Description
Subject:- Medicinal chemistry 2
Semester:- 5th sem
Course:- Bachelor of Pharmacy B Pharmacy
Medicinal Chemistry-IIl ANT-HELMINTICS WWW.REMIXEDUCATION.IN ANTHELMINTICS • ANTHELMINTICS ARE DRUGS THAT HAVE THE CAPABILITY OF RIDDING THE BODY OF PARASITIC WORMS OR HELMINTHS • HELMINTHS THAT INFECT HUMAN HOSTS ARE DIVIDED INTO TWO CATEGORIES, OR PHYLA: • A) PLATYHELMINTHES (FLATWORMS)- INCLUDE THE CLASSES CESTODE (TAPEWORMS) AND TREMATODE (FLUKES OR SCHISTOSOMES) • B) ASCHELMINTHES OR NEMATODES (ROUNDWORMS)- ROUNDWORM, HOOKWORM, PINWORM, AND WHIPWORM. THESE WORMS ARE CYLINDRICAL IN SHAPE, WITH SIGNIFICANT VARIATIONS IN SIZE, PROPORTION, AND STRUCTURE www.remixeducation.in ANTHELMINTICS • NEMATODE INFECTIONS • ANCYLOSTOMIASIS OR HOOKWORM INFECTION- AMERICAN HOOKWORM (NECATOR AMERICANUS) AND THE “OLD WORLD” HOOKWORM (ANCYLOSTOMA DOUDENALE). • ENTEROBIASIS OR PINWORM INFECTION- ENTEROBIUS VERMICULARIS • ASCARIASIS OR ROUNDWORM INFECTIONS- ASCARIS LUMBRICOIDES • TRICHURIASIS OR WHIPWORM INFECTIONS- TRICHURIS TRICHIURA • TRICHINOSIS OR TRICHINA INFECTION- TRICHINELLA SPIRALIS • FILARIASIS- WUCHERERIA BANCROFTI, BRUGIA MALAYI, AND BRUGIA TIMORI www.remixeducation.in ANTHELMINTICS • CESTODE AND TREMATODE INFECTIONS • CYSTICERCOSIS OR TAPEWORM INFECTION • BEEF TAPEWORM (TAENIA SAGINATA) • PORK TAPEWORM (TAENIA SOLIUM) • DWARF TAPEWORM (HYMENOLEPIS NANA) • FISH TAPEWORM (DIPHYLLOBOTHRIUM LATUM) • SCHISTOSOMIASIS OR BLOOD FLUKES- SCHISTOSOMA HEMATOBIUM, SCHISTOSOMA MANSONI, AND SCHISTOSOMA JAPONICUM www.remixeducation.in DIETHYLCARBAMAZINE CITRATE • HIGHLY WATER-SOLUBLE CRYSTALLINE COMPOUND THAT HAS SELECTIVE ANTHELMINTIC ACTIVITY • IT IS EFFECTIVE AGAINST VARIOUS FORMS OF FILARIASIS, INCLUDING BANCROFT, ONCHOCERCIASIS, AND LAVIASIS • IT IS ALSO ACTIVE AGAINST ASCARIASIS • MECHANIM- NOT CLEARLY KNOWN • SUGGESTION- INHIBITION OF MICROTUBULE POLYMERIZATION AND DISRUPTION OF PREFORMED MICROTUBULES • OR INTERFERENCE WITH ARACHIDONIC ACID METABOLISM • ADVERSE REACTIONS- ANAPHYLACTIC REACTIONS, INTENSE PRURITUS, AND OCULAR COMPLICATIONS www.remixeducation.in THIABENDAZOLE • OCCURS AS A WHITE CRYSTALLINE SUBSTANCE THAT IS ONLY SLIGHTLY SOLUBLE IN WATER BUT IS SOLUBLE IN STRONG MINERAL ACIDS. • THIABENDAZOLE IS A BASIC COMPOUND WITH A PKA OF 4.7 THAT FORMS COMPLEXES WITH METAL IONS • MECHANISM- INHIBITS THE HELMINTH-SPECIFIC ENZYME FUMARATE REDUCTASE (IMPORTANT ENZYME IN HELMINTHES THAT APPEARS TO BE INVOLVED IN OXIDATION OF NADH TO NAD FOR ATP PRODUCTION) • ALSO ARREST NEMATODE CELL DIVISION IN METAPHASE BY INTERFERING WITH MICROTUBULE ASSEMBLY AND EXHIBIT A HIGH AFFINITY FOR TUBULIN, THE PRECURSOR PROTEIN FOR MICROTUBULE SYNTHESIS www.remixeducation.in THIABENDAZOLE • HAS BROAD-SPECTRUM ANTHELMINTIC ACTIVITY • IT IS USED TO TREAT ENTEROBIASIS, STRONGYLOIDIASIS (THREADWORM INFECTION), ASCARIASIS, UNCINARIASIS (HOOKWORM INFECTION), AND TRICHURIASIS (WHIPWORM INFECTION) • ALSO USED TO RELIEVE SYMPTOMS ASSOCIATED WITH CUTANEOUS LARVA MIGRANS (CREEPING ERUPTION) AND THE INVASIVE PHASE OF TRICHINOSIS. • WIDELY USED IN VETERINARY PRACTICE TO CONTROL INTESTINAL HELMINTHS IN LIVESTOCK www.remixeducation.in MEBENDAZOLE • BROAD-SPECTRUM ANTHELMINTIC THAT IS EFFECTIVE AGAINST VARIOUS NEMATODE INFESTATIONS, INCLUDING WHIPWORM, PINWORM, ROUNDWORM, AND HOOKWORM • MECHANISM- IRREVERSIBLY BLOCKS GLUCOSE UPTAKE IN SUSCEPTIBLE HELMINTHS, THEREBY DEPLETING GLYCOGEN STORED IN THE PARASITE • IT APPARENTLY DOES NOT AFFECT GLUCOSE METABOLISM IN THE HOST. IT ALSO INHIBITS CELL DIVISION IN NEMATODES • POORLY ABSORBED BY THE ORAL ROUTE • ADVERSE REACTIONS ARE UNCOMMON AND USUALLY ABDOMINAL DISCOMFORT • IT IS TERATOGENIC IN LABORATORY ANIMALS AND SHOULD NOT BE GIVEN DURING PREGNANCY www.remixeducation.in ALBENDAZOLE • BROAD-SPECTRUM ANTHELMINTIC THAT IS NOT CURRENTLY MARKETED IN NORTH AMERICA • WIDELY USED THROUGHOUT THE WORLD FOR THE TREATMENT OF INTESTINAL NEMATODE INFECTION • IT IS EFFECTIVE AS A SINGLE-DOSE TREATMENT FOR ASCARIASIS, NEW AND OLD WORLD HOOKWORM INFECTIONS, AND TRICHURIASIS • MULTIPLE-DOSE THERAPY WITH ALBENDAZOLE CAN ERADICATE PINWORM, THREADWORM, CAPILLARIASIS, CLONORCHIASIS, AND HYDATID DISEASE • EFFECTIVENESS OF ALBENDAZOLE AGAINST TAPEWORMS (CESTODES) IS GENERALLY MORE VARIABLE AND LESS IMPRESSIVE • WHITE CRYSTALLINE POWDER THAT IS VIRTUALLY INSOLUBLE IN WATER www.remixeducation.in ALBENDAZOLE • ORAL ABSORPTION OF ALBENDAZOLE IS ENHANCED BY A FATTY MEAL • DRUG UNDERGOES RAPID AND EXTENSIVE FIRST-PASS METABOLISM TO THE SULFOXIDE, WHICH IS THE ACTIVE FORM IN PLASMA • ELIMINATION HALF-LIFE OF THE SULFOXIDE RANGES FROM 10 TO 15 HOURS • HIGH DOSE CAN RESULT IN ADVERSE EFFECTS SUCH AS BONE MARROW DEPRESSION, ELEVATION OF HEPATIC ENZYMES, AND ALOPECIA www.remixeducation.in NICLOSAMIDE • OCCURS AS A YELLOWISH WHITE, WATER-INSOLUBLE POWDER • POTENT TAENIACIDE THAT CAUSES RAPID DISINTEGRATION OF WORM SEGMENTS AND THE SCOLEX • PENETRATION OF THE DRUG INTO VARIOUS CESTODES APPEARS TO BE FACILITATED BY THE DIGESTIVE JUICES OF THE HOST • NICLOSAMIDE IS WELL TOLERATED FOLLOWING ORAL ADMINISTRATION, AND LITTLE OR NO SYSTEMIC ABSORPTION OF IT OCCURS • A SALINE PURGE 1 TO 2 HOURS AFTER INGESTION OF THE TAENIACIDE IS RECOMMENDED TO REMOVE THE DAMAGED SCOLEX AND WORM SEGMENTS- MANDATORY www.remixeducation.in OXAMNIQUINE • ANTISCHISTOSOMAL AGENT THAT IS INDICATED FOR THE TREATMENT OF SCHISTOSOMA MANSONI (INTESTINAL SCHISTOSOMIASIS) INFECTION • MECHANISM- SHOWN TO INHIBIT DNA, RNA, AND PROTEIN SYNTHESIS IN SCHISTOSOMES • 6-HYDROXYMETHYL GROUP IS CRITICAL FOR ACTIVITY; • METABOLIC ACTIVATION OF PRECURSOR 6-METHYL DERIVATIVES IS CRITICAL • FREE BASE OCCURS AS A YELLOW CRYSTALLINE SOLID THAT IS SLIGHTLY SOLUBLE IN WATER BUT SOLUBLE IN DILUTE AQUEOUS MINERAL ACIDS AND SOLUBLE IN MOST ORGANIC SOLVENTS • DIZZINESS AND DROWSINESS ARE COMMON, BUT TRANSITORY, SIDE EFFECTS • SERIOUS REACTIONS, SUCH AS EPILEPTIFORM CONVULSIONS, ARE RARE www.remixeducation.in PRAZIQUANTEL • BROAD-SPECTRUM AGENT THAT IS EFFECTIVE AGAINST VARIOUS TREMATODES (FLUKES) • IT HAS BECOME THE AGENT OF CHOICE FOR THE TREATMENT OF INFECTIONS CAUSED BY SCHISTOSOMES (BLOOD FLUKES) • EFFECTIVE TREATMENT FOR FASCIOLOPSIASIS (INTESTINAL FLUKE), CLONORCHIASIS (CHINESE LIVER FLUKE), FASCIOLIASIS (SHEEP LIVER FLUKE), OPISTHORCHOSIS (LIVER FLUKE), AND PARAGONIMIASIS (LUNG FLUKE) • MECHANISM- INCREASES CELL MEMBRANE PERMEABILITY OF SUSCEPTIBLE WORMS, RESULTING IN THE LOSS OF EXTRACELLULAR CALCIUM. MASSIVE CONTRACTIONS AND ULTIMATE PARALYSIS OF THE FLUKE MUSCULATURE OCCURS, FOLLOWED BY PHAGOCYTOSIS OF THE PARASITE www.remixeducation.in PRAZIQUANTEL • ORAL ADMINISTRATION, ABOUT 80% OF THE DOSE IS ABSORBED • DRUG IS RAPIDLY METABOLIZED IN THE LIVER IN THE FIRST-PASS • WHITE CRYSTALLINE SOLID THAT IS INSOLUBLE IN WATER www.remixeducation.in IVERMECTIN • IS A MIXTURE OF 22,23-DIHYDRO DERIVATIVES OF AVERMECTINS B1A AND B1B PREPARED BY CATALYTIC HYDROGENATION • AVERMECTINS ARE MEMBERS OF A FAMILY OF STRUCTURALLY COMPLEX ANTIBIOTICS PRODUCED BY FERMENTATION WITH A STRAIN OF STREPTOMYCES AVERMITILIS • IVERMECTIN IS ACTIVE IN LOW DOSAGE AGAINST A WIDE VARIETY OF NEMATODES AND ARTHROPODS THAT PARASITIZE ANIMALS • STRUCTURE- PENTACYCLIC 16-MEMBERED–RING AGLYCONES GLYCOSIDICALLY LINKED AT THE 3-POSITION TO A DISACCHARIDE THAT COMPRISES TWO OLEANDROSE SUGAR RESIDUES • SIDE CHAIN AT THE 25-POSITION OF THE AGLYCONE IS SEC-BUTYL IN AVERMECTIN B1A, WHEREAS IN AVERMECTIN B1B, IT IS ISOPROPYL www.remixeducation.in AVERMECTINS B1A (-C2H5) AND B1B (-CH3) www.remixeducation.in IVERMECTIN • IVERMECTIN CONTAINS AT LEAST 80% OF 22,23-DIHYDROAVERMECTIN B1A AND NO MORE THAN 20% 22,23-DIHYDROAVERMECTIN B1B • WIDESPREAD USE IN VETERINARY PRACTICE IN THE UNITED STATES AND MANY COUNTRIES THROUGHOUT THE WORLD FOR THE CONTROL OF ENDOPARASITES AND ECTOPARASITES IN DOMESTIC ANIMALS • IT HAS BEEN FOUND EFFECTIVE FOR THE TREATMENT OF ONCHOCERCIASIS (“RIVER BLINDNESS”) IN HUMANS, AN IMPORTANT DISEASE CAUSED BY THE ROUNDWORM ONCOCERCA VOLVULUS • MECHANISM- IT BLOCKS INTERNEURON–MOTOR NEURON TRANSMISSION IN NEMATODES BY STIMULATING THE RELEASE OF THE INHIBITORY NEUROTRANSMITTER GABA www.remixeducation.in DIETHYLCARBAMAZINE CITRATE- SYNTHESIS N, N-diethyl-4-methyl-1-piperazin 1-methylpiperazine Carbonyl chloride Citric acid www.remixeducation.in Nitration MEBENDAZOLE- SYNTHESIS Reduction 4-chlorobenzophenone 3,4-diaminobenzophenone methyl chloroformate S-methylthiourea N-methoxycarbonyl-S-methylthiourea www.remixeducation.in THANK YOU WWW.REMIXEDUCATION.IN