Anthelminthic Drugs Notes PDF

Anthelminthic Drugs and Taenia solium) are cattle and pigs, respectively. Humans become infected by eating raw it is estimated that over half the world's or undercooked meat contain...

Anthelminthic Drugs and Taenia solium) are cattle and pigs, respectively. Humans become infected by eating raw it is estimated that over half the world's or undercooked meat containing the population may be infected with larvae, which have encysted in the gastrointestinal helminths. animals' muscle tissue. Inhabitants of tropical and subtropical H. nana may exist as both the adult (the low-income countries are most at risk. intestinal worm) and the larval stage in Children often become infected with one the same host, which may be human or or more species almost as soon as they are rodent born and may remain infected throughout their lives. In some cases e.g. Intestinal roundworms: Ascaris threadworms, these infections result lumbricoides (roundworm), Enterobius mainly in discomfort and do not cause vermicularis (threadworm/pinworm , substantial ill health. Trichuris trichiura (whipworm), Schistosomiasis (bilharzia) and Strongyloides stercoralis, Necator hookworm disease, can produce severe americanus and Ankylostoma duodenale morbidity. (hookworms). Worm infections are also a major cause Infection through undercooked meat or for concern in veterinary medicine, contaminated food (roundworm, affecting both domestic pets and farm threadworm and whipworm), whereas animals. hookworm is generally acquired when their larvae penetrate the skin. Classes of worms: the nemathelminths (nematodes, Tissue worms: roundworms) Flukes: Schistosoma haematobium, the platyhelminths (flatworms) is Schistosoma mansoni, and Schistosoma subdivided into the trematodes (flukes) japonicum. and the cestodes (tapeworms). These cause schistosomiasis (bilharzia). The adult worms of both sexes live and Almost 350 species of helminths have mate in the veins or venules of the gut been found in humans, and most colonize wall or the bladder. the gastrointestinal tract. Intestinal worms: Tissue roundworms: Trichinella spiralis, Tapeworms: Dracunculus medinensis (guinea worm) Taenia saginata, Taenia solium, and the filariae, which include Hymenolepis nana and Wuchereria bancrofti, Loa loa, Diphyllobothrium latum. The usual Onchocerca volvulus and Brugia malayi. intermediate hosts of the two most common tapeworms (Taenia saginata 1|Page  The adult filariae live in the Kinetics: lymphatics, connective tissues or Only 10% of mebendazole is absorbed mesentery of the host and produce live after oral administration, fatty meal embryos or microfilariae, which find increases absorption. their way into the bloodstream. They It is rapidly metabolized, the products may be ingested by mosquitoes or being excreted in the urine and the bile similar biting insects when they feed. within 24-48 hours. It is generally given as a single dose Hydatid tapeworm. These are cestodes of for threadworm, and twice daily for 3 the Echinococcus species for which days for hookworm and roundworm canines are the primary hosts, and sheep infestations. the intermediate hosts. The primary, intestinal stage does not Thiabendazole is rapidly absorbed from occur in humans. Still, under certain the gastrointestinal tract, metabolized and circumstances humans can function as the excreted in the urine in conjugated form. intermediate host, in which case the It is given twice daily for 3 days for larvae develop into hydatid cysts within guinea worm and Strongyloidiasis the tissues. infestations, and for up to 5 days for Drugs 1) BENZIMIDAZOLES This group of broad-spectrum agents hookworm and roundworm includes mebendazole, thiabendazole, infestations and albendazole. Mechanism: Act by inhibiting the polymerization of Albendazole is also poorly absorbed but, helminth β-tubulin, thus interfering with like mebendazole, this may be increased microtubule-dependent functions such as by food, especially fats. glucose uptake. It is metabolized extensively by first- However, the effect takes time to develop pass metabolism to the sulfoxide and and the worms may not be expelled for sulfone metabolites. The former is likely several days. Cure rates are generally to be the pharmacologically active between 60 and 100% with most species. parasites. Unwanted effects are a few : 2|Page  ❖ gastrointestinal disturbances can The plasma half-life of the parent occasionally occur. compound is 60-90 minutes. ❖ headache, dizziness, and drowsiness have been reported Praziquantel is considered to be a very and allergic reactions (fever, safe drug with minimal side effects in rashes) can occur. therapeutic dosage. Mebendazole should not be given to They include gastrointestinal pregnant women or children less than 2 disturbance, dizziness, aching in muscles years old. and joints, skin eruptions, and low-grade fever. 2) Praziquantel: is a highly effective Praziquantel is considered safe for broad-spectrum anthelminthic pregnant and lactating women drug. It is the drug of choice for all forms of 3) Piperazine: schistosomiasis and is the agent generally Piperazine is used to treat infections with used in large-scale schistosome the common roundworm (Ascaris eradication programs. lumbricoides) and the threadworm (Enterobius vermicularis). Mechanism: Mechanism: The drug disrupts Ca2+ homeostasis in It reversibly inhibits neuromuscular the parasite by binding to consensus transmission in the worm, probably protein kinase C-binding sites in a β by acting like GABA, the inhibitory subunit of schistosome voltage-gated neurotransmitter, or GABA-gated calcium channels. chloride channels in nematode muscle. This induces an influx of the ions, a The paralyzed worms are expelled rapid and prolonged contraction of alive by normal intestinal peristaltic the musculature, and eventual movements. paralysis and death of the worm. Praziquantel also disrupts the tegument of Piperazine is given orally, some is the parasite, unmasking novel antigens, absorbed. and as a result, it may become more It is partly metabolized, and the susceptible to the host's normal immune remainder is eliminated, unchanged, via responses. the kidney. Kinetics When used to treat roundworm, Given orally, is well absorbed; much of piperazine is effective in a single dose. the drug is rapidly metabolized to For threadworm, a longer course (7 inactive metabolites on first passage days) at lower dosage is necessary through the liver, and the metabolites are excreted in the urine. Unwanted effects are uncommon: gastrointestinal disturbances, 3|Page  urticaria worms in the lymphatics, but it has little Bronchospasm action on microfilariae in vitro. It has paresthesia, vertigo, and incoordination. been suggested that it modifies the parasite so that it becomes susceptible to 4) NICLOSAMIDE the host's normal immune responses. It Niclosamide is widely used for the may also interfere with helminth treatment of tapeworm infections arachidonate metabolism. together with praziquantel. Mechanism: 6) LEVAMISOLE The scolex (the head of the worm with the parts that attach to the host intestinal Levamisole is effective in infections cells) and a proximal segment are with the common roundworm (A. irreversibly damaged by the drug. lumbricoides). It has a nicotine-like The worm separates from the intestinal action, stimulating and subsequently wall and is expelled. blocking the neuromuscular junctions. The paralyzed worms are then expelled For Taenia solium, the drug is given in a into the faces. Ova are not killed. single dose after a light meal, followed Given orally the drug is rapidly absorbed by a purgative 2 hours later;. and is widely distributed crossing the This is necessary because the damaged blood-brain barrier. It is metabolized in tapeworm segments may release ova. the liver to inactive metabolites, which For other tapeworm infections, it is not are excreted via the kidney. Its plasma necessary to give a purgative after half-life is 4 h. administration of niclosamide. It has immunomodulatory effects and has in the past been used to treat various solid There is negligible absorption of the drug tumors. from the gastrointestinal tract. It can cause central nervous system (CNS) and GI disturbances as well as Unwanted effects are few, and : several other unwanted effects, including Nausea and vomiting can occur. agranulocytosis. 5) Diethylcarbamazine 7) IVERMECTIN: Diethylcarbamazine is a piperazine derivative that is active in filarial First introduced in 1981 as a veterinary infections caused by W. bancrofti and L. drug, ivermectin loa. Effective against W. bancrofti, which Diethylcarbamazine rapidly removes the causes elephantiasis. A single dose kills microfilariae from the blood circulation the immature microfilariae of O. volvulus and has a limited effect on the adult but not the adult worms. 4|Page  Ivermectin is also the drug of choice for onchocerciasis, which causes river blindness and reduces the incidence of this disease by up to 80%. It is also active against some roundworms: common roundworms, whipworms, and threadworms Chemically, ivermectin is a semisynthetic agent derived from a group of natural substances, the avermectins, obtained from an actinomycete organism. The drug is given orally and has a half- life of 11 h. MOA: It is thought to kill the worm either by: opening glutamate-gated chloride channels (found only in invertebrates) and increasing Cl− -conductance; or by binding to GABA receptors or by binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an increase in transmission, leading to motor paralysis. Unwanted effects include skin rashes and itching but in general, the drug is very well tolerated. One interesting exception in veterinary medicine is the CNS toxicity seen in Collie dogs. 5|Page