ANTHELMINTIC DRUGS DR ABDUL LATIF MAHESAR Department of
ANTHELMINTIC DRUGS DR. ABDUL LATIF MAHESAR Department of Medical Pharmacology KSU Pharma Team 1
Trematodes Flat worms Cestodes Helminth Tissue type Round worms (Nematodes) Intestinal type 3
Nematodes A) INTESTINAL ROUND WORMS Ascaris lmubricoides (common round worm) Enterobius vermicularis (pinworm) Trichuris trichuria (whipworm) Strongyloids stercoralis (threadworm) Strongyloidiasis Ancylostoma duodenale & Necator americanus (hookworm) B) TISSUE ROUND WORMS Trichinella spiralis. (Trichinosis) Dracunculus medinensis (guineaworm) Dracunculiasis 4
Other round worms FILARIAE, includes: Wuchereria bancrofti (filariasis) 2. Loa loa (loiasis) 3. Onchocerca volvulus (onchocerciasis) River blindness. 4. Brugia malayi and B. timori 1. 5
Cestodes (tape worms) 1. 2. 3. 4. 5. Tenia saginata (Beef tapeworm) Tenia solium (Pork tapeworm), Cysticercosis (Pork tapeworm larval stage) Hymenolepis nana (Dwarf tapeworm) Diphyllobothrium latum (Fish tapeworm) 6
Hydatid tape worm Echinococcus species 7
TREMATODES/FLUKES (leaflike) Schistosoma mansoni Schistosoma hematobium Schistosoma Japonicum Paragonimus species Paragonimiasis Fasciolopsis buski Fasciola hepatica Clonorchis sinensis 8
ANTIHELMINTIC DRUGS BENZIMIDAZOLEs 1. ALBENDAZOLE: It possess broad-spectrum activity. It is the drug of choice for treatment of 1. Hydatid disease and 2. Neurocysticercosis. It is also a major drug the treatment of (intestinal nematodes) : 1. Ascariasis, 2. Trichuriasis, 3. Strongyloidiasis, 4. Enterobius vermicularis (pinworm), 5. Nector americanus, & Ancylostoma duodenale (Hookworms) infections. 9
Albendazole cont’d Mechanism of action: Inhibits microtubule synthesis and glucose uptake It has larvicidal effects on hydatid disease, cysticercosis, ascariasis, and hookworm infection. Also, ovicidal in ascariasis , ancylostomiasis (hookworm), trichuriasis 10
Pharmacokinetics of Albendazole: It is a benzimidazole carbamate It is administered orally, and absorbed erratically (unpredictable), absorption can be increased with fatty meal. It is metabolized in the liver rapidly to its active metabolite albendazole sulphoxide. (1 st pass metabolism) 11
Contnued It has a plasma half life of 8 -12 hours Sulphoxide is mostly (80%) protein bound , distributed to the tissues and enters the bile, cerebrospinal fluid, and the hydatid cyst. urinary excretion 12
Clinical uses of albendazole: It is administered on empty stomach when used against intraluminal parasites but with fatty meal when against tissue parasites. 1. Ascariasis, trichuriasis, hookworm, pin worm infection (intestinal): Acheives 100% cure in pinworm infection and high cure rates for others or marked reduction in eggs counts. 13
2. Hydatid diseases: Drug of choice, with meals. Bone cyst may require treatment for 1 year. If patients are to be treated surgically, both albendazole and praziquantel are used preoperatively for one month to reduce cyst fluid leakage. After surgery albandazole should be continued for a whole month. 14
Albendazole cont’d Neurocysticercosis: It is the drug of choice. It is effective for symptomatic parenchymal and interventricular cysts. Less effective in arachnoid cyst. It is superior to Praziquantel for neurocysticercosis for the following: 3. 1. 2. 3. 4. 5. 4. Shorter course of treatment. It is cheaper It is co-administeration with steroid increases its absorption It is better in penetration arachnoid space. . It is also effective for ocular cysts. Other infections: Drug of choice in cutaneous and visceral larvea migrans , intestinal cappillariasis, microsporidial infections, gnathostomiasis, trichinosis, clonorchiasis, opisthorchiasis, toxocariasis, and loiasis. 15
It is used along with cotricosteroid to decrease the inflammation caused by dying organism, and it also reduces the duration of course During the acute phase of cysticercotic encephalitis, albandazole is contraindicated and corticosteroid is indicated instead. N. B: In intestinal nematodes, treatment in days But in hydatid disease & Neurocysticercosis, the treatment take longer duration 16
Albendazole con’d Adverse effects: In short term use there is no significant adverse effects. In long term use: abdominal distress, headache, fever, fatigue, alopecia , increased liver enzymes , pancytopenia. Blood counts and LFT should be carried out regularly. Not given during pregnancy and in hypersensitive people. Safety in children is not established in children below 2 years of age. 17
MEBENDAZOLE (Vermox) it is a synthetic benzimidazole it has wider spectrum and is safe Mechanism of action: Similar to albendazole Effecacy influenced by: GI transit time, intensity of infection, and strain of parasite. It is also used to kill hook worm, pin worm , ascaris and trichuris eggs. 18
Mebendazole con’t Pharmacokinetics: 1. 2. 3. 4. 5. 6. Less than 10% of orally administered drug is absorbed Absorption increases with fatty meals Absorbed drug is 90% protein bound It is converted to inactive metabolites rapidly in liver. It has half life of 2 -6 hours It is primarily excreted in bile. 19
Mebendazole con’t Clinical uses: It is taken orally before or after meal, tablets should be chewed before swallowing. Ascaris lumricoides , trichuris trichura , hookworm and trichstrongylus; It is useful drug in case of mixed infection by these parasites. in adults and children over 2 years cure rate is 90 -100 % except hookworm but a marked reduction in worm burden occurs 20
Mebendazole cont’d Intestinal cappilliaris Trichinosis: It has limited efficacy against adult worm. Corticosteroids coadministered in sever infection. 21
Mebendazole con’d Adverse effects and precautions: 1. No adverse effects in short term therapy except for mild GI disturbances. 2. With high dose hypersensitivity reactions, agranulocytosis , alopecia, elevation of liver enzymes. 3. Contraindicated in pregnancy. 4. Used with caution under 2 years of age may cause convulsion in this group. 5. carbamazepine or phneytoin ↓ conc. Cimetidine ↑ conc. 6. used with caution in cirrhosis 22
Thiabendazole It is benzimidazole. It is tasteless and insoluble in water. It is a chelating agent and forms stable complexes with metals including iron but does not bind with calcium. It is rapidly absorbed orally It has half life of 1. 2 hrs It is completely metabolized in liver and 90% is excreted in urine It can also get absorbed through the skin. Thus, could be applied in creams. 23
Thiabendazole con’d: Mechanism of action: similar to other benzimidazoles. It is ovicidal for some parasites. It also possesses immunosuppressive, antipyretic, and mild antifungal and scabicidal (destroying the itch mite causing scabies ) effects. 24
Clinical uses: Should chewed be given after meals and tablets should be For strongyloides (threadworms) infections: cure rate is 93% For cutaneous larval migrans thiabendazole cream is effective and applied topically or given orally Also effective for intestinal capillariasis and scabiasis. 25
Thiabendazole cont’d 1. 2. 3. 4. 5. 6. Adverse reactions and contraindications: It is more toxic than other benzamidazoles GI disturbances Pruritus, headache, drowsiness, neuropsychiatric symptoms rarely may cause tinnitus, bradycardia, hypotension, hyperglycemia, convulsions, neutropenia and other adverse effects may occur. Irreversible live failure. Fatal Stevens–Johnson syndrome (inflammation of the skin) Not used in children below the weight of 15 kg, during pregnancy, hepatic and renal diseases. 26
PYRANTEL PAMOATE It is a broad-specturm antihelminthic It is not effective against trichuriasis (whipworms) and trichostrongylus orientalis infections, yet oxantel pamoate is considered effective against trichuriasis. Both drugs can be combined for their synergistic effect. Pharmacokinetics: It is poorly absorbed orally. Active mainly against luminal organisms. Half of the drug is excreted unchanged in the feces. Mechanism of action: It is a depolarizing neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinesterase leading to the paralysis of worms followed by their expulsion from the GIT. 27
Pyrantel pamoate (cont’d) Efficacy and clinical uses: it is very effective against mature and immature luminal organisms, but not effective against migratory stages in the tissues or against ova Enterobius vermicularis (pinworm). Ascaris lumbricoids (common roundworm) Ancylostoma duodenale (hookworm) single dose for light infection but a 3 -day course is necessary for heavy infection especially N americanus infection. 28
Pyrantel pamoate cont’d: Adverse effects are infrequent 1. GI disturbance 2. Drowsiness, headache , insomnia. 3. Rash, fever and mild. Contraindications: 1. Should not be used in liver diseases. 2. Pregnancy 3. In children under 2 years of age 29
PIPERAZINE Only used for the treatment of ascariasis. It is readily absorbed orally and excreted in urine Mechanism of action: It causes paralysis of ascaris by blocking acetylcholine at the myoneural junction, expelling the live worm by normal peristalsis. 30
Piperazine cont’d Treatment is continued for 3 -4 days or repeated after one week in case of heavy infections. 31
Piperazine cont’d Adverse effects: 1. GI disturbances 2. Neurotoxicity, allergic reactions serum sickness like syndrome Contraindications 1. Epilepsy or chronic neurologic disease 2. Impaired liver or kidney functions 3. Pregnancy 4. Malnutrition 32
Drugs used for treating human intestinal nematodes (single dose unless otherwise stated Ascariasis Hookworm enterobius tricuris strongyloides Piperazine ++ + ++ - - Pyrantel pa ++ ++ ++ - - Albendazole ++ ++ ++ + + Mebendazole ++ ++ ++ + + Thiabendazole n/a n/a Ivermectin n/a n/a ++ ++ 33
Drug treatment for tape worm(cestodes) infection Niclosamide Praziquantel Albendazole 34
NICLOSAMIDE It is useful for the treatment of adult tape worm (cestodes) infestation Mechanism of action: Adult worm is rapidly killed by inhibition of the oxidative phosphorylation or stimulation of ATPase activity. has no effect on ova Pharmacokinetics: It is not absorbed from the gut Neither drug nor its metabolites are found in the blood or urine. 35
Niclosamide cont’d Clinical uses: A. T. Saginata (Beef tape worm), T. solium (pork tapeworm), Diphyllobothrium latum (fish tapeworm) In case of T. solium after 2 hrs of treatment, purge of magnesium sulphate should be given to eliminate all mature segments. Not effective against cysticercosis or hydatid disease. b/c it’s not absorbed from the gut Hymenolepis nana H diminuta and Dipylidium caninum Alternative for Fasciolopsis buski, Heterophyes heterophyes, Metagonimus yokogawi. 36
Niclosamide cont’d Adverse effects: Mild, infrequent and transitory GI disturbances Alcohol consumption should be avoided Not indicated in children under 2 years of age or pregnancy. 37
Diethylcarbamazine The drug of choice for the treatment of filariasis, loiasis and tropical eosinophilia. Pharmacokinetics: It is a synthetic derivative of piperazine Rapidly absorbed from the gut It has a half life of 2 -3 hours which increases in alkaline urine up to 10 hours. Equilibrates with all tissues except fat It is excreted in urine unchanged. Dosage is reduced in urinary alkalosis and renal impairment. 38
DIETHYLCARBAMAZINE con’d Mechanism of action: It immobilizes microfilariae in tissues and alters its surface structure, making them more susceptible to destruction by host defense mechanism Unknown mechanism against adult worms It also possesses an immunosuppressive effects It has no teratogenic effects on experiment animals 39
DIETHYLCARBAMAZINE con’d It is a drug of choice for the treatment tissue cestodes, W. bancrofti, B. malayi, B. timori, and Loa loa. Microfiliariae are rapidly killed. Adult worms are killed slowly requiring several courses of treatment. Adult worms are either killed or sterilized. It is highly effective against L. loa. 40
DIETHYLCARBAMAZINE con’d Anti histamines and corticosteroids are given in allergic manifestations. Complete years. Cure may be require several courses of treatment over 1 -2 The drug may be used in prophylaxis for loiasis, bancroftian, and Malayan filariasis Tropical (pulmonary) eosinophilia Mansonella streptocerca 41
DIETHYLCARBAMAZINE con’d Drug induced/ Reactions induced by Dying parasites: Fever , malaise, papular rash, headache, GI disturbance, cough, chest, muscle, joint pain Leukocytosis, proteinurea, ↑ eosinophilia Retinal hemorrhage Encephalopathy Lymphangitis and lymphadenopathy. 42
DIETHYLCARBAMAZINE con’d 1. 2. 3. 4. Contraindications and cautions Hypertension Renal disease Patient suspected of having malaria Patients with lymphangitis 43
IVERMECTIN It is the drug of choice for treatment of strongyloidasis and onchocerciasis It is a macrocyclic lactone It is used orally and is rapidly absrobed, possesses wide volume of distribution about 50 L. It has a half-life of 16 hrs It is exclusively excreted in feces 44
IVERMECTIN cont’d Mechanism of action: It intensifies GABA –mediated transmission of signals in peripheral nerves paralyzing the worm. In onchocerciasis it is microfilaricidal. It does not kill the adult worm 45
IVERMECTIN cont’d Clinical uses: Onchocerciasis: with the 1 st treatment, patients with microfilariae in the cornea or anterior chamber may be treated with corticosteroid. 46
IVERMECTIN cont’d Strongyloidiasis: in immunosuppresed patient, repeated treatment is often needed. Bancrofti filaricidal: as it is mirofilaricidal It is also used for scabies, lice, and cutaneous larva migrans. Eliminates adcarid worms Reduces microfilariae in Brugia malayi and M ozzardi. 47
IVERMECTIN cont’d Adverse effects: 1. Fatigue 2. dizziness, 3. GI disturbance In Onchocerciasis: 1. Mazotti reaction: fever, headache, dizziness, somnolence (state of being drowsy), weekness, rash , diarrhea, arthralagia, hypotension, lymphadenitis, peripheral edema due to killing of microfiliariae, for this steroids may be necessary for several days 2. Swelling and abscess at site of adult worm 3. Punctuate corneal opacities. 48
IVERMECTIN con’d 1. 2. 3. 4. Contraindication: other drugs that enhance GABA activity e. g Barbiturates, bnezodiazepines, valproic acid. pregnancy Impaired blood brain barrier Children under 5 years of age. 49
BITHIONOL It is the drug of choice for the treatment of fascioliasis (sheep liver fluke) It is also used as an alternative for praziquantel in treating pulmonary paragonimiasis Repeat doses in case of cerebral paragonimiasis. Pharmacokinetics: It is orally administered and excreted in urine. 50
BITHIONOL Adverse effects: 1. GI disturbance 2. Dizziness, headache 3. Pruriuts , urticaria, Leucopenia Contraindications and precautions: 1. hepatitis, 2. leucopenia 3. Used with caution under 8 years of age. 51
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