Pharmacology lecture slides on Anti helminths drugs, Lecture slides for 300level BMLS degree of Babcock University

1. PHARMACOLOGY OF
ANTIHELMINTHIC DRUGS
MRS KALE T.F.
DEPT OF PHARMACOLOGY
BCCHMS

2. INTRODUCTION
• Helminthiasis, also known as worm infection, is any macroparasitic
disease of humans and other animals in which a part of the body is
infected with parasitic worms known as helminths.
• There are numerous species of these parasites, which are broadly
classified into tapeworms (cestodes), flukes (trematodes),
and roundworms (nematodes).
• They often live in the gastrointestinal tract of their hosts, but they
may also burrow into other organs, where they induce physiological
damage.
• Antihelmintic, any drug that acts against infections caused by
parasitic worms (helminths).

3. Amoebiasis

4. Introduction
• Amoebiasis is an infection with the intestinal protozoa
Entamoeba histolytica that infects the bowel.
• About 90% of infections are asymptomatic.
• Remaining 10% produce a spectrum of clinical syndromes.
• The symptoms of amoebiasis include loose stool, abdominal
cramping, and stomach pain.

6. Epidemiology
• Worldwide in distribution
• 3rd most common parasitic death
• India, China, Mexico, Africa, South America
• 2-60% prevalence(based on ELISA and PCR
studies from stool samples)
• 100,000 deaths/yr
• 500 million infections
• 50 million cases/yr

7. Epidemiological determinants
• Agent
• Virulence factor
• Host factor
• Environmental factor
• Mode of transmission
• Incubation period

8. Host factor
• People in developing countries
that have poor sanitary
conditions
• Immigrants from developing
countries
• Travellers to developing
countries
• People who live in institutions
that have poor sanitary
conditions
• HIV-positive patients
• Men who have sex with men
• All age groups affected
• No gender or racial differences
• Night soil for Agriculture.
• Severe in children, old, pregnant
• Develops antiamoebic
antibodies in tissue invasion
• Liver abscesses due to
amoebiasis are 10 times more
frequent in adults than in
children
• Amoebic liver abscess 7 times
more in men than women
• Predominance among men aged
18-50 years
• Increased among
postmenopausal women
• Hormonal effect and alcohol can
be risk factors

9. Modes of transmission
• Faeco -oral route
– Contaminated water and food
– Direct hand to mouth(cysts under finger nails)
– Vegetables irrigated with sewage polluted
water
• Agency of flies, cockroaches, rats, etc.
• Sexual contact via oral-rectal route
• Incubation period (2- 4 weeks)

10. Life Cycle of E. histolytica

11. Amoebiasis Manifestations
• Most cases of amoebiasis have very mild symptoms or none.
• Wide spectrum, from asymptomatic infection to luminal amoebiasis
and amoebic colitis .
• Clinical symptoms are usually vague .
• More severe infection may cause fever, profuse diarrhoea,
vomiting, abdominal pain, jaundice, anorexia, and weight loss.
• Invasive intestinal amoebiasis (dysentery, colitis, appendicitis, toxic
mega colon).

12. Prevention
• Primary prevention
 Sanitation-safe disposal of
human excreta, good sanitary
practice like washing hands
after defecation and before
eating.
 Water supply-water
filtration(sand filters), boiling.
 Food hygiene- prevent fecal
contamination of food and
drink, vegetables washed
properly .
 Health education- food
handlers and public.
• Secondary prevention
 Early diagnosis
 Treatment

13. Treatment of Symptomatic case:- (amoebic colitis and amoebic
liver abscess)

14. Nematodes

16. ASCARIASIS
• One of the most common worm infections in people worldwide
• Caused by Ascaris Lumbricoides
• Ascariasis occurs most often in children in tropical and subtropical
regions of the world — especially in areas with poor sanitation and
hygiene.
• Ascaris lumbricoide is the largest nematode (roundworm)
parasitizing the human intestine.
• Ascaris lumbricoides is an intestinal worm found in the small
intestine of man.

17. Nematodes
INTESTINAL ROUND WORMS
 Ascaris lmubricoides (common
round worm)
 Enterobius vermicularis
(pinworm)
 Trichuris trichuria (whipworm)
 Strongyloids stercoralis
(threadworm)  Strongyloidiasis
 Ancylostoma duodenale &
Necator americanus (hookworm)
TISSUE ROUND WORMS
 Trichinella spiralis. (Trichinosis)
 Dracunculus medinensis
(guineaworm)  Dracunculiasis
TREMATODES/FLUKES (leaf-
like)
Schistosoma mansoni
Schistosoma
hematobium
Schistosoma Japonicum
Paragonimus species 
Paragonimiasis
Fasciolopsis buski
Fasciola hepatica
Clonorchis sinensis
Hydatid tape worm
 Echinococcus species

18. Life cycle of Ascaris lumbricoides
• Adult worms live in the lumen of the small
intestine. A female may produce
approximately 200,000 eggs per day, which
are passed with the feces .
• Unfertilized eggs may be ingested but are not
infective. .
• Depending on the environmental conditions
(optimum: moist, warm, shaded soil). After
infective eggs are swallowed .
• The larvae hatch
• Invade the intestinal mucosa, and are carried
via the portal, then systemic circulation to the
lungs.
• The larvae mature further in the lungs (10 to
14 days), penetrate the alveolar walls, ascend
the bronchial tree to the throat, and are
swallowed .
• Upon reaching the small intestine, they
develop into adult worms. Between 2 and 3
months are required from ingestion of the
infective eggs to oviposition by the adult
female. Adult worms can live 1 to 2 years.

20. Risk Factors
• Age: Most people who have ascariasis are 10 years old or
younger. Children in this age group may be at higher risk
because they're more likely to play in dirt.
• Warm climate: In the United States, ascariasis is more
common in the Southeast, but it's more prevalent in
developing countries with warm temperatures year-round.
• Poor sanitation: Ascariasis is widespread in developing
countries where human feces are allowed to mix with local
soil.

21. COMPLICATIONS
• Visceral damage,
peritonitis and
inflammation
• Enlargement of
the liver or spleen
• Intestinal
blockage
• Bowel obstruction
• Allergies
• Malnutrition
• Abdominal discomfort
• Abdominal cramping
• Abdominal swelling
(especially in children)
• Fever
• Coughing and/or
wheezing
• Nausea
• Vomiting
• Passing roundworms
and their eggs in the
stool
SYMPTOMS OF
ASCARIASIS

22. PREVENTION
• Keeping good sanitation conditions is the only way to prevent the
infection of Ascaris.
• Pollution of soil with human faeces should be avoided.
• Vegetable should be thoroughly washed and properly cooked
before use.
• Finger nails should be regularly cut to avoid the collection of dirt
and eggs below them.
• Hands should be properly washed with some antiseptic soap before
touching edibles or eating.

23. Treatment
• Infections with A. lumbricoides are easily treated with a
number of anthelmintic drugs:
• Pyrantel pamoate given as a single dose of 10 mg/kg.
• Levamisole given as a single dose of 2.5 mg/kg.
• Mebendazole given as a single dose of 500 mg.
• Albendazole given as a single dose of 400 mg

24. ANTIHELMINTIC DRUGS
BENZIMIDAZOLEs
1. ALBENDAZOLE:
• It possess broad-spectrum activity. It is the drug of choice for
treatment of
1. Hydatid disease and
2. Neurocysticercosis.
• It is also a major drug in the treatment of (intestinal nematodes) :
1. Ascariasis,
2. Trichuriasis,
3. Strongyloidiasis,
4. Enterobius vermicularis (pinworm),
5. Nector americanus, & Ancylostoma duodenale (Hookworms)
infections.

25. Mechanism of Action: Albendazole
• Inhibits microtubule synthesis and glucose uptake
• It has larvicidal effects on hydatid disease,
cysticercosis, ascariasis, and hookworm infection.
• Also, ovicidal in ascariasis , ancylostomiasis
(hookworm), trichuriasis
25

26. Pharmacokinetics: Albendazole
• It is a benzimidazole carbamate
• It is administered orally, and absorbed
erratically (unpredictable), absorption can be
increased with fatty meal.
• It is metabolized in the liver rapidly to its
active metabolite albendazole sulphoxide. (1st
pass metabolism).
26

27. Cont’d
• It has a plasma half life of 8-12 hours
• Sulphoxide is mostly (80%) protein bound , distributed
to the tissues and enters the bile, cerebrospinal fluid, and
the hydatid cyst.
• urinary excretion.
27

28. Clinical uses of Albendazole
• It is administered on empty stomach when used
against intraluminal parasites but with fatty meal
when against tissue parasites.
1. Ascariasis, trichuriasis, hookworm, pin worm
infection (intestinal):
Acheives 100% cure in pinworm infection and
high cure rates for others or marked reduction in
eggs counts.
28

29. 2. Hydatid diseases:
Drug of choice, with meals.
• If patients are to be treated surgically, both albendazole
and praziquantel are used preoperatively for one month
to reduce cyst fluid leakage. After surgery albendazole
should be continued for a whole month.
29

30. Albendazole cont’d
3. Neurocysticercosis: It is the drug of choice.
It is effective for symptomatic parenchymal and
interventricular cysts. Less effective in arachnoid cyst.
• It is superior to Praziquantel for neurocysticercosis for
the following:
1. Shorter course of treatment.
2. It is cheaper
3. It’s co-administration with steroid increases its
absorption
4. It is better in penetration arachnoid space..
5. It is also effective for ocular cysts.
30

31. Albendazole cont’d
Adverse effects:
 In short term use there is no significant adverse effects.
 In long term use: abdominal distress, headache, fever,
fatigue, alopecia , increased liver enzymes, pancytopenia.
Blood counts should be carried out regularly.
 Not given during pregnancy and in hypersensitive people.
 Safety in children is not established in children below 2 years
of age.
31

32. 2. MEBENDAZOLE
• It is a synthetic benzimidazole
• It has wider spectrum and is safe
• MOA: Similar to albendazole
Efficacy influenced by: GI transit time, intensity of
infection, and strain of parasite.
It is also used to kill hook worm, pin worm , ascaris and
trichuris eggs.
32

33. Mebendazole con’td
Pharmacokinetics:
1. Less than 10% of orally administered drug is
absorbed
2. Absorption increases with fatty meals
3. Absorbed drug is 90% protein bound
4. It is converted to inactive metabolites rapidly in
liver.
5. It has half life of 2-6 hours
6. It is primarily excreted in bile.
33

34. Mebendazole con’td
Clinical uses:
• It is taken orally before or after meal, tablets should be
chewed before swallowing.
• Ascaris lumbricoides , trichuris trichura , hookworm
and trichstrongylus; It is a useful drug in case of mixed
infection by these parasites.
• In adults and children over 2 years cure rate is 90-100
% except hookworm but a marked reduction in worm
burden occurs.
34

35. Cont’d
Adverse effects and precautions:
1. No adverse effects in short term therapy except for mild GI
disturbances.
2. With high dose hypersensitivity reactions, agranulocytosis
, alopecia, elevation of liver enzymes.
3. Contraindicated in pregnancy.
4. Used with caution for children under 2 years of age may
cause convulsion in this group.
5. carbamazepine or phneytoin  ↓ conc. Cimetidine  ↑
conc.
6. used with caution in cirrhosis.
35

36. 3. Thiabendazole
 It is a benzimidazole. It is tasteless and insoluble in water.
 It is a chelating agent and forms stable complexes with
metals including iron but does not bind with calcium.
 It is rapidly absorbed orally.
 It has half life of 1.2 hrs.
 It is completely metabolized in liver and 90% is excreted in
urine.
 It can also get absorbed through the skin. Thus, could be
applied in creams.
36

37. Thiabendazole cont’d:
• MOA: similar to other benzimidazoles.
• It is ovicidal for some parasites.
• It also possesses immunosuppressive, antipyretic,
and mild antifungal and scabicidal (destroying the itch
mite causing scabies ) effects.
37

38. Clinical uses:
• Should be given after meals and tablets should be
chewed.
• For strongyloides (threadworms) infections:cure rate
is 93%.
• For cutaneous larval migrans thiabendazole cream is
effective and applied topically or given orally.
• Also effective for intestinal capillariasis and
scabiasis.
38

39. Thiabendazole cont’d
 Adverse reactions and contraindications:
1. It is more toxic than other benzamidazoles.
2. GI disturbances
3. Pruritus, headache, drowsiness, neuropsychiatric
symptoms rarely may cause tinnitus, bradycardia,
hypotension, hyperglycemia, convulsions,
neutropenia and other adverse effects may occur.
4. Irreversible liver failure.
5. Fatal Stevens–Johnson syndrome (inflammation of
the skin)
6. Not used in children below the weight of 15 kg,
during pregnancy, hepatic and renal diseases.
39

40. 4. PYRANTEL PAMOATE
• It is a broad-specturm antihelminthic
• It is not effective against trichuriasis (whipworms), yet
oxantel pamoate is considered effective against trichuriasis.
Both drugs can be combined for their synergistic effect.
• Pharmacokinetics:
• It is poorly absorbed orally. Active mainly against luminal
organisms.
• Half of the drug is excreted unchanged in the feces.
• Mechanism of action:
• It is a depolarizing neuromuscular blocking agent that
• causes release of acetylcholine and inhibition of
cholinesterase leading to the paralysis of worms followed by
their expulsion from the GIT.
40

41. Pyrantel pamoate
Efficacy and clinical uses:
• it is very effective against mature and immature luminal
organisms, but not effective against migratory stages in the
tissues or against ova.
• Enterobius vermicularis (pinworm).
• Ascaris lumbricoides (common roundworm)
• Ancylostoma duodenale (hookworm) single dose for light
infection but a 3-day course is necessary for heavy infection.
41

42. Pyrantel pamoate cont’d:
• Adverse effects are infrequent and mild.
1. GI disturbance.
2. Drowsiness, headache, insomnia.
3. Rash, fever.
• Contraindications:
1. Should not be used in liver diseases.
2. Pregnancy
3. In children under 2 years of age
42

43. 5. PIPERAZINE
• Only used for the treatment of ascariasis.
• It is readily absorbed orally and excreted in urine
• Mechanism of action:
It causes paralysis of ascaris by blocking acetylcholine at
the myoneural junction, expelling the live worm by
normal peristalsis.
Treatment is continued for 3-4 days or repeated after one
week in case of heavy infections.
43

44. Piperazine cont’d
• Adverse effects:
1. GI disturbances
2. Neurotoxicity, allergic reactions serum sickness like
syndrome
• Contraindications
1. Epilepsy or chronic neurologic disease
2. Impaired liver or kidney functions
3. Pregnancy
4. Malnutrition
44

45. Drugs used for treating human intestinal
nematodes (single dose unless otherwise
stated
Ascariasis Hookworm enterobius tricuris strongyloides
Piperazine ++ + ++ - -
Pyrantel pamoate ++ ++ ++ - -
Albendazole ++ ++ ++ + +
Mebendazole ++ ++ ++ + +
Thiabendazole n/a n/a n/a n/a ++
Ivermectin n/a n/a n/a n/a ++
45

46. Drug treatment for tape
worm(cestodes) infection
• Niclosamide
• Praziquantel
• Albendazole
46

47. 6. NICLOSAMIDE
 It is useful for the treatment of adult tape worm (cestodes)
infestation
 Mechanism of action:
 Adult worm is rapidly killed by inhibition of the oxidative
phosphorylation or stimulation of ATPase activity.
 No effect on ova
 Pharmacokinetics:
 It is not absorbed from the gut
 Neither drug nor its metabolites are found in the blood or
urine.
47

48. Niclosamide
• Clinical uses:
A. T. Saginata (Beef tape worm), T. solium (pork tapeworm)
• In case of T. solium after 2 hrs of treatment, purge of
magnesium sulphate should be given to eliminate all
mature segments.
• Not effective against cysticercosis or hydatid disease.
it’s not absorbed from the gut.
48

49. Niclosamide cont’d
• Adverse effects:
• Mild, infrequent and transitory GI disturbances
• Alcohol consumption should be avoided
• Not indicated in children under 2 years of age or pregnancy.
49

50. 7. Diethylcarbamazine
• The drug of choice for the treatment of filariasis,
loiasis and tropical eosinophilia.
• Pharmacokinetics:
• It is a synthetic derivative of piperazine
• Rapidly absorbed from the gut
• It has a half life of 2-3 hours which increases in
alkaline urine up to 10 hours.
• Equilibrates with all tissues except fat
• It is excreted in urine unchanged.
• Dosage is reduced in urinary alkalosis and renal
impairment.
50

51. DIETHYLCARBAMAZINE
• Mechanism of action:
• It immobilizes microfilariae in tissues and alters its surface
structure, making them more susceptible to destruction by host
defense mechanism.
• Unknown mechanism against adult worms.
• It also possesses an immunosuppressive effects.
• It has no teratogenic effects on experiment animals.
51

52. DIETHYLCARBAMAZINE
• It is a drug of choice for the treatment tissue
cestodes,
Wuchereria bancrofti, and Loa loa.
• Microfiliariae are rapidly killed. Adult worms are
killed slowly requiring several courses of treatment.
Adult worms are either killed or sterilized.
• It is highly effective against Loa loa.
52

53. DIETHYLCARBAMAZINE cont’d
 Anti histamines and corticosteroids are given in allergic
manifestations.
 Complete Cure may be require several courses of treatment
over 1-2 years.
 The drug may be used in prophylaxis for loiasis, bancroftian,
and Malayan filariasis
 Tropical (pulmonary) eosinophilia
 Mansonella streptocerca
53

54. DIETHYLCARBAMAZINE cont’d
 Drug induced/ Reactions induced by Dying parasites:
 Fever , malaise, rash, headache, GI disturbance, cough, chest,
muscle, joint pain
 Leukocytosis, proteinurea, ↑ eosinophilia
 Retinal hemorrhage
 Encephalopathy
 Lymphangitis and lymphadenopathy.
54

55. DIETHYLCARBAMAZINE cont’d
• Contraindications and cautions
1. Hypertension
2. Renal disease
3. Patient suspected of having malaria
4. Patients with lymphangitis
55

56. 8. IVERMECTIN
• It is the drug of choice for treatment of
strongyloidasis and onchocerciasis
• It is a macrocyclic lactone
• It is used orally and is rapidly absrobed,
possesses wide volume of distribution about 50
L.
• It has a half-life of 16 hrs
• It is exclusively excreted in feces
56

57. IVERMECTIN cont’d
• Mechanism of action:
• It intensifies GABA –mediated transmission of signals
in peripheral nerves  paralyzing the worm.
• In onchocerciasis it is microfilaricidal. It does not kill
the adult worm.
• Clinical uses:
• Onchocerciasis: with the 1st treatment, patients with
microfilariae in the cornea or anterior chamber may be
treated with corticosteroid.
57

58. IVERMECTIN cont’d
• Strongyloidiasis: in immunosuppresed patient,
repeated treatment is often needed.
• Bancrofti filaricidal: as it is mirofilaricidal
• It is also used for scabies, lice, and cutaneous
larva migrans.
• Eliminates adcarid worms
• Reduces microfilariae in Brugia malayi and M
ozzardi.
58

59. IVERMECTIN
• Adverse effects:
1. Fatigue
2. dizziness,
3. GI disturbance
• In Onchocerciasis:
1. Mazotti reaction: fever, headache,
dizziness, somnolence (state of being
drowsy), weakness, rash ,diarrhea,
arthralagia, hypotension, lymphadenitis,
peripheral edema due to killing of
microfiliariae, for this steroids may be
necessary for several days
2. Swelling and abscess at site of adult
worm.
59
• Contraindication:
1. other drugs that
enhance GABA
activity e.g
Barbiturates,
benzodiazepines,
valproic acid.
2. pregnancy
3. Impaired blood
brain barrier
4. Children under 5
years of age.