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Anti-Malarial drugs

Protozoal disease
infected female anopheles mosquito
WHO estimates
300-500 million cases year
> 1 million death

India- NVBDCP- 1.5 million confirmed cases

Types of Malarial Parasite
Plasmodium falciparum
Plasmodium vivax
Plasmodium malariae
Plasmodium ovale
Most of the serious complications and death
occur due to Plasmodium falciparum

Classification of Anti Malarial Agents: 1
Chemical Structure
4-Aminoquinolines : Chloroquine, Amodiaquine

8-Aminoquinoline: Primaquine, Bulaquine

Cinchona alkaloid : Quinine
Sesquiterpine lactones: Artesunate, Arteether, Artemether
Biguanides: Proguanil
Diaminopyrimidine : Pyremethamine
Quinoline methanol : Mefloquine
Sulfonamides : Sulfadoxine
Phenanthrene methanol : Halofantrine
Tetracycline: Doxycycline,
Acridine : Mepacrine
Naphthoquinone Atovaquone

Life Cycle of the Malarial Parasite
Antimalarial Therapy
Causal prophylaxis
Suppressive prophylaxis
Clinical cure
Radical cure
Classification- Stage of Parasite affected
Stage Drugs
Blood schizonticidal drugs Erythrocytic phase Chloroquine,
Terminates clinical illness Artemissin,

Tissue schizonticidal drugs Tissue form of plasmodium Primaquine,

Gametocidal drugs Destroy sexual forms of Primaquine
parasite Quinine
Prevent transmission to
Hypnozoiticidal Destroy persistent liver Primaquine
stages of P vivax , P ovale
Acts by :
concentrating in parasite food vacuoles,
preventing the polymerisation of the hemoglobin
breakdown product, heme, into hemozoin, and
thus eliciting parasite toxicity (plasma membrane
damage) due to the buildup of free heme.
Chloroquine, Quinine, Mefloquine.
Oral absoption-Excellent
Partly metabolized in liver and slowly excreted in
Adverse effects
-Cardiac depresssion
-CNS toxicity
-Retinal damage
Should not be coadministered with mefloquine,
amiodarone and other anti-arrythmics
Oral absorption is good but quite slow
Highly plasma protein bound
Metabolised by liver and secreted in bile
Quinine & Quinidine
First-line therapies for falciparum malaria.

Oral administration.

Higher plasma levels and half-life in infected persons

than in healthy controls, but toxicity is not increased,
apparently because of increased protein binding.
MOA: is unknown, it may act like chloroquine
Adverse Effects

Cinchonism: Hypersensitivity reactions

Tinnitus, Hypoglycemia
Too-rapid IV infusions :
Severe hypotension
IV Quinidine : ECG

Visual Disturbances
Black water fever
rare severe illness
marked hemolysis ,

Proguanil & Pyrimethamine
Proguanil is cyclized in the body to a triazine
derivative(cycloguanil) which inhibits
plasmodial DHFRase.
Half life: 16-20hr
Pyrimethamine is a directly acting inhibitor of
plasmodium DHFRase.
High affinity for plasmodial enzyme(-2000 times
greater than for the mammalian enzyme)
Proguanil and Pyrimethamine
Sulfonamide-Pyrimethamine Combination

Supra-additive synergistic combination due to

sequential block.
Both components are slow acting, the
combination acts faster, so that it can be
employed as a clinical curative, particularly for
By addition of sulfonamide, development of
resistance to pyrimethamine is retarded.
Sulfonamide-Pyrimethamine Combination
Radical cure
prevents relapse in P vivax and P ovale
Hemolytic anemias- G-6PD status should
be evaluated
Not given parenterally- causes hypotension
Contraindicated in Pregnancy and infants
MOA- unknown
None should be used as single agents because their action
is much slower than that of standard antimalarials.
Tetracycline : erythrocytic schizonts , but not active against
liver stages.
Doxycycline : falciparum malaria in conjunction with
quinine, allowing a shorter and better-tolerated course of
that drug, it has also become a standard
chemoprophylactic drug.
Artemisinin derivatives
Artemisinin: used orally.

Analogs are:
Artesunate (water-soluble; oral, IM, IV and rectally),

Artemether (lipid-soluble; oral, IM, and rectally),

Dihydroartemisinin (water-soluble; oral).

They are very rapidly acting blood schizonticides against
all human malaria parasites, no effect on hepatic stages.
Artemisinin derivatives
The parasite when it infects a RBC, it consumes Hb within its digestive vacuole,
liberating free heme, The iron in heme interacts with Artemisinin producing
reactive oxygen radicals which damage the parasite leading to its death
Or inhibition of a parasite calcium transporter.

Artemisinin-based combination therapy is now the standard for treatment

of uncomplicated falciparum malaria in nearly all areas endemic for falciparum

A/E: GI disturbance, dizziness, neutropenia, anemia,

hemolysis, elevated liver enzymes, allergic reactions.

Halofantrine & Lumefantrine
Against erythrocytic (but not other) stages
of all four malaria species.
MOA: unknown.

A/E : GI disturbance, cough, rash, headache,

pruritus, and elevated liver enzymes, dose-
related prolongation of QT and PR intervals
For treatment and prevention of malaria, administered orally.

MOA: disrupting mitochondrial electron transport and thus

interferes with ATP production.
It collapses plasmodial mitochondrial membrane
It is active against tissue and erythrocytic schizonts.

Proguanil potentiates its antimalarial action and prevents

emergence of resistance

A/E: GI disturbance, Fever, Rash, Headache