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)
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
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
