ANTHELMINTIC DRUGS

Helminths are macroscopic, multiceullar organism having their own digestive system, excretory, reproductive and nervous systems

Helminths

NEMATHELMINTHSPseudosacelom

PLATYHELMINTHSAcoelom ate

TREMATODES CESTODES

Nematodes Long, round bodies, unsegmented worms,

tapered at both ends. Most found primarily in intestine. Attached to the mucosa and feed host blood

and tissue fluid. EX: Ascaris lumbricoides (roundworm),

Trichuris trichiura (whipworm),

Enterobius vermicularis (pinworm),

Ancylostoma duodenale & Necator americanes (hookworms)

Enterobius vermicularis(Pin worm)

Wuchereria bacncrofti (Filarias)

(Nemathelminths)

»Contd.,

ROUND WORM Hookworm

filariasis Pin worm male, female

Tapeworm whipworm

Onchocerciasis Fasiola hepatica

Hydateid cyct

Symptoms:- Abdomianl pain Diarrhoea Pruritis In severe condition cause anaemia

Thread worm - small intestine. Remain asymptomatic for years but in

immuno compromised person there may tissue invasion.

Guinea worm – ingestation. larvae which are inhabit in ponds.

Penetrate to intestinal wall and migrate through connective tissue, develop female produce larvae.

Filarial worms differ from other nematodes -thread like and are found in blood tissues and lymphatics.

Enter - bite of infected fly or mosquito.

Larvae then enter lymphatics and lymph nodes causing fever, eosinophilia and lymphadenitis.

»Contd.,

Chronic infestation may cause elephantiasis lymphatic obstruction

Migrate to other subcutaneous tissue may produce nodules and blindness.

Platyhelminths

Trematodes (Flukes)

Ex:- Blood flukes ( Schistosomiasis)

Liver flukes (Clonorchiasis)

Lung Flukes (Paragonimiasis)

Intestinal flukes(Fasciolopsiasis)

Cestodes( Tape worm)

Ex:-Beef tape worm (Taenia saginata)

Pork tape warm (Taenia solium)

Fish tape worm (Diphyllobothrum latum)

Dwarf tape warm (Hymenolepis nana)

»Contd.,

Trematodes (Flukes) Non segmented Acquired - ingestion of food Mature in intestinal track Migrate and mature in liver- Liver flukes Lung – Lung flukes

Causes: Diarrhoea Abdominal pain Anorexia

»Contd.,

Liver flukes: Bile duct obstruction Liver enlargement Cirrhosis of liver Diarrhoea

Lung flukes: Cough Haemoptysis Chest pain

»Contd.,

Blood flukes:

Skin

Lung

Liver

Mature

Blood

Haematuria

Frequent & painful micturation

Abdominal pain

Cestodes:

Ribbon shaped Intestinal parasites Head, neck followed by segments Head hold- intestinal walls No digestive system - host nutrients

WORM INFESTATION GLOBAL HEALTH PROBLEM.

MORE SO IN TROPICAL COUNTRIES.

WORMS CAN CAUSE G. I. T. AND GENERAL SYMPTOMS.

Drugs used to get the body rid off the helminths (worm) are called anthelmintic drugs.

Vermicide Vermifuge

Act by: Neuromuscular function Microtubular function Ca2+ permeability Energy metabolism

Against nematodes:Pyrantel (NMJ)

Levimasole “

Piperazine “(GABA)

Ivermectin “

Diethyl carbamazine

Thiabendazole

Trematodes:Metrifonate NMJ

Oxamniauine

Bithionol (ATP,Energy)

Tribendazole

»Contd.,

Against cestodes:Niclosamide (ATP, Energy)

Against trematodes & cestodesPraziquantel Ca+2

Broad spectrum anthelminticsBenzimidazole group

M- Mebendazole

A- Albendazole

N- Niclosamide

I- Ivermectin

P- Pyrantel

A- Albendazole*

L- Levamisole

P- Praziquantel

D- DEC

MEBENDAZOLE :

B. S. ANTHELMINTIC EFFECTIVE AGAINST :

* ASCARIASIS.(R)

* ENTROBIASIS. (P)

* TRICHURIS. (Whip)

* ANKYLO STOMA DUODENALE. (Hook)

* NECTAR AMERICANIS. (Hook)

* ONCOCERCIASIS.

* TAENIA ECHINOCOCUS.

*DRUG OF CHOICE FOR TREATMENT OF HYDATID

DISEASE»Contd.,

MOA:

Helminths cytoskeketal structuers Mictofilaments,

microtubles, β-tubulins

Microtubles formation by β-tubulins

Inhibtion β-tubulines

Inhibition of glucose uptake

Disruption of metabolic pathway

»Contd.,

* Immobilization and slow death

* Selective disappearance of cytoplasmic micro

tubules in worms

* These effect not seen in host

* Clearance of worms may take 3 days.

PHARMACOKINETICS :

* POORLY ABSORBED FROM G.I.T.

* RAPIDLY METABOLISE BY LIVER

P.B -90% t1/2- 2-6hrs.

DOSE : 100 MG. B. D. X 3 Days. »Contd.,

UNTOWARD EFFECTS :

WEL TOLERATED

ALLERGY

NEUTROPAENIA

ALOPECIA

CI:- Liver cirrhosis

Pregnancy teratogenic

Childrens <1y

RARELY

ALBENDAZOLE (ZENTEL)

* Broad spectrum anthelmintic

* Actions similar to mebendazole

PHARMACOKINETICS :

* Single dose therapy 400mg

* DOC for cestodes+ nematodes

* well tolerated Benzimidazole carbamate

* Administered orally , absorption increased with a fatty meal

* Metabolized in the liver

* active metabolite albendazole sulfoxide

MAY CAUSE : G. I. T. DISTURBANCES

LONG TERM THERAPY :ALOPAECIA, LIVER DAMAGE, BONE

MARROW »Contd.,

THERAPEUTIC USES OF MEBENDAZOLE :

ASCARIASIS AND ANKYLOSTOMIASIS(HOOK) (M+ Pyrental) 400 MG. SINGLE DOSE.

ENTEROBIASIS.1OO TO 200 MG. SINGLE DOSE REPEAT AFTER 4 WEEKS.

HYDATID DISEASE 15 MG/KG. I.V. DAILY X 4 WEEKS.

STRONGYLOIDASIS. 400 MG. DAILY X 3 DAYS .

TRICHURIASIS. 400 MG. SINGLE DOSE.

larvicidal in hydatid ,cysticercosis , ascariasis and hook worm infections.

Ovicidal in ascariasis ,hookworm , trichuriasis

THIABENDAZOLE :

M. O. A. : inhibits mitochondrial fumarate reeducates in helminths.

SPECTRUM :

effective against wide variety of nematodes infesting G. I. T.

THERAPEUTIC USES :

D. O. C. for Strongyloides stercolis (Rw)

Cutaneous larvamigrants

Visceral larva migrants .

Hydatid disease 15 mg/kg. i.v. daily x 4 weeks.

Filariasis along with DEC

SIDE EFFECTS :

Anorexnia, Nausea, Vomiting

Dizziness, Headache.

PYRENTAL :NN agonist – release Ach

It inhibits cholinestrase enzyme

Persistent depolarization type neuromuscular block.

Spastic muscle paralysis.

VERMIFUGE.

SPECTRUM :

highly effective against : Intestinal acc.

pin worm

round worm

less effective against :

hook worms.»Contd.,

PHARMACOKINETICS : POORLY ABSORBED

SIDE EFFECTS : MILD G. I. T. SYMPTOMPS HEADACHE DIZZINESS FEVER SGOT DOSE : 10 MG./ KG. SINGLE DOSE

Levamisole: Rapid absorbed-git Metabolized by liver Half life 3-4hr restricted to ascariasis and hook worm MOA: NN agonist It has immunostimulant properties

SIDE EFFECTS :

Usually mild

* GIT Disturbances

* Drowsiness

PIPERAZINE : M. O. A. -* GABA agonist , Cl- muscle , hyperpolarization

* Causes flascid paralysis.

* live worms are expelled by normal peristalsis, acts as

vermifuge.

KINETICS :

Rapid absoration p. o.

20 % excreted unchanged in urine

DOSE : 3 to 5 gm on 2 consequitive

CI: Pregnant teratogenic

Epilepsy patient

IVERMECTIN : (MECTIZAN)

* Macrocylic lactone antibiotics

* Acts as GABA agonist

* Cause paralysis of parasite

SPECTRUM :

Effective against broad range of parasites and

arthopodes.

widely used in veterinary practice.

I – D. O. C. - Oncocerciasis (M.Filarial)

150 mg / Kg. Single dose

II – SCABIES : 200 MCG / KG Single oral dose.

»Contd.,

ADVERSE REACTIONS :

* MOSTLY DUE TO DEATH OF MICROFILARIA

* ITCHING.

* SKIN EDEMA.

* ARTHRALGIA.

* HEADACHE

* FEVER.

CI: Not pregnancy

<5 yrs

PRAZEQUENTEL :M. O. A. : * Permeability to calcium and

vacuolations.* Produce muscle contraction * Tegumental damage and death.

Spectrum : Effective against wide variety of cestodes and

tremetodes.*SCHISTOSOMIASIS.

- LIVER FLUKES. - LUNG FLUKES.

*Taeniasis. *Neuro Cysticercosis. (ALBEN)

KINETICS : Absorbed P. O.

»Contd.,

THERAPEUTIC USES :

I – TAENIA SOLIUM.

II – SCHISTOSOMIASIS.

DOSE : TAENIASIS – 10 MG/KG.SINGLE DOSE POST

TREATMENT PURGATIVE

SIDE EFFECTS :

ABDOMINAL DISCOMFORT.

NAUSEA.

HEADACHE.

HALLUCINATIONS.

PSYCHOSIS.

NICLOSAMIDE :M. O. A. :Inhibit aerobic phosphorylation of ADP

Energy production. Produce vermicidal action.

SPECTRUM : Effective against cestodes all tape worms except t. echynococcus.

* T. SAGINATA * T. SOLIUM * Hymenolepis nana* D. LATUS

KINETICS : not absorbed p. o.

»Contd.,

THERAPEUTICS USES : D. O. C. FOR :

T. SAGINATA

Dwarf tape warm

D. LATUS

Against T. Solium effective but should be avoided .

Cystecercosis in T. solium as not effective on ova.

SIDE EFFECTS :

Well tolerated

Occasional G. I. T. upset can cause

PURGATIVE SHOULD ALWAYS BE GIVEN.

BEPHENIUM : ( ALCOPAR)* Inhibition of oxidative phosporylation cause ATP

synthesis * It acts as vermifuge

spectrum : ROUND WORM HOOK WORM (ANKYLOSTOMA)WIPE WORM.

ADVERSE EFFECTS :NAUSEA VOMTING DIARHEA

OVER ALL SAFE DRUG CAN BE ADMINISTERESIN ANEEMIC, PREGNANT AND ELDERLY PATIENTS

DIETHYL CARBAMAZINE (HETRAZEN) :* Piperazine derivative

* Inactive in vitro

* Sensitizes microfilaria surface - become

susceptible to phagocytosis.

* It enhances cell mediated immunity

KINETICS : Rapid absorption p. o. Metabolized in liver Excreted in urine in 30 hrs.

»Contd.,

THERAPEUTIC USES :

* FILARIASIS

6 – 12 MG / KG DAILY X 2 WKS.

* Tropical eosinophilia

6 MG./ KG. DAILY X 7 – 10 DAYS

DRUG INDUCED EFFECTS :

* ANOREXIA.

* HEADACHE.

* DROWSINESS.

* ALLERGIC REACTIONS.

PARASITE INDUCED EFFECTS: Dye worm-proteins, enzymes

Fever, Skin rashes, severe itching, N, V, Headache, chest pain,

Muscle & joint pain (MAZZOTTI reaction)

Metrifonate: It is OP compound. Effective only against Schistosoma

haematobium. P t1/2 2hrs, but metabolite eliminated 24-48

SD Cholinergic side effect

CI : pregnancy NMJ

OXAMNIQUINE: Tetrahydroquinoline derivative Effective only against Schistosoma mansoni

MOA: Fluke first esterifies oxamniquine – alkylates

parasite DNA Intercalation in the parasite DNA. Block protein & Nucleic acid

SIDE EFFECS: CNS most common: Drow,Dizzi,Dull Seizures at high dose.

1 2 3 4 5 6

ROUND WORM HOOK WORM THREAD WORM T. ECHINCOCUS T. SOLIUM T. SAGINATA

MEBENDAZOLE 400 M. G.

SINGLE DOSE

MEBENDAZOLE400 MG.

SINGLE DOSE

MEGENDAZOLE100 TO 200 MG.SINGLE DOSE

REPEAT AFTER 4 WKS.

MEBENDAZOLE 15 MG. / KG.I. V. DAILY X 4 WKS.

PRAZIQUENTEL10 MG/KG.

SINGLE DOSE

NICLOSAMIDE 1 GM 2 DOSE AT 1

HR.

ALBENDAZOLE ALBENDAZOLE ALBENDAZOLE ALBENDAZOLE NICLOSAMIDE PRAZIQUENTEL

PYRENTEL PYRENTEL PIPERAZINE ---------------------- --------------------- --------------------

PIPERAZINE BEPHENIUM BEPHENIUM ---------------------- ------------------------ ------------------------

ANTHELMINTIC DRUGS IN NUT

SHELL