Antiaembic and antimalarial drugs By Dr Mohamed Abd

Anti-aembic and antimalarial drugs By Dr. Mohamed Abd Al. Moneim Attia

Classifications n 1 -Tissue amoebicidial: Ø Metronidazole(Flagyl) Chloroquine Emetine and Dihydroemetine n 2 -Luminal amebicidal; Ø Ø Ø Diloxinade & etofamide Iodoquinol & clioquinol Paromomycin & Tetracycline

Mechanism of action: Ferrodoxine oxidoreductase enzyme 5 -nitroimidazole Free radical Electron ransfer Multiple DNA breaks No replication No transcription No repair

Metronidazole n Indications: Ø Tissue amoebicidal: ( intestinal, hepatic, pulmonary) Ø Giardiasis Ø Trichominasis

Ø Anaerobic infection: e. g - serious infection caused by bacteroid fragilis -enterocolitis cause by cl. difficil -acute ulcerative vaginitis -decubitus lesion -to reduce postoperative infection following abdominal surgery

n Ø Ø Ø Ø Side effects: GIT: bad taste in mouth, angular stomatitis, dry mouth Dark red urine CNS: headache, insomnia, parathesia Blood: leucopenia & thrombocytopenia Disulfiram like reaction in alcoholism Phlebitis if given IV Mutagenesis and carcinogenesis in mammalian cell culture

Contraindication & Cautions Be caution if prescribe drugs to: Patients with hepatic, brain, or blood disorders. n Don't give it to pregnant , lactating or young age. n It increases the effects of oral anticoagulant by decreasing its metabolism. n

Chloroquine n n Reach high concentration in liver so it is effective in hepatic amoebiasis with little or no effect on intestinal or lumenal one. Indication: Ø Prevention of amoebic liver abscess during ttt of intestinal amoebiasis treatment of amoebic liver abscess in case of failure or contraindication to flagyl Following metronidazole for ttt of amoebic hepatitis n Side effects: see antimalarial Ø Ø

Emetine & dihydroemetine: They inhibit protein synthesis by preventing translocation n Indication: n Ø Ø Ø Alternate therapy to metronidazole in treatment of intestinal or hepatic amoebiasis Side effects: Cardiotoxic: hypotension and ECG changes Pain at site of injection Muscular ache, tenderness, stiffness & weakness

Diloxanide Furoate Ø Ø Ø -luminal amoebicidial -not absorbed from GIT -used to eradicate amoebae present in intestinal lumen -flatulence, dryness of mouth and vomiting are infrequent side effects -the drug is contraindicated in pregnancy and in children below 2 years of age

Iodoquinol n n n -luminal amoebicidial -used to eradicate amoebae present in intestinal lumen -Side effects: Ø Ø n Thyroid enlargement due to high iodine content of the drug N/V and diarrhea -Contraindication: Ø Ø Ø Thyroid, renal or hepatic disease Shouldn't be used for prophylaxis or ttt of travelers or non specific diarrhea Stop it if persistent diarrhea or iodine reaction occur

Anti Malaria PATHOPHYSIOLOGY and life cycle: Anopheles mosquito inoculates sporozoites to human. Sporozoites invade liver cells ( primary tissue phase). Merozoites released from liver & invade erythrocytes. Merozoites multiply, red cell enlarges ( blood schizont). blood schizont ruptures, merozoites invade more RBCs. Repeated cycles cause clinical illness, fever, etc. In P. vivax & P. ovale some merozoite invade liver cells ( secondary tissue phase) & become dormant ( hypnozoites ) hypnozoites may develop again and cause relapse. In P. falciparum & P. malariae no second liver phase. Some merozoite -- gametocytes-- mosquito -- sporozoites

Life cycle of malaria

Anti- malarial drugs n n Classifications; 1 -clinical cure: drugs used to treat the acute attack of malaria by acting on the erythrocyte stage of the parasite n n v v v v 1 -chloroquine-sensitive malaria: chloroquine 2 -chloroquine-resistance malaria: -Quinie -mefloquine -pyremethamine & proguanil -sulphadoxine -combination: Fansidar = sulphadoxine + pyremethamine Fansimaf = sulphadoxine + pyremethamine + mefloquine

II-chemoprophylaxis: 1 -clinical prophylaxis: suppress the clinical manifestation of malaria by killing parasite as soon as they reach the RBCs. chloroquine, proguanil, fansidar 2 -antirelapse therapy in P. vivax and ovale only by killing the dormant stage in liver. Primaquine 3 -prevent transmission by killing the gametocytes: primaquine , progunail , pyremethamine

Chloroquine, hydroxy-chloroquine, amodiaquine. CHLOROQUINE: Mechanism and anti-malarial action: Chloroquine , accumulates in acid p. H of RBCs & food vacuoles of plasmodia, ↓ polymerization of heme to hemozoin (food of malarial parasites). Heme accumulates & cuases death of plasmodia. Blood schizonticidal of all types of plasmodium. Not effective against liver stages.

Uses: Treatment : Drug of choice for acute attack of P. vivax, ovale, malariae, & non-resistant falciparum. • (P. falciparum is becoming resistant) Prophylaxis: Effective in P. vivax & ovale regions. Also for P. falciparum in non-resistant regions. Other uses: Hepatic amoebiasis & some autoimmune diseases ( like, rheumatoid arthritis & SLE ).

Adverse effects: Neurological: headache, anorexia, malaise, optic neuritis & rarely seizures. CVS: Cardiac depression, vasodilation & fall of blood pressure. Give slow IV infusion & monitor cardiac functions. Heamatologic: Heamatolysis in G 6 PD deficiency. Cautions/ Contraindications: ☻Visual defects, epilepsy, heart failure.

HYDROXY-CHLOROQUINE: - Less likely to cause optic neuritis. -Used in rheumatoid artharitis. AMODIAQUINE: - Can cause agranulocytosis. - Recommended for chloroquine resistant malaria.

Quinine n Therapeutic uses: Ø Treatment of acute attack of chloroquine resistant P. falciparum n Side effects: Ø Ø Cinnchonism : sweeting, nausea, vomiting, diarrhea, ringing in ear, blurring of vision Hypoglycemia Hypotension and arrhythmias Black water fever due to excessive haemolysis of RBCs in the form of fever, acute renal failure and jaundice

Mefloquine: n Therapeutic Ø Ø Treatment of acute attack of chloroquine resistant P. falciparum especially mild and moderate cases chemoprophylaxis n side Ø Ø uses: effects: headache vertigo and visual disturbance psychosis , hallucination and confusion

Antifolate; (pyremethamine, progunail, s ulphonamides): n Therapeutic Ø Ø uses: Treatment of acute attack of chloroquine resistant P. falciparum in combination with Quinine Chemoprophylaxis in chloroquine resistant P. falciparum n Side effects: see antimicrobials

Primaquine: n n n n Therapeutic uses: The only drug that used in prevention of relapse in P. vivax and ovale because it affects the dormant liver stage It has no effect on erythrocytic stage (not used in acute attack) Prevent transmission of infection from human to mosquito by killing the gametocytes Side effects: Haemolysis in G 6 PD deficiency Purities methaemoglobinemia manifested by cyanosis