Pharmacotherapy of Antihelminthic agents

1. Presented By
Dr. Manoj Kumar
Assistant Professor
Department of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

2.  Helminthes; means worms
 Prevalent globally; 1/3rd of world population infected.
 But, more common in developing countries with poorer
personal and environmental hygiene.
 They are commonly transmitted through feco-oral
route.
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3.  Clinical symptoms arise mainly due to the toxins
production.
 Acute or chronic blood loss leading to anemia.
 Diarrhoea, Dysentery.
 Abdominal pain
 Subcutaneous nodules
 Allergic Reactions, Urticaria
 Injury to visceral organs
 Intestinal or lymphatic obstruction
 Conjunctivitis, Retinitis, Blindness
 Hepatosplenomegaly
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4.  Macroscopic, multicellular organisms
◦ Own digestive, excretory, reproductive, nervous system
 Types
 Nematodes
Roundworm (Ascaris lumbricoides)
Hookworm (Ancylostoma duodenale)
Whipworm (Trichuris trichura)
Threadworm (Strongyloides stercoralis)
Pinworm (Enterobius vermicularis)
Filaria (Wuchereria bancrofti)
Guinea worm (Dracunculus medinensis)
Onchocerciasis (Onchocerca volvus)
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5. ◦ Platyhelminths/ Flat worms
 Trematodes (flukes)
 Blood fluke (Schistosomiasis)
 Liver fluke (Clonorchiasis)
 Intestinal flukes, lung flukes
o Cestodes (tape worms)
 Beef tape worm (Taenia saginata)
 Pork tapeworm (Taenia solium)
 Fish tapeworm (D. latum)
 Dwarf tapeworm (H.nana)
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6.  Get attached to intestinal mucosa
 Depriving him for food
 Feed on host blood & tissue fluid
 Causing blood lose
 Injury to organs
 S/S : abdominal pain, diarrhoea, purities, anemia
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7. Relative
incidence
of helminth
infections
worldwide

8.  Used in treatment of infestation with helminthes
◦ Vermicide: Kill worms
◦ Vermifuge: Expel worms
 Selective toxicity for parasites: Safe
 MOA: Interfering with
◦ Neuromuscular functions
◦ Micro tubular functions
◦ Ca+2 permeability
◦ Energy metabolism
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11.  Mebendazole, Albendazole, Thiabendazole
 Against nematodes, cestodes including larva migrans
 MOA
Inhibit polymerization of β-tubulin
Inhibit glucose uptake
Deplete glycogen stores
Death
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12.  Mebendazole is a synthetic benzimidazole.
 Introduced in 1972
 Broad spectrum of anthelmintic activity & a low
incidence of adverse effects.
 It is a drug of choice in the treatment of infections
by whipworm eggs, pinworm, hookworms, and
roundworm.
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13.  Memendzol
 Bind to β tubulin of parasite
 Inhibit polymerization
Inhibit synthesize to microtubule
Decrease several metabolic activity of parasite
 Inhibit glucose uptake in parasite
 Inhibit glycogen storage.
 Parasite death
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14.  Minimal absorption in intestines.
 Less than 10% of orally administered is absorbed.
 The absorbed drug is bound to protein (> 90%), rapidly
converted to inactive metabolites.
 Fatty food enhance absorption.
 Half -life of 2-6 hours.
 75 – 90% of oral dose passed in the faeces.
Dose: – 100 mg chewable tablet.
- 100 mg/5ml suspension.
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15. Roundworm
Hookworm
Whipworm
10 mg twice a days for 03 consecutive
day. No fasting, purging or any other
preparation of the patient is needed.
Pinworm
100 mg single dose repeated after 2-3
weeks (to kill the ova that have develop to
later.
Trichinosis
200 mg BD for 04 days less effective then
albandazole.
Hydratid disease
200-400 mg BD or TDS for 3-4 weeks,
less effective then albandazole.
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16.  Well tolerated even by patient in poor health.
 Mild- nausea, vomiting, diarrhea, and abdominal pain have
been reported infrequently.
 High-dose hypersensitivity reactions (rash, urticaria),
granulocytopenia, alopecia, and elevation of liver enzymes.
 Teratogenic in animals,
 Contraindicated in pregnancy and in children 2yr. of age
because of rare reports of convulsions in this age group.
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17.  It is a prodrug congener of memendazole.
 Broad spectrum anti-helminthic
PK
◦ Fatty meals increase absorption
◦ Wide distribution in tissues, bile, CSF, hydatid cyst
◦ Active metabolite, t1/2: 8-12 hrs
◦ Given empty stomach for intestinal worms
Dose: 400 mg, single dose regime
 Weak microfilaricidal action, kills cysticerci, hydatid larvae
 Good antihelminthic activity in tissues
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18.  The active metabolite of albendazole is achieve a higher
concentration(100 times more) then memendazole.
 Albendazole is better tolerated.
 Effective is single dose in most infections.
 Superior to memendazole in the treatment of infections
by threadworm, pinworm, hookworms, hydatid disease,
filariasis and roundworm.
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19.  Miner and similar to memendazole nausea, vomiting,
diarrhea and abdominal pain .
 High-dose jaundice, fever, weakness, hypersensitivity
reactions (rash, urticaria), alopecia, insomnia
 Teratogenic in animals
 Avoided in pregnancy.
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20.  Fist broad spectrum anthelmintic agent.
 Inhibit development of eggs of worms and kills larva apart
of all intestinal.
 Rapidly absorbed
 Half- life of 1-2 hrs
 Completely metabolized in liver
 90% is excreted in urine
 Can also absorbed through skin.
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21.  More toxic than other benzimidazoles
 GI disturbances
 Purities, headache, drowsiness, psychoneurotic symptoms.
 Irreversible liver failure.
 Stevens –Johnson syndrome
 Not used in young children , pregnancy, hepatic and renal
diseases.
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22.  Introduced in 1969 for pinworms infection in children.
 Son extended against roundworm, hookworm.
 Efficacy again – ascaris, enterobius and ancylostoma is
high and comparable to memendazole
 Neuromuscular blockade
 Only small proportion absorbed from GIT
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23. Pyrantel pamoate
Stimulate nicotinic cholinergic receptor in the worm
Persistent depolarization
Inhibits cholinesterase
Spastic paralysis of worm
Unable to attach to intestinal wall
Paralysed worms are expelled
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24. Adverse effects:
 Infrequent mild GI disturbance
 Drowsiness, headache, insomnia, rash, fever
Contraindications & Cautions
 Liver dysfunction.
 Pregnancy
 Children under 2 years of age
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25.  Only recommended for the treatment of ascariasis
 Cure rate 90% for 2 days treatment.
 Readily absorbed orally and excreted unchanged in urine
MOA:
 Paralysis of ascariasis by blocking Ach at myoneural
junction.
 Treatment is continued for 3-4 days or repeated after one
week in case of heavy infections.
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26.  GI disturbance.
 Neurotoxicity, allergic reactions .
Contraindications
 Epilepsy or a history of epilepsy.
 Impaired liver or kidney functions.
 Pregnancy.
 Chronic neurologic disease.
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27.  Second-line drug for treatment of most tapeworm
infections like Taenia saginata, T.salium, H.nana and
pinworm.
Mechanism of action:
 Adult worm( not ova) is rapidly killed by inhibition of
oxidative phosphorylation.
Pharmacokinetics:
 Poorly absorbed from gut & excreted in urine.
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28.  Treatment of most forms of tapeworms.
 Not effective against cysticercosis or hydatic
disease.
 Given in the morning on empty stomach.
 Purgative is necessary to purge all dead segments
& prevent liberation of ova.
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29.  Mild, infrequent GI disturbance
 Alcohol consumption should be avoided
 Not indicated in children under 2 yrs of age or in
pregnancy.
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30. MOA
 Rapidly taken up by worms
 Leakage of intracellular Ca++ causing paralysis
 Worms lose grip on intestinal wall including tissues and
veins.
 Acts against all stages of worms including larvae
ADRs –
 Drowsiness, Dizziness, Urticaria.
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31.  Drug of choice for the treatment of filariasis and tropical
eosinophilia.
Pharmacokinetics:
Rapidly absorbed from gut
 Half- life is 4-12 hours
 The drug should be given after meals
 It is excreted in urine as unchanged forms.
 Dosage is reduced in urinary alkalosis and renal impairment.
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32.  Immobilizes microfilariae and alters their surface
structure,
 Displacing from tissues & making them susceptible
to destruction by host defense mechanism.
 It has immunosuppressive effects
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33.  Fever, malaise, head ache, loss of appetite, GI disturbance,
cough, Chest pain, weakness, dizziness, rash, pruritus,
enlargement of lymph node, bronchospasm, fall BP and
joint pain.
 Leucocytosis
 Retinal hemorrhage
 Encephalopathy
C/I: Hypertension, Renal disease, pregnancy.
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34.  Ivermectin is a semi synthetic analog of avermectin B
obtained from streptomyces avermitilis.
 Given only orally.
 Rapidly absorbed.
 Does not cross BBB.
 Half- life is 16 hrs.
 Excretion in feces.
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35.  Acts on the parasites glutamate-gated Cl- channel
receptors
 Chloride influx increased, hyperpolarization occurs ,
resulting in paralysis of the worm.
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36.  Drug of choice for cutaneous larva migrans &
strongyloidiasis.
 It is also used for scabies, lice .
 Filariasis.
 Onchocerciasis
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37.  Mild - Fatigue, dizziness, nausea, abdominal pain,
constipation, lethargy and ECG changes.
 Killing of microfilaria result in a Mazotti reaction
( fever, Urticaria, headache, hypotension,
tachycardia, peripheral edema)
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38.  Use with other drugs that enhance GABA e.g
Barbiturates, bnzodiazepines, valproic acid.
 Pregnancy
 Meningitis
 Children under 5 years of age.
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39.  MOA: Neuromuscular blockade
 Status
◦ Used only in ascaris, hookworm infestation
 Also a immunomodulator
◦ Restore depressed T cell functions
◦ Useful in vitiligo, oral ulcers
 Adverse effects
◦ Nausea, vomiting, abdominal discomfort, headache
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41.  Caused by the louse Pediculus humanus.
 Lice can infest scalp, body or pubic region.
Drugs used:
 1. Permethrin 1% lotion or cream is rubbed over
the scalp, allowed to remain for 10 minutes and
then washed off.
 2. Ivermectin (200 ug/kg) may be used orally as a
single dose.
 3. DDT 2% lotion, gammaxane 2% shampoo,
malathion 0.5% lotion
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