anthelmintic drugs
DESCRIPTION
DR.ABDUL LATIF MAHESAR Department of Medical Pharmacology KSU. ANTHELMINTIC DRUGS. Pharma Team. تنبيه. في هذه السلايدات قمنا بما يلي: حذف المقدمة في كيفية انتقال العدوى واشكالها والاكتفاء فقط بأسماء الديدان وأصنافها حذف الجرعات من ناحية الكمية وفترة استخدامها - PowerPoint PPT PresentationTRANSCRIPT
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ANTHELMINTIC DRUGSANTHELMINTIC DRUGS
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DR.ABDUL LATIF MAHESARDepartment of Medical PharmacologyKSU
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تنبيهتنبيه
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: يلي بما قمنا الساليدات هذه فيواشكالها • العدوى انتقال كيفية في المقدمة حذف
وأصنافها الديدان بأسماء فقط واالكتفاءاستخدامها • وفترة الكمية ناحية من الجرعات حذف
على للحصول الدكتور لساليدات العودة يمكنكمالذكر السالفة المعلومات
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NematodesNematodesA) INTESTINAL ROUND WORMS Ascaris lmubricoides (common round worm) Enterobius vermicularis (pinworm) Trichuris trichuria (whipworm) Strongyloids stercoralis (threadworm)
Strongyloidiasis Ancylostoma duodenale & Necator americanus
(hookworm)
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B) TISSUE ROUND WORMSTrichinella spiralis. (Trichinosis)Dracunculus medinensis (guineaworm) Dracunculiasis
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Other round wormsOther round worms
FILARIAE, includes: 1.Wuchereria bancrofti (filariasis)2. Loa loa (loiasis)3. Onchocerca volvulus (onchocerciasis)
River blindness. 4. Brugia malayi and B. timori
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Cestodes (tape worms)1. Tenia saginata (Beef tapeworm) 2. Tenia solium (Pork tapeworm),3. Cysticercosis (Pork tapeworm larval stage)4. Hymenolepis nana (Dwarf tapeworm) 5. Diphyllobothrium latum (Fish tapeworm)
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Hydatid tape wormHydatid tape worm Echinococcus species
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TREMATODES/FLUKES (leaf-TREMATODES/FLUKES (leaf-like)like)Schistosoma mansoni Schistosoma hematobium Schistosoma JaponicumParagonimus species ParagonimiasisFasciolopsis buskiFasciola hepaticaClonorchis sinensis
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ANTIHELMINTIC DRUGSANTIHELMINTIC DRUGSBENZIMIDAZOLEs 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
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Albendazole cont’dAlbendazole 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
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Pharmacokinetics of Albendazole: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. (1st pass metabolism)
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ContnuedContnued 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
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Clinical uses Clinical uses of albendazole: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.
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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.
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Albendazole cont’dAlbendazole cont’d
3. 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: 1. Shorter course of treatment.2. It is cheaper3. It is co-administeration with steroid increases its absorption4. It is better in penetration arachnoid space..5. It is also effective for ocular cysts.
4. Other infections: Drug of choice in cutaneous and visceral larvea migrans , intestinal cappillariasis, microsporidial infections, gnathostomiasis, trichinosis, clonorchiasis, opisthorchiasis, toxocariasis, and loiasis.
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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 daysBut in hydatid disease & Neurocysticercosis, the
treatment take longer duration
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Albendazole con’dAlbendazole 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.
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MEBENDAZOLE (Vermox)MEBENDAZOLE (Vermox) it is a synthetic benzimidazole it has wider spectrum and is safe
Mechanism of action: Similar to albendazoleEffecacy 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.
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Mebendazole con’tMebendazole con’t
Pharmacokinetics:1. Less than 10% of orally administered drug is absorbed2. Absorption increases with fatty meals3. Absorbed drug is 90% protein bound4. It is converted to inactive metabolites rapidly in liver.5. It has half life of 2-6 hours6. It is primarily excreted in bile.
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Mebendazole con’tMebendazole 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
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Mebendazole cont’dMebendazole cont’d Intestinal cappilliaris Trichinosis: It has limited efficacy against adult
worm.Corticosteroids coadministered in sever infection.
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Mebendazole con’dMebendazole con’dAdverse 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
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ThiabendazoleThiabendazole 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.
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Thiabendazole con’d: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.
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Clinical uses:Clinical uses:
Should be given after meals and tablets should be chewed
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.
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Thiabendazole cont’dThiabendazole cont’d
Adverse reactions and contraindications:1. It is more toxic than other benzamidazoles2. GI disturbances3. Pruritus, headache, drowsiness, neuropsychiatric symptoms
rarely may cause tinnitus, bradycardia, hypotension, hyperglycemia, convulsions, neutropenia and other adverse effects may occur.
4. Irreversible live failure.5. Fatal Stevens–Johnson syndrome (inflammation of the skin)6. Not used in children below the weight of 15 kg, during
pregnancy, hepatic and renal diseases.
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PYRANTEL PAMOATEPYRANTEL PAMOATEIt 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.
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Pyrantel pamoate (cont’d)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.
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Pyrantel pamoate Pyrantel pamoate cont’d:cont’d:Adverse effects are infrequent and mild.1. GI disturbance2. Drowsiness, headache ,insomnia.3. Rash, feverContraindications:1. Should not be used in liver diseases.2. Pregnancy3. In children under 2 years of age
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PIPERAZINEPIPERAZINEOnly 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.
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Piperazine cont’dPiperazine cont’d
Treatment is continued for 3-4 days or repeated after one week in case of heavy infections.
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Piperazine cont’dPiperazine cont’dAdverse effects:1. GI disturbances2. Neurotoxicity, allergic reactions serum sickness
like syndromeContraindications 1. Epilepsy or chronic neurologic disease2. Impaired liver or kidney functions3. Pregnancy4. Malnutrition
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Drugs used for treating human intestinal nematodes Drugs used for treating human intestinal nematodes (single dose unless otherwise stated(single dose unless otherwise stated
Ascariasis Hookworm enterobius tricuris strongyloides
Piperazine ++ + ++ - -
Pyrantel pa ++ ++ ++ - -
Albendazole ++ ++ ++ + +
Mebendazole ++ ++ ++ + +
Thiabendazole n/a n/a n/a n/a ++
Ivermectin n/a n/a n/a n/a ++
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Drug treatment for tape worm(cestodes) Drug treatment for tape worm(cestodes) infectioninfection
Niclosamide Praziquantel Albendazole
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NICLOSAMIDENICLOSAMIDE 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.
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Niclosamide cont’dNiclosamide 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.
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Niclosamide cont’dNiclosamide 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.
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DiethylcarbamazineDiethylcarbamazine 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.
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DIETHYLCARBAMAZINE con’dDIETHYLCARBAMAZINE 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
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DIETHYLCARBAMAZINE con’dDIETHYLCARBAMAZINE con’dIt 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.
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DIETHYLCARBAMAZINE con’dDIETHYLCARBAMAZINE con’d
Anti histamines and corticosteroids are given in allergic manifestations.
Complete Cure may be require several courses of treatment over 1-2 years.
The drug may be used in prophylaxis for loiasis, bancroftian, and Malayan filariasis
Tropical (pulmonary) eosinophilia Mansonella streptocerca
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DIETHYLCARBAMAZINE con’dDIETHYLCARBAMAZINE con’dDrug 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.
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DIETHYLCARBAMAZINE con’dDIETHYLCARBAMAZINE con’d Contraindications and cautions1. Hypertension 2. Renal disease3. Patient suspected of having malaria4. Patients with lymphangitis
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IVERMECTINIVERMECTIN It is the drug of choice for treatment of
strongyloidasis and onchocerciasis It is a macrocyclic lactoneIt 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
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IVERMECTIN cont’dIVERMECTIN 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
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IVERMECTIN cont’dIVERMECTIN cont’dClinical uses: Onchocerciasis: with the 1st treatment,
patients with microfilariae in the cornea or anterior chamber may be treated with corticosteroid.
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IVERMECTIN cont’dIVERMECTIN 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 wormsReduces microfilariae in Brugia malayi
and M ozzardi.
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IVERMECTIN cont’dIVERMECTIN cont’d Adverse effects:1. Fatigue2. 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 worm3. Punctuate corneal opacities.
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IVERMECTIN con’dIVERMECTIN con’d Contraindication: 1.other drugs that enhance GABA activity
e.g Barbiturates, bnezodiazepines, valproic acid.
2. pregnancy3.Impaired blood brain barrier4.Children under 5 years of age.
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BITHIONOLBITHIONOL 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.
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BITHIONOLBITHIONOLAdverse effects:1. GI disturbance2. Dizziness,headache3. Pruriuts ,urticaria,LeucopeniaContraindications and precautions:1. hepatitis, 2. leucopenia3. Used with caution under 8 years of age.
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