1.
Dr Anant Khot
Associate Professor
Dept. of Pharmacology,
AIIMS, Nagpur

2.
Introduction
 Problem statement: Infections with
helminths affect > 2 billion people
worldwide
 Metazoa: Worms pathogenic for
humans
 Classification:
1) Round worms ( Nematodes)
2) Flat worms :
a) Flukes ( Trematodes)
b) Tapeworms ( Cestodes)

3.
Nematodes
 Major nematode parasites of humans
include the,
a) Soil-transmitted helminths ( STH’s)
b) Filarial nematodes
 Susceptible population- School aged
children ( especially for STH infections)
 Role of mass prophylaxis

4.
Ascaris lumbricoides (roundworm)
Trichuris trichiura (whipworm)
Ancylostoma duodenale (Hookworms)
Necator americanus
Strongyloides stercoralis (threadworm)
Enterobius vermicularis (pinworm)
Trichinella spiralis (trichinosis)
N
E
M
A
T
O
D
E
S

5.
Cutaneous & visceral larva migrans
Trichostrongylus species
Angiostrongylus cantonensis
W bancrofti, Brugia malayi, Loa loa
Onchocerca volvulus (onchocerciasis)
Dracunculus medinensis (guinea worm)
Capillaria philippinensis (intestinal capillariasis)

6.
Flukes (trematodes) Tapeworms (cestodes)
Schistosoma haematobium
(bilharziasis)
Taenia saginata (beef
tapeworm)
Schistosoma mansoni &
japonicum
Diphyllobothrium latum (fish
tapeworm)
Clonorchis sinensis (liver
fluke), Opisthorchis species
Taenia solium (pork
tapeworm)
Paragonimus westermani
(lung fluke)
Cysticercosis (pork
tapeworm larval stage)
Fasciola hepatica (sheep
liver fluke)
Hymenolepis nana (dwarf
tapeworm)
Fasciolopsis buski (large
intestinal fluke)
Echinococcus granulosus
(hydatid disease);
Echinococcus
multilocularis
Metagonimus yokogawai
(small

7.
Drugs used in Rx
helminthiasis
 For nematodes:
Benzimidazoles (BZ), Pyrantel
pamoate, Ivermectin,
Diethylcarbamazine (DEC)
 For trematodes:
Praziquantel
 For cestodes:
Albendazole, Niclosamide, Praziquantel

8.
Benzimidazoles
 M.O.A: Inhibition of microtubule
polymerization by binding to β-tubulin
 Biochemical changes:
 Inhibition of mitochondrial fumarate
reductase
 Reduced glucose transport
 Uncoupling of oxidative phosphorylation.

9.
 Irreversible damage occurs in GI cells
of the nematodes, resulting in
starvation, death, & expulsion by the
host
 While highly injurious to nematodes,
this fundamental disruption of cellular
metabolism also offers treatment for a
wide range of parasitic diseases.

10.
Pharmacokinetics
 Thiabendazole is soluble in water;
mebendazole & albendazole are poorly
soluble in aqueous solution
 Mebendazole has low systemic
bioavailability (22%) – poor absorption +
rapid first-pass hepatic metabolism
 Co-administration of cimetidine will ↑
plasma levels of mebendazole

11.
 Albendazole- variable & erratic
absorption
 Absorption is enhanced by the
presence of fatty food & by bile salts
 Albendazole is rapidly metabolized to
albendazole sulfoxide, which has
potent anthelminthic activity
 Albendazole sulfoxide ~ 70% PPB &
has a variable plasma t1/2 of 4-15 hrs

12.
Therapeutic uses
 Thiabendazole- Cutaneous larva
migrans
(Thiabendazole (15%)- BD/TID for 5
days)
 Mebendazole:
It is an effective drug for treatment of GI
nematode infections
 For HAT infections: For Trichuriasis, it
is better than Albendazole
 Mebendazole 100 mg BD x 3 days

13.
 A single 500 mg tablet administered
once
 If the patient is not cured 3 wks after
Rx, a second course should be given
 Enterobiasis: A single 100 mg is taken;
a 2nd dose should be given after 3 wks
 A/E: Mild GI Side effects
 High doses: Allergic reactions,
alopecia, reversible neutropenia,
agranulocytosis & hypospermia

14.
 Reversible elevation of serum
transaminases- on long-term Rx
 Mebendazole Rx → Occipital seizures
 Mebendazole is teratogenic in animals
& therefore contraindicated in
pregnancy.
 Note: WHO recommends its use for
infected pregnant women in the 2 & 3
trimesters

15.
Albendazole
 In STH infestation →For adults &
children >2 yrs age- Rx is single dose
400 mg orally
 Hydatid Disease → is the T.O.C for
medical therapy & is a useful adjunct to
surgical removal or aspiration of cysts
 Dose: 400 mg twice daily with meals for
28 days, THEN 14 drug-free days x 3

16.
 Neurocysticercosis → for symptomatic
parenchymal or intraventricular cysts
Dosage: 400 mg BD for up to 21 days.
 Microsporidial intestinal infections in
patients with AIDS
 It is combined with either DEC or
ivermectin in programs directed toward
controlling lymphatic filariasis

17.
Adverse effects
 Transient mild GI symptoms ~ 1% of
treated individuals
 M.c side effect is liver dysfunction
 Other S/E- severe headache, fever,
fatigue, loss of hair, leukopenia &
thrombocytopenia
 Caution: Autoinduction
 The safety in pregnancy & in children
< 2 years of age has not been
established.

18.
Pyrantel Pamoate
 It is a broad-spectrum antihelminthic,
highly effective for treating pinworm,
ascaris, and Trichostrongylus orientalis
infections.
 NM blocking agent that causes the
release of acetylcholine & inhibition of

19.
 Dose is 11 mg (base)/kg (Max-
1gm/dose) given orally once with or
without food
 For pinworm, the dose is repeated in 2
wks
 A/E: Mild & transient, including nausea,
vomiting, diarrhoea, abdominal cramps,

20.
Piperazine
derivatives
 Piperazine: It is highly effective against
both A lumbricoides & Enterobius
vermicularis
 M.O.A: It causes hyperpolarization of the
ascaris muscles by GABA agonistic action
 Opening Cl– channels causes relaxation &
depresses responsiveness to the
contractile action of Ach Flaccid

21.
Salient features
 It is often given with the purgative
 Dose: Roundworm infestation- 4 gm OD
for 2 consecutive days
 Ability to relax ascarids, making it useful
Rx of intestinal obstruction due to
roundworm
 It can be used during pregnancy

22.
Diethyl carbamazine
 Diethylcarbamazine, a synthetic
piperazine derivative, is marketed as a
citrate salt.
 M.O.A: It immobilizes microfilariae and
alters their surface structure, displacing
them from tissues & making them more
susceptible to destruction by host
defense mechanisms.

23.
 PK: It is rapidly absorbed from the GIT;
after a 0.5 mg/kg dose, peak plasma
levels are reached within 1–2 hours.
 The plasma t1/2 is 2–3 hrs in the
presence of acidic urine but about 10
hours if the urine is alkaline, a
Henderson-Hasselbalch trapping effect

24.
Therapeutic uses
 For control & Rx of lymphatic filariasis
 For Rx of tropical pulmonary eosinophilia
 D.O.C for treatment of loiasis
 Annual single-dose combination
chemotherapy (DEC+Albendazole )–
control of LF in areas where
onchocerciasis and loiasis are not

25.
Adverse effects
 Therapeutic doses (6mg/kg)- Direct
toxic reactions to DEC are rarely severe
 Major A/E result directly or indirectly
from the host’s response to destruction
of the parasite
 Delayed reactions to dying adult worms
may result in lymphangitis, abscess

26.
 Heavy Loa loa infestation– retinal
haemorrhages & encephalopathy can
occur
 In patients with onchocerciasis, the
Mazzotti reaction typically occurs within
a few hours after the first dose
 DEC is safe during pregnancy

27.
 Other filaricidal drugs include:
 Macrofilaricidal: Albendazole,
doxycycline
 Microfilaricidal : Ivermectin

28.
Ivermectin
 It is a semisynthetic macrocyclic lactone
derived from the soil actinomycete
Streptomyces avermitilis.
 M.O.A: It appears to paralyze
nematodes & arthropods by intensifying
GABA–mediated transmission of signals
in peripheral nerves.

29.
 PK: 3/6 mg tablet taken on an empty
stomach
 The drug has a wide tissue distribution;
but does not enter CNS, sequestrated in
liver & fat
 It has a long terminal t1/2~ 57 hrs.
 Excretion of the drug and its metabolites

30.
Uses
 Onchocerciasis
 Strongyloidiasis
 Lymphatic filariasis – in regions where
onchocerciasis, loiasis or both are
endemic
 It is effective in controlling scabies, lice,
& cutaneous larva migrans & in

31.
Adverse effects
 In filarial infection, it causes a Mazzotti-
like reaction to dying microfilaria
 In strongyloidiasis treatment, infrequent
adverse effects include fatigue, dizziness,
nausea, vomiting, abdominal pain, &
rashes.
 In onchocerciasis treatment, adverse
effects are principally from the killing of
microfilariae and can include

32.
 Fever, headache, dizziness,
somnolence, weakness, rash,
increased pruritus, diarrhoea, joint and
muscle pains, hypotension,
tachycardia, lymphadenitis,
lymphangitis, and peripheral oedema.
 Some patients develop corneal
opacities and other eye lesions

33.
PRAZIQUANTEL
 M.O.A: ↑ Cell permeability to calcium →
uncontrolled calcium influx →↑ muscle
contraction & paralysis
 Tegument vacuolization & disintegration
 PK: Given PO, absorption enhanced by
food
 Plasma t1/2 is short (1.5 hrs)

34.
Uses
 Tapeworm infestation:
 T.saginata & T.solium-10 mg/kg single
dose
 H Nana, D Latam- 15-25 mg/kg single
dose
 Neurocysticercosis: 50 mg/kg TDS for 2
wk

35.
Adverse effects
 Headache, dizziness, drowsiness, &
lassitude; others include nausea, vomiting,
abdominal pain, loose stools, pruritus,
urticaria, arthralgia, myalgia, & low-grade
fever.
 In neurocysticercosis, neurologic
abnormalities may be exacerbated by
inflammatory reactions around dying

36.
Niclosamide
 Adult worms are rapidly killed due to the
inhibition of oxidative phosphorylation or
stimulation of ATPase activity.
 Injured tapeworms are partly digested in
the intestine (T solium-dead segment
release ova larva formation-penetrate
its wall & cause visceral cysticercosis

37.
Uses
 The adult dose of niclosamide is 2 g
once, given in the morning on an empty
stomach.
 Single treatment is effective for D.
latum, T. saginata, and T. solium
tapeworms.
 H diminuta & D caninum infections are
cured with a 7-day course of treatment

38.
Others
 Triclabendazole-Approved for treatment
fascioliasis in persons ≥6 years of age.
 Bithionol is an alternative to
triclabendazole for the Rx of fascioliasis
& an alternative to praziquantel for the
Rx of paragonimiasis.
 Doxycycline-filariasis and

39.
 Metrifonate (trichlorfon): It is a safe, low-
cost alternative drug for the treatment of
Schistosoma haematobium infections
 Moxidectin: Approved by the FDA in
2018 for the treatment of onchocerciasis
in persons ≥12 years old.

40.
 Oxamniquine: It is an alternative to
praziquantel for the treatment of S
mansoni infections

41.
Thank you