 150-300 mg QID oral ; 200-600mg I.v. 8 hourlyDALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml and 600 mg/4ml inj.

TETRACYCLINESTetracyclines are napthacene derivatives.The napthacene nucleus is made up by fusion of 4 partially unsaturated cyclohexane radicals and hence the name tetracyclines.Tetracyclines are bacteriostatic.

On the basis of chronology of development, convenience of description, divided into 3 groups.Group IGroup IITetracyclineDemeclocylineOxytetracyclineMethacycline Group IIIDoxycyclineMinocyclineMechanism of action :Tetracyclines are thought to inhibit bacterial protein synthesis by binding to the 30 S bacterial ribosome and preventing the access of aminoacyl tRNA to the acceptor (A) sites on the mRNA ribosome complex.

Antimicrobial activity :Gram+ve and ve cocci are sensitive Gram+ve bacilli are inhibitedEntero bactereae are highly resistantSpirochetes and Borrelia are quite sensitive All rickettsiae and chlamydiae are highly sensitive Pharmacokinetics :Incompletely absorbed from GITAbsorption is impaired by iron or zinc salts[due to chelation of cations]They cross the placenta and enter fetal circulation and amniotic fluid Widely distributed in liver ,bone marrow and spleenThey accumulate in dentine and enamel of unerupted teeth Primarily excreted in urine through kidney

Adverse effects :GIT-epigastric burning, nausea, vomiting,diarrhoeaHepatoxicityRenal toxicityEffects on teeth-Orthophosphate complexThrombophlebitisHypersensitivity Reactions SuperinfectionAntianabolic effect

Dose :Tetracycline 1-2g per day in adultsChildren over 8yrs -25 to 50mg /kg daily in 2 to4 divided doses Doxycyline 100mg,12hrs first day followed by 100mg once a dayChildren over 8yrs 4-5mg /kg/day divided into 2 equal doses during first 24hrsTERRAMYCIN, RESTECLIN-250,500mg cap,50mg/ml in10ml vial injDOXT, NOVADOX, TETRADOX-100mg cap.

Precaution :Not to be used in pregnancy, lactation and in childrenAvoided in patients on diureticsUsed cautiously in renal and hepatic insufficiencyDo not mix injectable Tc with Pn- inactivation occursUses :Mixed infectionsVenereal diseasesAtypical Pneumonia, Cholera, Brucellosis, Plague,Rickettsial infectionsAlternate to Pn/Ap, Ciprofloxacin,AzithromycinOther situations UTI,amoebiasis, chronic lung disease

QUINOLONES These are entirely synthetic antimicrobials having a quinolone structure that are active primarily against gram ve bacteria.These are quinolone antimicrobials having one or more fluorine substitutions.

Mechanism of action :The FQs inhibit the enzyme bacterial DNA gyrase, which nicks double stranded DNA.The DNA gyrase consists of two A and two B subunits; A subunit carries out nicking of DNA, B subunit introduces ve supercoils and then a subunit reseals the strands.First generation FQs :Norfloxacin OfloxacinCiprofloxacinPefloxacinSecond generation FQs :LomefloxacinLevofloxacinSparfloxacinGatifloxacinMoxifloxacin

CIPROFLOXACINFirst generation FQ active against a broad range of bacteria especially gram ve aerobic bacilli.Highly susceptible : E coli, shigella, N meningitis, K pneumoniae, Proteus, H influenza, Enterobacter, V. cholerae, S. typhi, N gonorrhoea.Moderately susceptible :Staph aureus, brucella, M. tuberculosis

Microbiological features :Rapid bactericidal activity and high potency.Relatively long post antibiotic effect on enterobacteriaceae pseudomonas and staph.Low frequency of mutational resistance.Low protective intestinal streptococci and anaerobes are spared.Active against many lactam and amino glycoside resistant bacteria.Less active at acidic pH.Phramocokinetics :Rapidly absorbed on oral, food delays absorption.High tissue penetration, concentration in lung sputum, muscle, bone. Excreted primarily in urine.

Adverse effect :GIT Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent.CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures are rare.Skin/hypersensitivity rashes, pruritis, urticaria.Tendonitis and tendon ruptureUses :UTIGonorrhoeaChancroidBacterial gastroenteritisGr-ve septicaemiasProphylaxisTyphoidBone, soft tissue, wound infection.RTITuberculosisMeningitisConjunctivitis

CIFRAN, CIPLOX, CIPROBID, CIPROLET 250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops.

ANTIAMOEBIC AND OTHER ANTIPROTOZOAL DRUGS METRONIDAZOLE :It is the prototype nitroimidazole and found to be highly active amoebicide.Antiprotozoal activity :Broad spectrum cidal activity against protozoa and anaerobic bacteria such as B fragilis, Fusobacterium.Metronidazole is selectively toxic to anaerobic microorganisms. Metronidazole has been found to inhibit cell mediated immunity and cause radiosensitization.

Pharmacokinetics :Completely absorbed from the small intestine. Widely distributed in the body It is metabolized in liver primarily by oxidation and glucuronide conjugation, and Excreted in urine.Adverse effects :Side effects relatively frequent but mostly not serious,Anorexia, nausea, metallic taste and abdominal cramps are the most common.

Looseness of stool is occasional,Headache, glossitis, dryness of mouth, dizziness, rashes and transient neutropenia.Prolonged administration may cause peripheral neuropathy and CNS effectsSeizures have followed by high doses.Thrombophebitis of injected vein.Contraindications :In neurological disease, blood dyscrasias, first trimester of pregnancy, chronic alcoholism.

Uses :AmoebiasisGiardiasisTrichomonas vaginitis.Anaerobic bacterial infectionsPseudomembranous enterocolits.Ulcerative gingivitisHelicobacter pylori gastritis/peptic ulcerGuinea worm infestation.FLAGYL, METROGYL, METRON, ALDEZOLE 200, 400 mg tab, 200 mg/5ml susp.

TINIDAZOLE It is an equally efficacious congener of metronidazole, similar to it in every way except. Metabolism is slower. Incidence of side effects is lower. Metallic taste, nausea, rashes TINIBA, TRIDAZOLE, 300, 500, 1000 mg tab, 800 mg/400 ml I.V.

Role of antibiotics in endodontics (jr of Dent 26 (2001) 539-48)I ENDODONTICS AND THERAPEUTIC ANTIBIOTICS 1) Adjunct to operative treatment 2) Contingency treatment 3) Antibiotics at Obturation 4) Antibiotics for perio-endo lesion 5) which antibiotic II TOPICAL ANTIBIOTICS AND ENDODONTICS 1) Pulpitis 2) Pulp capping 3) Root canal therapy 4) Flare- ups 5) Perio endo lesion 6) Tooth avulsionIII ANTIBIOTIC PROPHYLAXIS AND ENDODONTICS

What are local anesthetics?Local anesthetic: are agents which block conduction impulses in nerves. When applied locally, they produce loss of sensation in the desired area.

Classification INJECTABLE SURFACE ANAESTHETIC Low potency, short duration Soluble Procaine Cocaine Chloroprocaine LidocaineIntermediate potency and duration Tetracine Lidocaine (Lignocaine) Insoluble Prilocaine BenzocaineHigh potency, long duration Butylaminobenzoate Tetracaine Oxyethazine Bupivacaine Ropivacaine Dibucaine

Mechanism

Local anesthetics block the conduction in peripheral nerves that inhibited the nerve to excited and created anesthesia.

The anesthetic is a reversible reaction. It binds and activates the sodium channels.

Pharmacological actions1) Effect on sensation: Block pain and temperature, later they produce loss of sensation for touch and pressure

2) CNS- stimulation-euphoria, restlessness and tremors3) CVS- All LA except, cocaine produces vasodilatation and so hypotension. Cocaine produces vasoconstriction and so hypertensive effect4) other actions- relaxant effect on smooth muscles and NM blockade

Absorption, fate and excretionLA not absorbed through intact skin. But absorption occur through mucous membranes.They are usually administered through S.C. administration. Vasoconstrictors like adrenaline prolong their action LA metabolised in the liver and plasma by hydrolysis

Adverse reactions1) Dermatitis, asthmatic attack and anaphylactic reactions2) Cardiovascular symptoms like hypotension and cardiac arrest3) Central effect like euphoria, excitation, restlessness, tremors, and convulsions

Therapeutic uses1) Surface anaesthesia2) Infiltration anaesthesia 3)Nerve block anaesthesia4) Spinal anesthesia5) Systemic use

LidocaineIn 1940, the first modern local anesthetic agent was lidocaine, trade name XylocaineIt developed as a derivative of xylidineLidocaine relieves pain during the dental surgeriesBelongs to the amide class, cause little allergenic reaction; its hypoallergenicSets on quickly and produces a desired anesthesia effect for several hoursIts accepted broadly as the local anesthetic in United States today

Antimuscarinic drugsNatural alkaloids (and derivatives)Atropine (Sal-Tropine)Scopolamine (Scopace, Transderm-Scop)Synthetic quaternary ammonium drugsGlycopyrrolate (Robinul)Propantheline (Pro-Banthine)Ipratropium (Atrovent)Other synthetic drugsBenztropine (Cogentin)Tolterodine (Detrol)

Pharmacologic effects:atropine as a prototype

Dose

(mg)

Effects

0.5

Slight cardiac slowing; some dryness of mouth; inhibition of sweating

1.0

Dryness of mouth; thirst, mild tachycardia; mild pupillary dilation

2.0

Tachycardia; palpitation; marked dryness of mouth; dilated pupils; some blurring of vision

5.0

All above more marked; difficulty in speaking, swallowing; headache; fatigue; dry, hot skin; urinary, GI inhibition

10+

All above more marked; ataxia; excitement; delirium; coma

Therapeutic usesAntisialogogues for dentistry

Drug

Dose (mg)

Onset time

Atropine sulfate

(Sal-Tropine)

0.4-1.2

0.5-1 hr

Scopolamine HBr

(Scopace)

0.4-0.8

0.5-1 hr

Glycopyrrolate (Robinul)

1-2

0.5-0.75 hr

Propantheline Br

(Pro-Banthine)

7.5-30

0.5-0.75 hr

Astringents and styptics:Used in our restorative clinic for bleeding control prior to impressions and placements of subgingival restorations. Mechanism of action: denatures blood and tissue proteins, which then agglutinate and form plugs that occlude the capillary orifices.

-Nephrostat-active ingredient is 25% aluminum chloride-Viscostat-active ingredient is 20% ferric sulfate

Vasoconstrictor- epinephrine (epinephrine solution and dry cotton pellets impregnated with racemic epinephrine are available for topical application)- tetrahydrozoline (0.5%) and oxymetazoline (0.5%)

CONCLUSIONThe up-to-date dentist, and the endodontist in particular, must be prepared to handle any pharmacologic exigency. One must know not only actions and reactions to drugs but also indications and contraindications, as well as side effects, toxicity, half life, any interaction the newly prescribed drug may have with other drugs the patient may be taking

REFERENCESEndodontics 5thedn. John I Ingle. K.D. Tripathi 4 th edn.Endodontic Therapy 6th edn.Franklin S. Weine.Endodontics Cohen. Role of antibiotics in endodontics. (jr of Dent 26 (2001) 539-48)Pathways of the pulp 9TH edn.