for pharamcolgy students

1. PRESENTATION ON
ANTI MALERIAL DRUGS
RABIYA AHSAN
M.PHARM(PHARMACOLOGY)
1ST YEAR (second sem.)
INTEGRAL UNIVERSITY. LUCKNOW
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2. Introduction
Malaria is an acute infectious disease caused by five species of the
protozoal genus Plasmodium
• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale.
• Plasmodium malariae .
• Plasmodium knowlesi.
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3. Phases of parasites life cycle
1. Asexual cycle
2. Sexual cycle
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6. 4 aminoquinolines
(Pharmacological actions of cloroquine)
Antimalarial activity: High against erythrocytic forms of vivax, ovale,
malariae & sensitive strains of falciparum
• Gametocytes of vivax
• No activity against tissue schizonts
• Resistance develops due to efflux mechanism
Other parasitic infections: Giardiasis, taeniasis, extra instestinal
amoebiasis
Other actions: Depressant action on myocardium, direct relaxant effect on
vascular smooth muscles, antiinflammatory, antihistaminic , local
anaesthetic.
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8. Pharmacokinetics
• Well absorbed, 60 % protein bound .
• Selective accumulation in retina: occular toxicity.
• T1/2 = 3-10 days increases from few days to weeks .
Adverse drug reactions
• Intolerance: Nausea, vomiting, anorexia.
skin rashes, angioneurotic edema, photosensitivity, pigmentation,
exfoliative dermatititis .
Long term therapy may cause bleaching of hair.
Rarely thrombocytopenia, agranulocytosis, pancytopenia.
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9. Resistance
• Plsmodium falciparum is now resistant to chloroquine in most of the
part.
• Resistance appears to result from enhanced efflux of the drug from
parasitic vesicles as result from enhanced efflux of the drug from
parasitic vesicles as a mutation in plsmodium transporter genes.(pfcrt
gene)
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10. Quinine
Pharmacological actions
1. Antimalarial action: Erythrocytic forms of all malarial parasites including
resistant falciparum strains . Gametocidal for vivax & malariae
2. Local irritant effect: Local pain sterile abcess.
3. Cardiovascular: depresses myocardium, ↓ excitability, ↓ conductivity,
↑ refractory period.
4. Miscellaneous actions: Mild analgesic, antipyretic activity , stimulation
of uterine smooth muscle.
Adverse drug reactions
1. Idiosyncrasy : similar to cinchonism but occurs in therapeutic doses
2. Cardiovascular toxicity: cardiac arrest, hypotension ,fatal arrhythmias
3. Black water fever
4. Hypoglycemia 10

11. 8 aminoquinoline groups
Primaquine
• Inhibit electron transfer chain
• Use to Prevent the transmission of disease.
• Exact mode of action is not know.
• There is one hypothesis that an active metabolic product of the
primaquine may behave as a powerful oxidising agent which
cause damage to sensitive erythrocytes as well as paracytes.
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13. • Resistance to atovaquone is rapid and result from a single point
mutation in the gene of cytochrome b.
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15. Dihydrofolate reductase inhibitors
Proguanil
• Biguanide converted to cycloguanil active compound
• Act slowly on erythrocytic stage of vivax & falciparum
• Prevents development of gametes.
Adverse effects:
• Stomatitis, mouth ulcers, larger doses depression of
myocardium , megaloblastic anemia
• Not a drug for acute attack
• Causal prophylaxis: 100 – 200 mg daily
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Proguanil,
pyrimethamine
Bind sulphonamide
(sulphodoxine)
Drugs affecting synthesis and utilization of folate

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Diaminopyrimidines

18. Inhibit DNA replication transcription
Artemisinin.
Generate carbon centered free radical by breaking down ferrrous
porphyrin IX
• This radical cause alkylation of protein or damage the cell membrane.
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Sesquiterpine lactone derivative
Resistance develops due to efflux mechanism

20. Antibiotics
• Doxycline and tetracycline used in acute attack of malaria and
chemopropylaxis purpose.
• Sometimes given in combination with other drug.
• Clindamycin is also used.
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Resistance
• By pumping of tetracycline from inside to outside
• By forming plasmid mediated protecting protein.
Tetracycline

22. Clindamycin
Drug
• Clindamycin (oral or IV)
Mechanism of amalctosobion
• Inhibit the ribosomal translocation
Uses
• Treatment of malaria
Adverse Effects
• Always use in combination with quinine-quinidine
• Diarrhea, nausea, rash
Resistance
• Same as tetracycline
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24. THANK YOU
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