**Pharmacology: Lesson 17: Antimalarial Drugs**

I. Introduction

Malaria is a dangerous infectious disease caused by the *Plasmodium* parasite, transmitted through the *Anopheles* mosquito. It can be fatal if not treated promptly.

II. Types of Antimalarial Drugs

1. Classification based on the Plasmodium life cycle stage:

• Sporontocidal drugs: Prevent or inhibit the formation of oocysts and sporozoites, blocking disease transmission.

• Examples: Primaquine, Proguanil.

• Gametocytocidal drugs: Destroy gametocytes before they enter red blood cells.

• Example: Primaquine (only effective against *P. falciparum*).

• Blood schizonticidal drugs: Act against the parasite stage within red blood cells (often when fever occurs), reducing fever episodes.

• Tissue schizonticidal drugs: Target the extra-erythrocytic stage of *Plasmodium spp.*, preventing relapses and achieving radical cure.

• Example: Primaquine.

• Hypnozoitocidal drugs: Act against hypnozoites, the dormant stage of the parasite, for preventive treatment.

• Example: Proguanil.

2. Classification based on mechanism of action:

• Group I: Fast-acting drugs:

• 4-aminoquinolines: Chloroquine, Amodiaquine, Piperaquine.

• Amino-alcohols: Quinine.

• Group II: Slow-acting drugs:

• Folinic acid antagonists: Proguanil, Pyrimethamine.

• Folic acid antagonists: Sulfonamides, Sulfones.

• Plasmodium respiratory inhibitors: Atovaquone.

• Drugs acting on the peroxide group: Artemisinin and its derivatives.

3. Classification based on origin:

• Natural antimalarial drugs: Quinine, Artemisinin.

• Synthetic antimalarial drugs:

• 4-aminoquinoline derivatives: Chloroquine, Amodiaquine, Piperaquine.

• 8-aminoquinoline derivatives: Primaquine.

• Aryl-amino-alcohol derivatives: Quinine and its derivatives.

• Biguanide derivatives: Proguanil, Cycloguanil.

4. Antibiotic Antimalarials:

• Cyclines: Tetracycline, Doxycycline, TIGECYCLIN.

• Macrolides and their analogs: Erythromycin, Azithromycin, Lincomycin.

• Fluoroquinolones: Ofloxacin, Norfloxacin.

• Rifampicin.

III. Common Antimalarial Drugs

1. Chloroquine:

• Group: 4-aminoquinoline derivative, Group I: fast-acting.

• Mechanism of action:

• Increases the pH within the parasite’s cell vacuole.

• Interferes with nucleoprotein synthesis.

• Inhibits key enzymes in DNA and RNA production.

• Effect: Destroys blood schizonts, reducing fever episodes.

• Combined use: Amodiaquine + Sulfadoxine + Pyrimethamine.

2. Quinine:

• Group: Aryl-amino-alcohol derivative.

• Mechanism of action:

• Binds to ferriprotoporphyrin IX, produced during hemoglobin degradation, making it toxic to the parasite.

• Agglutinates hemozoin, a pigment derived from hemoglobin, depriving the parasite of a food source.

• Note:

• Quinidine is effective against the malaria parasite and is 2-3 times more potent than quinine, but its side effect of cardiac arrhythmias is very dangerous, so it is only used for severe malaria treatment.

3. Primaquine:

• Group: 8-aminoquinoline derivative.

• Mechanism of action: Destroys gametocytes, tissue schizonts, prevents relapses, and achieves radical cure.

• Note:

• Not used for malaria treatment because of its poor effect on schizonts.

• Contraindicated in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

4. Proguanil:

• Group: Biguanide derivative.

• Mechanism of action: Destroys hypnozoites, providing preventive treatment.

• Note:

• Not used for malaria treatment, only used when other drugs cannot be used.

5. Artemisinin:

• Main active ingredient: Sweet Wormwood herb.

• Mechanism of action: Free radical effect, altering the morphology of the parasite membrane.

• Note:

• Artemisinin and its derivatives are poorly absorbed in short-wave UV (< 210 nm), so they cannot be directly quantified using UV spectroscopy.

6. Malarone® (GSK):

• Main ingredients: Atovaquone – Proguanil.

• Effect: Prevents chloroquine-resistant malaria (Malaria CQR).

7. Fansidar®:

• Main ingredients: Sulfadoxine + Pyrimethamine.

• Effect: Inhibits folic acid metabolism, with a long-lasting effect.

IV. Precautions

• Use drugs as prescribed by a doctor: Do not self-medicate or use drugs incorrectly.

• Adhere to dosage and treatment duration: Use drugs according to the doctor’s instructions, do not discontinue treatment prematurely or overdose.

• Monitor drug side effects: Inform your doctor of any side effects that occur.

• Note contraindications: Some antimalarial drugs are contraindicated in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

• Use mosquito control measures: Use mosquito nets, apply insect repellent, wear long sleeves and pants, and sleep in an air-conditioned room.

V. Conclusion

Malaria is a dangerous disease, but it can be effectively prevented and treated if detected and managed promptly.

Note: This article provides information only and does not replace the advice of a doctor. You should consult with a doctor for appropriate advice and treatment.