Pharmacology PPT

1. Chemotherapy of helminth
infestation
Dr Chintan Doshi

2. INTRODUCTION
 Helminth are multicellular worm with digestive, excretory, nervous, and
reproductive system.
 HELMINTHIASIS is a disease in which a part of body is infested with one or more
intestinal parasitic worms such as round worm, tapeworms or fluckers.
 The worms usually infest the intestine but sometimes, they may invade other
organs

3. HELMINTH CAN BE DIVIDED INTO 2 MAJOR CLASSES
HELMINTHS
Phylum
PLATYHELMINTHS
(FLAT WORMS)
CESTOIDEA TREMATODA
Phylum
NEMATHELMINTHS
(ROUND WORMS)
NEMATODA

4. CLASSIFICATION OF HELMINTH
Nematodes( round worm)
Tissue worms
Wuchereriabancrofti
(Filariasis)
Brugia malayi(Filariasis)
Loa loa(loiasis)
Onchocercasis (River blindness)
Dracunculus medinensis
(Dracunculiaiss)
Intestinal human nematodes
Enterobiunvermicularis(Pin worm)
Ascaris lumbricoides(Roundworm)
Trichuris trichiura(Whipworm)
Necator americanu(Hookworm)
Ancylostoma duodenale(Hookworm)
Strongyloides stercoralis
(Thread worm)

5. Trematodes(flukes)
Blood flukes Schistosoma species Schistosomiasis
Lung flukes Paragonimus species Paragonimiasis
Intestinal
/ hepatic flukes
Fasciola hepatica
Clonorchis sinensis
Schistosome fluke

6. Cestodes(tapeworms)
Intestinal adult worms Taenia saginata
Taenia solium
Diphyllobothrium latum
Hymenolepis nana
Larval tissue cysts Taenia solium cysticercosis
Echinococcus granulosus Hydatid disease
Echinococcus multilocularis Hydatid disease

7. Antihelminthic drugs
 Benzimidazoles (BZ)
 The discovery by Brown and co-workers that thiabendazole possessed potent
activity against GI nematodes.
 Albendazole
 Mebendazole
 Thiabendazole
 Triclabendazole

8. Mechanism of action Disturb the
formation of
microtubules
inside the
worm cell and
Transport
glucose
molecules in to
the cell by
endocytosis
polymerization
D
D
D
 No microtubules inside worm
cell
 Glucose molecule cannot be
transported inside the cell by
endocytosis
SELECTIVE FOR THE NEMATODAL
ISOFORM OF BETA TUBULIN

9. GENERAL ADVERSE EFFECT
General side effect:
 Abdominal pain
 Diarrhoea
 Dizziness
 Headache
 Insomnia
 Loss of appetite
 Hypersensitivity
 Vomiting
 Granulocytopenia
 Alopecia
 Jaundice
Thiabendazole has
more adverse effect
compare to other BZ
Liver failure and
Stevens-Johnson
syndrome rarely

10. THERAPEUTIC USES
ALBENDAZOLE
• 400 mg single dose (adults)
Round worm
Ascaris lumbricoides
• 400 mg single dose (adults)
• 200 mg single dose (1-2 yrs)
Hook worm
Ancylostoma duodenale
Necator americanus
• 400 mg single dose (adults)
• 200 mg single dose (1-2 yrs)
Whip worm
Trichuris trichiura
As First Choice Of Drug

11. • 400 mg BD for 28 days with fatty
meals.
• Along with corticosteroid.
CYSTICERCOSIS
Taenia solium
• 400 mg BD for 28 days with fatty
meals.
HYDATID DISEASE
ECHINOCOCCOIS
• Caused by Hookworm
Cutaneous Larva Migrants
Visceral Larva Migrants

12. AS SECOND CHOICE DRUG
• Strongyloides Stercoralis
THREAD WORM
• +diethylcarbamazine or ivermectin
LYMPHATIC FILARIASIS
• Enterobius vernicularis
PIN WORM

13. MEBENDAZOLE
 Therapeutic uses
• 100 mg BD for 3 days
Round worm
Hook worm
• 100 mg single dose repeat after 2 weeks
Pin worm
Trichinosis

14. VISCERAL LARVA MIGRANTS
TAENIA SAGINATA
Hydatid disease
Mebendazole is an alternative drug to metronidazole in guinea worm infection: also
preferred drug for multiple infections

15. PYRANTEL PAMOATE,OXANTEL PAMOATE
 Introduced in 1969
 PHARMACOKINETICS
 Poor absorbed from GIT(10-15% of an oral dose).
 Active against luminal helminth.
 Excretion : <15% in urine as parent drug metabolites major
portion in feces.

16. Mechanism of action
Depolarizing Neuromuscular Blocking
Agent
Activation of nicotinic receptor of NMJ
Persistence depolarization
Contraction and spastic paralysis of worm
Loose their attachment to intestinal
lumen and expelled in feces

17. Adverse effect
 Headache
 Dizziness
 Rash
 Fever
 Safety in pregnancy
 Safety in children below 2 year not established

18. THERAPEUTIC USES
 Ascaris
 Ancylostoma and Enterobius
 Necator and Strongyloides:3 day course suggested

19. PIPERAZINE
 Introduced in 1950
 A secondary cyclic amine
 PHARMACOKINETICS
 Orally absorbed from GIT
 Metabolized in liver
 Excreted in urine

20. MECHANISM OF ACTION
Flaccid Paralysis Expels Alive Worms
Hyperpolarization & Relaxation Of Muscle
Activate GABA gated Cl- Channels in nematode muscle
GABA receptor Agonistic

21. ADVERSE EFFECT
 General side effect
 Toxic dose produce convulsion
death due to respiratory failure
 Neurotoxic and allergic reaction rarely
 Contraindication
In patient of epilepsy
In patient with impaired renal and hepatic functions

22. DIETHYLCARBAMAZINE
 Developed in 1948
 Synthetic piperazine derivative available as citrate salt
 PHARMACOKINETICS
 Rapidly absorbed
 Distributed all over body except fat
 Metabolized in liver
 Excreted in urine as N-Oxide metabolite and extra urinary roots
 Plasma half life 4-12 hrs

23. MECHANISM OF ACTION
Alter microfilarial membrane surface characteristics
Overstimulation of neuromuscular system of the parasite and
increased motility
Inhibits acetylcholinesterase production by parasites, es
lysosomal enzymes β-glucuronidase and acid phosphatase that
are involved in phagocytosis
induce nitric oxide which is essential for the rapid sequestration
of microfilariae by diethylcarbamazine citrate

24. THERAPEUTIC USES
• 2mg/kg TDS is a first line drug
• patient becomes noninfective to mosquitoes in 7
days
• 12 days to 3 weeks treatment for radical cure
LYMPHATIC FILARIASIS
• 300 mg weekly
LOASIS
• 2 mg/kg orally TDS for 7 days
TROPICAL EOSINOPHILIA

26. ADVERSE EFFECT
 TWO TYPE
 1] Pharmacological dose depended
 Headache
 Malaise
 2] Allergic reaction to dying filarial parasite
 Rash, Pruritus
 Enlargement of lymph nodes,
 Bronchospasm
 Fall in BP

27. IVERMECTIN
 PHARMACOKINETICS
 Well absorbed
 Widely distributed in the body
 Metabolized in liver by CYP3A4
 Long t1/2 48-60 hrs

28. MECHANISM OF ACTION
Acts through glutamate gated cl- channels
Cl- depended hyperpolarization
Paralysis of worms and are expelled alive

29. Adverse effect
 Pruritus, giddiness, nausea,
 Abdominal Pain, constipation,
 Lethargy and transient ECG Changes

30. THERAPEUTIC USES
 DRUG OF CHOICE
• River blindness
ONCHOCERCIASIS
• Higher cure rate
DISSEMINATED STRONGYLOIDIASIS
• 200 mcg/kg single dose
Pediculosis (lice infestation) and Scabies

31. • Single annual dose with 400 mg albendazole for 5-6 yrs
LYMPHATIC FILARIASIS

32. PRAZIQUANTEL
 Synthetic isoquinoline-pyrazine derivative.
 PHARMACOKINETICS
 Well absorbed (80%)
 Metabolized in liver
 Plasma half life 1-3 hrs
 Crosses blood brain barrier
 Excreted as metabolite in urine

33. MECHANISM OF ACTION
spasms and paralysis of the worms' muscles by a rapid
Ca 2+ influx inside the schistosome by acting on voltage gated
ca++ channels.

34. ADVERSE EFFECTS
 GENERAL SIDE EFFECTS
 CONTRAINDICATION
 Ocular cysticercosis because of the risk of severs eye damage resulting from
occlusion due to dead parasites.
 PREGNANCY
 CHILDREN BELOW 5 YRS

35. THERAPEUTIC USE
• 20 mg/kg BD
SCHISTOSOMIASIS
• 20 mg/kg TDS
S. JAPONICUM
• 10 mg/kg single dose in morning
T.SOLIUM, T SAGINATA

36. • 50 mg/kg divided in 3 dose for 15 days
NEUROCYSTOCERCOSIS
• 75 mg/kg OD for 1 or 2 days
FOR OTHER FLUKES
Except F. hepatica
• 15-25 mg/kg single dose in morning
D.LATUM, H.NANA