For Under Graduates & Practioners

1. Antimalarial drugs
DR V R PATKAR

2. Plasmodium specieswhich
infect humans
Plasmodium vivax (tertian):
Plasmodium ovale (tertian)
Plasmodium falciparum (tertian)
Plasmodium malariae (quartan)
Plasmodium knowlesi:

3. Schizogony
(asexual)
Man :Intermediate host
Mosquito :Definitivehost
Life cycleof the malarialparasite
Truecausal prophylactics
Causal
prophylactics
Supressives
Gametocidal
Sporonticide
Sporogeny
(sexual)

4. • Classification of antimalarial drugs
– Therapeutic classification
– Chemical classification

5. Therapeuticclassification
• Causalprophylaxis: (Primary tissue
schizonticides)
– Destroy parasite in liver cells and prevent invasionof
erythrocytes
– Primaquine, proguanil
• SupressivesProphylaxis:
– Supressthe erythrocytic phase and thus attack of
malarial fever canbe used asprophylactics
– Chloroquine, proguanil, mefloquine, doxycycline

6. Therapeuticclassification
• Clinical cure: erythrocytic schizonticides
– used to terminate an episode of malarialfever
• Fastacting high efficacy
– Chloroquine, quinine, mefloquine, atovaquone,
artemisinin
• Slow acting low efficacydrugs
– Proguanil, pyrimethamine, sulfonamides,
tetracyclines

7. Therapeuticclassification
• Radical curatives:
– Eradicate all forms of P.vivax& P.ovalefrom thebody
– Supressive drugs +hypnozoitocidal drugs
– For vivax: primaquine 15 mg daily for 14days
• Gametocidal:
– Destroy gametocytes and prevent transmission
– Primaquine, artemisinin – against all plasmodia
– Chloroquine, quinine – Pl Vivax
– Proguanil ,pyrimethamine – prevent development
of sporozoites

8. Chemicalclassification
• 4 aminoquinolines:
– Chloroquine, Hydroxychloroquine,Amodiaquine,Pyronari
dine
• 8 aminoquinolines:
– Primaquine, Tafenoquine,Bulaquine
• Cinchona alkaloids:
– Quinine, Quinidine
• Quinoline methanol:
– Mefloquine
• Biguanides
– Proguanil, Chlorproguanil

9. Chemicalclassification
• Diaminopyrimidines
– Pyrimethamine
• Sulfonamides
– Sulfadoxine, dapsone
• Tetracyclines:
– tetracycline, doxycycline
• Naphthoquinone:
– Atovaquone
• Sesquiterpene lactones:
– Artesunate, artemether, arteether

10. • Chloroquine:
– Synthesized by Germans in 1934 ( resochin)
– d & l isomers, d isomer is lesstoxic
– Clat position 7 confers maximal antimalarial
efficacy

11. Hemoglobin Globin utilized by
malarial parasite
Heme(highly toxic for malaria parasite)
(+) HemePolymerase
Chloroquine
Quinine,
mefloquine (-)
Hemozoin (Not toxic to plasmodium)
Mechanism of action

12. Pharmacologicalactions
1. Antimalarial activity:
– High against erythrocytic formsof
vivax, ovale, malariae & sensitive strainsof
falciparum
– Gametocytes of vivax
– No activity against tissueschizonts
– Resistance develops due to effluxmechanism
1. Other parasitic infections:
– Giardiasis, taeniasis, extrainstestinal amoebiasis
2. Other actions:
– Depressant action on myocardium, directrelaxant
effect on vascularsmooth
muscles, antiinflammatory, antihistaminic ,local

13. Pharmacokinetics
• Well absorbed, tmax 2-3 hrs , 60 %protein
bound
• Concentrated in liver , spleen, kidney, lungs,
leucocytes
• Selectiveaccumulation in retina: occular
toxicity
• T1/2 =3-10 days increasesfrom few daysto
weeks

14. Adversedrug reactions
• Intolerance:
– Nausea, vomiting, anorexia
– skin rashes, angioneurotic edema,
photosensitivity, pigmentation, exfoliative
dermatititis
– Longterm therapy may causebleaching of hair
– Rarely thrombocytopenia, agranulocytosis,
pancytopenia

15. Adversedrug reactions
• Occular toxicity: High dose prolongedtherapy
– Temporary loss of accommodation
– Lenticular opacities, subcapsular cataract
– Retinopathy: constriction of arteries, edema,blue
black pigmentation , constricted field ofvision.
• CNS:
– Insomnia, transient depression seizures,
rarely neuromyopathy & ototoxicity
• CVS:
– ST& Twave abnormalities, abrupt fall in BP&
cardiac arrest in children reported

16. Dosage
• 600 mg of basestat
• 300 mg baseafter 8 hours
• 150 mg of baseBDfor 2days
• 200 mg oral tablet of chloroquinephosphate
consists of 150 mgbase

17. Chloroquine isadministered inloading dose
in malaria
• Chloroquine is well absorbed after oral
administration. It is extensively tissuebound
and sequestrated by tissues particularly
liver, spleen, kidney it hasgot largeapparent
volume of distribution
• Soit is given in loading dose to rapidlyachieve
the effective plasmaconc.

18. Therapeuticuses
1. Hepatic amoebiasis:
2. Giardiasis
3. Clonorchis sinensis
4. Rheumatoid arthritis
5. Discoid Lupus Erythematosus
6. Control manifestation of leprareaction
7. Infectious mononucleosis

19. Uses
• Malaria:
– uncomplicated resistant falciparum malaria
– Cerebral malarial
• Myotonia congenita: 300 to 600 mg BD/TDS
• Nocturnal muscle cramps: 200 – 300mg
before sleeping
• Spermicidal in vaginalcreams
• Varicose veins: along with urethane causes
thrombosis & fibrosis of varicose veinmass

20. – Interferes with oxygen transportsystem
• Primaquine:
– Mechanism of action:
Primaquine
Converted to
electrophiles
Generates reactive
oxygen species

21. Antimalarial action
• Liver hypnozoites
• Weakaction against erythrocytic stageof
vivax, soused with supressivesin radicalcure
• No action against erythrocytic stageof
falciparum
• Has gametocidal action and is most effective
antimalarial to prevent transmission disease
against all 4species

22. Adverseeffects
• Gastrointestinal:
– epigastric
distress, abdominal cramps ,
• Hemopoetic:
– mild
anemia, methaemoglobinem
ia, cyanosis, hemolytic
anemia in G6PDdeficiency
• Avoided during
pregnancy, G6PDdeficient

23. Uses
• Primary useis radical cure of relapsingmalaria
15 mg daily for 14 dayswith dose of
chloroquine
• Falciparum malaria 45 mg of single dosewith
chloroquine curative doseto kill gametes &
cut down transmission of malaria.

24. • Tafenoquine:
– More active slowly metabolized analog of
primaquine, hasadvantage that it canbe givenon
weekly basis.
• Bulaquine:
– Congener of primaquine developed in india
– Comparable antirelapse activity when used for 5
days
– Partly metabolized to primaquine
– Better tolerated in G6PDdeficiency

25. • Tab.Chloroquine phosphate 250 mg
– Contains 150 mg of base
– Give4 tablets stat , 2 tablets after 8 hours and ,1
tablet BDfor 2 days
• Patients who cannot takeorally
– 3.5 mg/kg IM every 6 hrs for 3days
• Tabprimaquine 15 mg ODfor 14 daysin
Plasmodium vivax, ovale
• Primaqine 45 mg single dose for falciparum
after chloroquine (gametocidal)
Acute attack of chloroquinesensitive
malaria: