Anti-Helminthic Agents PDF

1 Anti-helminthic Agents & Drugs Used for Treatment of Ectoparasitic Infections DR T. N CHIDUMAYO 8/28/2024  2 LEARNING OBJECTIVES 01 02 03 Describe the...

1 Anti-helminthic Agents & Drugs Used for Treatment of Ectoparasitic Infections DR T. N CHIDUMAYO 8/28/2024  2 LEARNING OBJECTIVES 01 02 03 Describe the Understand the Identify the therapeutic uses mechanisms of toxicities and of antihelmintic actions of contraindications and ectoparasitic antihelmintic and of antihelmintic infections ectoparasitic and ectoparasitic drugs. drugs. drugs. 8/28/2024  3 Introduction Helminths are worms that invade human hosts. There are three types of helminths: nematodes (roundworms), trematodes (flukes), and cestodes (tapeworms). Anthelmintics act either locally within the GI tract to cause expulsion of worms, or systemically against helminths residing outside the GI tract. Treatment of loiasis or onchocerciasis may tissue damage in large parasite burden due to destruction of the microfilariae (Mazzotti-like reaction). 8/28/2024 8/28/2024 4  5 PRAZIQUANTEL 8/28/2024  6 Effective against cestode (tapeworm) and trematode (fluke) infections. Paralysis of the worm due to increased cell membrane permeability of calcium. Praziquantel Target the tegument (skin equivalent). Increases calcium influx increases muscle contraction and eventual paralysis followed by (Biltricide) death. At higher doses, liberate antigens that stimulate a host immune response against it. Most effective drug against all types of fluke infections: blood fluke infections (schistosomiasis), intestinal and liver fluke infections, and lung fluke infections (paragonimiasis). 8/28/2024  7 Abdominal pain, nausea, and diarrhea. Headache, dizziness, and drowsiness (no driving Side Effects or operating machinery) of Serious and Rare CNS effects: seizures, Praziquantel intracranial hypertension, in neurocysticercosis. Inflammatory reactions to dead parasites. Corticosteroids co-administered to reduce inflammation. 8/28/2024  8 BENZIMIDAZOLES 8/28/2024  9 Mechanism of action: Albendazole and mebendazole: Binds to β-tubulin, to inhibit polymerization and microtubule assembly. Albendazole Impairs glucose uptake by nematodes to (Albenza) and decreased ATP production and immobilize Mebendazole the intestinal parasite Cleared from the GI tract. (Vermox) Structural differences in β-tubulin between humans and parasites Mutations in β-tubulin that prevent binding of drug 8/28/2024  10 Roundworm infections caused by Ascaris lumbricoides, Capillaria philippinensis, Enterobius vermicularis (pinworm), Necator americanus (hookworm), and Trichuris trichiura (whipworm). Cestodes E. granulosus and E. multilocularis. Indications: Benzimidazoles Albendazole is used to treat cysticercosis and cystic hydatid disease, for which it is the drug of choice. Limited solubility in water, and coadministration with a fatty meal to enhance absorption. 8/28/2024  11 GI distress during short-term therapy. Serious and Rare side effects: Agranulocytosis & Side Effects alopecia Benzimidazoles Teratogenic in animals. They are used in pregnancy, but only after a careful risk-benefit assessment. Thiabendazole (Mintezol) has wide nematodes spectrum but, limited clinical use due to toxicity. 8/28/2024  12 IVERMECTIN 8/28/2024  13 Mechanism of Action: Ivermectin (Mectizan) Tonic paralysis of nematode musculature. Binds to glutamate-activated Cl– channels in nerve or muscle cells. Hyperpolarization from increased intracellular chloride concentration. Ivermectin has no effect on adult parasites Developing larvae Blocks egress of microfilariae from the uterus of female worms. 8/28/2024  14 Indication: Ivermectin 8/28/2024  Drug of choice for oral treatment of onchocerciasis, lymphatic filariasis and tropical pulmonary eosinophilia caused by W. bancrofti and Brugia malayi.  A single annual dose of for mass chemotherapy  The drug of choice for human strongyloidiasis.  Ivermectin is as effective as diethylcarbamazine (DEC) for controlling lymphatic filariasis, and useful in regions where onchocerciasis, loiasis are endemic.  15 Absorption impaired in patients with disseminated strongyloidiasis. Lipophilic, is widely distributed, and has a very long elimination half-life of 55 to 60 hours Pharmacokinetics of Ivermectin Excreted in faeces. A P-glycoprotein efflux pump drug transporter in the endothelium of brain microvasculature reduce ivermectin penetration into the CNS Rare CNS side effects in humans. 8/28/2024  16 Well tolerated by uninfected humans. In onchocerciasis, the destruction of the Common microfilariae can cause reactions. Side Effects: Ivermectin In filarial infections: Mazzotti-like reaction to dying microfilariae. Ivermectin is not approved for use in children younger than 5 years or pregnant women 8/28/2024  17 OTHER ANTHELMINTHIC DRUGS 8/28/2024  18 Diethylcarbamazine (Hetrazan) MOA: Decreases microfilariae muscular activity, causing dislocation Disrupts membranes, making them susceptible to host defense mechanisms. Drug of choice in: Loiasis, despite host response induced toxicity Lymphatic filariasis Tropical pulmonary eosinophilia caused by Wuchereria bancrofti and Brugia malayi. 8/28/2024  19 Pharmacokinetics and Side Effects: Diethylcarbamazine Its plasma half-life increases if the urine is alkaline. Host destruction of parasites results, in severe but reversible reactions. Leukocytosis, retinal hemorrhages and ocular complications. Tachycardia, rash, fever, encephalitis. Lymph node enlargement and swelling. 8/28/2024  20 Selectively produces depolarizing neuromuscular blockade and inhibition of acetylcholinesterase (AChE) of the worm Pyrantel Paralysis and flashes out intestinal pamoate nematodes. (Antiminth) Useful in roundworm, hookworm, and pinworm. 8/28/2024  21 Blocks response to acetylcholine Altered parasite membrane permeability and paralysis. Paralysis through neuromuscular junction by promoting actions of γ-aminobutyric acid (gaba). Piperazine Effective in ascariasis and enterobiasis. (Vermizine) Well absorbed from the GI tract Side effects: Urticaria & bronchospasm Rare CNS effects: dizziness, paresthesias, vertigo, incoordination 8/28/2024  22 Levamisole blocks nicotinic receptors at the neuromuscular junction, which results in paralysis. Niclosamide interfere with oxidative phosphorylation Other or activate ATPases. Antihelminths Levamisole and Niclosamide are used for the Diphyllobothrium latum Bithionol is an alternative alternative to praziquantel for Fasciola hepatica (sheep liver fluke infection) and acute pulmonary paragonimiasis. Inhibits parasite respiration. 8/28/2024  23 DRUG THERAPY OF SCABIES AND PEDICULOSIS 8/28/2024  24 Efficient acaricide and drug of choice. Drugs used in the Applied as an emulsion treatment Itching may respond calamine liniment. of scabies: Benzyl Slight irritant and has an unpleasant smell. Benzoate Effective in pediculosis, but not recommended because it has weak ovicidal activity and short duration of action. 8/28/2024  25 Ivermectin Repeat dose after two weeks gives almost 95% cure. Other Drugs Monosulphiram: Acaricide solution or incorporated in soap Used in Recommended for the prophylaxis of scabies. Scabies Mild irritation and monosulphiram is related chemically to disulfiram in alcohol use Crotamiton: Lotion or cream 8/28/2024  26 Synthetic pyrethroid cream or lotion. Drugs Used Pediculocide with residual effect for in two weeks. Pediculosis: Permethrin May cause local reactions Preferred over benzene hexachloride (GBH) 8/28/2024  27 Pediculocidal And Ovicidal Organophosphorus Compound For Rapid Treatment Of Head Lice, Even Patients Resistant To Permethrin. Drugs Used Well Tolerated pediculosis: Malathion Applied And Left In Place For 8-12 Hours And Repeated 7 Days Later. Inflammable Because Of Alcohol Base. 8/28/2024  28 Drugs Used in Pediculosis: DDT DICOPHANE (DDT) : Pediculocide dusting powder Prolonged residual effect lethal to larvae which hatch out later. It has a bad odour and is inflammable. For pediculosis capitis, permethrin cream/lotion is preferred for initial treatment. In resistant cases, ivermectin is safe and highly effective The other drugs used are Gamma BHC, DDT and kerosene. 8/28/2024  29 During a colonoscopy on an 80-year-old Filipino woman, a live worm is encountered. Clinical Scenario The gastroenterologist asks how long the patient has been in the United States. Why is the physician interested in this information in relation to this discovery? 8/28/2024  30 Schistosomiasis is the most likely diagnosis, given the patient’s geographic origin. Answer to Treatment of this flatworm is with praziquantel. Praziquantel is not effective in early infection Scenario of schistosomiasis. If the patient has been in the United States for a while, where infection with the helminth is less likely, treatment is likely to be effective immediately. 8/28/2024