1. Anthelmintic Drugs

2. INTRODUCTION
Humans are the primary hosts for the most of helminthic infections.
Most worms produce in human sexually by producing eggs and larvae
These pass out of body and infect the secondary host
Imature forms invade humans via skin or GIT and mature to adult worms with characterstic tissue distribution.

3. Types (clinical)
1. Worms live in hosts alimentary canal. 2. Worms or larvae live in other tissues of host body like muscles , viscera , menninges , lungs, subcutaneous tissues.

4. A) INTESTINAL ROUND WORMS (NEMATODES)
Ascaris lmubricods (common round worm)
Enterobius vermicularis (pin worm)
Trichuris trichuria ( whip worm)
Strongyloids stercoralis ( thread worm)
Ankylostoma dudenale (hook worm)

5. B)TAPE WORMS (CESTODES)
Taenia saginata(Beaf) ,
Taenia solium(Pork)
Humans become infected by eating raw or under cooked meat containing larvae of infected cattle or pig which has encysted in the animal muscle tissue.
In some conditions this larvae may develop in humans resulting cysticercosis (i.e. larvae gets encysted in the muscle and viscera or more seriously in the brain or eye.)

6. 2. TISSUE WORMS A.TREMATODES(Schisotomes)OR FLUKES(leaf like)
Schistosoma haematobium
Schistosoma Japonicum
Schistosoma mansoni
(These cause SCHISTASOMIASIS) also called (BILHARZIA) means disease of blood vessels.
Adult worms of both sex live and mate in veins or venules of the gut wall or the bladder, eggs pass into the bladder or gut and produce inflammation of these organs , resulting in haematuria or loss of blood in feces.

7. B. TISSUE ROUND WORMS Trichnella spiralis.
Eggs hatch in water and develop in to miracidia(1st stage of larva of trematode and further develop in the body of snail), which enter to 2ndry host a particular species of snail ,where it develops to free swimming cercarae (final free-swimming stage of a trematode),These infect humans by penetrating to skin
B. TISSUE ROUND WORMS
Trichnella spiralis.
Dracunulus medinensis (guinea worm)larva migrate from intestine to tissue of leg or foot and protrude out by making ulcer

8. FILARIAE includes Wuchereria bancrofti Loa loa Onchocerera volvulus
Brugia malayi

9. Adult filariae live in the lymphatics,and cause lymphadenitis and swelling of limb. connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream.
They are ingested by mosquitoes or similar insects, they develop to larvae in 2ndry host and pass to mouth parts of insect and
re-injected to humans

10. C. Hydatid tape worm Echinococcus species .
These are cestodes ,primary in canines (dogs) and sheep as intermediate host.
humans can act intermediate host in which larvae develop to hydatid cyst with in tissue.

11. Ascaris lumbricoids ( common round worm)

12. filariasis

13. Hookworm

14. Pinworm male ,female

15. Tapeworm

16. whipworm

17. Dircrocoelium dendriticum

18. Fasiola hepatica

19. Tricuris tricura

20. Trichinela spiralis

21. elephantiasis

22. Hydateid cyct

23. cysticercosis

24. Anthelminthic Drugs
Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting helminths.
May act by causing :
paralysis of the worm.
damaging the worm leading to partial digestion or rejection by immune mechanisms.
interfere with the metabolism of the worm.

25. Mebendazole Benzimidazole introduced in 1972 broad-spectrum SPECTRUM:
100% cure rate in roundworm, hook worm (both species), Enterobius and Trichuris infestations, Upto 75% cure shown in tapeworms.
It expels Trichinella spiralis from intestines and regression of hydatid cysts in the liver
but is much less active on Strongyloides, H. nana
efficacy in killing larvae from muscles is uncertain.

26. Mechanism Of Action action is slow: takes 2-3 days to develop.
Inhibits microtubule synthesis that irreversibly impairs glucose uptake , intestinal parasites are immobilized and die slowly.
It kills hookworm, pin worm , ascariasis and trichuris eggs.
Hatching of nematode eggs and their larvae are also inhibited.

27. Pharmacokinetics less than 10% of orally administered drug is absorbed
Absorption increases with fatty meal.
Absorbed drug is 90 % protein bound
Converted to inactive metabolites .
Half- life of 2-6 hours
Excreted in urine .

28. Adverse Effects & Precautions
Short term therapy.Mild GI disturbance.
High dose : hypersensitivity reactions, agranulocytosis , alopecia ,elevation of liver enzymes .
Used with caution under 2ys of age may cause convulsion.
Contraindicated in pregnancy. .

29. Clinical Uses Tablets should be chewed before swallowing. Pinworm
trichuriasis
hookworm
ascaris infections.
Whipworm
Enterobius
Trichinella spiralis
Hydatid disease
in adults and children over 2 years cure rate is % except hookworm it is less.

30. Albendazole broad-spectrum activity excellent tolerability
single dose administration
Spectrum of action:
ascariasis, hookworm (both species) and enterobiasis, trichuriasis, strongyloidosis, Tapeworms, hydatid disease and hookworm.
kills cysticerci, hydatid larvae, ova of ascaris/hookworm and is also effective in cutaneous larva migrans.
weak microfilaricidal action.

31. Mechanism Of Action as mebendazole
larvicidal in : hydatid ,cysticercosis , ascariasis and hook worm infections.
Ovicidal in ascariasis ,hookworm , trichuriasis

32. Pharmacokinetics Benzimidazole carbamate
Administered orally , absorption increased with a fatty meal
Metabolized in the liver to the active metabolite albendazole sulfoxide
Plasma half life hours
sulfoxide is mostly protein bound distributes well to tissues and enters bile, CSF & hydatid cysts.
Metabolites are excreted in urine

33. Plasma half life 8-12 hours
Pharmacokinetics
Plasma half life hours
sulfoxide is mostly protein bound distributes well to tissues and enters bile, CSF & hydatid cysts.
Metabolites are excreted in urine

34. Adverse Effects
In short term(1-3 days): No significant adverse effects. only gastrointestinal side effects.
In long term use :
abdominal pain, headache ,fever ,fatigue, alopecia , jaundice and neutropenia.
Not given during pregnancy, hypersensitive peoples & children under 2 years .

35. USES
Used on empty stomach when used against intestinal worms but with a fatty meal when used against cysticercosis, hydatid and cutaneous larva migrans .
Ascaris, hookworm, Enterobius and Trichuris
Tapeworms and strongyloidosis
Trichinosis
Neurocysticercosis
Cutaneous larva migrans
Hydatid disease
Filariasis

36. Thiabendazole first benzimidazole polyanthelmintic Introduced in 1961,
Spectrum:
all species of nematodes infesting the g.i.t.-roundworm, hookworm, Enterobius, Trichuris, Strongyloides and Trichinella spiralis.
inhibits the eggs of worms and kills larvae.
symptomatic relief in cutaneous larva migrans, Trichinella spiralis larvae, guinea worm disease.

37. mechanism of action same as mebendazole.
has antiinflammatory, analgesic and antipyretic actions.
well absorbed from g.i.t.

38. Adverse effects are frequent often interfere with normal activity.
Nausea, vomiting, loss of appetite, headache, giddiness are most common.
It can impair alertness-driving and operation of machinery should be prohibited.
Itching, abdominal pain, diarrhoea.

39. Clinical uses
Because of frequent side effects and poor patient acceptability used only when other better tolerated drugs are ineffective.
strongyloidosis
Cutaneous larva migrans
Trichinosis-intestinal infestation and larvae in muscles

40. PYRANTEL PAMOATE It is a broad specturm anthelmintic SPECTRUM:
Threadworm, roundworm ,hookworm, Ascaris, Enterobius and Ancylostoma, Necator infestation.
It is less active against Strongyloides and inactive against Trichuris and other worms.
Pharmacokinetics:
It is poorly absorbed orally ,
Half of the drug is excreted unchanged in the feces. .

41. Mechanism of action:
It is a depolrazing neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinestrase leads to paralizes of worms
activation of nicotinic cholinergic receptors in the worms resulting in persistent depolarization slowly developing contracture and spastic paralysis.
Worms are then expelled.

42. Adverse Effects Infrequent mild GI disturbance
drowsiness , headache ,insomnia.
Rash ,fever
Contraindications
Pregnancy
Children under 2 years of age

43. clinical uses it is very effective against luminal organisms.
It is not effective against migratory stages in the tissues or against ova
Entrobius vermicularis (pin worm)
Ascariasis lumbricoids (common round worm
Ankylostoma dudenale (hook worm) single dose for light infection but a 3 days course is necessary for heavy infection.especially N amerianus.

44. Piperazine Introduced in 1950
highly active drug against Ascaris and Enterobius
Mechanism of action:
causes hyperpolarization of Ascaris muscle
by a GABA agonistic action
opening Cl- channels
that causes relaxation and depresses responsiveness to contractile action of ACh.
Flaccid paralysis
worms are expelled alive
It does not affect neuromuscular transmission in man.

45. PHARMACOKINETICS fraction of the oral dose of piperazine is absorbed.
partly metabolized in liver ; excreted in urine.
ADVERSE EFFECTS
safe and well tolerated.
Nausea, vomiting, abdominal discomfort and urticaria
Dizziness and excitement occur at high doses
toxic doses produce convulsions; death is due to respiratory failure.
CONTRAINDICATIONS:
in renal insufficiency
in epileptics
CLINICAL USES:
Only recommended for the treatment of ascariasis cure rate 90% for 2 days treatment.

46. LEVAMISOLE, TETRAMISOLE
Tetramisole :- in the late 1960s.
recemic; levo isomer (levamisole):- more active and is preferred.
Both are active against many nematodes, but use is restricted to ascariasis and ancylostomiasis.
Strongyloides larvae are killed, but adult worms are not sensitive.
MECHANISM OF ACTION:
The ganglia in worms are stimulated causing tonic paralysis and expulsion of live worms.
Interference with carbohydrate metabolism (inhibition of fumarate reductase) may also be contributing.

47. Uses For Ascaris infestation
Levamisole is a second line drug for A. duodenale
It is less efficacious against Necator.
ADVERSE EFFECTS
nausea, abdominal pain, giddiness(an impulsive scatterbrained manner), fatigue, drowsiness or insomnia .

48. Diethyl carbamazine citrate (DEC)
Developed in 1948
it is the first drug for filariasis.
Pharmacokinetics:
absorbed after oral ingestion
distributed all over the body
metabolized in liver and excreted in urine.
Excretion is faster in acidic urine.
Plasma t1/2 of usual clinical doses is 4-12 hours, depending on urinary pH.

49. SPECTRUM highly selective effect on microfilariae (Mf).
active against Mf of W. bancrofti and B. malayi, Loa loa, onchocerca volvulus .
Mechanism Of Action
Immobilizes microfilariae
alters their surface structure
displacing them from tissues
making them susceptible to destruction by host defense mechanism

50. USES Filariasis Tropical eosinophilia
Loa loa and 0. volvulus infections
ADVERSE EFFECTS
Nausea, loss of appetite, headache,weakness and dizziness
A febrile reaction with rash, pruritus, enlargement of lymph nodes and fall in BP
Leukocytosis and mild albuminuria

51. lvermectin extremely potent semisynthetic derivative
obtained from Streptomyces avermitilis,
SPECTRUM:
choice for single dose treatment of onchocerciasis and strongyloidosis.
highly effective in bancroftian, brugian filaria,cutaneous larva migrans and ascariasis, while efficacy against Enterobius and Trichuris is moderate.
Certain insects, notably scabies and head lice are killed by ivermectin.

52. MECHANISM OF ACTION
Paralyze nematodes by intensifying GABA- mediated transmission of signals in peripheral nerves.
PHARMACOKINETICS
well absorbed orally,
widely distributed in the body, but does not enter CNS,
sequestrated in liver and fat,
long terminal t1/2 of hours.
SIDE EFFECTS
pruritus, giddiness, nausea, abdominal pain, constipation, lethargy and transient ECG changes

53. PHARMACOKINETICS well absorbed orally,
widely distributed in the body, but does not enter CNS,
sequestrated in liver and fat,
long terminal t1/2 of hours.
SIDE EFFECTS
pruritus, giddiness, nausea, abdominal pain, constipation, lethargy and transient ECG changes

54. USES Filariasis Strongyloidosis other intestinal nematodes scabies
pediculosis

55. Niclosamide highly effective SPECTRUM:
Against cestodes infesting man –Taenia saginata, T. solium, Diphyllobothrium latum and Hymenolepis nana, aswell as threadworm.
MECHANISM OF ACTION:
The drug appears to act by inhibiting oxidative phosphorylation in mitochondria
interfering with anaerobic generation of ATP by the tapeworm.

56. PHARMACOKINETICS tasteless and nonirritating.
minimally absorbed from g.i.t.
no systemic toxicity occurs
It is well tolerated
Adverse effects
minor abdominal symptoms
Malaise, pruritus and light headedness are rare.
safe during pregnancy and in patients with poor health.

57. Praziquantel novel anthelmintic
wide ranging activity against Schistosomes, other trematodes, cestodes and their larval forms but not nematodes.

58. MECHANISM OF ACTION rapidly taken up by susceptible worms
act by causing leakage of intracellular calcium from the membranes contracture and paralysis.
tapeworms lose grip of the intestinal mucosa and are expelled.
Flukes and schistosomes are also dislodged in tissues and veins.
Praziquantel is active against adult as well as juvenile and larval stages of tapeworms.
At relatively higher concentrations, it causes vacuolization of the tegument and release of the contents of tapeworms and flukes followed by their destruction by the host.
This action appears to be more important in cases of schistosomes and flukes.

59. Pharmacokinetics rapidly absorbed from intestines
absorption is enhanced by ingesting it with food.
high first pass metabolism in liver which limits its systemic bioavailability.
It crosses blood-brain barrier and attains therapeutic concentrations in the brain and CSF.
The plasma t1/2 is short (1.5 hours).
Metabolites are excreted chiefly in urine.

60. Adverse effects
nausea and abdominal pain, headache, dizziness and sedation.
When used for schistosomes and visceral flukes, symptoms like itching, urticaria, rashes, fever and bodyache occur as a reaction to the destroyed parasites.
No interaction with food, alcohol or tobacco has been noted.

61. Clinical uses Tapeworms T. saginata, T. solium H. nana, O. latum
Neurocysticercosis
Schistosomes
Other flukes

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