Anthelmintic Agents PDF

ANTHELMINTIC AGENTS ANTHELMINTIC AGENTS Anthelmintics are a group of antiparasitic antibiotics that treat infections by parasitic worms or helminths. Types of Helminths: Roundworms Flukes Tapeworms Thorny-headed worms Agents: Albendazole...

ANTHELMINTIC AGENTS ANTHELMINTIC AGENTS Anthelmintics are a group of antiparasitic antibiotics that treat infections by parasitic worms or helminths. Types of Helminths: Roundworms Flukes Tapeworms Thorny-headed worms Agents: Albendazole Niclosamide Bithionol Oxamniquine Diethylcarbamazine Citrate Piperazine Doxycycline Praziquantel Ivermectin Pyrantel Pamoate Mebendazole Thiabendazole Metrifonate (trichlorfon) Albendazole Mechanism of Action: Albendazole, a benzimidazole derivative, binds to free B- tubulin in parasite cells. This results in selective inhibition of parasite microtubule polymerisation and inhibition of microtubule-dependent glucose uptake. Insufficient glucose causes a lack of adenosine triphosphate (ATP) resulting in the death of the parasite. Significant ADR and Side effects: Significant: Bone marrow suppression, aplastic anaemia, agranulocytosis; mild to moderate elevation of liver enzymes, hepatitis, acute liver failure. Blood and lymphatic system disorders: Leucopenia, neutropenia. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea. General disorders and administration site conditions: Fever. Nervous system disorders: Dizziness, headache. Skin and subcutaneous tissue disorders: Alopecia. Albendazole Mechanism of Action: Albendazole, a benzimidazole derivative, binds to free B- tubulin in parasite cells. This results in selective inhibition of parasite microtubule polymerisation and inhibition of microtubule-dependent glucose uptake. Insufficient glucose causes a lack of adenosine triphosphate (ATP) resulting in the death of the parasite. Significant ADR and Side effects: Significant: Bone marrow suppression, aplastic anaemia, agranulocytosis; mild to moderate elevation of liver enzymes, hepatitis, acute liver failure. Blood and lymphatic system disorders: Leucopenia, neutropenia. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea. General disorders and administration site conditions: Fever. Nervous system disorders: Dizziness, headache. Skin and subcutaneous tissue disorders: Alopecia. Albendazole Significant Drug interactions: Cimetidine, Dexamethasone , and Praziquantel Carbamazepine, Phenobarbital and Phenytoin Spectrum of Activity: Albendazole, a broad-spectrum oral antihelminthic Ascariasis, trichuriasis, and hookworm and pinworm infections Hydatid disease Neurocysticercosis The drug should not be given to patients with known hypersensitivity to other benzimidazole drugs or to those with cirrhosis. Bithionol Mechanism of Action: It competitively inhibits electron transfer, resulting in impaired anaerobic energy metabolism and trematode death. Its parasite specificity is due to its unique target in the parasite respiratory chain. Significant ADR and Side effects: Spectrum of Activity: Diarrhea Narrow spectrum (liver and rumen fluke infections). Abdominal cramps Fasciola hepatica Anorexia Paragonimus westermani Nausea Vomiting Dizziness Headache. Skin rashes Diethylcarbamazine Citrate Mechanism of Action: Diethylcarbamazine is an anthelmintic that is used in the treatment of lymphatic filariasis. It is active against the microfilariae and adult worms of W. bancrofti, B. malayi, B. timori and Loa loa but only against the microfilariae of O. volvulus. It is also used in treatment of toxocariasis. Repeated courses may be necessary. Significant ADR and Side Effects: Spectrum of Activity: Fever Wuchereria bancrofti GI disturbances Brugia malayi Severe hypersensitivity reactions may occur Brugia timori Encephalitis and retinal haemorrhage. Loa loa Significant Drug interactions: Ivermectin or Albendazole Corticosteroids or Immunosuppressive drugs Certain antiepileptics or antifungals Doxycycline Mechanism of Action: Reversibly binds to 30s ribosomal subunit and possibly the 50s ribosomal subunits, blocking the binding of aminoacyl tRNA to the mRNA and inhibiting bacterial protein synthesis. Doxycycline Significant ADR and Side Effects: Spectrum of Activity: Permanent teeth discoloration Gram positive bacteria Enamel hypoplasia Gram negative bacteria Photosensitivity Aerobic bacteria Benign intracranial hypertension Anaerobic bacteria Overgrowth of non-susceptible bacteria Spirochetes and mycoplasma Exacerbation of SLE-Jarisch-Herxheimer reaction Decrease fibula growth Significant Drug Interactions: Barbiturates Rifampicin Carbamazepine Phenytoin Additional: May deminish the effect of oral contraceptives May increase plasma concentration of cyclosporine May potentiate hypoglycemic effect of sulfonylureas Ivermectin Mechanism of Action: Ivermectin binds to glutamate-gated chloride channels — pushing the channels open to increase the flow of chloride ions. This hyperpolarizes the cell membrane, paralyzing, and killing them. Ivermectin Significant ADR and Side Effects: Spectrum of Activity: Fatigue Onchocerciasis (riverblindness) Dizziness Strongyloidiasis Nausea Scabies Vomiting Lymphatic filariasis Abdominal pain Hookworm infections Rashes Ascaris lumbricoides (roundworm) Trichuris trichiura (whipworm) Significant Drug Interactions: Enterobius vermicularis (pinworm) Warfarin - increase bleeding risk Antiplatelet agents - increase bleeding risk (e.g., aspirin, clopidogrel) Anticonvulsants - reduced ivermectin efficacy. (e.g., carbamazepine, phenytoin) Rifampicin - decreases ivermectin levels, reducing efficacy. Antifungal agents - increases ivermectin levels. (e.g., ketoconazole, itraconazole) Biological source: Streptomyces avermitilis Mebendazole Mechanism of Action: Mebendazole works by selectively inhibiting the synthesis of microtubules via binding to colchicine binding site to B-tubulin, thereby blocking the polymerization of tubulin dimers in intestinal cells of parasites. Mebendazole Significant ADR and Side Effects: Spectrum of Activity Mild nausea Roundworm Vomiting Hookworm Diarrhea Whipworm Abdominal pain Threadworm (pinworm) Trichinosis Rare Side Effects: Hypersensitivity (rash, urticaria) Agranulocytosis Alopecia Elevation of liver enzymes Significant Drug Interaction: Cimetidine - increase the plasma concentration of mebendazole Potentially fatal - concomitant use with mebendazole may lead to Stevens-Johnson Syndrome or Toxic epidermal necrolysis. Metrifonate (trichlorfon) Mechanism of Action: Acts as a prodrug and is converted nonenzymatically into dichlorvos, an organophosphate. Dichlorvos inhibits acetylcholinesterase, leading to accumulation of acetylcholine at nerve synapses, causing paralysis of susceptible organisms Significant ADR and Side Effects: Spectrum of Activity Transient cholinergic effects such as: Effective primarily against Schistosoma Salivation haematobium (urinary schistosomiasis). Sweating Abdominal cramps Nausea Diarrhea Significant Drug Interaction: risk or severity of adverse effects can be increased when Metrifonate is combined with Acetylcholine. Niclosemide Mechanism of Action: Inhibits oxidative phosphorylation in the mitochondria of tapeworms, leading to depletion of ATP. Significant ADR and Side Effects: Spectrum of Activity GI disturbances (e.g. nausea, retching, abdominal pain) Taenia saginata (Beef Tapeworm) lightheadedness, Taenia solium (Pork Tapeworm) pruritus. Diphyllobothrium latum (Fish Tapeworm) Nausea Fasciolopsis buski (large intestinal fluke) Vomiting Significant Drug Interaction: Alcohol: Risk of disulfiram-like reactions. --Headache, Low blood pressure, Severe flushing, Palpitations, Nausea, Thirst, Chest pain, Dizziness, and Abdominal discomfort May reduce the absorption of other medications due to gastrointestinal effects. like: Acetaminophen,Acyclovir,Albendazole Oxamniquine Mechanism of Action: iactivated by schistosome enzymes into a reactive ester, which binds to DNA.that cause irreversible inhibition of DNA synthesis and leads to the death of the parasite. Oxamniquine Significant ADR and Side Effects: Spectrum of Activity Common: Active against Schistosoma mansoni Dizziness (intestinal schistosomiasis). Drowsiness Ineffective against S. haematobium or S. japonicum. Headache Nausea Rare: Seizures Allergic reactions (rash, urticaria) Significant Drug Interaction: Sedatives and alcohol: May potentiate CNS depressant effects. Piperazine Mechanism of Action: Spectrum of Activity: Hyperpolarization of Ascaris muscle by a GABA agonistic action. Opening of CL Narrow-spectrum CHANNELS causes relaxation depresses responsiveness to contractile action of ACh. - limited for roundworms Significant ADR and Side Effects: Nausea Vomiting Abdominal discomfort Dizziness Excitement Convulsions Death Significant Drug Interactions: Antacids - may reduce absorption CNS depressants - may enhance sedative effects MAOIs - may increase risk of hypertensive crisis Praziquantel Mechanism of Action: Spectrum of Activity: Increase the permeability of trematode and cestode cell Broad-spectrum membranes to calcium. - trematodes (flukes); all species of Schistosoma, cestodes (tapeworms) Significant ADR and Side Effects: Headache, dizziness, drowsiness, and lassitude; others include nausea, vomiting, abdominal pain, loose stools, pru- ritus, urticaria, arthralgia, myalgia, and low-grade fever Significant Drug Interactions: Carbamazepin, Phenytoin, Rifampin and Dexamethasone Pyrantel Pamoate Mechanism of Action: A neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinesterase; this results in paralysis of worms, followed by expulsion. Spectrum of Activity: Broad-spectrum - directed against pinworm, roundworm, and hookworm infections. Significant ADR and Side Effects: Infrequent, mild, and transient — nausea, vomiting, diarrhea, abdominal cramps, dizziness, drowsiness, headache, insomnia, rash, fever, and weak- ness Significant Drug Interactions: Ampicillin and Acetaminophen Thiabendazole Mechanism of Action: Same as that of other benzimidazoles. Spectrum of Activity: Broad-spectrum - Nematodes, Hookworm, Roundworm and Pinworm Significant ADR and Side Effects: Nausea, Vomiting, Abdominal Pain, Diarrhea, Impairment of Alertness and Itching. Significant Drug Interactions: Theophylline References: Katzung B.G. (2018). BASIC AND CLINICAL PHARMACOLOGY. 14TH Edition MIMS  REPORTERS: KALEV SISON CHARIS JOY SUPSUP AHRON FRIAS TAMONDONG MARIETTA ANN TORIO THANK YOU FOR LISTENING!