Anti-aembic and anti-malarial drugs

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Anti-aembic and anti-malarial drugs

• By
• Dr.Mohamed Abd AlMoneim Attia

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Classifications

• 1-Tissue amoebicidial
• Metronidazole(Flagyl)
• Chloroquine
• Emetine and Dihydroemetine
• 2-Luminal amebicidal
• Diloxinade etofamide
• Iodoquinol clioquinol
• Paromomycin Tetracycline

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metronidazole
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Mechanism of action

• 5-nitroimidazole

Ferrodoxine oxidoreductase enzyme
Free radical
Electron ransfer
Multiple DNA breaks
No transcription
No replication
No repair
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Metronidazole

• Indications
• Tissue amoebicidal
• ( intestinal,hepatic,pulmonary)
• Giardiasis
• Trichominasis

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

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

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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.

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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

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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

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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

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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

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• 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

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Life cycle of malaria
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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 malariachloroquine
• 2-chloroquine-resistance malaria
• -Quinie
• -mefloquine
• -pyremethamine proguanil
• -sulphadoxine
• -combination
• Fansidar sulphadoxine pyremethamine
• Fansimaf sulphadoxine pyremethamine
  mefloquine

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• 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

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• 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.

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• 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 ).

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• 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.

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

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Quinine

• Therapeutic uses
• Treatment of acute attack of chloroquine
  resistant P.falciparum
• Side effects
• Cinnchonism sweeting,nausea,vomiting,diarrhea,ri
  nging 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

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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

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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

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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

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