ANTHELMINTIC

DRUGS
Dr. Amit Shah
 HELMINTHS
CESTODES TREMATODES NEMATODES
(TAPEWORMS) (FLUKES) (ROUNDWORMS)

Diphyllobothrium latum Clonorchis sinensis Ancylostoma duodenale

(Broad fish tapeworm) (Chinese liver fluke) (Old World hookworms)
Echinococcus granulosus Paragonimus westermani Necator Americanus
(Dog tapeworm) (Lung fluke) (New World hookworms)
Taenia saginata Schistosoma Ascaris lumbricoides
(Beef tapeworm) (Blood fluke) (Giant roundworm)
Taenia solium Enterobius vermicularis
(Pork tapeworm) (Pinworm)
Strongyloides stercoralis
(threadworm)
Dracunculus medinensis
(Guinea worm)
Wuchereria bancrofti
(Filarial worm)
 ANTHELMINTIC DRUGS

FOR CESTODES FOR TREMATODES FOR NEMATODES

(TAPEWORMS) (FLUKES) (ROUNDWORMS)

Albendazole Praziquantel Albendazole

Niclosamide Mebendazole

Praziquantel Thiabendazole

Diethylcarbamazine

Ivermectin

Pyrantel pamoate
MEBENDAZOLE

 Benzimidazole
 Broad-spectrum anthelmintic activity
 100% cure rate for round worm, hook worm, enterobius
(less for Strongyloides) and trichuris (not for tissue
Trichinella spiralis)
 75% effective for tape worms but not for H. nana
 Hydatid cyst: prolonged treatment
 Hatching of nematode eggs and larva inhibited and
Ascaris eggs are killed
 MOA:
 Slow in action, takes 2-3 days to develop
 Blocks glucose uptake in the parasite and depletion of
glycogen store
 Microtubular protein “ß-tubulin” – inhibits
polymerization
 Intracellular mictotubules are gradually lost
 Pharmacokinetics:
 Minimal absorption
 75-90% is passed unabsorbed in the faeces
 Excreted mainly in urine as inactive metabolite
 Uses: Available as 100 mg chewable tablet and 100
mg/ml suspension
 Roundworm; Hookworm; Whipworm: 100 mg twice a day
for 3 consecutive days. No fasting, purging or any other
preparation of the patients is needed.
 Enterobius: 100 mg single dose + repeat after 2-3 weeks
 Trichinella spiralis: 200 mg twice daily for 4 days
 Hydatid cyst: 200-400 mg twice daily for 3-4 weeks
 Adverse Effects: No adverse effects with short term
therapy
 Mild GIT disturbances- nausea, diarrhoea and abdominal
pain
 Allergic reactions, granulocytopenia, loss of hair and
elevation of liver enzymes
 Expulsion of Ascaris from mouth or nose
 Pregnancy - ????
ALBENDAZOLE

 Congener of Mebendazole
 Comparable efficacy with mebendazole for round worm,
hook worm and enterobius
 Less effective against trichuris
 More effective against strongyloides
 Trichinella effectiveness is almost same
 More effective in tape worm (including H. nana) and
hydatid larvae and ova of ascaris and hook worm
 Weak microfilarial action and cutaneous larva migrans
 Pharmacokinetics:
 Moderate and inconsistent oral absorption
 Fatty meals enhance absorption
 Fraction absorbed is converted to “sulfoxide” metabolite –
active
 Active metabolite penetrates brain with t1/2 of 8-9 Hrs –
Basis of Tissue Anthelmintic action
 For intestinal worm given in empty stomach and for tissue
action – with fatty meals
 Uses: 400 mg tablet and 200 mg/ 5 ml suspension
 Roundworm; Hookworm; Whipworm: 400 mg single dose
 Tape worm: 400 mg for 3 days
 Cutaneous larva migrans: treatment of choice - 400 mg
for 3 days
 Neurocysticercosis: treatment of choice – 400 mg twice
daily for 1-2 weeks
 Hydatid disease: 400 mg BD for 4 weeks, repeat after 2
weeks up to 3 courses. Treatment of choice before and
after surgery
 Filariasis: with DEC or Ivermectin – in lymphatic filariasis
 Used in mass programs – yearly dose for microfilaraemia
transmission
 Contraindicated in pregnancy
 Adverse Effects: Well tolerated
 Mild GIT disturbances- nausea, diarrhoea and abdominal
pain
 Dizziness
 Prolonged use (in hydatid or in cysticercosis): headache,
fever, alopecia, jaundice and neutropenia
THIABENDAZOLE

 1st benzimidazole introduced in 1961

 Cover all species of nematodes infesting the g.i.t.
 Frequent adverse effects: Nausea, vomiting, loss of
appetite, headache, giddiness, impair alertness, itching,
abdominal pain, diarrhoea
 Uses: Only when other drugs are ineffective
 Strongyloidosis
 Cutaneous larva migrans
 Trichinosis: intestinal infestation and larvae in muscles
PYRANTEL PAMOATE

 Originally for thread worm but extended to hook worm

and round worms
 Less active against necater, strongyoides and trichuris
 MOA:
 Activation of nicotininic cholinergic receptors
 Persistent depolarization leading to contracture and
spastic paralysis – expelling of worms
 Piperazine causes flaccid paralysis – antagonizing action
 Pharmacokinetics: Only 10-15% is absorbed
 ADRs: free from ADRs
 Mild GIT symptoms, tasteless, non-irritant and abnormal
migration to tissues is not provoked
 Safety in pregnancy and children below 2 years not
established
 Uses: 250 mg tabs and 50 mg/ml suspension
 Used in Ascaris, entarobius and ancylostoma – single dose
 3 days course for necater and strongyloides
PIPERAZINE

 Highly active drug against Ascaris and Enterobius – but

2nd choice drug
 Less/not active against hook worms
 MOA:
 Hyperpolarization of Ascaris muscles GABA agonistic
action of Cl- channel opening
 Decreased responsiveness to ACh contractile response –
flaccid paralysis
 Recover – purgation required
 Does not excite Ascaris for abnormal migration
 ADRs: usually well tolerated
 Nausea, vomiting
 Dizziness and convulsion in high doses
 Contraindicated in renal insufficiency and epileptics
 Uses:
 Round worm infestation – 4 gm once a day for 2 days
 Used in Intestinal obstruction
 Safe in pregnancy
LEVAMISOLE

 Levo isomer of Tetramisole

 Tonic paralysis of worms and expulsion of live worms -
by stimulating ganglia of worms
 Inhibition of fumerate reductase enzyme: carbohydrate
metabolism interfered
 Dose: 50/100/150 mg single dose
 Use: Ascariasis and A. duodenale
 Immunomodulator
 Safe and well tolerated – mass treatment of round
worms
DIETHYL CARBAMAZINE
CITRATE (DEC)

 First drug for filariasis

 It is synthetic piperazine derivative
 Highly selective effect on microfilariae (Mf) of W.
bancrofti and B. malayi
 Active against Mf of Loa loa and Onchocerca volvulus
 Reduces worm burden in ascariasis, but efficacy is low
 MOA:
 Alteration of Mf membrane – to be readily phagocytosed
by tissue monocytes
 Hyperpolarization and muscular weakness
 Pharmacokinetics:
 Rapidly absorbed from gut
 T1/2: 2-3 hours; increases in alkaline urine to 10 hrs
 It is excreted in urine unchanged
 Dosage is reduced in urinary alkalosis and renal dz
 USES:
 Filariasis: 2 mg/kg TDS with total dose of 72–126 mg/kg
spread over 12 days to 3 weeks. More than one course
may be needed with a gap of 3–4 weeks.
 Tropical eosinophilia: DEC (2–4 mg/kg TDS) for 2–3 wks
 Loa loa and O. volvulus
 Adverse Effects: common but generally not serious
 Nausea, loss of appetite, headache, weakness and
dizziness
 Leukocytosis and mild albuminuria
 A febrile reaction with rash, pruritus, enlargement of
lymph nodes and fall in BP may occur due to mass
destruction of Mf and adult worms
 This is usually mild but may be severe
 Minimized by starting with a low dose (0.5 mg/kg)
 DEC should be temporarily withheld
 Antihistaminics and/or corticosteroids given
IVERMECTIN

 Obtained from Streptomyces avermitilis

 Drug of choice for Onchocercosis volvulus and
Strongyloides and equal to DEC in Filaria
 Also effective against cutaneous larva migrans and
ascariasis – also scabies and head lice
 Acts via special type of glutamate gated Cl- channel
found only in invertebrates
 Such channels are absent in man, flukes and tape worms
 Potentiation of GABA activity – paralysis of muscles of
worms
 Absorbed well orally, widely distributed but not in CNS,
long half-life – 48 to 60 Hrs

 Uses: 3/6 mg tablets

 Filaria: single dose 0.2 mg per kg with 400 mg
Albendazole annually for 5-6 years
 Strongyloides: 0.2 mg/kg single dose
 O. volvulous

 ADRs: Pruritus, giddiness, nausea, abdominal pain and

sudden ECG changes
NICLOSAMIDE

 Against tape worms – saginata, solium, latum and nana

 Inhibition of oxidative phosphorylation in mitochondria
and interference of anaerobic generation of ATP
 Injured worms are digested or expelled (purgation)
 But with T. solium – dangerous visceral cysticercosis
 Regimen: available as 0.5 gm tabs
 2 gm stat – repeat after 1 Hr and saline purgation
 2 gm daily for 5 days in H. nana infestation
 ADRs: well tolerated, no systemic toxicity
 Can be given in pregnancy
PRAZIQUANTEL

 Novel anthelmintic with wide range of action

 Action: Schisosomiasis and other Trematodes, cestodes
but not nematodes
 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
 Vacuolization of membrane and release of contents
 Pharmacokinetics:
 Rapidly absorbed and enhanced by food
 High first pass metabolism
 Crosses BBB and attains therapeutic conc. In CSF
 Phenytoin, carbamazepine and steroids induce
metabolism – failure of therapy
 ADRs:
 Bitter in taste, produce nausea and vomiting and
abdominal pain
 Headache, dizziness and sedation
 Urticaria, rash, fever etc. - destroyed flukes
 Uses: available as 500 mg/600 mg tabs
 First line of drug in all tape worms except
Neurocysticercosis (10-25 mg/kg per day single dose)
 Neurocysticercosis (50-100mg/kg/day for 2 weeks)
 First line of drug in all schistosome infestations and flikes
except Fasciola hepatica (50-75 mg/kg/day)
 Infecting Organism Drug of Choice
Roundworms (nematodes)
Albendazole or pyrantel pamoate or
A. lumbricoides (roundworm)
mebendazole
T. trichiura (whipworm) Mebendazole or albendazole
N. americanus; A. duodenale Albendazole or mebendazole or
(hookworm) pyrantel pamoate
S. stercoralis (threadworm) Ivermectin
E. vermicularis (pinworm) Mebendazole or pyrantel pamoate
Mebendazole or albendazole; add
T. spiralis (trichinosis)
corticosteroids for severe infection
Cutaneous larva migrans (creeping
Albendazole or ivermectin
eruption)
Visceral larva migrans Albendazole
W. bancrofti (filariasis); B. malayi
(filariasis); tropical eosinophilia; L. loa Diethylcarbamazine
(loiasis)
O. volvulus (onchocerciasis) Ivermectin
D. medinensis (guinea worm) Metronidazole
 Infecting Organism Drug of Choice

Flukes (trematodes)

Schistosoma Praziquantel

C. sinensis (liver fluke) Praziquantel

P. westermani (lung fluke) Praziquantel

Tapeworms (cestodes)

T. saginata (beef tapeworm) Praziquantel or niclosamide

D. latum (fish tapeworm) Praziquantel or niclosamide

T. solium (pork tapeworm) Praziquantel or niclosamide

Cysticercosis (pork tapeworm) Albendazole

E. granulosus (hydatid disease) Albendazole