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Anti-aembic and anti-malarial drugs
By
Dr.Mohamed Abd AlMoneim Attia
Classifications
1-Tissue amoebicidial: Metronidazole(Flagyl) Chloroquine Emetine and Dihydroemetine 2-Luminal amebicidal; Diloxinade & etofamide Iodoquinol & clioquinol Paromomycin & Tetracycline
Mechanism of action:
5-nitroimidazole Ferrodoxine oxidoreductase enzyme
Free radical
Multiple DNA breaks
No replication No transcriptionNo repair
Electron ransfer
Metronidazole
Indications: Tissue amoebicidal:
( intestinal,hepatic,pulmonary) Giardiasis Trichominasis
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
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. Don't give it to pregnant , lactating or young
age. It increases the effects of oral anticoagulant
by decreasing its metabolism.
Chloroquine
Reach high concentration in liver so it is effective in hepatic amoebiasis with little or no effect on intestinal or lumenal one.
Indication: 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 Side effects: see antimalarial
Emetine & dihydroemetine:
They inhibit protein synthesis by preventing translocation
Indication: 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
-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 2years of age
Iodoquinol -luminal amoebicidial -used to eradicate amoebae present in intestinal
lumen -Side effects:
Thyroid enlargement due to high iodine content of the drug N/V and diarrhea
-Contraindication: 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 MalariaPATHOPHYSIOLOGY 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
Classifications; 1-clinical cure: drugs used to treat the acute
attack of malaria by acting on the erythrocyte stage of the parasite
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 pH 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 G6PD 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
Therapeutic uses: Treatment of acute attack of chloroquine resistant P.falciparum
Side effects: 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:
Therapeutic uses: Treatment of acute attack of chloroquine
resistant P.falciparum especially mild and moderate cases
chemoprophylaxis
side effects: headache vertigo and visual disturbance psychosis ,hallucination and confusion
Antifolate;(pyremethamine,progunail,sulphonamides): Therapeutic uses: Treatment of acute attack of chloroquine
resistant P.falciparum in combination with Quinine
Chemoprophylaxis in chloroquine resistant P.falciparum
Side effects: see antimicrobials
Primaquine: 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 G6PD deficiency Purities methaemoglobinemia manifested by cyanosis
الرحيم الرحمن الله بسم
ما ) لها وسعها إال نفسا الله اليكلفاكتسبت ما عليها و كسبت
أخطأنا أو نسينا إن تؤاخذنا ال ربنا
على حملته كما إصرا علينا تحمل ال و ربناقبلنا من اللذين
اعف و به لنا طاقة ال ما تحملنا ال و ربناموالنا أنت ارحمنا و لنا واغفر عنا
الكافرين القوم على (فانصرنا
العظيم الله صدق
توفيق من كان ما و هذامن كان ما و الله فمننسيان أو سهو أو خطا . الشيطان من و فمني
URTI:Throat infections
بحمدك و اللهم سبحانكاليك نتوب و نستغفرك