PHARMACOLOGY

By MARY RAMIREZ

1 GENERAL PRINCIPLES 1 2 TOPICAL ANTI INFECTIVE AGENTS 9 3 CHEMOTHERAPY OF PARASITIC DISEASES 21 4 SULPHONAMIDES AND URINARY TRACT ANTISEPTIC AGENTS 41 5 MODES OF ACTION OF ANTIBIOTICS 55 6 LACTAM ANTIBIOTICS 71 7 ANTIBIOTICS THAT AFFECT PROTEIN SYNTHESIS 93 8 ANTIBIOTICS THAT INTERFERE WITH CYTOPLASMIC MEMBRANE FUNCTION 111 9 ANTIBIOTICS AFFECTING NUCLEIC ACID SYNTHESIS AND MISCELLANEOUS ANTIBIOTICS 115 10 ANTIFUNGAL AGENTS 119 11 ANTIVIRAL AGENTS 133 12 ANTI NEOPLASTIC AGENTS 145 13 ANTI TUBERCULOSIS AND ANTI LEPROTIC AGENTS 169 14 ADENOHYPOPHYSEAL HORMONES 181 15 THYROID AND PARATHYROID HORMONES 197 CONTENTS 16 SEX HORMONES 211 17 ADRENOCORTICOIDS 239 18 INSULIN AND ORAL HYPOGLYCEMIC AGENTS 251 19 DIURETIC AGENTS 269 20 DRUGS ACTING ON GIT 283 21 DIAGNOSTIC AGENTS 311 22 DRUGS ACTING ON BLOOD 323 23 MYOCARDIAL DISEASES 351 24 CARDIAC GLYCOSIDES 361 25 ANTI ANGINAL AGENTS 381 26 ANTI ARRHYTHMIC AGENTS 391 27 ANTI HYPERTENSIVE AGENTS 409 28 FAT SOLUBLE VITAMINS 435 29 WATER SOLUBLE VITAMINS 451 30 IMMUNO MODULATORS 479 1 GENERAL PRINCIPLES 1 1 1 1 1 1 1 1 INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION PATHOGENS ARE MICROORGANISMS THAT CAN CAUSE A DISEASE CONDITION BOTH IN MAN AND ANIMALS NOT VERY LONG AGO AT THE BEGINNING OF THIS CENTURY NEITHER THE CAUSATIVE AGENTS OF INFECTIVE DISEASES NOR THE ACTIVE INGREDIENTS OF THE TRADITIONAL REMEDIES WHICH WERE USED TO CURE THE INFECTIONS COULD BE IDENTIFIED WITH THE INTRODUCTION OF THE SCIENCE OF MICROBIOLOGY IT WAS SOON POSSIBLE TO GROW BACTERIA IN CULTURE THE SCIENTIFIC PRACTICE OF ORGANIC CHEMISTRY AND THE RATIONAL APPLICATION OF MICROBIOLOGY RESULTED IN THE BIRTH OF VARIOUS ANTIMICROBIAL SUBSTANCES THE TERM MICROBIOLOGY CAN BE DEFINED IN VARIOUS WAYS AND IT ESSENTIALLY INCLUDES THE STUDY OF MICROORGANISMS BACTERIOLOGY IS THE SCIENCE THAT DEALS WITH THE STUDY OF BACTERIA WHILE MYCOLOGY COVERS THE STUDY OF FUNGI THESE TYPICAL UNICELLULAR MICROSCOPIC ORGANISMS ARE WIDELY DISTRIBUTED IN THE AIR WATER SOIL IN THE BODIES OF LIVING PLANTS AND ANIMALS AND IN THE DEAD ORGANIC MATTERS SOME DERMATOPHYTES DO NOT INVADE LIVING TISSUES BUT THEY SURVIVE ON THE DEAD TISSUE STRUCTURES OF STRATUM CORNEUM OF THE SKIN HAIRS AND THE NAILS MILD ENDOGENOUS DEFENCE LINE IS PROVIDED BY THE SECRETION OF SEBUM SWEAT MUCOUS SALIVA TEARS GASTRIC AND INTESTINAL JUICES WHICH HELPS TO WASH AWAY THE MICROORGANISMS FROM VARIOUS BODY SURFACES WHEREAS THE STRONGER DEFENCE MECHANISMS INCLUDE INFLAMMATORY MECHANISMS E G PHAGO CYTOSIS AND IMMUNOLOGICAL RESPONSES THE IMMUNE RESPONSE TO INFECTION ESPECIALLY TO VIRAL INFECTION MAY LEAD TO SIGNIFICANT DAMAGE TO THE CELL OR A TISSUE THE FIRST SIGNIFICANT EVENT REPORTED IN THE HISTORY OF CHEMOTHERAPY WAS THE INTRODUCTION OF MAGIC ANTISYPHILITIC BULLET SALVARSON BY PAUL EHRLICH IN 1909 IT WAS FOLLOWED BY THE REPORT OF SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF PRONTOSIL BY DOMAGK IN 1935 HE REPORTED THE EFFECT OF PRONTOSIL RUBRUM AN AZO DYE AGAINST STREPTOCOCCAL INFECTION THE IN VIVO CONVERSION OF PRONTOSIL TO THE ACTIVE SULPHONAMIDE MOIETY WAS LATER FOUND TO BE RESPONSIBLE FOR ITS ANTIBACTERIAL ACTIVITY THIS OBSERVATION THEN INITIATED THE DEVELOPMENT OF MORE SAFER AND EFFECTIVE SULPHONAMIDES IN 1929 PENICILLIUM NOTATUM A LABORATORY CONTAMINANT GROWING ON AGAR PLATE WAS FOUND TO INHIBIT THE GROWTH OF STAPHYLOCOCCUS GROWING IN THE SAME PLATE WITH THE ISOLATION OF PENICILLIN FROM THIS FUNGUS BY FLOREY CHINA AND COWORKERS A NEW ERA OF ANTIBACTERIAL AGENTS WAS OPENED SUBSEQUENTLY MANY NATURAL AND SEMISYNTHETIC ANTIBIOTICS WERE DEVELOPED BY CHANGING THE NATURE OF THE SIDE CHAIN OF THE PARENT NUCLEUS THIS MODIFICATION IN THE STRUCTURE CREATED VARIATION IN THE ANTIBACTERIAL AND PHARMACOKINETIC PARAMETERS OF THE BASIC SKELETON 1 20 000 A O 8 000 A O DNA RNA PROTEIN CELL WALL CELL MEMBRANE 70 S SUBUNIT 50S SUBUNIT 30 S SUBUNIT FIG 1 1 MICROSCOPIC ORGANISM MICROORGANISMS COMPRISES ALGAE FUNGI BACTERIA VIRUSES AND PROTOZOA BACTERIA AND FUNGI ARE DEVOID OF CHLOROPHYLL WHILE IT IS PRESENT IN ALGAE THE MAIN STRUCTURAL FEATURES OF A MICRO SCOPIC ORGANISM ARE REPRESENTED IN ABOVE FIG 1 1 THE MAJOR CLASSES OF MICROORGANISMS ARE AS FOLLOWS I BACTERIA A BACTERIAL CELL CONSISTS OF CELL WALL CYTOPLASMIC MEMBRANE CYTOPLASM FLAGELLA CAPSULE AND FIMBRIAE ETC WHICH HELPS IN CARRYING OUT VARIOUS FUNCTIONS OF THE CELL THE CYTOPLASMIC MEMBRANE ENCLOSES THE THICK VISCOUS SEMIFLUID OR ALMOST JELLY LIKE COLOURLESS TRANSPARENT MATERIAL WHICH IS KNOWN AS PROTOPLASM OTHER STRUCTURES VISIBLE IN PROTOPLASM ARE NUCLEUS VACUOLES MESOSOMES MITOCHONDRIA RIBOSOMES POLYSACCHARIDES LIPIDS METACHROMATIC GRANULES ETC ALTHOUGH THE VAST MAJORITY OF BACTERIA ARE HARMLESS OR BENEFICIAL A FEW PATHOGENIC BACTERIA CAN CAUSE INFECTIOUS DISEASES THE MOST COMMON BACTERIAL DISEASE IS TUBERCULOSIS CAUSED BY THE BACTERIUM MYCOBACTERIUM TUBERCULOSIS BESIDES THIS PATHOGENIC BACTERIA CONTRIBUTE TO OTHER GLOBALLY IMPORTANT DISEASES SUCH AS PNEUMONIA STREPTOCOCCUS AND PSEUDOMONAS THEY ALSO CAUSE SOME FOOD BORN ILLINESSES SHIGELLA SP SALMONELLA SP INFECTIONS SUCH AS TETANUS TYPHOID FEVER DIPTHERIA AND SYPHILIS ARE ALSO INITIATED BY BACTERIA II PROTOZOA IT CAN BE DIFFERENTIATED FROM THE REMAINING CLASSES ON THE GROUND OF MORPHOLOGICAL PHYSIOLOGICAL AND NUTRITIONAL CHARACTERISTICS III VIRUSES VIRUSES ARE ULTRA MICROSCOPIC MICRO ORGANISMS RANGING FROM 0 1 0 3 IN DIAMETER THEY CAN BE CULTIVATED ONLY IN THE LIVING CELLS AND ARE PARASITES OF PLANTS ANIMALS OR EVEN BACTERIA THEY JUST CONTAIN A NUCLEIC ACID CORE AND A PROTEIN COAT THEY ARE RICH IN NUCLEIC ACID AND POSSESS ONLY ONE TYPE OF NUCLEIC ACID EITHER RNA OR DNA THEY DIFFER FROM OTHER DISEASE PRODUCING PATHOGENS ON THE BASIS OF THEIR SMALLER SIZE SIMPLER CHEMICAL COMPOSITION LACK OF METABOLIC ENZYMES LACK OF PROTEIN SYNTHETIC MACHINERY AND A HOST CELL DEPENDENT MECHANISM OF MULTIPLICATION INFECTIONS SUCH AS SMALLPOX INFLUENZA MUMPS MEASLES CHICKENPOX EBOLA AND RUBELLA ARE SOME COMMON INFECTIONS CAUSED BY VIRUSES IV FUNGI THESE ARE USUALLY MULTICELLULAR PLANT ORGANISMS DEVOID OF CHLOROPHYLL THEY HAVE DIFFERENT SHAPES AND SIZES FUNGI ARE THE MOST COMMON CAUSE OF DISEASE IN CROPS AND OTHER PLANTS LIFE THREATENING FUNGAL INFECTIONS IN HUMANS MOST OFTEN OCCUR IN IMMUNOCOMPROMISED PATIENTS OR VULNERABLE PEOPLE WITH A WEAKENED IMMUNE SYSTEM ALTHOUGH FUNGI ARE COMMON PROBLEMS IN THE IMMUNOCOMPROMISED POPULATION AS THE CAUSATIVE AGENTS OF SKIN NAIL OR HAIR INFECTION THEY RANGE FROM SINGLE CELL MICROSCOPIC YEAST TO GIANT MULTICELLULAR MUSHROOMS 2 THEY INCLUDES A ACTINOMYCES THESE ARE ANAEROBIC ORGANISMS THAT GROW AS THIN BRANCHING FILAMENTS ACTINOMYCOSIS A DISEASE CAUSED BY ACTINOMYCETES AFFECTS LUNGS CAUSING PNEUMONIA B YEAST THESE ARE SPHEROIDAL CELLS THAT REPRODUCE BY BUDDING THEY MOST FREQUENTLY GIVE RISE TO ABCESSES IN THE BRAIN OR LUNGS OR TO THE MENINGITIS C YEAST LIKE FUNGI THEY ARE NORMALLY PRESENT IN THE MOUTH ARMS OR VAGINA OF HEALTHY ADULT THEY MAY CAUSE PRURITUS ANI PRURITUS VULVAE THRUST LIKE CONDITION IN MOUTH OPHTHALMIC CANDIDIASIS OR MONILIAL STOMATITIS CANDIDIASIS IS ONE SUCH INFECTION CAUSED BY AN ORGANISM CANDIDA ALBICANS IT THRIVES NORMALLY IN ALIMENTARY TRACT AND VAGINA OF THE HEALTHY HUMANS CANDIDIASIS ALSO INFLUENCES CORTICOSTEROID THERAPY D FILAMENTOUS FUNGI MICROSPORUM TRICHOPHYTON ASPERGILLUS AND PENICILLIUM MOULDS ARE SOME EXAMPLES OF FILAMENTOUS FUNGI THEY ARE CHARACTERISED BY THE PRESENCE OF LONG FILAMENTS I E HYPHAE WHICH ARE ARRANGED IN IRREGULAR TRIANGLES I E MYCELIA ASPERGILLOSIS CAUSED BY ASPERGILLUS MOST FREQUENTLY AFFECTS LUNGS BUT EXTRAPULMONARY SYSTEMIC INFECTION INVOLVING BRAIN OR KIDNEY MAY ALSO OCCUR OTHER INFECTIONS LIKE RINGWORM TINEA TINEA CIRCINATS SKIN TINEA PEDIS ATHLETE S FOOT TINEA CAPITIS SCALP AND ONYCHOMYCOSIS NAILS ARE ALSO CAUSED BY MEMBERS OF THIS GROUP E DIMORPHIC FUNGI THIS CATEGORY INCLUDES HISTOPLASMA HISTOPLASMOSIS OR RETICULOENDOTHELIAL CYTOMYCOSIS SPOROTRICHUM E G SPOROTRI CHOSIS AND BLASTOMYCES BLASTOMYCOSIS INFECTIONS IN HUMANS USUALLY OCCUR BY INHALATION OF INFECTIOUS SOILBORNE SPORES V ALGAE ALGAE ARE RELATIVELY SIMPLE ORGANISMS THEY MAY BE UNICELLULAR PRIMITIVE TYPE OR IN SOME CASES ARE AGGREGATION OF SIMILAR CELLS ALGAE ARE FOUND MOST COMMONLY IN AQUATIC ENVIRONMENTS OR IN DAMP SOIL WHATEVER MAY BE THE SIZE OR COMPLEXITY ALL ALGAE CELLS CONTAIN CHLOROPHYLL AND THUS ARE CAPABLE OF PHOTOSYNTHESIS 1 2 1 2 1 2 1 2 BACTERIAL CELL BACTERIAL CELL BACTERIAL CELL BACTERIAL CELL WALL WALL WALL WALL THE BACTERIAL CELL WALL IS ABOUT 10 25 IN THICKNESS IT IS A POROUS AND PERMEABLE STRUCTURE THAT CONTROLS THE FLOW OF VARIOUS SOLUTE MOLECULES IN AND OUT OF THE BACTERIAL CELL IT ENCLOSES THE CYTOPLASMIC MEMBRANE THAT ACTS AS A PHYSICOCHEMICAL BARRIER DUE TO ITS SEMIPERMEABLE NATURE IT IS ABOUT 5 10 M THICK AND CONSISTS OF POLYMERIZING ENZYMES THAT ARE INVOLVED IN FORMATION OF CELL WALL AND OTHER EXTRACELLULAR SUBUNITS CYTOPLASMIC MEMBRANE ENCLOSES A THICK VISCOUS SEMIFLUID OR ALMOST JELLY LIKE COLOURLESS TRANSPARENT MATERIAL KNOWN AS PROTOPLASM OTHER STRUCTURES VISIBLE IN PROTOPLASM ARE NUCLEUS VACUOLES MESOSOMES POLYSACCHARIDES LIPIDS RIBOSOMES METACHROMATIC GRANULES ETC THE MAIN FUNCTION OF CYTOPLASM IS TO SYNTHESIZE ENZYMES AND OTHER PROTEINS NECESSARY FOR THE FUNCTIONING OF BACTERIAL CELL MANY BACTERIAL BODIES CONTAIN GRANULES RICH IN NUCLEOPROTEINS STARCH STORED GLYCOGEN FATS OR LIPIDS A NUMBER OF BACILLI ARE MOTILE DUE TO PRESENCE OF FLAGELLA THE ORGANELLES OF LOCOMOTION CHEMICALLY BACTERIAL CELL WALL IS COMPOSED OF DIAMINOPIMELIC ACID MURAMIC ACID TEICHOIC ACID AMINO SUGARS AMINO ACIDS CARBOHYDRATES AND LIPIDS IN GRAM POSITIVE BACTERIA CELL WALL IS COMPOSED OF A PEPTIDOGLYCAN MUCOPEPTIDE OR GLYCOPEPTIDE OR MUREIN 3