Ant helmintic pharmacology

1. ANTHELMINTIC DRUGS
Dr . Dinesh Babu ,MBBS,MD
Asst Prof
Dept of Pharmacology
Annapoorana medical college & Hospital , Salem

4. CHEMOTHERAPY OF HELMINTIC INFECTION
• For Nematodes –
Diethylcarbamazine (DEC),
 ivermectin,
Mebendazole ,
 Pyrantel pamoate,
Thiabendazole
• For trematodes – Praziquantel
• For cestodes – Albendazole & Niclosamide

5. Mebendazole

6. • It is Benzimidazole
• Broad-spectrum antihelmintic activity
• It produces nearly 100% cure rate/reduction in
egg count in round worm,hook worm,
Enterobius & Trichuris infection
• H.nana is insensitive

7. M.O.A
• Site of action – microtubular protein ‘β –
tubulin’ of the parasite
• Binds to β – tubulin with high affinity and
inhibits its Polymerization
• Intercellular microtubles in the parasite cells
are gradually lost

8. In addition
• It blocks glucose uptake by inhibiting some
mitochondrial enzymes and depletes its
glycogen stores
• Haatching nematodes eggs & their larvae are
also inhibited

9. Pk
• Absorption is minimal from intestine
• 75-90% of an oral dose is passed in the faeces
• The fraction absorbed is excreted mainly as
inactive metabolites in urine/faeces

10. ADR
• It is well tolerated even by patients with poor
health
• When Mebendazole used in Heavy infection
Diarrhoea
Nausea
Abdominal pain

11. • At high doses
• Expulsion of Ascaris from mouth or nose have
occurred , due starvation / slow death of the
parasite
Allergic reaction
Loss of Hair
Granulocytopenia

12. Uses – As first choice of drug. . .
• Round worms
( Ascaris lumbricoides)
100 mg BD x 3 days
• Hook worms
( Ancylocystoma
duodenale & Necator
americanus)
100 mg BD x 3 days

13. • Thread worm
( Enterobius
vermicularis)
100mg OD x 2-3 weeks
• Whip worm
( Trichuris trichura)
100mg BD x 3 days

14. As alternative drug . . . .
• Whip worm (
Trichinella sprialis )
200 mg BD x 4 days
• Dog tap worm (
Hydatid disease)
200-400 mg BD/TDS
x 3-4 weeks

15. Albendazole

16. Albendazole
• Congener of mebendazole
• One dose treatment has cure rates in
ascariasis, hook worm, entrobius
• A 3 day treatment has cure rate in H.nana
• Results in treating hydatid & Hook worm is
good compared to Mebendazole
• M.O.A – Similar to Mebendazole

17. Pk
• Absorption after oral administration is good
• Its absorption is enhanced with fatty meal
• First pass metabolism – albendazole is
converted into Sulfoxide metabolite which has
potent antihelmintic action
• Widely distributed in the body and has high
tissue pentration , enters brain
• Eliminated in urine ( half life is 8.5 hrs)

18. ADR
• Albendazole is well tolerated and has only G.I
side effects
• Few patients , it produced Dizziness
• Prolonged use in Hydatid & Cysticercosis –
Headache , fever , alopecia ,neutropenia ,
jaundice

19. Uses – As first choice of drug. . .
• Round worms ( Ascaris lumbricoides)
• Hook worms ( Ancylocystoma duodenale &
Necator americanus)
• Thread worm ( Enterobius vermicularis)
400 mg single dose ( adult )
200 mg single dose ( 1-2 yrs)

20. • Whip worm ( Trichinella sprialis )
400 mg OD x 3 days
• Dog tap worm ( Hydatid disease)
400 mg BD x 4 weeks
Repeat 2-3 weeks if required
upto 3 course
• Tapeworm ( Neurocysticercosis)
400 mg BD x 8-15 days
Pead dose – 15 mg/kg/day

21. As alternative drug. . .
• Thread worm ( Strongyloides stercoralis) &
Whip worm ( Trichuris trichura)
• Filariasis
• Tapeworm – Taenia saginata , taenia solium
400 mg single dose ( adult )
200 mg single dose ( 1-2 yrs)

22. Pyrantel Pamoate

23. • It was introduced for thread worm infection in
children ; use soon extend to roundworm,
hook worm
• It is active against trichuris & other worms
• PIPERAZINE antagonizes the action of pyrantel
pamoate
• Pk – 10-15% of an oral dose is absorbed
• ADR – G.I symptoms , headache,
dizziness ,tastless

24. M.O.A
Contracture & Spastic paralysis of worm
Persistant depolarization
Activation of nicotinic cholinergic receptors

25. USES- As first choice of drug. . .
• Round worms ( Ascaris lumbricoides)
• Hook worms ( Ancylocystoma duodenale &
Necator americanus)
• Thread worm ( Enterobius vermicularis)
Single dose of 10 mg/kg is required

26. PIPERAZINE

27. PIPERAZINE
• It is highly active against ascaris , enterobius
• Because of availability of more convenient and
better tolerated drugs – albendazole
/mebendazole , piperazine is not used
frequently
• It is safe in Pregnancy

28. PIPERAZINE - M.O.A
Flaccid paralysis & Expels alive worms
Hyper polarization & Relaxation of ascaris muscle
GABA agonist action & opening of cl- channels

29. • Pk
Moderate oral absorption
Partly metabolized in liver & excreted in urine
• ADR
Nausea , vomiting, abdominal discomfort ,
utricaria
At high dose - dizziness , excitement
At toxic dose – convulsion , death due paralysis
of respiratory failure
• C/I – Renal insufficiency , epileptics

30. As a second choice of drug. . .
• Round worms ( Ascaris lumbricoides)
• Thread worm ( Enterobius vermicularis)
Adult – 4 g OD x 2 days
Peadiatric – 0.75 g / year of age
50 mg/kg OD x 7 days

31. LEVAMISOLE & TETRAMISOLE

32. • Both are active against many nematodes , but
use is restricted to Ascariasis &
anycylocystomiasis
M.O.A
Ganglia in worm are stimulated causing tonic
paralysis & expulsion of live worms
Interfere with carbohydrate metabolism –
inhibition of fumarate reductase also
contributing
• ADR – Nausea , abdominal pain, giddiness,
fatigue

33. Uses – As second choice of drug
• Round worm ( Ascaris lumbricoides) &
• Hook worm ( Ancylocystoma duodenale)
Adult - 150 mg single dose
Children – 100 mg ( 20-39 kg)
- 50 mg ( 10-19 kg)

34. Diethyl carbamazine citrate ( DEC)

35. DEC
• DEC is the 1st drug for filariasis
• It is highly selective effect on microfilariae
• Pk – well absorbed orally
• Widely distributed in the body
• Metabolized by liver & excreted in urine
• Plasma half-life = 4 – 12 hrs

36. • M.O.A - Alteration of organelle membranes of
the microfilariae ( Mf) promoting cell death
• DEC kills only Mf , not the adult worm – so
different schedules are used for radical cure
• 2mg/kg TDS produces symptomatic relief ; Mf
disappear from blood and patient become non-
infective in 7 days of treatment

37. • Filariasis - Wucharia bancrofti
2 mg/kg TDS x 7 days
• Topical pulmonary eosinophilia
2 – 4 mg/kg TDS x 2 -3 weeks
• Loa loa & O. volvulus can treated by DEC
DEC - uses

38. IVERMECTIN

39. • Potent semisynthetic derivative obtained from
Streptomyces avermitilis
• M.O.A
• Acts on Specialized – glutamate gated cl-
channels
Tonic paralysis

40. • Ivermectin targets only the parasite not human
GABAergic transmission
• Reasons are – low affinity for mammalian
GABA receptors & presence of Blood Brain
Barrier ( BBB)
• Pk –
 orally absorbed
 Widely distributed
 Half life = 2-3 days

41. ADR
• Pruritis
• Nausea
• Abdominal pain
• Constipation
• Lethargy
• Transient ECG changes

42. USES - Ivermectin
• Thread worm – Strongyloides stercoralis
• Filariasis – Wucheria bancroftia
• Cutaneous larva migrans & River Blindness
• Ascariasis
• Scabies & Pediculosis

43. Praziquantel

44. Praziquantel
• Noval anthelmintic drug
• Has wide range activity – against
schistosomes, trematodes & cestodes
• M.O.A - acts on specific type of Ca2+
channel causes leakage of intercellular Ca2+
from the memberane
• Contracture & paralysis of the parasite

45. • Worm loses the grip in GIT & expelled out
• Pk
• Rapidly absorbed from intestine
• First pass metabolism , excreted in urine
• Along with food , absorbtion
• Enzyme inducers - metabolism

46. ADR
• No systemic toxicity
• Bitter in taste – nausea & abdominal pain
• Headache, dizziness & sedation
• Rashes , urticaria , fever , itching & Body
pain

47. USES . . .
• Tapeworm infections :
• T.Saginata , T.solium – 10mg/kg single dose in
morning
• H.nana, D.latum - 15-25mg/kg single dose in
morning
• In heavy infestation, retreatment after a week
is desirable

48. • Neurocysticerosis – 2nd Drug of choice
• 50-100 mg/kg daily in 3 doses x 15 days
• Schistosomes
• 40 – 75mg/kg once as single / divided dose
• Other flukes
• DOC for flukes infestation except fasciola
hepatica
• 75 mg/kg/day x 1-2 days

49. NICLOSAMIDE

50. NICLOSAMIDE
• It is effective against cestodes infesting man –
T.saginata , T.sollium , D.latum , H.nana ,
thread worm
• It is safe in pregnancy
M.O.A – inhibiting oxidative phosphorylation
in mitochondria and interfering with
anaerobic generation of ATP by tapeworm

51. • After killing the tapeworm , it is partly
digested by human intestine
• In case of T.solium , digestion of the dead
segment can be hazardous , because
• Ova , released from them can develop into
larva  penetrate the intestinal wall
Visceral cysticercosis

52. • ADR
• Tasteless & non-irritating
• No systemic toxicity
• Minor abdominal symptoms
• Malaise , pruritus , light headedness are rare
• USES
• As 1st line – T.Saginata
• As 2nd line – T.Sollium

53. Treatment of Neurocysticercosis
• Causative agent : T.solium
• Due to migration of larvae from gut to various
tissue via blood stream
• On anthelmintic treatment , the larva dies and
its product induce an intense focal reaction
results in seizures and other neurological
symptoms

54. Treatment :
Albendazole & Praziquantel
Corticosteroids
Anti-convulsants
Advantages of Ablendazole over Praziquantel
Short course treatment
High cure rate
Corticosteroid enhances the absorption of
albendazole
Albendazole is cheaper

55. 1.How do helminths harm humans.
2.The spectrum of activity of Mebendazole.
3.The dose and duration of Treatment for Mebendazole.
4.Advantages of albendazole.
5.Mention the anthelmintic contra indicated safe in
pregnancy.
6.Mention the anthelmintic which modulates immune
system.
7.What is the drug of choice for the following infestation.
a. Ascariasis, b. Hook worm infestation, c. Guinea worm
infestation, d. Tape worm infestation, e. Hydatid disease,
f. Entero biosis, g. Cutaneous larva migrans

56. 8.Uses of diethyl carbamazine citrate.
9.The drug effects in neuro cysticercosis.
10.Comment of the following sentences
a) Helminthasis is a global problem
b) Drug resistance is a major problem in
anthelmintic
c) The Combination of Pyrantal pamoate and
piperzine citrate is very much effective.
d) Piperzine usage is safe in Myasthenia gravis.
11.The dose of anthelmintic in children.