By: Samuel Mwaniki

BACKGROUNDParasitic wormsTwo broad phyla:1.PlatyhelminthesCestodesTrematodes2.Nematodes

DRUGSClassified into1.Benzimidazoles : Albendazole, Thiabendazole,

Mebendazole.2.Prazinoisoquinolines: Praziquantel.3.Organophosphates: Metrifonate.4.Piperazines: Piperazine, Diethylcarbamazine.5.Others: Pyrantel, Niclosamide, Levamisole,

Ivermectin, Oxamniquine,

BENZIMIDAZOLESMoAVarious biochemical changes in susceptible

nematodes (both adults and larvae)Inhibition of mitochondrial fumarate

reductase in TCA cycle.Reduced glucose transport.Inhibit microtubule polymerization by

binding to beta-tubulin, hence immobilizing parasite and causing slow death.

Selective Toxicity:Higher affinity and binding to nematode beta-

tubulin compared to human beta-tubulin.

Spectrum of Activity

1. Thiabendazole Cutaneous larval migrans (15% cream bd,

5/7) S. stercoralis

High GIT toxicity thus replaced by other members.

2. Mebendazole

GIT nematodes (mixed infections): E. Vermicularis, A. lumbricoides, T. trichiura, Hookworms.

Tissue nematodes: T.spiralisHydatid cyst (Albendazole superior)

3. AlbendazoleMixed infectionsHydatid cyst; pre- and post surgeryS.stercoralis (Ivermectin and Thiabendazole

preferred)Neurocysticercosis caused by larva of

T.solium. Give glucocorticoids to prevent reaction from death of cysticerci.

With DEC or Ivermectin to control lymphatic Filariasis.

Pharmacokinetics1. ThiabendazoleRapidly absorbed from the GIT, metabolized

in liver and excreted in urine.2. MebendazoleOnly 10% absorbed from GIT, fatty meal

increases absorption. Rapidly metabolized and excreted in bile and urine within 24-48 hours.

3. AlbendazoleErratic absorption from GIT. Metabolised to

Albendazole sulphoxide (active).

Unwanted EffectsGIT disturbances: N, V and DCNS (rare): drowsiness, dizziness, headacheAllergic reactions (very rare)

PRAZIQUANTELMoACestodes: At low concentrations, causes

increased muscular activity followed by contraction and spastic paralysis, hence detachment of the worm from the host’s intestines.

Trematodes: At high concentrations, causes influx of calcium ions across tegument resulting in damage and exposure of antigens. Host mounts immune response against the parasite.

Clinical UsesCestodes: T.saginata, T.solium, D.latum,

H.nana ;10-20mg/ kg stat, repeat after 7-10 days.

Liver, lung and intestinal flukes: F.hepatica, P.westermani, F.buski; 25mg/kg tds, 1 day.

Blood flukes: Schistosomes; 40-60mg/kg single dose.

Nematodes not affected.

Pharmacokinetics Readily absorbed.Extensive 1st pass metabolism producing

inactive hydroxylated metabolites.Excreted in urine and bile.80% plasma protein bound. Half life of 1-3

hours.

Unwanted Effects:Abdominal discomfortCNSOthers (rarely): fever, priritis, urticaria,

rashes, arthralgia and myalgia

METRIFONATEMoAAn orgnophophate.Prodrug; converted to dichlorvos in vivo.Potent inhibitor of cholinesterase enzyme

resulting in paralysis. Moves from venous plexus to small arteries and finally to lungs where they are encased hence death.

Ova not affected.

Uses S.haematobium: 10mg/kg stat, repeat twice

at 2 week intervals.

PharmacokineticsRapidly absorbed.Metabolized non enzymatically at

physiological PH.Cleared from plasma within 8 hours.

Unwanted Effects:GIT disturbances.CNS effects.Inhibition of host’s cholinesterase enzyme (no

significant effects)Foetal damage?

CAUTION! – administer with Atropine to prevent organophosphate toxicity in host.

OXAMNIQUINEMoACauses DNA intercalation.

Selective ToxicityParasite accumulates drug more than host.

Uses:S.mansoni: both immature and mature forms

affected. Adult male more than female.Sensitivity differs geographically hence wide

range of doses. Tropical Africa (30-60 mg/kg in 2 divided doses), S. America ( 15 mg/kg)

PharmacokineticsWell absorbed.1st pass effect in gut and liver – inactive

metabolites.Excreted in urine.Half life of 1-2 hours. Fully eliminated within

10-12 hours.

Unwanted EffectsGITCNS stimulation – hallucinations,

convulsions.Allergic manifestations appearing long after

treatment – antigens from dead flukes.

IVERMECTINMoABlocks glutamate, GABA and other ligand

gated chloride channels in the microfilaria, hence inducing tonic paralysis, immobilization and death .

Prevents egression of microfilaria from uterus of the female.

Selective Toxicity100 fold higher affinity for nematode GABA

activity compared to host.

Uses:Drug of choice for O.volvulusMass chemotherapy in combination with

Albendazole where O.volvulus, W.bancrofti, L.loa infections co-exist. Single annual dose for 4-6 years.

S.stercoralis, A.lumbricoides, T.trichiura, E.vermicularis

ScabiesHead liceCutaneous larval migrans

PharmacokineticsRapid absorption reaching peak plasma

concentrations in 4-5 hours.Distributed in liver and adipose tissue.Metabolized to inactive metabolites in liver.Excreted in bile.

Unwanted Effects:Mild Mazzoti like reactions due to antigenic

materials released by dead microfilaria – mild (itching); use H1 antagonists, severe (fever, hypotension, headache, myalgia); use glucocorticoids.

C/I in late stage HAT; compounds CNS depression.

DIETHYLCARBAMAZINEMoAInhibition of microtubule polymerization and

destruction of preformed microtubules.Causes release of antigens by microfilaria,

hosts mounts immune response hence killing parasite.

Interferes with parasite’s arachidonate metabolism.

Rapidly clears microfilaria from blood. No effect on adult worms.

Uses:Drug of choice for Filariasis caused by: W.b,

L.l, B.m, B.tO.v (2nd choice)Cutaneous larval migrans caused by dog and

cat hookwormsVisceral larval migrans caused by dog and

cat round worms.

Pharmacokineticss:Rapid absorption.Disributed in all body tissue s except adipose

tissue.Partial metabolism in liver.Excreted in urine. Cleared from body within

48 hours.

Unwanted Effects:1.Drug relatedGITCNS2. Antigens released from dead microfilaria

(Mazzoti reaction)Mild: rash, urticariaSevere: intense itching, lymphadenopathy, fever,

tachcardia, hypotension, headache, arthralgia.

Management: H1 antagonists, Glucocorticoids.

Discuss the rationale for the widespread use of broad spectrum antihelminthics, giving examples of helminths and drugs used against them.