Antimalarial drugs important very drug.pptx

Antimalarial drugs important very drug

1. Antimalarial Drugs Dr. Mohamed Mubarak MBBS MSc. Clinical Pharmacology

2. Objectives By the end of this lecture the student should be able to: 1. List the drugs that used in treatment of Malaria. 2. R ecognized the mechanism of action, therapeutic uses, pharmacokinetics and side effects of Chloroquine . 3. Recognized the mechanism of action, therapeutic uses, pharmacokinetics, side effects, drug interactions and pregnancy uses of A rtemether . 11/12/2017 Dr. Mohamed Mubarak

3. 4. Recognized the mechanism of action, therapeutic uses, pharmacokinetics, side effects, of Lumefantrine 5. Recognize the uses of Artemether with Lumefantrine ( Coartem ) in treatment of Malaria. 6. Recognized the mechanism of action, therapeutic uses, pharmacokinetics, side effects, of Quinine. 11/12/2017 Dr. Mohamed Mubarak

4. Malaria What’s Malaria … ? Causative Organism … Life cycle … 11/12/2017 Dr. Mohamed Mubarak

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6. Treatment of Malaria Challenges… Drugs that used in the treatment of Malaria: 1. Artemether / lumefantrine . COARTEM 2. Quinine/Quinidine 3 . Chloroquine . ARALEN 4 . Primaquine 5. Meoquine . LARIAM 6. Pyrimethamine DARAPRIM 7 . Atovaquone-proguanil . MALARONE 11/12/2017 Dr. Mohamed Mubarak

7. Chloroquine It was the drug of choice in the treatment of P. falciparum malaria . Mechanism of Action: the parasite digests the host cell’s hemoglobin to obtain essential amino acids. T his process also releases large amounts of soluble heme , which is toxic to the parasite . To protect itself, the parasite polymerizes the heme to hemozoin . Chloroquine specifically binds to heme , preventing its polymerization to hemozoin . A ccumulation of heme result in lysis of both the parasite and the red blood cell. 11/12/2017 Dr. Mohamed Mubarak

8. Pharmacokinetics: R apidly and completely absorbed following oral administration . H as a very large volume of distribution and concentrates in erythrocytes , liver, spleen, kidney, lung, and melanin-containing tissues, and leukocytes. The drug also penetrates the central nervous system (CNS) and traverses the placenta. 11/12/2017 Dr. Mohamed Mubarak

9. Adverse effects: G astrointestinal upset . Headaches . B lurred vision [Note : An ophthalmologic examination should be routinely performed]. Resistance : It has become a serious medical problem throughout Africa, Asia, and most areas of Central and South America . 11/12/2017 Dr. Mohamed Mubarak

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11. A rtemether Mechanism of action: Not well understood. It inhibits glucose and protein synthesis of the parasite resulting in reduce growth of the parasite. It may i ncrease intracellular calcium concentration which causes cell death. Indications: Moderate Malaria. Sever Malaria “alternative to Quinine” 11/12/2017 Dr. Mohamed Mubarak

12. Pharmacokinetics: Intramuscular admin. Absorption: Peak concentration after 2 hours. Metabolism: Hepatic to active metabolites “ dihydrartimisin ” Drug interactions: Should not be used with enzyme inhibitors drugs. Side Effects: Bradycardia . Prolong Q-T interval in ECG. Hypotension. Pregnancy: Category X. 11/12/2017 Dr. Mohamed Mubarak

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14. Artemether with Lumefantrine Famous Brand name for this combination is: ( Coartem ). Coartem is the most updated drug in treatment of Malaria. Lumefantrine mechanism of Action: E xactly unknown, it inhibits nucleic acid and protein synthesis. Indication: Uses Artemether with lumefantrine in treatment of Malaria (resistant to Artemether alone). 11/12/2017 Dr. Mohamed Mubarak

15. Lumefantrine Pharmacokinetics : Absorption: increases with food. 99% Protein binding. Metabolism: Extensivly metabolised by liver enzyme CYP 450. Half life : has long half-life 4-5 days, much longer than artemether . Side Effects: Artemether with Lumefantrine cause headache, dizziness, Prolong QT interval in ECG. 11/12/2017 Dr. Mohamed Mubarak

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17. Quinine Mechanism of Action: Not well understood. Interferes with heme polymerization, resulting in death of the erythrocytic form of the plasmodial parasite . Indications: Sever Malaria. Cerebral Malaria. Other antimalarial resistance. Malaria in Preganncy . 11/12/2017 Dr. Mohamed Mubarak

18. Pharmacokinetics: Absorption: well absorbed after oral admin. Also given intravenous infusion. well distributed throughout the body . Metabolism in Liver Adverse effects: Cinchonism ( headache, sweating, nausea, vomiting, tinnitus, and vertigo).” reversible effects”. Hemolytic anemia “Should be stopped”. Hypoglycaemia . 11/12/2017 Dr. Mohamed Mubarak

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20. Conclusion Antimalarial drugs . Chloroquine Pharmacology . Artemether Pharmacology. Artemether with Lumefantrine . Qunine Pharmacology. 11/12/2017 Dr. Mohamed Mubarak

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22. Thank you … 11/12/2017 Dr. Mohamed Mubarak