This document discusses drug therapy for helminthiasis (worm infections). It describes the types of worms that cause helminthiasis and the mechanisms and uses of various anthelmintic drugs. Key drugs discussed include mebendazole, albendazole, diethylcarbamazine, ivermectin, pyrantel pamoate, piperazine, levamisole, praziquantel, oxamniquine, and metrifonate. Treatment approaches for neurocysticercosis are also summarized.

1. DRUG THERAPY OF
HELMINTHIASIS
Dr. Kartik

2. OBJECTIVES OF LECTURE
INTRODUCTION , WHAT IS HELMINTHIASIS
TYPES OF WORMS
TREATMENT OF NEUROCYSTICERCOSIS
CHOICE OF DRUGS FOR HELMINTHIASIS
PHARMACOLOGY OF DRUGS
MEBENDAZOLE DIETHYLCARBAMAZINE – DEC
ALBENDAZOLE IVERMECTIN
PYRANTEL PAMOATE NICLOSAMIDE
PIPERAZINE PRAZIQUANTEL
LEVAMISOLE OXAMNIQUINE

3.  WORM-
- long cylindrical structure and no true legs.
- Size varying from less than 1 mm to more than 1 meter.
Helminthology  study of parasitic worms
 HELMINTHIASIS
disease in which a part of the body is infested with parasitic
worms .
vermifuge  drugs that expel infesting helminths.

4. DRUG THERAPY OF HELMINTHIASIS
Larvae
young (juvenile) form , migrate into tissues
larvae causes
• Injury to organs
• blood loss
• secret toxins
• intestinal or lymphatic obstruction
• helminths – present in intestine, some live in tissues
resistance has not been a problem

5. HOOKWORM
Ancylostoma duodenale
Necator americans
FILARIA
Wuchereia bancrofti
Brugia malayi
ROUNDWORM
Ascaris lumbricoides
TAPEWORMS (cestodes)
Taenia saginata
Taenia solium
Hymenolepis nana
Neurocysticercosis
THREADWORM
Enterobius vermicularis
GUINEAWORM
Dracunculus medinensis
Trichinella spiralis HYDATID DISEASE (cestodes)
Echinococcus granulosus
WHIPWORM
Trichuris trichiura

6. HELMINTHIASIS
Nemathelminths-
Nematodes
– round worm, hook, whip, thread,
- pin, filariasis, guniea worms, onchocercea
-Platyhelminths
-trematodes - flukes
-Cestodes – tape worm
T. saginata beef tape worm
T. solium  pork tape worm

7. Most of antihelmintic drugs interfere with
- NM function
- Ca++ entry
- Metabolism
- microtubular function

9. MEBENDAZOLE
• Hymenolepis. nana  NOT EFFECTIVE
100% cure rate
Roundworm (ascaris lumbricoides)
hook worm (ancylostoma duodenale)
threadworm (Enterobius)
whipworm (Trichuriasis)
75% cure rate tapeworms
Trichinella spiralis

10. MECHANISM OF ACTION of mebendazole:
•block glucose uptake in parasite
and
depletion of its glycogen stores.
•site of action  intracellular microtubular protein ‘-
tubulin’ of parasite
Mebendazole  inhibits polymerization of ‘-tubulin’
 gradually microtubules lost Immobilization and
death of worms expulsion of worms from body is
slow and completed in few days after drug treatment.

11. ADVERSE EFFECTS of mebendazole:
• hepatotoxicity - most common
• starvation of the parasite and their slow death  expulsion of
Ascaris from mouth or nose .
- Allergic reactions, loss of hair, granulocytopenia
• Less systemic toxicity
• No fasting, No purging
CONTRAINDICATION
Pregnancy
children less than 2 years

12. Uses of mebendazole
1. Entrobius (THREAD WORM)
2. Hydatid disease (E. granulosus),
-- regression of hydatid cysts in the liver.
-- Treatment after resection of the cyst may prevent its regrowth.
3.Mix infestation: round worm, hook worm and whip worm
• 100 mg twice a day for 3 days.
4. Trichuriasis: mebendazole 500 mg single dose more effective
than albendazole

13. ALBENDAZOLE
•MOA similar to that of mebendazole.
One dose  cure ascariasis, hookworm, enterobiasis
 comparable to 3 day treatment with mebendazole.
•Broad spectrum drug
• less side effects

14. ALBENDAZOLE
• ↑ Absorption when the drug is taken with fatty meal
• able to exert antihelmintic activity in tissues as well.
• sulfoxide metabolite - active
• Glucocorticosteroids and praziquantel may increase level of
albendazole sulfoxide.
SIDE EFFECTS of albendazole
Hepatotoxicity - most common
No postdrug fasting/ purging is required.

15. USES OF ALBENDAZOLE:
1. Ascaris, hookworm, Enterobius and Trichuris:
hook worm infestation is also common in warm climate
and in large mountains  miner’s disease or tunnel
disease. Single dose – 400 mg
2.Tapeworms
3. Trichinosis:
3 day treatment expels the adult worm from intestine,
but has limited effect on larvae that have migrated to
muscles.

16. Uses of albendazole
6. lymphatic filariasis  as adjuvant single dose every
6 monthly with ivermectin or DEC
7. Cutaneous larva migrans: drug of choice, kills larvae
and relieves symptoms.
CONTRAINDICATION
IN PREGNANCY
children less than 2 years
Caution
hepatic or renal disease

17. THIABENDAZOLE
• Effective against nematodes infesting GIT
• Mechanism of action same as mebendazole
• Also has anti-inflammatory, antipyretic and analgesic action.
• Because of frequent side effects + poor patient acceptability,
 it is used only when other drugs are ineffective.

18. PYRANTEL PAMOATE
•Ascaris (roundworm),
•Enterobius (threadworm)
•Ancylostoma (hookworm)
•Lower cure rates (about 60%)  Necator (hook worm)
•inactive against Trichuris and other worms.
Mechanism of action:
•Depolarising NM blocking agent which cause spastic
paralysis.

19. PYRANTEL PAMOATE
abnormal migration of worms is not provoked.
•No fasting, purging is needed.
OXANTEL PAMOATE
Effective against trichuriasis as single dose

20. PIPERAZINE
•highly active against Ascaris and Enterobius
•hyperpolarization of Ascaris muscle by GABA-A
agonistic action & opening Cl channels
depresses responsiveness to contractile action of Ach
Flaccid paralysis & worms are expelled alive.
- purgative is given with it.

21. ADVERSE EFFECTS of piperazine
• toxic doses  convulsions
• death is due to respiratory failure.
Contraindication
• renal insufficiency
• epileptics.
• SAFE IN THE PREGNANCY.
• Because of its capacity to relax ascaris, it is of particular value in
intestinal obstruction due to roundworms.

22. LEVAMISOLE
use  ascariasis and ancylostomiasis
MECHANISM OF ACTION :
•Stimulate ganglia in worms  tonic paralysis and
expulsion of live worms.
•Interference with carbohydrate metabolism
•an immunostimulant as well: restores T cell
function.

23. DIETHYL CARBAMAZINE (DEC)
MECHANISM OF ACTION
Block arachidonic acid metabolism in microfilaria and host cell.
 lead to vasoconstriction and aggregation of platelets and
granulocytes around membrane.
• Alter Mf membranes  readily phagocytosed by tissue fixed
monocytes
• Muscular activity of the Mf and adult worms is also affected,
causing
hyperpolarization  dislodgement of worm
• Mf present in nodules and transudates not killed. e.g. in
hydrocele fluid

24. USES OF DEC:
1. Filariasis:
-- drug of choice  symptomatic relief ,
Mf disappear from blood
-- Prolonged treatment  radical cure
--Elephantiasis due to chronic lymphatic
obstruction is not affected by DEC, because
fibrosis of lymphatics is irreversible.
2. Tropical eosinophilia: DEC (2-4 mg/kg TDS) for 2-3
weeks

25. - Making urine alkaline  DEC conc. In plasma
and half life increases  enhanced therapeutic
effect and toxicity.

26. ADVERSE EFFECTS OF DEC
mass destruction of microfilaria and adult worms
so within few hours, A febrile reaction, MAZZOTTI REACTION:
rash, pruritus, enlargement of lymph nodes, Leukocytosis, mild
albuminuria and fall in BP.
minimized by starting with a low dose (0.5 mg/kg).
- When it occurs, DEC should be temporarily withheld , may persist for
1 wk and then subsides.
- ASPIRIN, antihistaminics and/ or corticosteroids given.

27. ADVERSE EFFECTS OF DEC
Ocular involvement
•uveitis, keratitis , retinal atrophy
•When microfilariae are near eyes
 and as a result of their death in optic
disc and retina  reaction may cause
permanent blindness

28. IVERMECTIN
•drug of choice for single dose treatment of
onchocerciasis and thread worm.
•highly effective in filariasis, cutaneous larva migrans
•moderate efficacy against Trichuris

29. MECHANISM OF ACTION - ivermectin
•Worm develop tonic (SPASTIC) paralysis
• acts through glutamate gated Cl channel
present in nerve or muslce cells of
nematodes  hyperpolarization
•Potentiation of GABAergic transmission in worm
•These channels are only present in nematodes and
hence not active against cestodes or trematodes.

30. IVERMECTIN - FILARIASIS
Regimens (every 6-12 months, single dose
combination)
• to prevent lymphatic filariasis
•in regions where lymphatic filariasis coexists
with onchocerciasis
1. ivermectin + albendazole
2. Diethylcarbamazine + albendazole
3. Ivermectin + DEC

31. Ivermectin
•Ivermectin has replaced DEC for onchocerciasis
•Only drug effective orally in – ectoparasite-
scabies
pediculosis.
SIDE EFFECTS of ivermectin
•reactions due to degeneration products of
Microfilaria
•transient ECG changes

32. Ivermectin
•cross blood brain barrier but due to
P-glycoprotein efflux pump
and
low affinity for CNS receptors
-- rarely cause CNS side effects  safe
-- contraindicated if BBB is obliterated because it acts
on GABA receptors in CNS.
•CONTRAINDICATION (Ivermectin)
child less than 5 years of age
during pregnancy.

33. NICLOSAMIDE
•highly effective –cestodes -2nd line drug
-- cestodes(tapeworms)–Tinea and Hymenolepis nana
-- Enterobious (threadworm/pinworm).
•inhibit oxidative phosphorylation in mitochondria
and interfere with anaerobic generation of ATP by
tapeworm.
•for tapeworm  stool examination for scolex

34. How cysticercosis develop with niclosamide
•NICLOSAMIDE
Kills scoleces and segments of cestodes but it
has no effect on ova.
 ova released as a result of damaged gravid
worms, develop into larvae which may cause
cysticercosis.
 Used for tapeworm infestation (alt to
praziquantel )

35. NICLOSAMIDE
•thorough purge is essential ( T. solium ), so that all
segments are passed out and cysticercosis does not
occur.
•For Hymenolepis. nana  no purgative is required.
ADVERSE EFFECTS of niclosamide
•Antabuse like reaction with alchohol
SAFE DURING PREGNANCY

36. PRAZIQUANTEL
•leakage of intracellular calcium from
membranes (stimulate ca++ influx)
contracture and paralysis
tapeworms lose grip of intestinal mucosa
and are expelled.

37. PRAZIQUANTEL
no activity – nematodes
•active against adult , juvenile, larval stages of
tapeworms.
•Absorption - enhanced by ingesting with food.
- high first pass metabolism
- crosses BBB.
•Praziquantel  contraindicated in ocular cysticercosis
as there can be irreversible occular damage.

38. ADVERSE EFFECTS of praziquantel
- Impaired alertness, arthralgia, myalgia
When used for schistosomes  itching, urticaria
•When used in neurocysticercosis inflammatory
reaction to praziquantel  manifested as
meningismus, seizures and mental abnormalities
treatment  analgesics and anticonvulsants.

39. USES of praziquntel:
1. Tapeworm
 T. solium (pork tapeworm),
T. saginata (beef tapeworm)
D. latum (fish tapeworm)
• T. solium  no chances of systemic cysticercosis
• Hymenolepis nana - single dose morning. In case of heavy
infestation, retreatment after 1 wk
2. Neurocysticercosis
3. Schistosomiasis (fluke infestation) Blood, Lung, Intestinal,
Liver

40. Oxamniquine
• cause spastic paralysis in helminths by
unknown mechanism
•treatment of schistosoma mansoni.
contraindicated in
• pregnancy
•epilepsy

41. TREATMENT OF NEUROCYSTICERCOSIS
cysticerci  larval form of tapeworm (T.
solium)
•cysts do not cause any problem
•larva dies and its products induce an intense
focal reaction
•Anthelmintic kills larvae and precipitates a
reaction, but prevents future episodes due to
spontaneous death of cysticerci.

42. In killing cysticerci, albendazole is preferred over praziquantel
for the following reasons:
1. Duration of treatment -- shorter (8-15 day) compared to
praziquantel
2. Cure rates in terms of resolution of symptoms and
disappearance of cysts are higher (=80%) with albendalzole
than praziquantel (55%)
3. Corticosteroids (which have to be given concurrently)
enhance the absorption of albendazole, but lower the blood
levels of praziquantel.
4. Cost: Albendazole is cheaper.

43. TREATMENT OF NEUROCYSTICERCOSIS
•Corticosteroids (prednisolone or dexamethasone ) 
2 days before and continued till 2 weeks after
completing anthelmintic course.
•necessary to suppress neurological reaction to
products of killed larvae.
•Absorption of both albendazole and praziquantel is
enhanced by ingesting them with food, particularly
fatty food.

44. TREATMENT OF NEUROCYSTICERCOSIS
•Corticosteroid  enhance absorption of albendazole
reduce absorption of praziquantel .
•seizures  anticonvulsant phenytoin or carbamazepine
for 6 months  induce metabolism of praziquantel
• parenchymal cysts respond to albendazole in 8-15 days
•intraventricular and subarachnoid cysts  1 month or
longer.

45. METRIFONATE
• Inhibits ACHE  increases ACH  persistant depolarization of
Nm receptors  induces spastic paralysis  paralyses adult
worm which move to lungs and are killed by immune system.
• Use : alternative to praziquantel in treatment of Schistosoma
haematobium
BITHIONOL
- DOC for Fasciola hepatica infections

46. DOXYCYCLINE
•Intracellular bacteria – rickettsia- lives
inside the filarial (wucheria bancrofti)
and onchocerca nematodes
• as an endosymbiont with these
parasite.
•Doxycycline eradicate that bacteria
TRIBENDIMIDINE
DERQUANTEL

47. Choice of drugs for Helminthiasis
WORM FIRST CHOICE DRUGS ALTERNATIVE
DRUGS
1 ROUNDWORM
Ascaris lumbricoides
Mebendazole,
Albendazole,
Pyrantel
Piperazine,
levamisole,
Ivermectin
2 HOOKWORM
Ancylostoma
duodenale
Necator americanus
Pyrantel,
Albendazole
Mebendazole,
Albendazole
Mebendazole
Levamisole
Pyrantel
3 THREADWORM
Enterobius
vermicularis
Albendazole
Mebendazole,
Pyrantel,
Piperazine
4 WHIPWORM
Trichuris trichiura
Mebendazole Albendazole

48. 5 Trichinella spiralis Albendazole Mebendazole
6 FILARIA
Wuchereia bancrofti,
Brugia malayi
Diethyl carbamazine,
Ivermectin
Albendazole
7 TAPEWORMS
Taenia saginata
Taenia solium
Hymenolepis nana
Neurocysticercosis
Praziquantel, Niclosamide
Praziquantel
Praziquantel
Albendazole
Albendazole,
Niclosamide, Albendazole
Niclosamide
Praziquantel
8
HYDATID DISEASE
Echinococcus
granulosus
Albendazole Mebendazole

49. ANTHELMINTIC
DRUG
MECHANISM OF
ACTION
EFFECT ON
WORMS
PREGNANCY SPECIFIC FEATURES
MEBENDAZOLE BLOCK GLUCOSE
UPTAKE, INHIBIT
MICROTUBULE
POLYMERIZATION
DEATH OF
WORMS
CONTRAINDICA
TED
NO FASTING OR PURGING
REQUIRE
ALBENDAZOLE SAME AS ABOVE SAME AS
ABOVE
SAME AS
ABOVE
CI < 2 YEARS
AGE
SAME AS ABOVE
CAUTION IN HEPATIC AND
RENAL DISEASE
PYRENTEL
PAMOATE
ACTIVATE
NICOTINIC
RECEPTORS IN
WORM
SPASTIC
PARALYSIS
NO FASTING OR PURGING
REQUIRED
- PIPERAZINE ANTAGONISED
ITS ACTION
PIPERAZINE HYPERPOLARIZAT
ION OF GABA
AGONISTIC
ACTION + OPEN
CHLORIDE
CHANNEL
FLACCID
PARALYSIS
SAFE PURGATIVE REQUIRED
LEVAMISOLE STIMULATE
GANGLIA,
INTERFERE WITH
CARBOHYDRATE
METABOLISM
TONIC
PARALYSIS
IMMUNOMODULATOR

50. ANTHELMINTIC
DRUG
MECHANISM OF ACTION EFFECT ON
WORMS
PREGNANCY SPECIFIC
FEATURES
DIETHYL-
CARBAMAZINE
(DEC)
BLOCK ARACHIDONIC
METABOLISM,
VASOCONSTRICTION AND
AGGREGATION OF PLATELETS
ALTER MICROFILARIA
MEMBRANE
IVERMECTIN GLUTAMATE GATED CHLORIDE
CHANNEL, POTENTIATE GABA-
RGIC TRNASMISSION
TONIC PARALYSIS CONTRAINDIC
ATED < 5
YEARS OF AGE
NICLOSAMIDE INHIBIT OXIDATIVE
PHOSPHORYLATION AND
INTEREFERE WITH ATP
PRODCUCTION
SAFE PURGING
ESSENTIAL
PRAZIQUENTAL LEAKAGE OF INTRACELLULAR
CALCIUM FROM MEMBRANE
CONTRACTURE
PARALYSIS
NICLOSAMIDE AND PIPERAZINE SAFE DURING PREGNANCY

51. NEMATODES –DRUG OF CHOICE
SOIL TRANSMITTED
HELMINTHS
ROUND WORM
HOOK WORM
WHIP WORM ALBENDAZOLE
THREAD WORM
ONCHOCERCA
VOLVULUS
IVERMECTIN
TRICHINELLA SPIRALIS FILARIASIS
LOA LOA
DIETHYLCARBAMAZIN
ENTEROVIRUS
VERMICULARIS DRAUNCULIASIS METRONIDAZOLE
CESTODES- DRUG OF CHOICE
NEUROCYSTICERCOSIS
ALBENDAZOLE
T. SOLIUM
T. SAGINATA PRAZIQUANTEL
H. NANA
D. LATUM
ECHINOCOCCUS
TREMATODES – DRUG OF CHOICE
LIVER FLUKE TRICLABENDAZOLE LUNG FLUKE
SCHISTOSOMA
PRAZIQUANTEL

52. Mebendazole is used in all, EXCEPT
a. Schistosomiasis b. hookwarm
c. Cysticercosis d. trichuriasis
Antihelmintic which acts by flaccid
paralysis of worm is
a. pyrantel pamoate b. Piperazine
c. Levamisole d. ivermectin