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MALARIA

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MALARIA

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  1. MALARIA

  2. ‘MAL’ – bad ; ‘aria’- air • Causative organism- Plasmodium falciparum. P. ovale, P. vivax, P. malariae • Transmission- bite of female anopheles mosquito

  3. PLASMODIUM LIFE CYCLE

  4. An infected female anopheles mosquito bites and injects parasites (Sporozoites) into the blood • Sporozoites invade liver cells and multiply

  5. The parasites burst from the liver cells as merozoites and are released into the blood stream. • Merozoites invade RBCs and multiply again. The RBCs eventually ruptures, allowing daughter merozoites to invade more RBCs. This cycle repeated, causing fever each time the parasite break free and invade.

  6. Some merozoites differentiated into Gametes. Female Anopheles feeds gametes are taken. They multiply in the stomach wall and migrate to her salivary gland.

  7. Classification • Blood Schizonticides -Those which act on erythrocytic parasites. • Eg: Chloroquine, Mefloquine, Quinine • Tissue Schizonticides -Those which eliminate dormant liver forms. • Eg: Primaquine. • Gametocides -Those which kill sexual stages and prevent transmission to mosquito. • Eg: Primaquine, chloroquine and quinine (vivax)

  8. Chemical Classification • 4 – Aminoquinolones Chloroquine, Amodiaquine • Quinoline- Methanol Mefloquine • Acridine derivative Mepacrine • Cinchona alkaloid Quinine • Biguanides Proguanil • Diaminopyrimidines Pyrimethamine • 8 - Aminoquinoline Primaquine, Bulaquine

  9. Sulfonamides Sulfadoxine, sulfamethopyrazine • Tetracycline Doxycycline • Sesquiterpine lactones Artesunate, artemether, arteether • Phenanthrene methanol Halofantrine • Napthoquinone Atovaquone

  10. Chloroquine • Rapidly acting erythrocytic schizonticide against all species of plasmodia • Controls clinical attacks in 1 – 2 days • No effect on pre/exo erythrocytic phases of the parasite • does not prevent relapses in vivax and ovale malaria

  11. MOA • Gets actively concentrated by intraerythrocytic plasmodia. • Accumalates in the acidic vesicle of the parasite. • Because of its basic nature – it increases the vesicular pH – interferes with degradation of Hb. • Prevents polymerization to hemozoin (Non-toxic) • Free heme damages the plasmodial membrane

  12. Resistance • Decreased ability to accumulate Chloroquine by the parasite. • Due to mutation in Chloroquine transporter protein. • Verapamil has shown to restore the concentrating ability.

  13. Other Actions • Effective against – E. histolytica, Giardia lamblia • Antiinflammatory, local irritant, local anaesthetic • Weak smooth muscle relaxant • Antihistaminic • Antiarrhythmic

  14. Kinetics • Good oral absorption. • Gets concentrated in liver, spleen, kidney, lungs, skin, leukocytes. • Selective accumulation in retina Ocular toxicity with prolonged use • t½ = 3 – 10 days • Can persist in the body for months

  15. Adverse Effects • Gastrointestinal disturbances, nausea , vomiting • Uneasiness, difficulty in sleeping • Hypotension, cardiac depression, arrhythmias and CNS toxicity convulsions • Loss of vision – due to retinal damage, corneal deposits • Loss of hearing, rashes, photoallergy, mental disturbances, myopathy, graying of hair. • Can be used in pregnancy

  16. Use • Clinical cure and suppressive prophylaxis of all types of malaria Dose: • 600 mg stat Dose • 300 mg 8 hrs later • 300 mg 24 hrs later • 300 mg 24 hrs later Parenteral Chloroquine – severe cases of falciparum malaria and in cerebral malaria (second choice to quinine)

  17. Uses 2. Extraintestinal amoebiasis 3. Rheumatoid Arthritis- hydroxychloroquine (less ocular toxicity) 4. DLE 5. Lepra reactions 6. Photogenic reactions 7. Infections mononucleosis

  18. Quinine • From Cinchona bark • Erythrocytic schizonticide • Effective in terminating acute attack of falciparum malaria. • Does not prevent recrudescence. • Can be taken orally, IV • t½ = 10 – 12 hrs; noncumulative

  19. Other actions • Local anaesthetic • Increases gastric secretion • Weak analgesic • Antipyretic • Decreases excitability of muscle fibre. • Stimulates myometrium • Hypotension, cardiac arrhythmias • Hypoglycemia

  20. Adverse Effects • “Cinchonism” – ringing in the ears. • Nausea, vomiting, headache, confusion, vertigo, visual defects • reversible • Hypotension, cardiac arrhythmias • Delirium , convulsions • Hemolysis & kidney damage

  21. Uses • Uncomplicated Chloroquine resistant malaria • Complicated / Cerebral malaria • Nocturnal Muscle cramps

  22. Mefloquine • 4-Quinoline methanol • Erythrocytic schizonticide • Use: chloroquine resistant malaria Dose- 15mg/kg; 750 mg once followed by 500mg 6-8hrs later -for prophylaxis-250 mg weekly

  23. Adverse effects • Nausea ,vomiting,abdominal pain, • Sleep & behavioral disturbances,dizziness, • Seizures , psychosis • Thrombocytopenia • Arrythmia or bradycardia

  24. Artemisinin • Sesquiterpene lactone • Derived from artemisia annua

  25. 3 semisynthetic derivatives dihydroartemisinin artesunate artemether (Water soluble) (reduced product) (Oil soluble) • Potent , fast acting antimalarial • Suited for treatment of severe P.falciparum malaria • and drug resistant infections

  26. Active against erythrocytic stages of P. vivax and falciparum • Slight gametocidal activity

  27. MOA • Heme iron catalyzes cleavage of endoperoxide bridge • Followed by rearrangement to produce carbon centered freeradical • Alkylates and damages the macrmolecules in the parasite

  28. Route of administration Oral- dihydroartemisinin, artemether,artesunate IM-artesunate, artemether IV-artesunate Rectal-artesunate • USES- severe P. falciparum malaria

  29. Adverse effects • Neurological changes • Changes in reticulocyte , neutrophil counts • QT prolongation

  30. Dose • artesunate (oral) - 100mg BD on 1st day 100mg OD -5 days IV/IM - 120mg on 1st day; later 60mg -4days • artemether IM – 80mg BD on 1st day, 80mg OD - 4days Recrudescence can be prevented by combining with mefloquine

  31. Malaria in pregnancy Chloroquine Proguanil Mefloquine

  32. REGIMENS FOR CHEMOPROPHYLAXIS A. Prophylaxis for infection with all species: - Chloroquine Phosphate tablet (300 mg base) One tablet weekly starting 1 week before entering endemic area. Continuing for four weeks after leaving.

  33. B. Prophylaxis for Infection with multi drug resistant strains: • Mefloquine Hydrochloride tablet – 250 mg 1 tablet weekly starting 1 week before entering endemic area and ending 4 weeks after leaving. OR - Doxycycline capsule – 100 mg – 1 capsule daily starting 1 day prior to travel to an endemic area and 4 weeks after leaving OR -malarone – 1 tablet per day 1-2 days prior to travel to an endemic area and 7 days after leaving OR Primaquine 30 mg daily several days before to 7 days later

  34. TREATMENT REGIMENS OF MALARIAL INFECTION A. Infection with all species - Chloroquine Phosphate Tab. 0.5 g(300 mg base) 2 tablets initially followed by 1 tablet at 6, 24 and 48 hours for Falciparum. • Infection with P.vivax, P.ovale - chloroquine (as above) + primaquine (15mg) per day for 14 days

  35. B. Infection for Chloroquine Resistant Infection • Quinine 650mg TID daily for 3-7 days + Doxycycline 100mg BD for 7 days OR Clindamycin 600mg BD for 7 days OR Fansidar 3 tabs once

  36. - Mefloquine Hydrochloride 750 mg to start followed by 500 mg after 12 hour. OR - Artesunate 4 mg/Kg on first day followed by 2 mg/Kg for next four days plus Mefloquine base 25mg/Kg on second day. OR Malarone 4 tablets daily for 3 days OR Halofantrine 500mg 6hrly for 3 doses ; repeat in 1 week

  37. C. Treatment for severe infection with Falciparum - Quinine gluconate I.V 10mg/Kg in 300 ml of Normal saline infused 1 to 2 hours. - Quinine Sulphate tablet 650 mg 8th hourly – 7 days

  38. THANK YOU