The document discusses various antimalarial drugs, classifying them as tissue schizontocides or blood schizontocides. It summarizes the mechanisms of action, pharmacokinetics, uses, and side effects of several common antimalarial medications including chloroquine, primaquine, mefloquine, quinine, pyrimethamine, tetracyclines, and artemisinin derivatives. It also describes various artemisinin-based combination therapies that are now widely used as first-line treatments for Plasmodium falciparum malaria.

2. Prophylaxis, treatment & prevention of
relapse.
Aims of antimalarial drugs
To prevent & treat clinical attack of malaria
To completely eradicate the parasite from pt.
To reduce the human reservoir of infec.,

4. CLASSIFICATION
Tissue schizontocides
• Primaquine
Blood schizontocides
• Chloroquine
• Mefloquine
• Quinine
• Proguanil
• Pyrimethamine
• Artemisinin derivatives
• Tetracyclines
• Halofantrine
• lumefantrine

5. CHLOROQUINE
4-Aminoquinoline derivative….

7. Other actions…
Anti inflammatory
Local anaesthetic
Weak smooth muscle relaxant
Anti histaminic
Anti arrhythmic

8. PHARMACOKINETICS
Plasma t1/2-3-10 days

10. USES
Clinical cure & Suppressive
prophylaxis
Extra intestinal amoebiasis
Rheumatoid arthritis
DLE
Lepra reaction
Photogenic reaction
Infectious mononucleosis

11. PRIMAQUINE
8-Aminoquinoline…

12. MECHANISM OF ACTION
As Oxidants
Schizonticidal action
Hemolysis
Methemoglobinemia

13. PHARMACOKINETICS
Plasma t1/2-3-6 hrs

14. Adverse effects
Abd. Pain
G.I. upset
Weakness in chest
CNS & CVS symptoms
Leucopenia
Hemolysis
Methaemoglobinemia
Tachypnoea
Cyanosis

16. Uses
Radical cure of vivax malaria
Primaquine 15 mg for adult,0.25
mg/kg for children - daily for 2
weeks with G6PD status testing.
Primaquine 45 mg(0.75mg/kg) +
Chloroquine 300 mg once a week
for 8-10 week without G6PD testing.
Radical cure of Falciparum malaria
Primaquine 45 mg single dose +
Curative dose of Chloroquine

17. MEFLOQUINE
Quinoline – Methanol derivatives…

18. PK
Plasma t1/2 – 2-3 weeks
High affinity to plasma protein
Adverse effect
Bitter in taste
Dizziness, nausea, vomiting
Diarrhoea
Abd. Pain
Sinus bradycardia
Rare events are haematological,
hepatic, cutaneous toxicity.

19. Interactions
Halofantrine/Quinidine/Quinine –
 QTc length
β blocker/Ca channel blocker/
Digitalis/Anti depressant –
exagerrated bradycardia/arrhythmia
Uses
Multi drug resistant P.falciparum
Prophylaxis of malaria among
travellers 5 mg/kg/week x 2-3 week

20. QUININE/QUINIDINE
Cinchona bark derivatives….

21. MOA is similar to Chloroquine
Less effective & more toxic
Other actions
Local irritant & anaesthetic
Systemic action
 Gastric secretion
Weak analgesic & antipyretic
Cardiac depressant,anti arrhythmic
Hypotensive
Hypoglycemia

22. PK
Oral absorbtion is complete
70% plasma bound – α1 acid glycoprotein
Adverse effect
Cinchonism
Ringing in ears
Nausea
Vomiting
Head ache
Mental confusion
Vertigo
Difficulty in hearing and visual defect
Diarrhoea
Marked perspiration

23. Uses…
Malaria
Uncomplicated resistant falciparum
malaria
2nd line to S/P – ACT
Quinine + Doxycycline x 7 days
Complicated & severe malaria
Quinine i.v. – DOC for cerebral malaria
Nocturanal muscle cramps
Δsis of myasthenia gravis
Along with Urethane in Varicose vein

24. PYRIMETHAMINE
Diaminopyrimedine derivative….

25.  Mechanism of action
 Directly acting inhibitor of plasmodial DHFRase
 PK
 Oral absorbtion is good
 Plasma t1/2 – 4 days
 Adverse effect
 Nausea
 Rashes
 Folate deficiency
 Megaloblastic anaemia & granulocytopenia

26. SULFONAMIDE-PYRIMETHAMINE
COMBINATION

27. Sulfadoxine & Sulfamethopyrazine –
Ultra long acting Sulfonamides
Along with artesunate,used in
chloroquine resistant malaria
S/P – DOC for Toxoplasmosis

28. TETRACYCLINES

29. Slow & weak erythrocytic
schizontocidal action
Along with quinine/S-P, used in
chloroquine resistant malaria
Doxycycline 200 mg/day + Artesunate
to treat Mefloquine/chloroquine/S-P
resistant P.falciparum
Doxycycline 100 mg/day – 2nd line
prophylactic for travellers

30. ARTEMISININ
DERIVATIVES
Short acting drug

31. Lysis in the parasite
Inhibits protein synthesis
Damages ER
Causes lipid peroxidation
Binds with membrane protein
Releases free radicals
Haeme interacts with Endoperoxide bridge in artemisinin

32. Artesunate
Prodrug(t½ - 30-60 min)
Active metabolite –
Dihydroartemisinin(t½ - 2-4 hrs)
Oral , i.v., i.m.
Artemether
Prodrug(t½ - 3-10 hrs)
α/β Arteether
t ½ - 23 hrs
PHARMACOKINETICS

33. Adverse effect
Nausea, vomitng, abd. Pain, itching & drug
fever
Abnormal bleeding, dark urine, ST segment
changes, QT prolongation, 1* A-V block
Transient reticulopenia & leucopenia
Uses
Orally – uncomplicated chloroquine/multi
drug resistant P.falciparum malaria
Parenterally - severe & complicated
P.falciparum malaria

34. ARTEMISININ-BASED COMBINATION
THERAPY(ACT)

35. • Artesunate 100 mg BD x 3
days + Mefloquine 750 mg on
2nd day & 500 mg on 3rd day
Artesunate -
Mefloquine
• Artemether 80 mg BD +
Lumefantrine 480 mg BD x 3
days
Artemether-
Lumefantrine
• Artesunate 100 mg BD x 3 day
+ Sulfadoxine 1500 mg +
pyrimethamine 75 mg single
dose
Artesunate-
sulfadoxine +
Pyrimethamine

37. Thank U…!