ENDODONTIC PHARMACOLOGYENDODONTIC PHARMACOLOGYASHA REDDYASHA REDDY

CONTENTSCONTENTS IntroductionIntroduction Antibiotic therapy in management of infectionsAntibiotic therapy in management of infections a- definitiona- definition b- principles of therapyb- principles of therapy c- principles of antibiotic selectionc- principles of antibiotic selection d- principles of antibiotic administrationd- principles of antibiotic administration ClassificationClassification a- based on chemical sructurea- based on chemical sructure b- type of organisms on which it actsb- type of organisms on which it acts c- bacteristatic/ bacteriocidalc- bacteristatic/ bacteriocidal d- chemotherapeutic spectrad- chemotherapeutic spectra Mechanism of actionMechanism of action Antibiotics commonly used in endodonticsAntibiotics commonly used in endodontics PenicillinsPenicillins CephalosporinsCephalosporins QuinolonesQuinolones TetracyclinesTetracyclines MacrolidesMacrolides Antifungal agentsAntifungal agents Antiviral agentsAntiviral agents Antibiotic Prophylaxis for Heart and Artificial Joint PatientsAntibiotic Prophylaxis for Heart and Artificial Joint Patients Analgesics used in endodonticsAnalgesics used in endodontics IntroductionIntroduction DefinitionDefinition PropertiesProperties Classification of PainClassification of Pain Pain PathwaysPain Pathways Management of painManagement of pain OpioidOpioid Non-opioidNon-opioid a- classificationa- classification b- mechanism of actionb- mechanism of action Anti-anxiety DrugsAnti-anxiety Drugs Other drugs Other drugs Root-canal IrrigantsRoot-canal Irrigants Intra-canal medicamentsIntra-canal medicaments Mummyfing agentsMummyfing agents StypticsStyptics ReferencesReferences

PHARMACOLOGY:PHARMACOLOGY: science of drugs and their interaction with the living systemsscience of drugs and their interaction with the living systems

DRUG (Def) (WHO) - a drug is defined as any substance or product that is DRUG (Def) (WHO) - a drug is defined as any substance or product that is used or intended to be used to modify or explore physiological systems or used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipientpathological states for the benefit of the recipient

Drugs are important in Endodontics to fight against Drugs are important in Endodontics to fight against 1. infections1. infections 2. pain2. pain 3.anxiety3.anxiety

ANTIBIOTIC THERAPY ANTIBIOTIC THERAPY IN MANAGEMENT OF INFECTIONSIN MANAGEMENT OF INFECTIONS Bacterial pathways to the pulp:Bacterial pathways to the pulp: 1. caries1. caries 2. periodontal disease2. periodontal disease 3. fractures3. fractures 4. dentinal tubules not covered 4. dentinal tubules not covered 5. Anachoresis5. Anachoresis Pulpal invasion begins with a mixed infection of aerobes and Pulpal invasion begins with a mixed infection of aerobes and anaerobesanaerobes As oxygen is depleted obligate anaerobic bacteria and As oxygen is depleted obligate anaerobic bacteria and facultative bacteria predominate.facultative bacteria predominate. Primary goal of endodontic treatment is to eliminate a Primary goal of endodontic treatment is to eliminate a hospitable place for microorganisms to grow.hospitable place for microorganisms to grow. 1. debridement of canal should be as thorough as possible1. debridement of canal should be as thorough as possible 2.total obturation of the space to close off the path for oral 2.total obturation of the space to close off the path for oral

bacteria to reach beyond the apexbacteria to reach beyond the apex 3. use of sterile technique to avoid introducing any new 3. use of sterile technique to avoid introducing any new

microbesmicrobes

But in situations where infections exist beyond the root canal it But in situations where infections exist beyond the root canal it is advisable to use systemic antibiotics.is advisable to use systemic antibiotics. Chemotherapy- is defined as the use of synthetic, Chemotherapy- is defined as the use of synthetic, semisynthetic, and naturally occuring chemicals that selectively inhibitsemisynthetic, and naturally occuring chemicals that selectively inhibit specific organisms causing disease.specific organisms causing disease.

ANTIBIOTICSANTIBIOTICS are antibacterial agents which are used to kill bacteria are antibacterial agents which are used to kill bacteria

without damage to the host.without damage to the host. 1. more appropriate term is antimicrobial agents1. more appropriate term is antimicrobial agents 2.they are obtained naturally as well as synthetically2.they are obtained naturally as well as synthetically

DefinitionsDefinitions Antimicrobials – are substances that kill or suppress the growth Antimicrobials – are substances that kill or suppress the growth or multiplication of microorganisms, either bacteria, viruses, fungi, or or multiplication of microorganisms, either bacteria, viruses, fungi, or parasites.parasites. Antibiotics – substances produced by microorganisms or by Antibiotics – substances produced by microorganisms or by synthetic chemical methods that have the capability to produce an synthetic chemical methods that have the capability to produce an antibacterial action.antibacterial action.

Principles of therapyPrinciples of therapy Presence of infectionPresence of infection State of host defensesState of host defenses Surgical drainage and incisionSurgical drainage and incision Presence of infection: Presence of infection: –– Local Signs of infection: pain, swelling, erythema, pus Local Signs of infection: pain, swelling, erythema, pus formation, and limitation of motion should be noted.formation, and limitation of motion should be noted.–– Systemic signs : fever, lymphadenopathy, malaise, toxic Systemic signs : fever, lymphadenopathy, malaise, toxic appearance, and leucocytosis.appearance, and leucocytosis. Non-infectious conditions:Non-infectious conditions:–– Removal of third molar, major surgeries of the maxillofacial Removal of third molar, major surgeries of the maxillofacial region – lead to swelling and pain.region – lead to swelling and pain. In the above conditions proper diagnosis plays a very In the above conditions proper diagnosis plays a very important roleimportant role State of host defenses:State of host defenses:–– Host defense mechanisms are the most important factor in the Host defense mechanisms are the most important factor in the final outcome of bacterial insult.final outcome of bacterial insult.–– It is provided by the white blood cells and antibodies produced.It is provided by the white blood cells and antibodies produced.–– It is necessary to evaluate the state of host defense It is necessary to evaluate the state of host defense mechanism.mechanism.–– Infections are ultimately cured by host than antibiotics is critical.Infections are ultimately cured by host than antibiotics is critical.–– Antibiotics help in conditions where the host has been Antibiotics help in conditions where the host has been overwhelmed by bacteria. overwhelmed by bacteria. Surgical drainage and incision :Surgical drainage and incision :–– It is an established principle of treatment of deep tissue It is an established principle of treatment of deep tissue infections.infections.

–– The objective is to drain pus from tissue spaces and to insert The objective is to drain pus from tissue spaces and to insert drains so that no pus accumulates in these spaces.drains so that no pus accumulates in these spaces.–– In odontogenic infections – removal of tooth, opening of the In odontogenic infections – removal of tooth, opening of the pulp chamber.pulp chamber.–– Surgical incision – in cellulitis without pus formation.Surgical incision – in cellulitis without pus formation.

Principles of antibiotic selectionPrinciples of antibiotic selection–– Identification of the causative organism.Identification of the causative organism.–– Determination of antibiotic sensitivity.Determination of antibiotic sensitivity.–– Use a specific, narrow spectrum antibioticUse a specific, narrow spectrum antibiotic–– Use the least toxic drug.Use the least toxic drug.–– Bacteriostatic vs Bactericidal.Bacteriostatic vs Bactericidal.–– Use of antibiotic with a proven history of success.Use of antibiotic with a proven history of success.–– Cost of the antibiotic.Cost of the antibiotic.–– Encourage patient compliance.Encourage patient compliance.

Identification of the causative organism:Identification of the causative organism: Can be done by isolating the organism from pus, blood, or Can be done by isolating the organism from pus, blood, or tissue.tissue. Antibiotic therapy is then either initial or definitive.Antibiotic therapy is then either initial or definitive. Initial empirical therapy may be started if the following criteria Initial empirical therapy may be started if the following criteria are met: are met: –– Site and features of infection are well defined.Site and features of infection are well defined.–– The circumstances leading to infection are known.The circumstances leading to infection are known.–– the organism/s causing the disease are known.the organism/s causing the disease are known. The typical odontogenic infection – aerobic and anaerobic The typical odontogenic infection – aerobic and anaerobic bacteria.bacteria.–– Approx 70% - mixed floraApprox 70% - mixed flora–– 25% - pure anaerobic25% - pure anaerobic–– 5% -aerobic.5% -aerobic. It has been reported that the bacteria found in cellulitis type of It has been reported that the bacteria found in cellulitis type of infections – aerobic bacteria.infections – aerobic bacteria. Chronic non-advancing abscess – anaerobic bacteria.Chronic non-advancing abscess – anaerobic bacteria. As the infection becomes severe- mixed floraAs the infection becomes severe- mixed flora

Odontogenic infectionsOdontogenic infections

Aerobic AnaerobicAerobic AnaerobicGram positive Gram positive cocci-30% Gram negativerods-70%S.Milleri peptosreptococci BacteroidsS. Salivarius streptococci fusobacteriumS.SanguisS. mutans.

BacteroidsBacteroids Porphyromonas Provetella Porphyromonas Provetella P .gingivalis More common .P .gingivalis More common .P .denticola P .melanogenicaP .denticola P .melanogenicaP.asaccharolytics P .denticolaP.asaccharolytics P .denticola P. IntermediaP. Intermedia P .buccae P .buccae Principles of antibiotic administrationPrinciples of antibiotic administration Proper doseProper dose Proper time intervalProper time interval Proper route of administrationProper route of administration Consistency in route of administrationConsistency in route of administration Combination of antibiotic therapyCombination of antibiotic therapy

Proper doseProper dose Minimum inhibitory concentration (MIC) of the drug should be Minimum inhibitory concentration (MIC) of the drug should be known.known. For therapeutic purposes the peak concentration of the For therapeutic purposes the peak concentration of the drug at the site of infection is 3-4times MIC.drug at the site of infection is 3-4times MIC. Therapeutic levels greater than 3-4times the MIC do not Therapeutic levels greater than 3-4times the MIC do not improve the results. Leads to toxicity and is wasteful.improve the results. Leads to toxicity and is wasteful. Increased doses are justified when the site is isolated from the Increased doses are justified when the site is isolated from the blood supply, like abcess or nonvital tissue.blood supply, like abcess or nonvital tissue. Sufficient antibiotic must be given to reach the therapeutic Sufficient antibiotic must be given to reach the therapeutic levels.levels. Sub therapeutic doses may mask the infection and suppress Sub therapeutic doses may mask the infection and suppress the clinical symptoms .the clinical symptoms .

May cause recurrence of infection.May cause recurrence of infection.

Proper time interval:Proper time interval: Knowledge of the pharmacokinetics of the drug should be Knowledge of the pharmacokinetics of the drug should be known.known. The usual dosage interval for therapeutic use of antibiotics is – The usual dosage interval for therapeutic use of antibiotics is – 4times the t4times the t½ (plasma half life)½ (plasma half life) Patient should be evaluated for h/o renal diseases. They have Patient should be evaluated for h/o renal diseases. They have reduced renal clearance and may require longer time interval reduced renal clearance and may require longer time interval between doses.between doses.

Proper route of administrationProper route of administration Serious, established infection – parenteral route.Serious, established infection – parenteral route. After initial response is achieved, the route of administration After initial response is achieved, the route of administration should not be changed immediately.should not be changed immediately. The infection may recur because the blood levels of the drug The infection may recur because the blood levels of the drug may be reduced.may be reduced. Bacteria are not eradicated until the antibiotic has beenBacteria are not eradicated until the antibiotic has been given for 5 or 6 days.given for 5 or 6 days. Combination of antibiotics Combination of antibiotics Combination should be avoided when not indicated.Combination should be avoided when not indicated. The result of combination:The result of combination:–– Broad spectrum exposure that leads to depression of the Broad spectrum exposure that leads to depression of the normal host flora and increased opportunity for resistant bacteria to normal host flora and increased opportunity for resistant bacteria to emerge.emerge. Indications :Indications :–– Necessity to increase the antibacterial spectrum, in patients Necessity to increase the antibacterial spectrum, in patients with life threatening conditions.with life threatening conditions.–– When increased bactericidal effect against a specific organism When increased bactericidal effect against a specific organism is required.is required.–– Prevention of emergence of resistant bacteriaPrevention of emergence of resistant bacteria

Patient monitoringPatient monitoring Response to treatment:Response to treatment:–– Patients rarely have a noticeable response – 24-48hrs.Patients rarely have a noticeable response – 24-48hrs.–– The response begins the second day.The response begins the second day.

–– Eradication of infection is generally achieved by the third day.Eradication of infection is generally achieved by the third day.–– Usually 7 - day course is indicated.Usually 7 - day course is indicated.–– If no improvement is seen on 3If no improvement is seen on 3rdrd or 4 or 4ththday- the patient should beday- the patient should be carefully re-evaluated.carefully re-evaluated.–– The antibiotic has to be reevaluatedThe antibiotic has to be reevaluated

CLASSIFICATION OF ANTIBIOTICSCLASSIFICATION OF ANTIBIOTICS Based on chemical structureBased on chemical structure Type of organisms on which it actsType of organisms on which it acts Bacteriostatic/BacteriocidalBacteriostatic/Bacteriocidal Chemotherapeutic spectraChemotherapeutic spectra

Classification of antimicrobialsClassification of antimicrobials Chemical structureChemical structure

Sulfonamides and related drugsSulfonamides and related drugs–– Sulfadiazine and othersSulfadiazine and others–– Sulfones – Dapsone (DDS), Paraaminosalicylic acid (PAS).Sulfones – Dapsone (DDS), Paraaminosalicylic acid (PAS).

Diaminopyrimidines Diaminopyrimidines –– TrimethoprimTrimethoprim–– PyrimethaminePyrimethamine

QuinolonesQuinolones–– Nalidixic acidNalidixic acid–– NorfloxacinNorfloxacin–– Ciprofloxacin etcCiprofloxacin etc

-lactam antibiotics -lactam antibiotics –– PenicillinsPenicillins–– CephalosporinsCephalosporins–– MonobactamsMonobactams–– CarbapenemsCarbapenems

TetracyclinesTetracyclines–– OxytetracyclineOxytetracycline–– Doxycycline etcDoxycycline etc

Nitrobenzene derivative Nitrobenzene derivative

–– ChloramphenicolChloramphenicol

AminoglycosidesAminoglycosides–– StreptomycinStreptomycin–– GentamicinGentamicin–– Neomycin etcNeomycin etc

Macrolide antibioticsMacrolide antibiotics–– ErythromycinErythromycin–– RoxithromycinRoxithromycin–– Azithromycin etcAzithromycin etc

Polypeptide antibioticsPolypeptide antibiotics–– Polymyxin-BPolymyxin-B–– ColistinColistin–– BacitracinBacitracin

Type of organisms against which primarily activeType of organisms against which primarily active

Antibacterial Antibacterial –– PenicillinsPenicillins–– AminoglycosidesAminoglycosides–– Erythromycin etcErythromycin etc Antifungal Antifungal –– GriseofulvinGriseofulvin–– Amphotericin BAmphotericin B–– Ketoconazole Ketoconazole AntiviralAntiviral–– IdoxuridineIdoxuridine–– AcyclovirAcyclovir–– AmantadineAmantadine–– Zidovudine etcZidovudine etc AntiprotozoalAntiprotozoal–– ChloroquineChloroquine–– PyrimethaminePyrimethamine–– MetronidazoleMetronidazole–– Diloxanide etcDiloxanide etc AnthelminticAnthelmintic–– MebendazoleMebendazole–– PyrantelPyrantel

–– NiclosamideNiclosamide–– Diethyl carbamazine etcDiethyl carbamazine etc

Bactericidal- the ability to kill the bacteriaBactericidal- the ability to kill the bacteria Bacteriostatic- the ability to inhibit or retard the growth of Bacteriostatic- the ability to inhibit or retard the growth of bacteriabacteria Bacteriostatic v/s BactericidalBacteriostatic v/s BactericidalChloramphenicol AminoglycosidesChloramphenicol Aminoglycosides Clindamycin Bacitracin Clindamycin Bacitracin erythromycin Cephalosporinserythromycin Cephalosporins sulfonamides Metronidiazolesulfonamides Metronidiazole Tetracyclines vancomycinTetracyclines vancomycin Trimethoprim Penicillins Trimethoprim Penicillins ciprofloxacinciprofloxacin streptomycin streptomycin cotrimoxazole cotrimoxazole

Chemotherapeutic SpectraChemotherapeutic Spectra Narrow spectrum Narrow spectrum Effective against only a few microorganisms with a very Effective against only a few microorganisms with a very

specific metabolic pathway or enzyme.specific metabolic pathway or enzyme.–– Penicillin G, streptomycin, erythromycinPenicillin G, streptomycin, erythromycin Broad spectrumBroad spectrum Useful in treating a wide variety of infectionsUseful in treating a wide variety of infections–– Ex: tetracycline, chloramphenical, cephalosporinsEx: tetracycline, chloramphenical, cephalosporins

Mechanism of actionMechanism of action

Antibiotics commonly used in Antibiotics commonly used in EndodonticsEndodontics

Penicillins Penicillins Cephalosporins Cephalosporins Quinolones Quinolones Tetracyclines Tetracyclines MacrolidesMacrolides Antifungal agentsAntifungal agents Anti-viral agentsAnti-viral agents

PENICILLINSPENICILLINS

PenicillinPenicillin These drugs act on the bacterial cell wall by:These drugs act on the bacterial cell wall by:–– Interfere with synthesis of peptidoglycan layer in cell Interfere with synthesis of peptidoglycan layer in cell wallwall–– bind to and inhibit activity of enzymes transpeptidases, bind to and inhibit activity of enzymes transpeptidases, so that cross-linking does not take place so that cross-linking does not take place These enzymes and related proteins-“penicillin-binding These enzymes and related proteins-“penicillin-binding proteins”proteins”–– When bacteria divide in the presence of When bacteria divide in the presence of ββ-lactam antibiotics- -lactam antibiotics- cell wall deficient forms are produced. The interior of the bacteria is cell wall deficient forms are produced. The interior of the bacteria is hyperosmotic, hyperosmotic, eventually cause cell lysiseventually cause cell lysis

BENZYL PENICILLIN (PENCILLIN G)BENZYL PENICILLIN (PENCILLIN G)–– PnG is a narrow spectrum antibiotic; activity is limited primarily PnG is a narrow spectrum antibiotic; activity is limited primarily to gram positive bacteria to gram positive bacteria

Antibacterial activity Antibacterial activity –– Most potent AMA, inhibits the growth of susceptible organism.Most potent AMA, inhibits the growth of susceptible organism.–– Mainly gram +ve, gram –ve cocci and some gram +ve bacilli Mainly gram +ve, gram –ve cocci and some gram +ve bacilli with exception of enterococci.with exception of enterococci.–– Cocci – Highly sensitive – Streptococci, Pneumococci, Staph. Cocci – Highly sensitive – Streptococci, Pneumococci, Staph. aureus, N. gonorrhoeae, N. meningitis aureus, N. gonorrhoeae, N. meningitis

–– Bacilli – B. anthracis, Corynebacterium diphtheriae, clostridium Bacilli – B. anthracis, Corynebacterium diphtheriae, clostridium tetany and spirochetes tetany and spirochetes –– Actinomyces israelii is moderately sensitiveActinomyces israelii is moderately sensitive

SEMI SYNTHETIC PENICILLINSSEMI SYNTHETIC PENICILLINS The major drawbacks of benzyl penicillin are :The major drawbacks of benzyl penicillin are :–– Inactivation by the gastric hydrochloric acidInactivation by the gastric hydrochloric acid–– Short duration of actionShort duration of action–– Poor penetration into CSFPoor penetration into CSF–– Activity mainly against gram +ve organismActivity mainly against gram +ve organism–– Possibility of anaphylaxisPossibility of anaphylaxis Attempts therefore have been made to synthesize penicillin freeAttempts therefore have been made to synthesize penicillin free from such drawbacks.from such drawbacks. P.chrysogenum produces natural penicillins which produce the P.chrysogenum produces natural penicillins which produce the 6 amino- penicillanic acid (6-APA) nucleus. 6 amino- penicillanic acid (6-APA) nucleus. The attachment of side chains are inhibited and instead variousThe attachment of side chains are inhibited and instead various organic radicals were substituted. organic radicals were substituted. Thus a variety of semi synthetic drugs are produced. Thus a variety of semi synthetic drugs are produced.

CLASSIFICATIONCLASSIFICATION Acid resistant alternative to penicillin G (Phenoxy methyl Acid resistant alternative to penicillin G (Phenoxy methyl penicillin)penicillin) Penicillinase resistant penicillins. (Methicillin,Cloxacillin)Penicillinase resistant penicillins. (Methicillin,Cloxacillin) Extended spectrum penicillins(ampicillin, amoxicillin)Extended spectrum penicillins(ampicillin, amoxicillin)

Acid resistant pencillinsAcid resistant pencillins : : Potassium phenoxymethyl penicillinPotassium phenoxymethyl penicillin (penicillin V) (penicillin V)–– Similar antibacterial spectrum like benzylpenicillin.Similar antibacterial spectrum like benzylpenicillin.–– More active against resistant staphylococciMore active against resistant staphylococci–– Less inactivated by the gastric acid.Less inactivated by the gastric acid.–– Plasma levels achieved is 2 to 5 times higher than Plasma levels achieved is 2 to 5 times higher than benzylpenicillin.benzylpenicillin.–– 50-70% is bound to plasma proteins.50-70% is bound to plasma proteins.–– 25% of drug is eliminated in urine25% of drug is eliminated in urine–– Administered in the dose of 250 –500 mg at 4-8 hours intervals,Administered in the dose of 250 –500 mg at 4-8 hours intervals, atleast 30 min before food.atleast 30 min before food.–– This can be used in less serious infections (pneumocci and This can be used in less serious infections (pneumocci and streptococci)streptococci)–– Dose –penicillin V 500 mg qid. Dose –penicillin V 500 mg qid.

Extended spectrum penicillinsExtended spectrum penicillins Amino penicillins :Amino penicillins :

–– Ampicillin Ampicillin –– –– Antibacterial activity is similar to that of PnG but is more Antibacterial activity is similar to that of PnG but is more effective than PnG against a variety of gram-ve bacteria effective than PnG against a variety of gram-ve bacteria –– Drug is effective against H.influenzae strep.viridans, Drug is effective against H.influenzae strep.viridans, N.gonorrhea, Salmonella, shigellae, Klebsilla and enterococci.N.gonorrhea, Salmonella, shigellae, Klebsilla and enterococci. Absorption, fate and excretion :Absorption, fate and excretion :–– Oral absorption is incomplete but adequate.Oral absorption is incomplete but adequate.–– Not degraded by gastric acid.Not degraded by gastric acid.–– Food interferes with absorption Food interferes with absorption –– Partly excreted in bile and partly by kidney Partly excreted in bile and partly by kidney –– 0.5-2 gm oral/IM or IV depending on severity of infection every 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours 6 hours –– Children : 25-50 mg/kg/dayChildren : 25-50 mg/kg/day–– AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap 100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj

AMOXICILLIN AMOXICILLIN ::

–– This is a semi-synthetic penicillin This is a semi-synthetic penicillin (amino-p-hydroxy-benzylpencillin)(amino-p-hydroxy-benzylpencillin)

–– Antibacterial spectrum is similar to Ampicillin but less effective Antibacterial spectrum is similar to Ampicillin but less effective than Ampicillin .than Ampicillin .–– Oral absorption is better; food does not interfere; higher and Oral absorption is better; food does not interfere; higher and more sustained blood levels are produced.more sustained blood levels are produced.–– It is less protein bond and urinary excretion is higher than that It is less protein bond and urinary excretion is higher than that of ampicillin.of ampicillin.–– Incidence of diarrhea is lessIncidence of diarrhea is less

DoseDose : : –– 500 mg tid/qid 500 mg tid/qid –– AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250, 500 AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.

USES :USES : TyphoidTyphoid Bronchitis Bronchitis

Urinary infectionUrinary infection SBESBE GonorrhoeaGonorrhoea

BETA LACTAMASE INHIBITORSBETA LACTAMASE INHIBITORS CLAVULANIC ACID CLAVULANIC ACID

–– Obtained from STREPTOMYCES CLAVULIGERUSObtained from STREPTOMYCES CLAVULIGERUS–– It has a Beta lactam ring – no antibacterial activityIt has a Beta lactam ring – no antibacterial activity–– Called as Suicide inhibitor –inactivated after binding to enzymeCalled as Suicide inhibitor –inactivated after binding to enzyme–– Permeates the outer layers of cell wall of gram-ve bacteriaPermeates the outer layers of cell wall of gram-ve bacteria

Pharmacokinetics :Pharmacokinetics :–– Oral absorption- rapidOral absorption- rapid–– Bioavailability-60%Bioavailability-60%–– Distribution similar that of amoxicillinDistribution similar that of amoxicillin–– Excretion-tubular secretionExcretion-tubular secretion UsesUses : :–– Staph aureus,H influenza, gonorrhoea and E coliStaph aureus,H influenza, gonorrhoea and E coli

Adverse effects :Adverse effects :–– Poor g.i. tolerance Poor g.i. tolerance –– HepatotoxicityHepatotoxicity

AUGMENTIN, AMONATE, ENHANCINAUGMENTIN, AMONATE, ENHANCINDOSE-Amox 250mg+clavulanic acid 125mg tab,1-2 tab TDS, DOSE-Amox 250mg+clavulanic acid 125mg tab,1-2 tab TDS,

severe infection 4 tabs 6 hourly severe infection 4 tabs 6 hourly

CEPHALOSPORINSCEPHALOSPORINS

Cephalosporium acremonium was the first source.Cephalosporium acremonium was the first source. They contain 7 amino cephalosporonic acid nucleus. They contain 7 amino cephalosporonic acid nucleus. Structurally they contain Structurally they contain ββ--lactam and dihydro thiazine rings. lactam and dihydro thiazine rings. Mechanism of actionMechanism of action : : –– Act by inhibiting bacterial cell was synthesis and are Act by inhibiting bacterial cell was synthesis and are bactericidal. bactericidal.

–– New derivatives are much more resistant than the older New derivatives are much more resistant than the older cephalosporinscephalosporins

ClassificationClassification First generation cephalosporin First generation cephalosporin

–– Good activity against gram +ve bacteria. (except enterococci). Good activity against gram +ve bacteria. (except enterococci). –– Most oral cavity anaerobes are sensitive.Most oral cavity anaerobes are sensitive.–– Parental Parental Oral Oral –– CEPHALOTHIN CEPHALOTHIN CEPHALEXINCEPHALEXIN–– CEFAZOLINCEFAZOLIN CEPHRADINE CEPHRADINE

CEFADROXIL CEFADROXIL

Cephalaxin and Cephadroxil : Cephalaxin and Cephadroxil : Useful in treating community acquired, respiratory and urinary Useful in treating community acquired, respiratory and urinary tract infections and in surgical prophylaxis. tract infections and in surgical prophylaxis. Not choice for systemic infections.Not choice for systemic infections. Dose: 250,500mg cap (6-8 hourly)Dose: 250,500mg cap (6-8 hourly) Cefazolin : Cefazolin : For antimicrobial prophylaxis in most surgical procedures. For antimicrobial prophylaxis in most surgical procedures. Given only IM / IV. Given only IM / IV. Dose :Dose :–– IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases). IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases).

–– SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, DROXYLDROXYL

Second generation CephalosporinsSecond generation Cephalosporins Increased activity against gram –ve organism. Increased activity against gram –ve organism. More active against anaerobes. More active against anaerobes. Parenteral Parenteral Oral Oral CEFUROXIME CEFUROXIME CEFACLOR CEFACLOR CEFOXITIN CEFOXITIN CEFUROXIME CEFUROXIME

Cefaclor:Cefaclor:–– is highly effective by oral route. is highly effective by oral route. –– More active against H. influenzae, E coli.More active against H. influenzae, E coli. Dose : Dose : –– 500mg tid 500mg tid –– KEFLOR, CEFTUM, CEFOGEN, FUROXILKEFLOR, CEFTUM, CEFOGEN, FUROXIL

Third generation cephalosporinThird generation cephalosporin They highly augmented against gram –ve enterobacter and They highly augmented against gram –ve enterobacter and pseudomonas. pseudomonas. Highly resistant to Highly resistant to -lactamase from gram –ve bacteria. -lactamase from gram –ve bacteria. Less active on gram +ve cocci Less active on gram +ve cocci –– Parenteral Parenteral Oral Oral –– CEFOTAXIME CEFOTAXIME CEFIXIME CEFIXIME –– CEFTIZOXIME CEFTIZOXIME CEFDINIR CEFDINIR –– CEFTRIAXONE CEFTRIAXONE CEFTIBUTEN CEFTIBUTEN –– CEFTAZIDIME CEFTAZIDIME –– CEFOPERAZONE CEFOPERAZONE Dose : Dose : –– 400mg daily400mg daily–– 200-400mg tab, bid.200-400mg tab, bid.–– CESPAN, CEFOPROX, PROCADAX, CEPODEM, ORFIXCESPAN, CEFOPROX, PROCADAX, CEPODEM, ORFIX

Fourth generation cephalosporinsFourth generation cephalosporins Developed in 1990 similar to that of 3rd generation.Developed in 1990 similar to that of 3rd generation. Highly resistant to Highly resistant to -lactamases. -lactamases. Active against many bacteria resistant to earlier drugs. Active against many bacteria resistant to earlier drugs. It has high potency and extended spectrum. It has high potency and extended spectrum. Effective in many serious infections.Effective in many serious infections. Parenteral Parenteral –– CEFEPINE, CEFPIROME CEFEPINE, CEFPIROME USES : USES : –– Serious and resistant hospital acquired infections. Serious and resistant hospital acquired infections. –– Septicemia, Septicemia, –– Lower respiratory tract infection.Lower respiratory tract infection. Dose : 1-2g IM / IV 12 hrly. Dose : 1-2g IM / IV 12 hrly. –– CEFROM, CEFORTH – 1g inj. CEFROM, CEFORTH – 1g inj. Uses-Uses- Alternatives to penicillins. Alternatives to penicillins. RTI, UTI and soft tissue infection RTI, UTI and soft tissue infection Penicillinase producing staph infection. Penicillinase producing staph infection. Septicemias. Septicemias. Surgical prophylaxis Surgical prophylaxis Meningitis, gonorrhea Meningitis, gonorrhea Typhoid Typhoid Mixed aerobic and anaerobic infections Mixed aerobic and anaerobic infections Infection by odd organism or hospital infections Infection by odd organism or hospital infections Prophylactic treatment in neutropenic patientsProphylactic treatment in neutropenic patients

QUINOLONESQUINOLONES Entirely synthetic antimicrobials.Entirely synthetic antimicrobials. Are active primarily against gram –ve bacteria.Are active primarily against gram –ve bacteria. Nalidixic acid- low potency, modest blood and tissue levels, Nalidixic acid- low potency, modest blood and tissue levels, limited spectrum, high resistancelimited spectrum, high resistance

Fluoroquinolones –(1 or more flourine substituition ) high Fluoroquinolones –(1 or more flourine substituition ) high potency, expanded spectrum, better tissue penetrance, slow potency, expanded spectrum, better tissue penetrance, slow resistance. They inhibit the enzyme bacterial DNA gyrase.resistance. They inhibit the enzyme bacterial DNA gyrase.

CIPROFLOXACINCIPROFLOXACIN First generation FQ active against a broad range of bacteria First generation FQ active against a broad range of bacteria especially gram –ve aerobic bacilli.especially gram –ve aerobic bacilli. Highly susceptibleHighly susceptible : : –– E coli, shigella, E coli, shigella, NN meningitis, K pneumoniae, Proteus, H meningitis, K pneumoniae, Proteus, H influenza, influenza, EnterobacterEnterobacter, V. cholerae, S. typhi,, V. cholerae, S. typhi, N N gonorrhoea.gonorrhoea. Moderately susceptibleModerately susceptible : :–– Staph aureus, brucella, M. tuberculosisStaph aureus, brucella, M. tuberculosis Microbiological features :Rapid bactericidal activity and high Microbiological features :Rapid bactericidal activity and high potency.potency. Relatively long post antibiotic effect on enterobacteria, Relatively long post antibiotic effect on enterobacteria, pseudomonas and staph.pseudomonas and staph. Low frequency of mutational resistance.Low frequency of mutational resistance. protective intestinal streptococci and anaerobes are spared.protective intestinal streptococci and anaerobes are spared. Active against many Active against many lactam and amino glycoside resistant lactam and amino glycoside resistant bacteria.bacteria. Less active at acidic pHLess active at acidic pH Adverse effectAdverse effect GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent.infrequent. CNS- Dizziness, headache, restlessness, anxiety, insomnia CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures are rare.and seizures are rare. Skin/hypersensitivity – rashes, pruritis, urticaria.Skin/hypersensitivity – rashes, pruritis, urticaria. Tendonitis and tendon ruptureTendonitis and tendon rupture CIFRAN, CIPLOX, CIPROBID, CIPROLET CIFRAN, CIPLOX, CIPROBID, CIPROLET Dose :Dose :

–– 250, 500,750 mg tab, 200mg/100 ml IV infusion, 3mg/ml eye 250, 500,750 mg tab, 200mg/100 ml IV infusion, 3mg/ml eye dropsdrops..

NORFLOXACINNORFLOXACIN It is less potent than ciproIt is less potent than cipro It attains lower concentration in tissues.It attains lower concentration in tissues. It is metabolized as well as excreted unchanged in urine.It is metabolized as well as excreted unchanged in urine. USES USES –– UTI and Genital infections.UTI and Genital infections.–– Bacterial diarrhea.Bacterial diarrhea. NORBACTIN, NORFLOX, UROFLOXNORBACTIN, NORFLOX, UROFLOX Dose :Dose :–– 200, 400, 800 mg tab, 3mg/ml eyedrops200, 400, 800 mg tab, 3mg/ml eyedrops

OFLOXACINOFLOXACIN Intermediate between Cipro and Norfloxacin in activity against Intermediate between Cipro and Norfloxacin in activity against Gr-ve bacteriaGr-ve bacteria More potent for Gr +ve organisms and anaerobesMore potent for Gr +ve organisms and anaerobes Good activity against chlamydia, alternative drug for nonspecificGood activity against chlamydia, alternative drug for nonspecific urethritis and atypical pneumonia.urethritis and atypical pneumonia. Inhibits M tuberculosis; active against M. leprae.Inhibits M tuberculosis; active against M. leprae. Used in multidrug regimensUsed in multidrug regimens Dose- 100,200mg tabDose- 100,200mg tab

TETRACYCLINESTETRACYCLINES

Have a nucleus of four cyclic rings.Have a nucleus of four cyclic rings. Obtained from soil actinomycetes.Obtained from soil actinomycetes. First to be introduced – chlortetracycline(1948)First to be introduced – chlortetracycline(1948) Then oxytetracycline followed. Then oxytetracycline followed. Tetracyclines are bacteriostatic.(inhibit protein synthesis by Tetracyclines are bacteriostatic.(inhibit protein synthesis by binding to 30s ribosomes)binding to 30s ribosomes) Broad spectrum antibioticsBroad spectrum antibiotics Antimicrobial activityAntimicrobial activity Gram +ve and –ve cocci are sensitive Gram +ve and –ve cocci are sensitive Gram +ve bacilli are inhibitedGram +ve bacilli are inhibited Entero bacteria are highly resistantEntero bacteria are highly resistant Spirochetes are quite sensitive Spirochetes are quite sensitive All rickettsiae and Chlamydia are highly sensitiveAll rickettsiae and Chlamydia are highly sensitive

Mechanism of action:Mechanism of action:–– Inhibit protein synthesis by binding to 30s ribosomesInhibit protein synthesis by binding to 30s ribosomes

Absorption and excretion:Absorption and excretion: Tetracyclines have chelating property – form insoluble Tetracyclines have chelating property – form insoluble complexes with calcium and other metals.complexes with calcium and other metals. Incompletely absorbed from gi tract. Absorbtion is better if Incompletely absorbed from gi tract. Absorbtion is better if taken on empty stomach.taken on empty stomach. Milk, iron preparations, and antacids-reduce their absorption.Milk, iron preparations, and antacids-reduce their absorption. Doxycycline and minocycline – completely absorbed, Doxycycline and minocycline – completely absorbed, irrespective of food.irrespective of food. They are concentrated in liver, spleen, bone and teeth.They are concentrated in liver, spleen, bone and teeth. Excreted by urineExcreted by urine

Adverse effects :Adverse effects : GIT- epigastric burning, nausea, vomiting, diarrhea GIT- epigastric burning, nausea, vomiting, diarrhea Liver damageLiver damage Renal failureRenal failure Effects on teeth & bones- Ca tetracycline chelate Effects on teeth & bones- Ca tetracycline chelate Mid pregnancy-5months deciduous teeth- brown, ill formed; Mid pregnancy-5months deciduous teeth- brown, ill formed; 3months-6yrs- permanent anterior teeth and molars; late pregnancy 3months-6yrs- permanent anterior teeth and molars; late pregnancy or childhood- suppression of bone growth.or childhood- suppression of bone growth. Hypersensitivity Reactions Hypersensitivity Reactions Super infection; Anti-anabolic effectSuper infection; Anti-anabolic effect

DOSEDOSE

Tetracycline – 250-500mg tds in adultsTetracycline – 250-500mg tds in adults Children over 8yrs -25 to 50mg /kg daily in 2 to 4 divided doseChildren over 8yrs -25 to 50mg /kg daily in 2 to 4 divided dose Doxycycline – 200mg initially, 100-200mg od.Doxycycline – 200mg initially, 100-200mg od. Ledermycin 150,300mg cap/tabLedermycin 150,300mg cap/tab RAMYCIN,RESTECLIN-250,500mgcap,50mg/ml in10ml vial inj RAMYCIN,RESTECLIN-250,500mgcap,50mg/ml in10ml vial inj DOXT, NOVADOX, TETRADOX-100mg cap.DOXT, NOVADOX, TETRADOX-100mg cap. Cyanomycin 50,100 mg capCyanomycin 50,100 mg cap

PrecautionPrecaution Not to be used in pregnancy, lactation and in childrenNot to be used in pregnancy, lactation and in children Avoided in patients on diureticsAvoided in patients on diuretics

Used cautiously in renal and hepatic insufficiencyUsed cautiously in renal and hepatic insufficiency Beyond expiry date should not be usedBeyond expiry date should not be used Do not mix injectable Tc with Pn- inactivation occursDo not mix injectable Tc with Pn- inactivation occurs

MACROLIDESMACROLIDES Antibiotics having macrocyclic lactone ring-Antibiotics having macrocyclic lactone ring- ERYTHROMYCIN-ERYTHROMYCIN- Isolated from Streptomyces erythreus (1952)Isolated from Streptomyces erythreus (1952) Alternative to penicillin Alternative to penicillin Bacteriostatic-low conc. Bacteriocidal- high concBacteriostatic-low conc. Bacteriocidal- high conc Water solubility is limited.solution remains stable only when Water solubility is limited.solution remains stable only when kept cold.kept cold. Acts by inhibiting protein synthesis.Acts by inhibiting protein synthesis. Combines with 50s ribosomes and intereferes with translocationCombines with 50s ribosomes and intereferes with translocation

Antibacterial activityAntibacterial activity Narrow spectrum antibioticNarrow spectrum antibiotic against penicillin resistant staphylococci.against penicillin resistant staphylococci. Active against gram +ve Active against gram +ve

Pharmacokinetics :Pharmacokinetics :–– Erythromycin base - acid labileErythromycin base - acid labile–– To protect it from gastric acid -Given with enteric coated - To protect it from gastric acid -Given with enteric coated - incomplete absorptionincomplete absorption–– Its acid stable esters are better absorbedIts acid stable esters are better absorbed–– Widely distributed in body Widely distributed in body –– Excreted through bileExcreted through bileDose :Dose : Adults 250 - 500mg 6hrlyAdults 250 - 500mg 6hrly Children 30 – 60mg/kg/dayChildren 30 – 60mg/kg/day Erythromycin base - ERYSAFE 250 mg tabErythromycin base - ERYSAFE 250 mg tab Erythromycin stearate -ERYTHROCIN – 250,500mg tabErythromycin stearate -ERYTHROCIN – 250,500mg tab

Adverse effectsAdverse effects : : GIT – epigastric pain GIT – epigastric pain

On high doses – hearing impairmentOn high doses – hearing impairment Hypersensitivity reactions – rareHypersensitivity reactions – rare

Uses :Uses :–– Substitute for penicillin, pencillin resistant infectionsSubstitute for penicillin, pencillin resistant infections–– Oral adm, safe and effectiveOral adm, safe and effective–– Perio/periapical/NUG/extractionPerio/periapical/NUG/extraction–– Prophylactic useProphylactic use

ROXITHROMYCINROXITHROMYCIN Semi synthetic - long acting, acid stable macrolide Semi synthetic - long acting, acid stable macrolide Antibacterial spectrum similar to erythromycinAntibacterial spectrum similar to erythromycin Dose Dose - - –– 150-300mg BD 30min before food 150-300mg BD 30min before food –– Children - 2.5-5mg/kg BDChildren - 2.5-5mg/kg BD–– ROXID, ROXIBID 150,300mg tab ROXID, ROXIBID 150,300mg tab –– 50mg kid tab,150 mg tab50mg kid tab,150 mg tab

CLINDAMYCINCLINDAMYCIN It is lincosamide antibiotic having similar action (macrolide 50s)It is lincosamide antibiotic having similar action (macrolide 50s) Bacteriostatic – low conc;Bacteriocidal – high conc Bacteriostatic – low conc;Bacteriocidal – high conc Most active against gram+ve cocci, C.diphtheriae, ActinomycesMost active against gram+ve cocci, C.diphtheriae, Actinomyces Highly active against – anaerobes (B fragilis)Highly active against – anaerobes (B fragilis) Pharmacokinetics :Pharmacokinetics :–– Oral absorption – goodOral absorption – good–– Distribution – skeletal and soft tissuesDistribution – skeletal and soft tissues–– Excreted in urineExcreted in urine Adverse effects :Adverse effects :–– Rashes ,UrticariaRashes ,Urticaria–– Abdominal pain Abdominal pain –– Superinfection -Enterocolitis &DiarrhoeaSuperinfection -Enterocolitis &Diarrhoea Uses :Uses :–– Anaerobic and mixed infections- alternative to Pn & macroAnaerobic and mixed infections- alternative to Pn & macro–– Abscess and bone infections-staphy and bacteroidsAbscess and bone infections-staphy and bacteroids–– Infective endocarditisInfective endocarditis Dose : Dose : –– 150-300 mg QID oral ; 200-600mg I.v. 8 hourly150-300 mg QID oral ; 200-600mg I.v. 8 hourly–– DALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml andDALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml and 600 mg/4ml inj600 mg/4ml inj

Antifungal agentsAntifungal agents Amphotericin B Amphotericin B –– obtained from - Streptomyces nodusus obtained from - Streptomyces nodusus –– Has a Macrocyclic ringHas a Macrocyclic ring–– BBinds to ergosterol inds to ergosterol present in the fungal cell membrane present in the fungal cell membrane and and generates poresgenerates pores–– Used in serious systemic fungal infectionsUsed in serious systemic fungal infections

Antifungal activity : fungicidal at high conc-static at low conc.Antifungal activity : fungicidal at high conc-static at low conc. Active against- Active against- –– candida albicans, histoplasma, cryptococcus neoformans, candida albicans, histoplasma, cryptococcus neoformans, aspergillusaspergillus Not absorbed orallyNot absorbed orally Dose :Dose :–– Administered iv as suspension DOCAdministered iv as suspension DOC–– Orally 50-100mg QIDOrally 50-100mg QID–– MYCOL 50mg vialMYCOL 50mg vial Adverse effects- Adverse effects- –– acute reactions, long term toxicityacute reactions, long term toxicity Uses : topically – oral,vaginal and cutaneous candidiasis.Uses : topically – oral,vaginal and cutaneous candidiasis.

NYSTATINNYSTATIN A polyene derived from A polyene derived from Streptomyces nourseiStreptomyces noursei Binds to sterols of fungal cell membraneBinds to sterols of fungal cell membrane Because of high systemic toxicity used as Because of high systemic toxicity used as Topical antifungal Topical antifungal agentagent.. 22ndnd choice to clotrimazole choice to clotrimazole 1 lac units-4 times a day, 10-14 days1 lac units-4 times a day, 10-14 days Mycostatin 5 lac U tabMycostatin 5 lac U tab

CLOTRIMAZOLE CLOTRIMAZOLE –– Effective in the topical treatment- Esp. athletes foot, otomycosisEffective in the topical treatment- Esp. athletes foot, otomycosis and oral, cutaneous candidiasis. and oral, cutaneous candidiasis. well tolerated although Local irritation and burning well tolerated although Local irritation and burning No systemic toxicity is seen after topical use.No systemic toxicity is seen after topical use. Dose :oropharyngeal candidiasis- 10mg troche -3 to 4 times Dose :oropharyngeal candidiasis- 10mg troche -3 to 4 times day.day. SURFAZ, CLOTRIN, CLODERM, 1% lotion, cream, powder SURFAZ, CLOTRIN, CLODERM, 1% lotion, cream, powder 100mg tab.100mg tab.

Candid 1% cream, gel, powder.Candid 1% cream, gel, powder.

KETACONAZOLE KETACONAZOLE

–– First oral effective broad spectrum antifungal drug.First oral effective broad spectrum antifungal drug.–– The oral absorption of KTZ is facilitated by gastric acidityThe oral absorption of KTZ is facilitated by gastric acidity–– Hepatic metabolism is extensive metabolites are excreted in Hepatic metabolism is extensive metabolites are excreted in urine.urine.–– The usual dose is 200 mg OD or BD The usual dose is 200 mg OD or BD –– FUNAZOLE, KETOVATE, FUNGICIDE, 200mg tab, 2% oint, FUNAZOLE, KETOVATE, FUNGICIDE, 200mg tab, 2% oint, cream, shampoo.cream, shampoo. Adverse effects :Adverse effects :–– Nausea and vomiting – loss of appetite, headache, paresthesia,Nausea and vomiting – loss of appetite, headache, paresthesia, rashes, hair loss.rashes, hair loss.

ANTI-VIRAL DRUGSANTI-VIRAL DRUGS.. AcyclovirAcyclovir –– Indications:Indications: Herpes simplex virus (HSV) 1 and 2 infections; Herpes simplex virus (HSV) 1 and 2 infections; severe genital HSV infections; HSV encephalitis; shingles and severe genital HSV infections; HSV encephalitis; shingles and chickenpox; ointment for genital herpes infections; cream for cold chickenpox; ointment for genital herpes infections; cream for cold sores sores –– Actions:Actions: Inhibits viral DNA replication Inhibits viral DNA replication

Rimantadine Rimantadine –– Indications:Indications: Prophylaxis and treatment of illness caused by Prophylaxis and treatment of illness caused by influenza A virus in adults; prophylaxis against influenza A virus in influenza A virus in adults; prophylaxis against influenza A virus in childrenchildren–– Actions:Actions: Inhibits viral replication, possibly by preventing the Inhibits viral replication, possibly by preventing the uncoating of the virusuncoating of the virus

ANTIBIOTIC PROPHYLAXIS FOR HEART ANTIBIOTIC PROPHYLAXIS FOR HEART AND ARTIFICIAL JOINT PATIENTSAND ARTIFICIAL JOINT PATIENTS

Antibiotics are used for two main reasons:Antibiotics are used for two main reasons: To treat infectionsTo treat infections To prevent infectionsTo prevent infections

Antibiotic prophylaxis is given in patients who are Antibiotic prophylaxis is given in patients who are immunocompromised, patients with heart ailments and patients immunocompromised, patients with heart ailments and patients with hip and joint prosthesiswith hip and joint prosthesis

Viridens streptococci are the causative organisms for Viridens streptococci are the causative organisms for seeding heart and implanted joints causing morbidity andseeding heart and implanted joints causing morbidity and death death

These s.viridens form colonies on heart valves trapping blood These s.viridens form colonies on heart valves trapping blood cells and fibrin and thereby reducing heart efficiency by hindering cells and fibrin and thereby reducing heart efficiency by hindering closure of the valvesclosure of the valves These sticky vegetations break off and lodge in small vessels atThese sticky vegetations break off and lodge in small vessels at distant sites causing ischemiadistant sites causing ischemia The goal of antibiotic prophylaxis is to prevent clinical infectionsThe goal of antibiotic prophylaxis is to prevent clinical infections by helping destroy small number of bacteria present before or by helping destroy small number of bacteria present before or introduced during treatment.introduced during treatment.

Oral procedures requiring prophylaxisOral procedures requiring prophylaxis

Requiring antibiotic prophylaxis

Not requiring prophylaxis

Extractions Periodontal procedures Implant placement Tooth reimplantation Placement of orthodontic bands Endodontic instrumentation

(beyond root apex) Periapical surgery Intraligamentary injection Prophylactic cleaning and procedures in which significant bleeding is anticipated

Operative and prosthodontic procedures with or without retraction cord LA injection Intracanal endodontic procedures Placement of removable appliances Impression taking Exfoliation of primary tooth Oral radiography Fluoride Post operative suture removal

Standard general prophylaxis

Amoxicillin Adults – 2gChildren -50mg/kg1hr before procedure.

Pts unable to take oral medications

Ampicillin Adults – 2gChildren -50mg/kgIM/IV 30mins before procedure

Penicillin allergic pts

ClindamycinCephalexin/cefadroxilAzithromycin/ clindamycin

Adults -600mg;child-20mg/kg.Adults -2g; child-50mg/kgAdults-500mg; child-15mg/kg.1hr before the procedure

Pts unable to take oral medications

Clindamycincefazolin

Adults-600mg; child- 20mg/kg.IVAdults-1g ; child- 25mg/kg IM/IV.30mins before procedure.

Additional guidelines for antibiotic prophylaxisAdditional guidelines for antibiotic prophylaxis In the case of delayed healing or of a procedure that involves In the case of delayed healing or of a procedure that involves infected tissues, additional doses of antibiotics may be needed, even infected tissues, additional doses of antibiotics may be needed, even though the bacteremia may lasts for no longer than 15mins after the though the bacteremia may lasts for no longer than 15mins after the procedure.procedure. Amoxicillin is the preferred oral antibiotic.Amoxicillin is the preferred oral antibiotic. If the pt is taking amoxicillin on a long term basis for some If the pt is taking amoxicillin on a long term basis for some reason, a different class of antibiotic should be used.reason, a different class of antibiotic should be used. If a high risk pt (prosthetic valve) has maintained a high level of If a high risk pt (prosthetic valve) has maintained a high level of oral health, oral antibiotic prophylaxis may be used for simple dental oral health, oral antibiotic prophylaxis may be used for simple dental procedures rather than parental regimen.procedures rather than parental regimen.

ANALGESICSANALGESICSUSED IN ENDODONTICSUSED IN ENDODONTICS

Introduction :Introduction :Pain is the number one reason people seek health care & has been Pain is the number one reason people seek health care & has been

deemed’’ the fifth vital sign.”deemed’’ the fifth vital sign.”The study of pain has in recent years diverged into many different The study of pain has in recent years diverged into many different

fields from pharmacology to psychology & neurobiology.fields from pharmacology to psychology & neurobiology.

Definition of pain:Definition of pain:

an unpleasant sensory or emotional an unpleasant sensory or emotional experience associated with actual or potential tissue damage or experience associated with actual or potential tissue damage or

described in terms of such damagedescribed in terms of such damage

a disagreeable sensation produced by the action of stimuli of a disagreeable sensation produced by the action of stimuli of harmful nature macbryde;1952harmful nature macbryde;1952

An unpleasant sensation occuring in varying degrees of An unpleasant sensation occuring in varying degrees of severity as a consequence of injury ,disease or emotional disorder.severity as a consequence of injury ,disease or emotional disorder.Medical thesaurusMedical thesaurus

Properties of painProperties of pain1) Threshold & intensity1) Threshold & intensity

If intensity is lower than the threshold - pain is not feltIf intensity is lower than the threshold - pain is not felt Weber –Fechners law:Weber –Fechners law: 100 fold increase in intensity =3 fold 100 fold increase in intensity =3 fold increase increase

in pain in pain 2)Adaptation2)Adaptation Pain receptors show no adaptation,pain continues asPain receptors show no adaptation,pain continues as long as receptors are stimulated.long as receptors are stimulated.

3) Localisation of pain3) Localisation of painSuperficial pain is comparatively better localised than deep pain. Superficial pain is comparatively better localised than deep pain.

Visceral pain is usually referredVisceral pain is usually referred

4)Emotional accompaniment:4)Emotional accompaniment: associated emotions are unpleasantassociated emotions are unpleasant

5) Influence of the rate of damage on the intensity of pain :5) Influence of the rate of damage on the intensity of pain :

If the rate of injury is high intensity of pain is also highIf the rate of injury is high intensity of pain is also highA very slowly growing tissue damaging agent eg: cancer at an early A very slowly growing tissue damaging agent eg: cancer at an early

stage may not produce pain at all.stage may not produce pain at all.

6) Double pain:6) Double pain:Due to the initial action on a-delta fibres;followed by c-fibres.fast pain Due to the initial action on a-delta fibres;followed by c-fibres.fast pain

is better localised than slow pain.is better localised than slow pain.

Biochemical basis of pain:Biochemical basis of pain: neurotransmittersneurotransmitters neuromodulatorsneuromodulatorsNeurotransmitters: Neurotransmitters: are substances that are synthesizedare substances that are synthesized& stored in the neuron for release during neural activity.& stored in the neuron for release during neural activity.NeuromodulatorsNeuromodulators are substances that modify the release of are substances that modify the release of

neurotransmitters from pre-synaptic terminalsneurotransmitters from pre-synaptic terminals

Neurotransmitters are classified into:Neurotransmitters are classified into:1) Excitatory agents: 1) Excitatory agents: Ach , norepinephrine, glutamate, substanceP,Ach , norepinephrine, glutamate, substanceP,histaminehistamine

2) Inhibitory agents:2) Inhibitory agents: serotonine, GABA, endorphins, glycine, somatostatin, serotonine, GABA, endorphins, glycine, somatostatin,

dopamine.dopamine.3) Inflammatory agents:3) Inflammatory agents: prostaglandins, bradykininprostaglandins, bradykinin

Glutamate:Glutamate:Amino acid secreted by pre-synaptic terminalsAmino acid secreted by pre-synaptic terminalsFound in the spinal cord dorsal horn & is associated with noxious Found in the spinal cord dorsal horn & is associated with noxious

input.input.Substance P Substance P ::

Polypeptide,composed of 11 amino acidsPolypeptide,composed of 11 amino acidsReleased at the terminals of primary nociceptive neuronsReleased at the terminals of primary nociceptive neurons Also released from spinal cord by stimulation with A-delta & Also released from spinal cord by stimulation with A-delta & C-fibresC-fibres

Serotonin:Serotonin: Secreted in the brain stem & project down to the spinal cordSecreted in the brain stem & project down to the spinal cord Imp. Inhibitory neurotransmitter in the C.N.SImp. Inhibitory neurotransmitter in the C.N.S Central serotoninis thought to potentiate endorphin analgesiaCentral serotoninis thought to potentiate endorphin analgesiaProstaglandins:Prostaglandins:PGE2 metabolised from arachidionic acidPGE2 metabolised from arachidionic acidSensitize nerve endings to nociceptive stimuliSensitize nerve endings to nociceptive stimuliBradykinin:Bradykinin: Released as part of the inflammatory reactionReleased as part of the inflammatory reaction Acts as an allogenic agent that excites all kinds of receptorsActs as an allogenic agent that excites all kinds of receptors Also sensitizes some high threshold receptorsAlso sensitizes some high threshold receptors Requires the presence of PG’s to act.Requires the presence of PG’s to act.

Classification of painClassification of pain Primary –injury ,neuropathic painPrimary –injury ,neuropathic pain Secondary-referred painSecondary-referred pain AcuteAcute ChronicChronicPrimary painPrimary pain:: inflammatory : following injury pain sets in & persists until healinginflammatory : following injury pain sets in & persists until healing

; characteristically produces hyperalgesia & allodynia; characteristically produces hyperalgesia & allodyniaHyperalgesia : an increased response to a stimulus that is normally Hyperalgesia : an increased response to a stimulus that is normally

painfulpainfulAllodynia : pain due to a stimulus that does not normally provoke Allodynia : pain due to a stimulus that does not normally provoke

pain.pain. Referred pain:Referred pain: pain in a part of body that is fairly remote from the site of originpain in a part of body that is fairly remote from the site of origin

ACUTE PAINACUTE PAIN Sharp,fast ,pricking typeSharp,fast ,pricking type Occurs in 0.1 secs of stimulusOccurs in 0.1 secs of stimulus Carried by large caliber myelinated A-delta fibersCarried by large caliber myelinated A-delta fibers

Speed of travel-6-30 m/secSpeed of travel-6-30 m/sec

CHRONIC PAINCHRONIC PAIN Slow,burning,achingSlow,burning,aching gradually increases after 1 sec of stimulusgradually increases after 1 sec of stimulus small caliber unmyelinated C-fiberssmall caliber unmyelinated C-fibers Speed of travel 0.5-2m/secSpeed of travel 0.5-2m/sec

Mechanism of oro – facial painMechanism of oro – facial pain ::

Impulses from the face and mouth enter the brainstem via theImpulses from the face and mouth enter the brainstem via the trigeminal nerve.the cell bodies of the trigeminal afferent neurons aretrigeminal nerve.the cell bodies of the trigeminal afferent neurons are located in the Gasserian ganglion.located in the Gasserian ganglion. The central axon synapses at the trigeminal spinal tract The central axon synapses at the trigeminal spinal tract nucleus of the pons.nucleus of the pons.Peripheral mechanisms Peripheral mechanisms Following neurogenic inflammation & local tissue injury -Following neurogenic inflammation & local tissue injury -activation of inflammatory mediators activation of inflammatory mediators Sensitize peripheral nociceptorsSensitize peripheral nociceptors

The sensory input from the face and the mouth is carried by The sensory input from the face and the mouth is carried by way of the fifth cranial nerve ;way of the fifth cranial nerve ;THE TRIGEMINAL NERVE.THE TRIGEMINAL NERVE. The cell bodies of the trigeminal afferent neurons are located inThe cell bodies of the trigeminal afferent neurons are located in the the Large Gasserian GanglionLarge Gasserian Ganglion Impulses carried by the trigeminal nerve enter directly into theImpulses carried by the trigeminal nerve enter directly into the brain stem in the region of the brain stem in the region of the PonsPons to synapse in the to synapse in the trigeminal trigeminal spinal tract nucleus.spinal tract nucleus. This region is very similar to the dorsal horn of the spinal cord This region is very similar to the dorsal horn of the spinal cord and is sometimes referred to as the medullary dorsal hornand is sometimes referred to as the medullary dorsal horn

The brain stem- trigeminal nucleus complex consists of The brain stem- trigeminal nucleus complex consists of the main sensory trigeminal nucleus which is rostrally the main sensory trigeminal nucleus which is rostrally

located and receives periodontal and some pulpal afferents;located and receives periodontal and some pulpal afferents; and the spinal tract of the trigeminal nucleus which is more and the spinal tract of the trigeminal nucleus which is more caudally located caudally located

Subnucleus oralis appears to be a significant area in this Subnucleus oralis appears to be a significant area in this trigeminal brain stem complex for oral pain mechanisms.trigeminal brain stem complex for oral pain mechanisms. Subnucleus caudalis has especially been implicated in Subnucleus caudalis has especially been implicated in trigeminal nociceptive mechanisms on the basis of trigeminal nociceptive mechanisms on the basis of electrophysiological observations of nociceptive neurons.electrophysiological observations of nociceptive neurons. S.caudalis is homologous to the S.caudalis is homologous to the substantiasubstantia gelatinosagelatinosa of the of the spinal dorsal hornspinal dorsal horn The marginal rim of the nucleus corresponds to lamina I of the The marginal rim of the nucleus corresponds to lamina I of the dorsal horndorsal horn

Motor nucleusMotor nucleus Another component of the trigeminal brain stem complex is the Another component of the trigeminal brain stem complex is the motor nucleus of the Vth nerve.motor nucleus of the Vth nerve. This area is involved interpretation of impulses that require This area is involved interpretation of impulses that require motor responses or reflexes.motor responses or reflexes.

The pathwayThe pathway Second order trigeminal neurons project to the thalamus from Second order trigeminal neurons project to the thalamus from synaptic junctions with primary afferents in the subnucleus caudalissynaptic junctions with primary afferents in the subnucleus caudalis As in the dorsal horn these interneurons represent three types As in the dorsal horn these interneurons represent three types of of Transmission CellsTransmission Cells or or T cellsT cells. They are . They are •• Wide dynamic range neurons (WDR)Wide dynamic range neurons (WDR)•• Nociceptive specific neurons (NS)Nociceptive specific neurons (NS)•• Low threshold mechanoreceptive (LTM) afferentsLow threshold mechanoreceptive (LTM) afferents The WDR and NS neurons dominate in lamina I,II,IV andThe WDR and NS neurons dominate in lamina I,II,IV and

comprise the trigeminal nociceptive pathway. They all comprise the trigeminal nociceptive pathway. They all receive input from cutaneous structures and at least half ofreceive input from cutaneous structures and at least half of them receive input from deep structures of the mouth and them receive input from deep structures of the mouth and face.face.

The endogenous pain inhibitingThe endogenous pain inhibiting mechanismmechanism

The degree to which a person reacts to pain varies The degree to which a person reacts to pain varies tremendously. This results partly from a capability of the brain itself totremendously. This results partly from a capability of the brain itself to suppress input of pain signals to the nervous system by activating a suppress input of pain signals to the nervous system by activating a pain control system, called an pain control system, called an analgesia system.analgesia system. Several transmitter substances are involved in the Several transmitter substances are involved in the analgesia system; especially involved are analgesia system; especially involved are EnkephalinEnkephalin or or Serotonin, Serotonin, secreted by many nerve fibers (enkephalinergic secreted by many nerve fibers (enkephalinergic or serotogenic neurons) derived from the Periventricular or serotogenic neurons) derived from the Periventricular nuclei and from the Periaqueductal gray areanuclei and from the Periaqueductal gray area These neurons synapse with the A and C fiber terminals at the These neurons synapse with the A and C fiber terminals at the substantia gelatinosa rolandi (SGR )which bring pain from the substantia gelatinosa rolandi (SGR )which bring pain from the periphery in the posterior horn of the spinal cord.periphery in the posterior horn of the spinal cord. These fibers when stimulated release enkephalin or serotonin These fibers when stimulated release enkephalin or serotonin an endogenous opiod peptide which inhibits the pain.an endogenous opiod peptide which inhibits the pain.

The pain phenomenonThe pain phenomenon:: Pain is always subjective due to modulation and cross over in Pain is always subjective due to modulation and cross over in the CNSthe CNS The process begins in the periphery where specialized nerve The process begins in the periphery where specialized nerve fibers receive a painful stimulus.fibers receive a painful stimulus.This information passes through the Spinal cord to reach the brain This information passes through the Spinal cord to reach the brain

and the brain interprets the information as painand the brain interprets the information as pain The spinal tract The spinal tract nucleus STN is divided into three regionsnucleus STN is divided into three regions

1) 1) Subnucleus OralisSubnucleus Oralis 2) 2) Subnucleus InterpolarisSubnucleus Interpolaris 3) 3) Subnucleus CaudalisSubnucleus Caudalis, which corresponds to the medullary dorsal , which corresponds to the medullary dorsal

hornhornTooth pulp afferent fibers go to all three subnucleiTooth pulp afferent fibers go to all three subnuclei

Detection of Odontogenic painDetection of Odontogenic painOdontogenic pain transmission is mediated primarily by the Odontogenic pain transmission is mediated primarily by the

peripheral sensory neurons of the trigeminal nerve.The peripheral peripheral sensory neurons of the trigeminal nerve.The peripheral terminals of these nerves innervate the dental pulp and other oral terminals of these nerves innervate the dental pulp and other oral tissues, whereas the central terminals release neurotransmitters tissues, whereas the central terminals release neurotransmitters such as substance P, which are involved in the initiation of painsuch as substance P, which are involved in the initiation of pain

These trigeminal sensory afferent neurons along with the sympatheticThese trigeminal sensory afferent neurons along with the sympathetic branches of the superior cervical ganglion and blood vessels, branches of the superior cervical ganglion and blood vessels, enter through the apical foramen of a tooth. together, these nerves enter through the apical foramen of a tooth. together, these nerves and blood vessels form the neurovascular bundle. These nerve and blood vessels form the neurovascular bundle. These nerve fibers are :fibers are :

Myelinated UnmyelinatedMyelinated UnmyelinatedA fibers ( alpha , beta, gamma & delta) C fibersΒ - 6-13 dia, 30-70 m/sec vel 0.5-1μ dia, 0.5-2 m/s velΔ - 1-5 microns dia, 5-15m/sec vel

Pulpal sensory nerve activity: Mainly there are three types of fibers are found in the pulp:

Alfa and Beta Fibers * Fast conducting * Role not known

A Delta fibersA Delta fibers Most common in dental pulpMost common in dental pulp They are referred to as NOCICEPTIVE FIBERSThey are referred to as NOCICEPTIVE FIBERS

Once beneath the odontoblastic layer they loose their myelin Once beneath the odontoblastic layer they loose their myelin sheath anastomose and form the PLEXUS OF RASHKOWsheath anastomose and form the PLEXUS OF RASHKOW The free nerve endings extend 200μ m into the dentinal tubulesThe free nerve endings extend 200μ m into the dentinal tubules ( pulpo dentinal complex)( pulpo dentinal complex) Produces momentary quick sharp painProduces momentary quick sharp pain

C nerve fibersC nerve fibers High threshold unmyelinated fibersHigh threshold unmyelinated fibers Run subjacent to delta fibersRun subjacent to delta fibers Not directly involved in the pulpodentinal complex and less Not directly involved in the pulpodentinal complex and less easily provokedeasily provoked Dull poorly localized painDull poorly localized pain Activate by intense heating or coolingActivate by intense heating or cooling Once activated the pain can radiate anywhere in the ipsilateral Once activated the pain can radiate anywhere in the ipsilateral face and jawsface and jaws Stimulated C fibers release inflammatory modulators such as Stimulated C fibers release inflammatory modulators such as substance P and calcitonin gene related peptide (CGRP)substance P and calcitonin gene related peptide (CGRP) More resistant to compromised blood flow than A delta fibersMore resistant to compromised blood flow than A delta fibers

ProcessingProcessing The input from the teeth and periradicular region is transmitted The input from the teeth and periradicular region is transmitted by the maxillary and mandibular branches of trigeminal nerve to the by the maxillary and mandibular branches of trigeminal nerve to the CNSCNS The primary afferent neurons enters the brain stem at the level The primary afferent neurons enters the brain stem at the level of the pons.of the pons. The primary neuron synapses with a second order neuron in The primary neuron synapses with a second order neuron in the sub nucleus caudalis region of the trigeminal spinal tract nucleusthe sub nucleus caudalis region of the trigeminal spinal tract nucleus From here the impulse is carried to the thalamus. From here the impulse is carried to the thalamus. The second order neuron crosses the brain stem to the The second order neuron crosses the brain stem to the opposite side of the brain and ascends to the higher centersopposite side of the brain and ascends to the higher centers

A delta fibers from the pulp synapse in the lamina I area of the A delta fibers from the pulp synapse in the lamina I area of the subnucleus caudalis and c fibers synapse in the lamina II and III subnucleus caudalis and c fibers synapse in the lamina II and III areas .areas . A delta neurons pass to the thalamus directly by the way of the A delta neurons pass to the thalamus directly by the way of the neospinothalamic tract.neospinothalamic tract. The pathway ascends to the thalamus directly and is said to The pathway ascends to the thalamus directly and is said to carry carry fast pain.its sharp and easy to localizefast pain.its sharp and easy to localize The second order C fibers neuron carries impulses via the the The second order C fibers neuron carries impulses via the the paleospinothalamic tractpaleospinothalamic tract

..

This passes through the reticular formation , where the This passes through the reticular formation , where the impulses are influenced by many modulating processes before they impulses are influenced by many modulating processes before they reach the thalamus, since these impulses take longer to reach the reach the thalamus, since these impulses take longer to reach the thalamus the pain is called thalamus the pain is called slow pain.( dull aching)slow pain.( dull aching) Once the nociceptive input reaches the sensory cortex in the Once the nociceptive input reaches the sensory cortex in the parietal lobe pain recognition occurs.parietal lobe pain recognition occurs. The cortex may rely on memory of previous experience of The cortex may rely on memory of previous experience of dental pain to recognize the input as pain.dental pain to recognize the input as pain. In addition to the trigeminal path pain is also mediated by In addition to the trigeminal path pain is also mediated by sympathetic and some parasympathetic afferent nerve fibers and 7sympathetic and some parasympathetic afferent nerve fibers and 7 thth, , 99thth and 10 and 10thth cranial nerves which supply the oral region. cranial nerves which supply the oral region.

PerceptionPerception The final step in the subjective process is perception , this The final step in the subjective process is perception , this happens when the input reaches the cortex.happens when the input reaches the cortex. And perception differs from patient to patient depending on pastAnd perception differs from patient to patient depending on past experience, emotional state,cultural factors etc.experience, emotional state,cultural factors etc. Orofacial pain may produce unreasonable anxiety in the patientOrofacial pain may produce unreasonable anxiety in the patient and this is why its important for the clinician to identify the source of and this is why its important for the clinician to identify the source of the pain..the pain..

Management of painManagement of pain Anaelgesics are drugs which relieve pain without loss of Anaelgesics are drugs which relieve pain without loss of

consciousness.consciousness. They offer symptomatic relief from pain without affecting its causeThey offer symptomatic relief from pain without affecting its cause They are of two classesThey are of two classes Opoid or morphine type of analgesicsOpoid or morphine type of analgesics Non-opiod or aspirin type of analgesics Non-opiod or aspirin type of analgesics

Opioid analgesics:Opioid analgesics: Opium is in use since 4000 BCOpium is in use since 4000 BC Opioid is a term used for drugs with morphine like actionsOpioid is a term used for drugs with morphine like actions Earlier called as Narcotic analgesicsEarlier called as Narcotic analgesics Classification:Classification: Agonists :Agonists : -natural opium alkaloids,eg morphine,codeine-natural opium alkaloids,eg morphine,codeine -synthetic opiods,eg. Pethidine, methadone-synthetic opiods,eg. Pethidine, methadone 2. Antagonists : Naloxone, Naltrexone.2. Antagonists : Naloxone, Naltrexone. 3. Mixed agonist-antagonists : Pentazocine, Nalbuphine, 3. Mixed agonist-antagonists : Pentazocine, Nalbuphine, Morphine :Morphine : Mechanism of action- act on specific opiod receptors.Mechanism of action- act on specific opiod receptors. - The opiod receptors are- The opiod receptors are mu, kappa, deltamu, kappa, delta - Endogenous opiod peptides released in response to pain are - Endogenous opiod peptides released in response to pain are

enkephalines, the endorphins, and dynorphinsenkephalines, the endorphins, and dynorphins

Relieves pain without loss of consciousnessRelieves pain without loss of consciousness It alters perception and reaction to painIt alters perception and reaction to pain Raises pain threshold and increases capacity to tolerate painRaises pain threshold and increases capacity to tolerate pain Euphoria and sedation add to its analgesic effectsEuphoria and sedation add to its analgesic effects Bioavailability- 20-40 %,onset of action is 15-20 min, duration Bioavailability- 20-40 %,onset of action is 15-20 min, duration of action- 3-5 hrof action- 3-5 hr Morphine produces adverse effects like nausea, Morphine produces adverse effects like nausea, vomiting ,dizziness, hypotensionvomiting ,dizziness, hypotension Morphine is Histamine liberator and this action is responsible Morphine is Histamine liberator and this action is responsible for allergic effectsfor allergic effects

Dose: 10-20mg IM/SC, 20 mg tab available ( ethyl morphine)Dose: 10-20mg IM/SC, 20 mg tab available ( ethyl morphine) Acute morphine poisoning may be accidental, suicidal or Acute morphine poisoning may be accidental, suicidal or homicidalhomicidal

Lethal dose- 250 mg ,coma and death occur due to res. failure Lethal dose- 250 mg ,coma and death occur due to res. failure and pulmonary oedemaand pulmonary oedema Gastric lavage with potassium permanganate to remove Gastric lavage with potassium permanganate to remove unabsorbed drugunabsorbed drug Specific antidote is naloxone- 0.4 -0.8 mg iv repeated every 10-Specific antidote is naloxone- 0.4 -0.8 mg iv repeated every 10-15 mins15 mins

Codeine and pethidine are other opiod analgesics used in 25-Codeine and pethidine are other opiod analgesics used in 25-30 mg dosages30 mg dosages They are less potent than morphineThey are less potent than morphine Their duration of action is much shorter and onset of action is Their duration of action is much shorter and onset of action is more rapid than morphinemore rapid than morphine

NON-STEROIDAL ANTI-INFLAMMATORYNON-STEROIDAL ANTI-INFLAMMATORY DRUGS ( NSAIDSDRUGS ( NSAIDS ) )

Aspirin type or non opioid analgesicsAspirin type or non opioid analgesics They have anti inflammatory , antipyretic and uricosuric They have anti inflammatory , antipyretic and uricosuric properties without addiction liabilityproperties without addiction liability The active principle ‘salicin’ was isolated from bark of willow The active principle ‘salicin’ was isolated from bark of willow tree and is converted into glucose and salicylic acid in the bodytree and is converted into glucose and salicylic acid in the body

CLASSIFICATIONCLASSIFICATION Salicylic acid derivative – Aspirin,Sodium salicylate,Salicylic acid derivative – Aspirin,Sodium salicylate, Para amino phenol derivatives- paracetamolPara amino phenol derivatives- paracetamol Pyrazolone derivatives- phenyl butazone, AzapropazonePyrazolone derivatives- phenyl butazone, Azapropazone Indole acetic acid derivatives- indomethacin,sulindacIndole acetic acid derivatives- indomethacin,sulindac Aryl acetic acid derivatives- Diclofenac,Ketoralac, TolmetinAryl acetic acid derivatives- Diclofenac,Ketoralac, Tolmetin Propionic acid derivatives- Ibuprofen, FenoprofenPropionic acid derivatives- Ibuprofen, Fenoprofen Anthranilic acid- Flufenamic acid,Mefenamic acidAnthranilic acid- Flufenamic acid,Mefenamic acid OxIcams- Piroxicam, TenoxicamOxIcams- Piroxicam, Tenoxicam Alkanones- nabumetone, Alkanones- nabumetone, Sulfonanilide derivatives- nimuselide, celecoxibSulfonanilide derivatives- nimuselide, celecoxib

Mechanisim of actionMechanisim of action Arachidonic acid liberated from membrane phospholipids during Arachidonic acid liberated from membrane phospholipids during

inflammation is converted to prostaglandins catalyzed by the inflammation is converted to prostaglandins catalyzed by the enzyme cyclo-oxygenaseenzyme cyclo-oxygenase

These prostoglandins produce hyperalgesia which sensitize nerve These prostoglandins produce hyperalgesia which sensitize nerve endings to pain and other mediators of inflammation like bradykininendings to pain and other mediators of inflammation like bradykinin and histaminand histamin

These NSAIDs inhibit the PG synthesis by inhibiting the enzyme These NSAIDs inhibit the PG synthesis by inhibiting the enzyme cyclo-oxygenasecyclo-oxygenase

SalicylatesSalicylates Are salts of salicylic acid eg: methyl salicylate, sodium Are salts of salicylic acid eg: methyl salicylate, sodium salicylate, acetyl salicylic acid(Aspirin)salicylate, acetyl salicylic acid(Aspirin) Used as anaelgesic,antipyretic and anti inflammatory actionsUsed as anaelgesic,antipyretic and anti inflammatory actions Gastric irritation is severe and leads to epigastric stress,nauseaGastric irritation is severe and leads to epigastric stress,nausea and vomitingand vomiting

PARA AMINO PHENOL DERIVATIVESPARA AMINO PHENOL DERIVATIVES Paracetamol (acetaminophen)Paracetamol (acetaminophen) It is a metabolite of phenacetinIt is a metabolite of phenacetin Has good analgesic,antipyretic but poor anti inflammatory Has good analgesic,antipyretic but poor anti inflammatory propertiesproperties Well absorbed orallyWell absorbed orally Acute paracetamol poisoning occurs in childrenAcute paracetamol poisoning occurs in children

SULFONANILIDE DERIVATIVESSULFONANILIDE DERIVATIVES Nimesulide : is a weak inhibitor of PG synthesis with a higher Nimesulide : is a weak inhibitor of PG synthesis with a higher affinity for COX-2 than COX-1affinity for COX-2 than COX-1 It inhibits leukocyte function, prevents the release of mediators It inhibits leukocyte function, prevents the release of mediators and in addition has antihistaminic and anti allergic propertiesand in addition has antihistaminic and anti allergic properties Dose: 50-100 mg BDDose: 50-100 mg BD Long term use can cause hepato toxicityLong term use can cause hepato toxicity Colecoxib and Rofecexib are other highly selective COX-2 Colecoxib and Rofecexib are other highly selective COX-2 inhibitorsinhibitors

DRUGDRUG DOSDOSAGEAGE

PROPEPROPERTIESRTIES

ADVANTADVANTAGESAGES

USESUSES

AspirinAspirin Salicylic acidSalicylic acid derivativederivative

AnalAnalgesicgesic -300--300-600mg/6-600mg/6-8hrs8hrsAnti-Anti-inflammatorinflammatory 4-y 4-

Good Good analgesic , analgesic , anti-pyretic, anti-pyretic, anti-anti-inflammatoryinflammatory Gastric Gastric irritantirritant

PowerfulPowerful anti-anti-inflammatory inflammatory and anti-and anti-platelet activityplatelet activity

Pyrexia,Pyrexia, headache,bacheadache,backache,kache, Rheumatic Rheumatic feverfever

6gm/day6gm/day

AcetaminAcetaminophen (Tylenol)ophen (Tylenol) Para- Para- aminophenol aminophenol derivativederivative

0.5-0.5-1gm(3-6 1gm(3-6 times daily)times daily)

Max-4gMax-4g

Good Good analgesic, antianalgesic, anti pyretic, poor pyretic, poor anti-anti-inflammatoryinflammatory

Less Less gastric irritationgastric irritation

As analgesic As analgesic Anti pyretic, Anti pyretic, chronic pulpitis, chronic pulpitis, peridontal abscessperidontal abscess

DiclofenaDiclofenac -Indole acetic c -Indole acetic acid derivativeacid derivative

50m50mg BD/TDSg BD/TDS

AnalgeAnalgesic, anti-sic, anti-pyretic, anti-pyretic, anti-inflammatoryinflammatory Gel for Gel for topical topical applicationapplication

Good Good concentration concentration in synovial in synovial fluid, adverse fluid, adverse effects mildeffects mild

Chronic Chronic inflammatory inflammatory conditions, conditions, rheumatoid arthritis, rheumatoid arthritis, osteoarthritis, acute osteoarthritis, acute pulpitis, periapical pulpitis, periapical abscessabscess

PiroxicamPiroxicam Oxicam Oxicam derivativederivative

20m20mg ODg OD

AnalgeAnalgesic, anti-sic, anti-pyretic, anti-pyretic, anti-inflammatoryinflammatory

Long Long actingacting Better Better toleratedtolerated

Arthritis, Arthritis, musculoskeletal musculoskeletal pain , post-operative pain , post-operative painpain

DRUG DOSE PROPERTIES ADVANTAGES USESPhenylbutazonePyrazolone derivative

100-200mg, BD

Good anti-inflammatory, poor analgesic,anti-pyretic, water retention causes oedema

Powerful anti inflammatory

Rheumatoid and osteoarthritis, gout, ankylosing spondilitis

IndomethacinIndole acetic acid derivative

25-50mg, 3-5 times/day

Analgesic, anti-pyretic, anti-inflammatoryToxicity is high

Potent anti inflammatory and analgesic

Rheumatoid, psoriatic and osteoarthritis, gout, ankylosing spondilitis, closure of PDA

CelecoxibRofecoxibCox-2 inhibitors

100-200mg twice daily50mg/day

Effective anti inflammatory agentCox2 inhibitor

Less side effects and less ulcerogenic

Rheumatoid and osteoarthritis

Ibuprofen 400-800mg Analgesic, anti- Adverse effects Analgesic, anti

Propionic acid derivative

TDS pyretic, anti-inflammatoryMilder than aspirin

milder, better tolerated

pyretic, soft tissue injuries, fractures, chronic pulpitis, periodontal and gingival abscess

Corticosteroids Used in cases of post endodontic flareupsInflammatory mediators are released into the tissues causing vascular dilatationGlucocorticoids are used to reduce the acute inflammatory response by suppressing vasodilatation, migration of PMN leucocytes, and phagocytosis and by inhibiting the formation of arachidonic acid from neutrophil and macrophage cell membrane phospholipids thus blocking cyclooxygenase and lipooxygenase pathways and respective synthesis of prostaglandins and leukotrienes

Glucocorticoids are secreted by adrenal gland in response to ultradian and circadian rhythms and to stressThey are available as systemic as well as topical formsCommonly used are

cortisone-20-300 mg/day hydrocortisone-20-240mg/day prednisone-5-60mg/day

FLEXIBLE PRESCRIPTION PLANFLEXIBLE PRESCRIPTION PLAN A flexible prescription plan minimises both post- operativeA flexible prescription plan minimises both post- operative pain and side pain and side

effects . The following goals are achieved by this plan:effects . The following goals are achieved by this plan: A maximally effective dose of the non-narcotic analgesic A maximally effective dose of the non-narcotic analgesic In rare cases in which patients still have moderate to severe pain,In rare cases in which patients still have moderate to severe pain,

to consider adding drugs that increase the NSAID’S analgesiato consider adding drugs that increase the NSAID’S analgesia

ANTI ANXIETY DRUGS(ANXIOLYTICS)ANTI ANXIETY DRUGS(ANXIOLYTICS) Anxiety is tension or apprehension which is a normal response Anxiety is tension or apprehension which is a normal response to certain situations in life.to certain situations in life. Universal human emotionUniversal human emotion

But when excessive and disproportionate to the situation it But when excessive and disproportionate to the situation it becomes disabling and needs treatmenbecomes disabling and needs treatmen

Classification :Classification : Benzodiazepines – Diazepam, Chlordiazepoxide, Lorazepam, Benzodiazepines – Diazepam, Chlordiazepoxide, Lorazepam, AlprazolamAlprazolam 5-HT agonist-antagonists – Buspirone, Gepirone, Ipsapirone5-HT agonist-antagonists – Buspirone, Gepirone, Ipsapirone ββ- Blockers- Propranolol- Blockers- Propranolol Others- Meprobamate, HydroxyzineOthers- Meprobamate, Hydroxyzine

Benzodiazepine:Benzodiazepine: Long acting- Diazepam ,FlurazepamLong acting- Diazepam ,Flurazepam Short acting- Timazepam, Lorazepam, TriazolamShort acting- Timazepam, Lorazepam, Triazolam Important action on CNS and include Important action on CNS and include 1- sedation & hypnosis1- sedation & hypnosis 2- reduction in anxiety2- reduction in anxiety 3- muscle relaxation3- muscle relaxation 4- anti convulsant effects4- anti convulsant effectsAdverse effects:Adverse effects: 1- drowsiness, confusion, amnesia, lethargy and impaired motor 1- drowsiness, confusion, amnesia, lethargy and impaired motor

coordinationcoordination 2- in some it causes paradoxical irritabality and anxiety2- in some it causes paradoxical irritabality and anxietyDosage: 5mg diazepam, .25mg triazolam given 1hr prior Dosage: 5mg diazepam, .25mg triazolam given 1hr prior Antagonist: FlumazenilAntagonist: Flumazenil

ββ-blockers:-blockers: Used in pts with prominent autonomic symptoms of anxiety like Used in pts with prominent autonomic symptoms of anxiety like tremors, palpitation and hypertensiontremors, palpitation and hypertension Propranolol is commonly usedPropranolol is commonly used Can be used as adjuvants to benzodiazepineCan be used as adjuvants to benzodiazepineDosage: 40-240mg( 6-12hrs)Dosage: 40-240mg( 6-12hrs)

Other drugs used in dentistryOther drugs used in dentistry

Root canal irrigantsRoot canal irrigants The four goals of irrigation are:The four goals of irrigation are: Lavage of debrisLavage of debris Tissue dissolutionTissue dissolution Antibacterial actionAntibacterial action LubricationLubrication

Ideal requirements of a root canal irrigant:Ideal requirements of a root canal irrigant: Gross debridement with dissolution of the organic debris.Gross debridement with dissolution of the organic debris. Should effectively flush out inorganic debris and dentinal Should effectively flush out inorganic debris and dentinal shavings.shavings. Lubricating action.Lubricating action. Eliminate the microorganisms.Eliminate the microorganisms. Non toxic.Non toxic. Economical.Economical. Capable of removal of the smear layer.(????)Capable of removal of the smear layer.(????)

TYPES OF ENDODONTIC IRRIGANTS:TYPES OF ENDODONTIC IRRIGANTS: Sodium hypochlorite.Sodium hypochlorite. Hydrogen peroxide.Hydrogen peroxide. Chelating Agents:Chelating Agents: # EDTA# EDTA # RC Preparation.# RC Preparation. # EDTAC# EDTAC # REDTA# REDTA # Salvizol# Salvizol Acid cleansers:Acid cleansers: # 2% potentiated acid.# 2% potentiated acid. # Phosphoric acid.# Phosphoric acid. # Lactic acid.# Lactic acid. # Citric acid.# Citric acid. # Tannic acid.# Tannic acid. Saline / Water.Saline / Water. Anesthetic solution.Anesthetic solution. Glyoxide.Glyoxide. Chlorhexidine gluconateChlorhexidine gluconate

INTRACANAL MEDICAMENTSINTRACANAL MEDICAMENTS Intracanal medicaments are an integral part of treatment and Intracanal medicaments are an integral part of treatment and important to success in endodontics.important to success in endodontics.

To achieve desired out come in rc treatment dr.louis I grossmanTo achieve desired out come in rc treatment dr.louis I grossman described three phases described three phases Bmp,chemical,sterlizationBmp,chemical,sterlization

USESUSES Elimination of microorganism ,To sterilize –destroy all viable Elimination of microorganism ,To sterilize –destroy all viable microorganisms ,to disinfect-destroy all pathogens microorganisms ,to disinfect-destroy all pathogens Rendering contents of canal inert,bychemical means-to Rendering contents of canal inert,bychemical means-to mummify,tofix,toneutralize mummify,tofix,toneutralize Prevention /control of post treatment pain,to alter the inflammatory Prevention /control of post treatment pain,to alter the inflammatory

response either by antimicrobial action or pharmacological actionresponse either by antimicrobial action or pharmacological action Types of medicamentsTypes of medicaments

Phenolics HalidesPhenolics HalidesNaocl EugenolNaocl EugenolCMCP potassium iodineCMCP potassium iodineParachlorophenol chloramines-TParachlorophenol chloramines-TCamphorated parachlorophenol (CPC) steroidsCamphorated parachlorophenol (CPC) steroidsMetacresylacetate Heavy metal saltsMetacresylacetate Heavy metal saltsCresol Ca(OH)2Cresol Ca(OH)2Creosote (beech wood) Antibiotics Creosote (beech wood) Antibiotics Thymol CombinationsThymol CombinationsAldehydes: - Aldehydes: - Formacresol Formacresol GlutaraldehydeGlutaraldehyde

MUMMIFYING AGENTSMUMMIFYING AGENTS Agents used to harden and dry the tissues of the pulp so as to Agents used to harden and dry the tissues of the pulp so as to make them resistant to infectionmake them resistant to infection Liquid formaldehyde: used with zinc oxide and glycerine to Liquid formaldehyde: used with zinc oxide and glycerine to harden tissuesharden tissues Iodoform and tannic acid are also used in combn with Iodoform and tannic acid are also used in combn with eugenol,phenol and glyceroleugenol,phenol and glycerol

ANTICOAGULANTSANTICOAGULANTS These are drugs used to reduce the coagulability of blood.These are drugs used to reduce the coagulability of blood. Coagulants used in vivo are Coagulants used in vivo are Heparin, low mol.wt heparinHeparin, low mol.wt heparin

heparinoids- Heparan sulphate, dextran sulphateheparinoids- Heparan sulphate, dextran sulphate Oral anticoagulants Oral anticoagulants a. coumarin derivatives: Bishydroxycoumarin(dicumarol)a. coumarin derivatives: Bishydroxycoumarin(dicumarol) Warfarin sodWarfarin sod b. Indandione derivative: Phenindioneb. Indandione derivative: Phenindione

HEPARIN:HEPARIN: -It is named ‘heparin’ becos it is obtained from liver.-It is named ‘heparin’ becos it is obtained from liver. -it is a large , highly ionized molecule, therefore not -it is a large , highly ionized molecule, therefore not absorbed orallyabsorbed orally -it does not cross blood brain barrier or placenta-it does not cross blood brain barrier or placenta -it is metabolized in liver by heparinase and is excreted in urine-it is metabolized in liver by heparinase and is excreted in urine it is released from mast cells and its richest sources are lung,liver it is released from mast cells and its richest sources are lung,liver

and intestinal mucosaand intestinal mucosa Dosage :Dosage : 5000-10,000 U every 4-6 hrs and is followed by continuos 5000-10,000 U every 4-6 hrs and is followed by continuos

infusion of 750-1000 U/hr till bleeding is controlledinfusion of 750-1000 U/hr till bleeding is controlled

Oral anti coagulants:Oral anti coagulants: Bishydroxy coumarin(Dicumarol)-200 U for Bishydroxy coumarin(Dicumarol)-200 U for 2 days. Side effects – g.i.t disturbances2 days. Side effects – g.i.t disturbances Warfarin sod.-10-15 U for 3-6 days.Warfarin sod.-10-15 U for 3-6 days. The main use of anticoagulants is to prevent thrombus and emboli The main use of anticoagulants is to prevent thrombus and emboli

complications by reducing the rate of fibrin formation in diseases complications by reducing the rate of fibrin formation in diseases like MI, deep vein thrombosis and pulmonary embolism,RHDlike MI, deep vein thrombosis and pulmonary embolism,RHD

STYPTICSSTYPTICS Are local hemostaticsAre local hemostatics Used to arrest local bleeding following extraction and other dentalUsed to arrest local bleeding following extraction and other dental

proceduresprocedures•• Adrenaline- 1:10,000 soln of adrenaline Adrenaline- 1:10,000 soln of adrenaline [soaked cotton][soaked cotton] 2. Thrombin powder2. Thrombin powder 3. Fibrin3. Fibrin 4. Gelatin foam4. Gelatin foam 5. Tannic acid5. Tannic acid

Agents Affecting SalivationAgents Affecting Salivation

Anti-cholinergic DrugsAnti-cholinergic Drugs-(cholinergic- antagonists,antimuscarine -(cholinergic- antagonists,antimuscarine agents or parasympatholytics)agents or parasympatholytics)

Commonly used is Atropine Sulfate(belladona alkaloid) given orally Commonly used is Atropine Sulfate(belladona alkaloid) given orally 0.3-1.2 mg/4-6 hourly0.3-1.2 mg/4-6 hourly

Other drugs are:Other drugs are:1.1. Glycopyrrolate given orally 1-2mg upto 8mg/ dayGlycopyrrolate given orally 1-2mg upto 8mg/ day2.2. Propatheline bromide orally 7.5-30mg upto 30mg/dayPropatheline bromide orally 7.5-30mg upto 30mg/day3.3. Scopolamine Butylbromide orally 10-20mgScopolamine Butylbromide orally 10-20mg4.4. Scopolamine Hydrobromide orally 0.4-0.8 mgScopolamine Hydrobromide orally 0.4-0.8 mgAnticholinergic drugs block the effects of ach and cholinergic drugsAnticholinergic drugs block the effects of ach and cholinergic drugs at muscarinic receptor sites.at muscarinic receptor sites.Adverse effects : inhibition of various physiological actions of ACHAdverse effects : inhibition of various physiological actions of ACHConstipation, nausea and vomitingConstipation, nausea and vomitingXerostomiaXerostomiaDryness of respiratory treeDryness of respiratory treeUrinary retentionUrinary retention

CHOLINERGIC DRUGSProduce effects that mimic ACHProduce effects that mimic ACHUsed in the management of xerostomiaUsed in the management of xerostomiaPilocarpine is used for the relief of xerostomia caused by radiation Pilocarpine is used for the relief of xerostomia caused by radiation therapy and in Sjogrens syndrometherapy and in Sjogrens syndromeDosage – 5mg tid(tablets)Dosage – 5mg tid(tablets)Other drug is Cevimeline hydrochlorideOther drug is Cevimeline hydrochlorideDosage-30 mg tid(capsules)Dosage-30 mg tid(capsules)

ReferencesReferences Pathways of the pulp, 9Pathways of the pulp, 9thth edition, Stephen Cohen. edition, Stephen Cohen. Book of Endodontics, 5Book of Endodontics, 5thth edition, Ingle edition, Ingle Endodontic Therapy, 6Endodontic Therapy, 6thth edition, S. Weine edition, S. Weine Essentials of Medical Pharmacology, 4Essentials of Medical Pharmacology, 4THTH Edition,K.D.Thripathi Edition,K.D.Thripathi The Dental Clinics of North America, 2002The Dental Clinics of North America, 2002 The Dental Clinics of North America, 2007The Dental Clinics of North America, 2007