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ANTIBIOTICSANTIBIOTICS
Dr shabeel pnDr shabeel pn
ROYAL DENTAL COLLEGEROYAL DENTAL COLLEGE
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INTRODUCTIONINTRODUCTION
GREATEST CONTRIBUTION OF 20GREATEST CONTRIBUTION OF 20TH CENTURY TO THERAPEUTICS
MORE IMPORTANT IN DEVELOPING COUNTRIES – INFECTIOUS DISEASES
MINIMAL EFFECT ON RECIPIENT MOST FREQUENTLY USED AS WELL
AS MISUSED DRUGS CHEMOTHERAPY
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HISTORY OF HISTORY OF CHEMOTHERAPYCHEMOTHERAPY
PRE-EHRLICH ERA:PRE-EHRLICH ERA: BEFORE 1981, EMPIRICAL USAGEBEFORE 1981, EMPIRICAL USAGE CINCHONA, MERCURY, CHAULMOOGRA OILCINCHONA, MERCURY, CHAULMOOGRA OIL PERIOD OF EHRLICH:PERIOD OF EHRLICH: FATHER OF CHEMOTHERAPYFATHER OF CHEMOTHERAPY DYES - “MAGIC BULLETS” DYES - “MAGIC BULLETS” METHYLENE BLUE(MALARIA),METHYLENE BLUE(MALARIA), TRYPTAN REDTRYPTAN RED MODERN ERA:MODERN ERA: AFTER 1935AFTER 1935
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MODERN ERAMODERN ERA
DOMAGK 1935 DOMAGK 1935 EFFICIENCY OF EFFICIENCY OF
‘PRONTOSIL’(SULFONAMIDE DYE)‘PRONTOSIL’(SULFONAMIDE DYE) SULFAPYRIDINESULFAPYRIDINE 11STST MARKETTED IN 1938 MARKETTED IN 1938 ANTIBIOSIS –PASTEUR 1877ANTIBIOSIS –PASTEUR 1877 -GROWTH OFANTHRAX BACILLI IN URINE-GROWTH OFANTHRAX BACILLI IN URINE INHIBITTED BY AIRBORNE BACERIAINHIBITTED BY AIRBORNE BACERIA FLEMMING 1929 : PENICILLIN- FLEMMING 1929 : PENICILLIN-
STAPHSTAPH CHAIN, ABRAHAM & FLOREY 1941CHAIN, ABRAHAM & FLOREY 1941
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DEFINITIONDEFINITION
““A CHEMICAL SUBSTANCE PRODUCED A CHEMICAL SUBSTANCE PRODUCED BY MICRO ORGANISMS, HAVING THE BY MICRO ORGANISMS, HAVING THE PROPERTY OF INHIBITING THE PROPERTY OF INHIBITING THE GROWTH OF OR DESTROYING OTHER GROWTH OF OR DESTROYING OTHER MICRO ORGANISMS IN HIGH MICRO ORGANISMS IN HIGH DILUTION”DILUTION”
EXCLUDES NATURAL SUBSTANCES EXCLUDES NATURAL SUBSTANCES LIKE ANTIBODIES AND ETHANOL, LIKE ANTIBODIES AND ETHANOL, LACTIC ACID , HYDROGEN LACTIC ACID , HYDROGEN PEROXIDE……PEROXIDE……
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CLASSIFICATIONCLASSIFICATION
TYPE OF ACTIONTYPE OF ACTION
1. 1. PRIMARILY BACTERIOSTATIC:PRIMARILY BACTERIOSTATIC: TETRACYCLINES, CHLORAMPHENICOLTETRACYCLINES, CHLORAMPHENICOL
ERYTHROMYCIN, ETHAMBUTOLERYTHROMYCIN, ETHAMBUTOL
2. 2. PRIMARILY BACTERICIDAL:PRIMARILY BACTERICIDAL: PENICILLINS, AMINOGLYCOSIDESPENICILLINS, AMINOGLYCOSIDES
POLYPEPTIDES, CEPHALOSPORINSPOLYPEPTIDES, CEPHALOSPORINS
VANCOMYCIN, CIPROFLOXACINVANCOMYCIN, CIPROFLOXACIN
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CLASSIFICATIONCLASSIFICATION
SPECTRUM OF ACTIVITYSPECTRUM OF ACTIVITY
1. BROAD SPECTRUM1. BROAD SPECTRUM TETRACYCLINES, CHLORAMPHENICOLTETRACYCLINES, CHLORAMPHENICOL
2. NARROW SPECTRUM2. NARROW SPECTRUM PENICILLIN G, STREPTOMYCIN, PENICILLIN G, STREPTOMYCIN,
ERYTHROMYCINERYTHROMYCIN
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CLASSIFICATIONCLASSIFICATION
BETA-LACTAM ANTIBIOTICS:BETA-LACTAM ANTIBIOTICS: PENICILLINS, PENICILLINS, CEPHALOSPORINS, CARBAPENEMSCEPHALOSPORINS, CARBAPENEMS
AMINOGLYCOSIDE ANTIBIOTICS: AMINOGLYCOSIDE ANTIBIOTICS: STREPTOMYCIN, GENTAMYCIN, KANAMYCIN, AMIKACINSTREPTOMYCIN, GENTAMYCIN, KANAMYCIN, AMIKACIN
TETRACYCLINES: TETRACYCLINES: TETRACYCLINE, DOXYCYCLINE, TETRACYCLINE, DOXYCYCLINE, MINOCYCLINE, OXYTETRACYCLINEMINOCYCLINE, OXYTETRACYCLINE
QUINOLONES: QUINOLONES: CIPROFLOXACIN, NORFLOXACIN, CIPROFLOXACIN, NORFLOXACIN, OFLOXACINOFLOXACIN
MACROLIDES: MACROLIDES: ERYTHROMYCIN, AZITHROMYCIN, ERYTHROMYCIN, AZITHROMYCIN, ROXITHRMYCIN, CLARITHROMYCINROXITHRMYCIN, CLARITHROMYCIN
NITROIMIDAZOLES:NITROIMIDAZOLES: METRONIDAZOLE, METRONIDAZOLE, TINIDAZOLETINIDAZOLE
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CLASSIFICATIONCLASSIFICATION
1.1. INHIBIT CELL WALL SYNTHESIS: INHIBIT CELL WALL SYNTHESIS: PENICILLIN, PENICILLIN, CEPHALOSPORIN, VANCOMYCIN, BACITRACINCEPHALOSPORIN, VANCOMYCIN, BACITRACIN
2.2. CAUSE LEAKAGE FROM MEMBRANES: CAUSE LEAKAGE FROM MEMBRANES: AMPHOTERICIN B, NYSTATINAMPHOTERICIN B, NYSTATIN
3.3. INHIBIT PROTEIN SYNTHESIS: INHIBIT PROTEIN SYNTHESIS: TETRCYCLINES, TETRCYCLINES, ERYTHROMYCIN, CHLORAMPHENICOLERYTHROMYCIN, CHLORAMPHENICOL
4.4. CAUSE MISREADING OF m-RNA CODE: CAUSE MISREADING OF m-RNA CODE: STREPTOMYCIN, GENTAMYCINSTREPTOMYCIN, GENTAMYCIN
5.5. INHIBIT DNA-GYRASE: INHIBIT DNA-GYRASE: CIPROFLOXACINCIPROFLOXACIN
6.6. INTERFERE WITH DNA FUNCTION:INTERFERE WITH DNA FUNCTION:RIFAMPIN, RIFAMPIN, METRONIDAZOLEMETRONIDAZOLE
7.7. INTERFERE WITH DNA SYNTHESIS: INTERFERE WITH DNA SYNTHESIS: IDOXURIDINEIDOXURIDINE
8.8. INTERFERE WITH INTERMEDIARY INTERFERE WITH INTERMEDIARY METABOLISM: METABOLISM: TRIMETHOPRIM, ETHAMBUTOLTRIMETHOPRIM, ETHAMBUTOL
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PENICILLINSPENICILLINS NATURAL PENICILLINS: NATURAL PENICILLINS: PENICILLIN G, PENICILLIN G,
PROCAINE PPROCAINE P BENZATHINE PBENZATHINE P
ACID RESISTANT PENICILLINS: ACID RESISTANT PENICILLINS: PHENOXYMETHYL P, PHENOXYETHYL PPHENOXYMETHYL P, PHENOXYETHYL P
PENICILLINASE RESISTANT PENICILLINASE RESISTANT PENICILLNS: PENICILLNS: METHICILLIN, NAFCILLIN, METHICILLIN, NAFCILLIN, CLOXACILLINCLOXACILLIN
EXTENDED SPECTRUM PENICILLINS: EXTENDED SPECTRUM PENICILLINS: CARBOXY P, UREIDO P, AMINO PCARBOXY P, UREIDO P, AMINO P
PENICILLINS WITH BETA-LACTAMASE PENICILLINS WITH BETA-LACTAMASE INHIBITORS:INHIBITORS:
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AMOXICILLINAMOXICILLIN SEMISYNTHETIC, EXTENDED SPECTRUMSEMISYNTHETIC, EXTENDED SPECTRUM AMINO PENICILLINAMINO PENICILLIN NO RESISTANCE TO PENICILLINASE OR NO RESISTANCE TO PENICILLINASE OR
OTHER BETA-LACTAMASESOTHER BETA-LACTAMASES MORE ACTIVE THAN NATURAL ONEMORE ACTIVE THAN NATURAL ONE MANY GRAM –VE MICROBES MANY GRAM –VE MICROBES (E. COLI, PROTEUS, (E. COLI, PROTEUS,
H. INFLUENZA, SALMONELLA, SHIGELLA)H. INFLUENZA, SALMONELLA, SHIGELLA)ALSOALSO ORAL ABSORPTION IS BETTER; FOOD DOES ORAL ABSORPTION IS BETTER; FOOD DOES
NOT INTERFERENOT INTERFERE MORE SUSTAINED BLOOD LEVELSMORE SUSTAINED BLOOD LEVELS LESS CHANCE OF DIARRHOEA COMPARED LESS CHANCE OF DIARRHOEA COMPARED
TO AMPICILLINTO AMPICILLIN
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AMOXICILLINAMOXICILLIN USES:USES:
-ACUTE INFECTIONS-ACUTE INFECTIONS
-RESPIRATORY, URINARY TRACT-RESPIRATORY, URINARY TRACT
INFECTIONSINFECTIONS
- MENINGITIS- MENINGITIS
-GONORRHOEA-GONORRHOEA
- TYPHOID FEVER- TYPHOID FEVER
- SUBACUTE BACTERIAL ENDOCARDITIS- SUBACUTE BACTERIAL ENDOCARDITIS
-CHOLECYSTITIS-CHOLECYSTITIS
- SEPTICAEMIAS AND MIXED - SEPTICAEMIAS AND MIXED INFECTIONSINFECTIONS
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BETA LACTAMASE BETA LACTAMASE INHIBITORSINHIBITORS
CLAVULANIC ACID:CLAVULANIC ACID: - STREPTOMYCES CLAVULIGEROUS- STREPTOMYCES CLAVULIGEROUS
- INHIBITS WIDE VARIETY OF B-LACTAMASES- INHIBITS WIDE VARIETY OF B-LACTAMASES
- REVERSIBLE INITIALLY, LATER COVALENT- REVERSIBLE INITIALLY, LATER COVALENT
- ‘SUICIDE INHIBITOR’, INACTIVATED AFTER BINDING- ‘SUICIDE INHIBITOR’, INACTIVATED AFTER BINDING
SULBACTUMSULBACTUM - SEMISYNTHETIC BETA LACTAMASE INHIBITOR- SEMISYNTHETIC BETA LACTAMASE INHIBITOR
- SIMILAR TO CLAVULANIC ACID IN ACTIVITY & - SIMILAR TO CLAVULANIC ACID IN ACTIVITY & STRUCTURESTRUCTURE
- ORAL ABSORPTION IS INCONSISTENT, SO GIVEN - ORAL ABSORPTION IS INCONSISTENT, SO GIVEN
PARENTARALLY PARENTARALLY
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DOSAGEDOSAGE
ORALORAL ADULT: 250-500mg Q8H ADULT: 250-500mg Q8H
(TRIHYDRATE)(TRIHYDRATE) CHILD: 125-250mg Q8HCHILD: 125-250mg Q8H
PARENTARAL PARENTARAL ADULT: 500mg IM (SODIUM)ADULT: 500mg IM (SODIUM) OR SLOW IV INJECTION EVERY 8 HRSOR SLOW IV INJECTION EVERY 8 HRS CHILD: 50-100mg/kg BODY WEIGHTCHILD: 50-100mg/kg BODY WEIGHT
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COMMERCIAL COMMERCIAL PRODUCTSPRODUCTS
BLUMOX - 6.5Rs/500mg CapBLUMOX - 6.5Rs/500mg Cap IMOX - 6.3Rs/500mg CapIMOX - 6.3Rs/500mg Cap ARISTOMOX- 5.7/CapARISTOMOX- 5.7/Cap - I.8/125mg Tab- I.8/125mg Tab BIG MOX - 3.0/250mg CapBIG MOX - 3.0/250mg Cap INMOX - 3.5/250mg TabINMOX - 3.5/250mg Tab - 6.5/500mg Cap- 6.5/500mg Cap INMOX-KID- 2.0/125mg TabINMOX-KID- 2.0/125mg Tab
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CHOICE OF ANTIBIOTICCHOICE OF ANTIBIOTIC
HOST RELATED FACTORSHOST RELATED FACTORS PATHOGEN RELATED FACTORSPATHOGEN RELATED FACTORS DRUG RELATED FACTORSDRUG RELATED FACTORS
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HOST FACTORSHOST FACTORS AGE: AGE: CHLORAMPHENIOL NOT IN NEWBORN(LIVER CHLORAMPHENIOL NOT IN NEWBORN(LIVER
ENZ)ENZ) TETRACYCLINES – CHILDREN BELOW 6TETRACYCLINES – CHILDREN BELOW 6 ACCUMILATE IN DEVELOPING TEETHACCUMILATE IN DEVELOPING TEETH
IMMUNOCOMPETENCY STATUSIMMUNOCOMPETENCY STATUS BACTEROSTATIC OR BACTERICIDALBACTEROSTATIC OR BACTERICIDAL PREGNANCY: PREGNANCY: RISK TO FETUSRISK TO FETUS ALLERGY: ALLERGY: LOCAL FACTORS: LOCAL FACTORS: PUS, NECROTIC MATERIALPUS, NECROTIC MATERIAL HEMATOMAHEMATOMA
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PATHOGEN FACTORSPATHOGEN FACTORS
EVALUATION OF ETIOLOGY:EVALUATION OF ETIOLOGY: NOT NON-SPECIFIC ANTIPYRETICSNOT NON-SPECIFIC ANTIPYRETICS
NOT FOR VIRAL DISEASES LIKE COLDNOT FOR VIRAL DISEASES LIKE COLD
BACTERIOLOGICAL BACTERIOLOGICAL EXAMINATION:EXAMINATION:
CULTURE & SENSITIVITYCULTURE & SENSITIVITY
CHANCE OF DRUG RESISTANCECHANCE OF DRUG RESISTANCE IF MANY STRAINS, MORE CHANCEIF MANY STRAINS, MORE CHANCE
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DRUG FACTORSDRUG FACTORS NATURE:NATURE: BACTERICIDAL PREFFEREDBACTERICIDAL PREFFERED BACTEROSTATIC NOT EFFECTIVE IN THEBACTEROSTATIC NOT EFFECTIVE IN THE ABSENCE OF INFLAMATION ABSENCE OF INFLAMATION SPECTRUMSPECTRUM DEFINITIVE THERAPY- NARROWDEFINITIVE THERAPY- NARROW EMPIRICAL THERAPY - BROADEMPIRICAL THERAPY - BROAD RELATIVE TOXICITYRELATIVE TOXICITY ROUTE OF ADMINISTRATIONROUTE OF ADMINISTRATION SENSITIVITYSENSITIVITY EVIDENCE OF CLINICAL EFFICACYEVIDENCE OF CLINICAL EFFICACY COSTCOST
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PREGNANCY SAFETY PREGNANCY SAFETY INDEXINDEX
SAFELY PRESCRIBING DRUGS IN SAFELY PRESCRIBING DRUGS IN PREGNANCY BASED ON US FDAPREGNANCY BASED ON US FDA
DO NOT IMPLY AN INCREASING DO NOT IMPLY AN INCREASING PROGRESSION OF RISK FROM A – XPROGRESSION OF RISK FROM A – X
BASED ON THE RISK OF REPRODUCTIVE BASED ON THE RISK OF REPRODUCTIVE AND DEVELOPMENTAL ADVERSE EFFECTS AND DEVELOPMENTAL ADVERSE EFFECTS AND RISK vs. BENEFIT CONSIDERATIONSAND RISK vs. BENEFIT CONSIDERATIONS
DRUGS IN DIFFERENT CATEGORIES MAY DRUGS IN DIFFERENT CATEGORIES MAY HAVE SIMILAR RISK, BUT CATEGORIZED HAVE SIMILAR RISK, BUT CATEGORIZED DIFFERENTLY DIFFERENTLY
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CATEGORY - A CATEGORY - A
CONTROLLED STUDIES IN WOMEN CONTROLLED STUDIES IN WOMEN FAIL TO DEMONSTRATE A RISK TO FAIL TO DEMONSTRATE A RISK TO THE FOETUS IN 1THE FOETUS IN 1STST TRIMESTER(NO TRIMESTER(NO EVIDENCE OF RISK IN OTHER EVIDENCE OF RISK IN OTHER TRIMESTERS) AND POSSIBILITY OF TRIMESTERS) AND POSSIBILITY OF FETAL HARM REMAINS REMOTEFETAL HARM REMAINS REMOTE
ASCORBIC ACID, BETACAROTENE -IN ASCORBIC ACID, BETACAROTENE -IN PROPER DOSEPROPER DOSE
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CATEGORY - BCATEGORY - B EITHER ANIMAL- REPRODUCTION STUDIES EITHER ANIMAL- REPRODUCTION STUDIES
HAVE NOT DEMONSTRATED A FETAL RISK HAVE NOT DEMONSTRATED A FETAL RISK BUT THERE ARE NO CONTROLLED STUDIES BUT THERE ARE NO CONTROLLED STUDIES IN PREG. WOMENIN PREG. WOMEN
OROR ANIMAL-REPRODUCTION STUDIES HAVE ANIMAL-REPRODUCTION STUDIES HAVE
SHOWN AN ADVERSE EFFECT (OTHER THAN SHOWN AN ADVERSE EFFECT (OTHER THAN DECREASE IN FERTILITY)THAT WAS NOT DECREASE IN FERTILITY)THAT WAS NOT CONFIRMED IN CONTROL STUDIES IN CONFIRMED IN CONTROL STUDIES IN WOMEN IN THE 1WOMEN IN THE 1STST TRIMESTER TRIMESTER
AMOXICILLIN, AMPICILLIN, AMPHOTERICIN BAMOXICILLIN, AMPICILLIN, AMPHOTERICIN B
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CATEGORY - CCATEGORY - C EITHER STUDIES IN ANIMALS HAVE EITHER STUDIES IN ANIMALS HAVE
REVEALED ADVERSE EFFECTS ON THE REVEALED ADVERSE EFFECTS ON THE FETUS(TERATOGENIC OR EMBROCIDAL FETUS(TERATOGENIC OR EMBROCIDAL OR OTHERS) AND THERE ARE NO OR OTHERS) AND THERE ARE NO CONTROLLED STUDIES IN WOMEN CONTROLLED STUDIES IN WOMEN
OROR STUDIES IN WOMEN AND ANIMALS ARE STUDIES IN WOMEN AND ANIMALS ARE
NOT AVAILABLENOT AVAILABLE (DRUGS SHOULD BE GIVEN ONLY IF (DRUGS SHOULD BE GIVEN ONLY IF
POTENTIAL BENEFIT JUSTIFIES THE POTENTIAL BENEFIT JUSTIFIES THE POTENTIAL RISK TO THE FETUS)POTENTIAL RISK TO THE FETUS)
CYCLOSPORIN, CIPROFLOXACIN, CYCLOSPORIN, CIPROFLOXACIN, CLARYTHROMYCINCLARYTHROMYCIN
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CATEGORY - DCATEGORY - D
THERE IS POSITIVE EVIDENCE OF THERE IS POSITIVE EVIDENCE OF HUMAN FETAL RISK, BUT THE HUMAN FETAL RISK, BUT THE BENEFITS FROM USE IN PREGNANT BENEFITS FROM USE IN PREGNANT WOMEN MAY BE ACCEPTABLE WOMEN MAY BE ACCEPTABLE DESPITE THE RISK.DESPITE THE RISK.
LIFE THREATENING CONDITION – LIFE THREATENING CONDITION – SAFER DRUGS CAN NOT BE USED OR SAFER DRUGS CAN NOT BE USED OR INEFFECTVEINEFFECTVE
AMIKACIN, CHLORTETRACYCLINE, AMIKACIN, CHLORTETRACYCLINE, BLEOMYCINBLEOMYCIN
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CATEGORY - XCATEGORY - X STUDIES IN ANIMALS OR HUMAN BEINGS STUDIES IN ANIMALS OR HUMAN BEINGS
HAVE DEMONSTRATED FETAL HAVE DEMONSTRATED FETAL ABNORMALITIES OR THERE IS EVIDENCE OF ABNORMALITIES OR THERE IS EVIDENCE OF FETAL RISK BASED ON HUMAN EXPERIENCE FETAL RISK BASED ON HUMAN EXPERIENCE OR BOTH, AND THE RISK OF USE OF DRUG IN OR BOTH, AND THE RISK OF USE OF DRUG IN PREGNANT WOMEN CLEARLY OUTWEIGHS PREGNANT WOMEN CLEARLY OUTWEIGHS ANY POSSIBLE BENEFIT. THE DRUG IS ANY POSSIBLE BENEFIT. THE DRUG IS CONTRAINDICATEDCONTRAINDICATED IN WOMEN WHO ARE OR IN WOMEN WHO ARE OR MAY BECOME PREGNANTMAY BECOME PREGNANT
TRIAZOLAM, TESTOSTERONE, THALIDOMIDETRIAZOLAM, TESTOSTERONE, THALIDOMIDE
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ANTIBOTIC ANTIBOTIC PROPHYLAXISPROPHYLAXIS
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REFERENCESREFERENCES ESSENTIALS OF MEDICAL ESSENTIALS OF MEDICAL
PHARMACOLOGYPHARMACOLOGY
K D TRIPATHIK D TRIPATHI PHARMACOLOGY & PHARMACOLOGY &
PHARMACOTHERAPEUTICSPHARMACOTHERAPEUTICS
R S SATOSKARR S SATOSKAR PRINCIPLES OF DENTAL PHARMACOLOGYPRINCIPLES OF DENTAL PHARMACOLOGY
NARESH KUMAR KHANNANARESH KUMAR KHANNA CURRENT INDEX OF MEDICAL CURRENT INDEX OF MEDICAL
SPECIALITIESSPECIALITIES INTERNET INTERNET
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THANK YOUTHANK YOU