L9 Anthelminthic Drugs

Question 1

Scientific name for Common Roundworm?

Answer 1

Ascaris Lumbricoides

Question 2

Scientific name for guinea worm?

Answer 2

Dracunculus Medinensis

Question 3

Scientific name for Human Pin Worm?

Answer 3

Enterobius Vermicularis

Question 4

Life Cycle of Enterobius Vermicularis (Human Pin Worm)?

Answer 4

1. Eggs on perineal folds (Larve within) mature within 4-6 hours
2. Embryonated egss ingested by human
3. Larvae hatch in small intestine
4. Adults in the lumen of Cecum
5. Gravid females migrate to perinatal region at night to lay eggs

Question 5

Features of Helminth Host-parasite Interface?

Answer 5

Outer Surface of Helminths Provide Primary Host-Parasite Interface

Tapeworms and Flukes: surface is a complex plasma membrane (protection against host-induced damage)

Nematodes: have a tough collagenous cuticle, normally resistant to immune attack

Worms release large amounts of soluble antigenic material via excretion/secretion (role in immunity and pathology

Question 6

Treatment of Cestodes (tapeworms)?

Answer 6

Praziquantel or Albendazole

Question 7

Treatment of Intestinal Nematodes?

Answer 7

Mebendazole/Albendazole
Pyrantel
Piperazine
Ivermectin

Question 8

Treatment of Tissue Nematodes?

Answer 8

Thiabendazole/Albendazole
Ivermectin
Metronidazole
DEC (piperazine derivative)

Question 9

Treatment of Schistosomes?

Answer 9

Praziquantel

Question 10

MOA of Anthelminthic Drugs ?

Answer 10

Anthelminthic Drugs: Must penetrate cuticle of worm or gain entry into its GI tract (difficult)

Drugs can act by:
1. Paralysis of the worm

2. Damage to cuticle, leading to partial digestion or rejection by immune system
3. Interfere with the metabolism of the worm - Metabolic requirements vary greatly between organisms => increased specificity

Question 11

Benzimidazoles Idications/MOA/Pharmacodynamics

Answer 11

Broad spectrum antihelminthic agents (Most commonly used)

MOA
Tubulin polymerization Inhibition => Inhibits Microtubule–dependent glucose uptake
400x more potent in helminths than mammalian tissue

Pharmacodynamics
Only 10% of Mebendazole absorbed, fatty meal increases absorption
Mebendazole not to pregnant women or kids <2yo

Tiabendazole rapidly absorbed and excreted in urine in 3 days.

Albendazole poorly absorbed, extensively and rapidly metabolized first pass

Question 12

Praziquantel Indications/MOA/Pharmacodynamics

Answer 12

Broad spectrum anthelminthic agent (schisto, cestodes)

Drug of choice for schistosome infections - all stages

MOA
alters Ca++ permeability of helminth cell muscle contraction=> paralysis, death of the worm

Pharmacodynamics
> Administered orally
> Rapidly absorbed (½ life is 60-90 min)
> Metabolized rapidly in liver and excreted in urine

Safe to give to pregnant women!! (No effect on human cells)

Question 13

Ivermectin Indications/MOA

Answer 13

Semi-synthetic agent derived from a group of natural substances, the avermectins,obtained from an actinomycete

Potent against filaria (nematodes) in man

MOA
Potentiates γ-aminobutyric acid (GABA) release (worm only) => Opens Cl- channels, increases Cl- conductance at neuromuscular junctions => Motor neuron hyperpolarization =>Worm paralysis (drug is in general well tolerated)

Question 14

Pyrantel Pamoate Indications/MOA

Answer 14

Broad spectrum agents (pinworm, hookworm, roundworm)

Drug of choice for certain nematode infections

MOA: depolarizing neuromuscular blocker ⇒ paralysis also inhibits cholinesterase

Question 15

Piperazine (DEC) Indications/MOA/Contraindications

Answer 15

Treat roundworm and threadworm

MOA: neuromuscular blocker ⇒ paralysis

__Contraindications__: NOT safe to use in pregnancy or impaired renal/hepatic function

Question 16

Factors linked to Resistance to Anthelminthic Agents?

Answer 16

Several factors have been linked to resistance phenomena (esp. veterinary) as follows:
- Drug efflux pump (P-glycoprotein)
- Impairment of high-affinity binding to parasite β- tubulin
- Alterations in structure of receptors

Question 17

Evasion of the Host Immune System by Helminths. Consequences of this?

Answer 17

Helminths appear to steer immune system away from local Th1 (cell-mediated) response
=> Promotion of a systemic Th2 (antibody-dependent) response
=> Production of anti-inflammatory cytokines, e.g. IL-10

Patients with wounds may heal better, good for the worm

“Hygiene Hypothesis”: Comparative absence of Crohn’s and other autoimmune diseases in the developing world may be associated with a high incidence of parasite infection. Rise of these disorders in the West is associated with high level of sanitation and reduced helminthic infection

Question 18

__________ have a tough collagenous cuticle, normally resistant to immune attack

Answer 18

Nematodes: have a tough collagenous cuticle, normally resistant to immune attack

Question 19

_________ and _________: surface is a complex plasma membrane (protection against host-induced damage)

Answer 19

Tapeworms and Flukes: surface is a complex plasma membrane (protection against host-induced damage)