Anthelmintic & Antimalarial Drugs

CHLOROQUINE
Pharmacological properties:
 It is a rapidly acting erythrocytic schizontocide against all species of plasmodia
 Controls most clinical attacks in 1–2 days with disappearance of parasites from
peripheral blood in 1–3 days.
 Therapeutic plasma concentrations are in the range of 15–30 ng/ml.
 Has no effect on pre- and exo-erythrocytic phases of the parasite.
Pharmacokinetics:
 Oral absorption is excellent.
 About 50% bound in the plasma.
 High affinity for melanin and nuclear chromatin.
 Gets tightly bound to these tissue constituents and is concentrated in liver, spleen,
kidney, lungs, skin, leucocytes and some other tissues.
 Its selective accumulation in retina is responsible for the ocular toxicity seen with
prolonged use.
 Partly metabolized by liver and slowly excreted in urine. The early plasma t½ varies
from 3–10 days.
Mechanism of action: It is actively concentrated by sensitive intraerythrocytic plasmodia,
higher concentration is found in infected RBCs. By accumulating in the acidic vesicles of
the parasite and because of its weakly basic nature, it raises the vesicular pH and thereby
interferes with degradation of haemoglobin by parasitic lysosomes. Polymerization of toxic
haeme to nontoxic parasite pigment hemozoin is inhibited by formation of chloroquine-
heme complex. Heme itself or its complex with chloroquine then damages the plasmodial
membranes. Clumping of pigment and changes in parasite membranes follow.
Adverse effects & Toxicity: Toxicity of chloroquine is low, but side effects are frequent
and unpleasant: nausea, vomiting, anorexia, uncontrollable itching, epigastric pain,
uneasiness, difficulty in accommodation and headache.

 Parenteral administration can cause hypotension, cardiac depression, arrhythmias.

 Prolonged use of high doses may cause loss of vision due to retinal damage. Corneal
deposits may also occur and affect vision.
 Loss of hearing, rashes, photoallergy, mental disturbances,and graying of hair can
occur on long-term use.
Contraindications: Caution is to be exercised in the presence of liver damage, severe g.i.,
neurological and haematological diseases. Attacks of seizures, porphyria and psoriasis may
be precipitated. Chloroquine should not be coadministered with mefloquine, amiodarone
and other antiarrhythmics.
Uses/Indications:
1. Chloroquine is the drug of choice for clinical cure and suppressive prophylaxis of
all types of malaria, except that caused by resistant P. falciparum.
2. Extraintestinal amoebiasis.
3. Rheumatoid arthritis.
4. Discoid lupus erythematosus—very effective; less valuable in systemic LE.
5. Lepra reactions.
6. Photogenic reactions.
7. Infectious mononucleosis- affords symptomatic relief

MEBENDAZOLE
Mechanism of action: The action of mebendazole on worms is rather slow, takes 2–3 days
to develop. It acts probably by blocking glucose uptake in the parasite and depletion of its
glycogen stores. Intracellular microtubules in the cells of the worm are gradually lost. The
site of action of mebendazole appears to be the microtubular protein ‘β-tubulin’ of the
parasite. It binds to β-tubulin of susceptible worms with high affinity and inhibits its
polymerization. Hatching of nematode eggs and their larvae are also inhibited. Ascaris ova
are killed.
Adverse effects: Diarrhoea, nausea and abdominal pain have attended its use in heavy
infestation. Incidents of expulsion of Ascaris from mouth or nose have occurred, probably
due to starvation of the parasite and their slow death. Allergic reactions, loss of hair and
granulocytopenia have been reported with high doses.
Use/Indication: Mebendazole is an anthelmintic, drugs that either kill (vermicide) or expel
(vermifuge) infesting helminths. Mebendazole is indicated for the treatment of
threadworms, whipworms, roundworms, hookworms etc. Mebendazole is one of the
preferred drugs for treatment of multiple infestations and is more effective than
albendazole in trichuriasis.