POD-2 Module
Anti-protozoal Drugs-I: Antimalarial
(Antimicrobial Chemotherapy)
Pre- LBL Questions
• Mention the two human stage of malaria disease?
• Which one is responsible for clinical symptoms?
• What does Cinchonism mean for you?
• What is the other indication for Quinidine?
• How sever cerebral malaria is treated?
• What is the drug of choice for the eradication of dormant liver
forms (Radical Cure)?
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Lecture objectives
By the end of the lecture, you should be able to:
• Identify the Malaria infection parasite life-cycle to determine
the drug targets.
• Understand and Discuss the common Anti-malarial drugs
classes with their main pharmacological features.
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Lecture contents
• A- Introduction: Malaria infection.
• B- Antimalarial drugs: Quinolines, Artemisinin, Cinchona alkaloids, Synthetic 4-
quinoline, Halofantrines, Antibiotics & Folate antagonists .
• C. References
• Basic & Clinical Pharmacology (Katzung).
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Malaria infections
• It is an infectious febrile disease caused by protozoa of genus
'Plasmodium’
• Transmitted to humans by the bites of infected female
mosquitoes of genus 'Anopheles'.
• Malaria is the most serious protozoal disease, accounting for
more than 1 million deaths a year.
• Multidrug-resistant Plasmodium falciparum is an increasing
problem in most parts of the world (combination regimen)
• Malaria is caused by four species of protozoa? Mention
them??
• A- Mosquito: Sporozoites
• B- Human: Liver: Pre-erythrocytic or tissue stages (schizonts) &
Blood: Erythrocytic stages (merozoites)
• Most antimalarials are toxic to the erythrocytic schizonts
(Schizonticides) and used to treat clinical attacks of malaria.
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A- QUINOLINES
(Chloroquine)
• Chloroquine: is Haem polymerase inhibitors.
• Selective toxicity for malarial parasites depends on
chloroquine concentrating mech. in parasitized cells.
✓Uses: Drug of choice in the treatment of non-falciparum
and sensitive falciparum malaria.
✓Preferred chemoprophylactic agent in malarious regions
without resistant falciparum malaria
✓Amebic liver abscesses that fail initial therapy with
metronidazole
✓Rheumatoid arthritis & Lupus erythematosus
• SE: Very well tolerated (prolonged use).
• Pruritus is common, Nausea, vomiting, abdominal pain,
headache, anorexia, malaise, blurring of vision, and
urticaria are uncommon.
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B- ARTEMISININ
(Artemether)
• Artemether:
• MOA: Mitochondrial electron transport inhibitors
• Uses: Artemisinin-based combination therapy is
now the standard for treatment of uncomplicated
falciparum malaria.
• SE: Very well tolerated, but Nausea, vomiting,
diarrhea, and dizziness.
• Rare serious toxicities: neutropenia, anemia,
hemolysis, elevated liver enzymes, and allergic
reactions.
• Irreversible neurotoxicity and embryotoxic in
animal (pregnancy)
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C- CINCHONA ALKALOIDs
(Quinine & Quinidine)
• Quinine & Quinidine:
• MOA:
• Uses: Parenterally & Orally for Treatment of Severe
Falciparum Malaria (cerebral)
• Rare Malarial Chemoprophylaxis
• Babesiosis infection.
• SE: Cinchonism (tinnitus, headache, nausea,
dizziness, flushing, and visual disturbances)
• Hemolysis (G6PD deficiency)
• Severe hypotension can follow too-rapid
intravenous infusion
• Hypersensitivity
• NB: Quinidine is a class I antiarrhythmic agents
• Primarily works by blocking the fast inward sodium
current (INa)
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D- Synthetic 4-quinoline
(Mefloquine & Primaquine)
• Mefloquine: Chemoprophylactic drugs for
chloroquine-resistant strains.
• SE: Neuropsychiatric toxicities, Leukocytosis,
thrombocytopenia.
• Primaquine:
• Uses: Drug of choice for the eradication of dormant
liver forms (Radical Cure).
• used for chemoprophylaxis against all malarial
species (Terminal Prophylaxis)
• Pneumocystis jiroveci Infection
• SE: Well tolerated
• Cardiac arrhythmias, hemolysis (G6PD deficiency)
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E- Halofantrine
(Halofantrine & Lumefantrine)
• Lumefantrine: an aryl alcohol related to
halofantrine.
• Treatment of P falciparum malaria in fixed
combination with artemether (Coartem)
• Used for Uncomplicated infections with
chloroquine-resistant P falciparum
• SE: Coartem can cause minor prolongation of the
QT interval, but this appears to be clinically
insignificant, and the drug does not carry the risk of
dangerous arrhythmias seen with halofantrine and
quinidine
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F- Antibiotics & Folate antagonists
(Doxycycline, Proguanil & Sulfa drugs)
• Antibiotics: Doxycycline (See Antibiotics)
• Used for traveler’s prevention in areas with multidrug-
resistant P falciparum (100 mg daily).
• active against erythrocytic schizonts of all human malaria
parasites.
• They are not active against liver stages.
• Folate antagonists: Proguanil & Sulfa drugs
• Proguanil: It is a prodrug, which is converted into active
metabolite 'cycloguanil’.
• It acts by inhibiting dihydrofolate reductase.
• Fansidar: It is a combination of Pyrimethamine &
Sulfadoxine (a sulfonamide).
• Uses: For prophylaxis & treatment of falciparum malaria.
• SE: Megaloblastic anemia
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Important Mnemonics to Remember
Pharmacology (Funny & Easy)
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■Al-Baha, 30. Janu. 2022, at 04:20 p.m.
