This document discusses antimalarial drugs. It provides information on: 1. Antimalarial drugs are used for prophylaxis, treatment, and prevention of malaria relapses. Malaria is caused by Plasmodium parasites transmitted via mosquito bites. 2. Common antimalarial drugs include chloroquine, mefloquine, quinine, primaquine, proguanil, pyrimethamine, and sulfadoxine-pyrimethamine combinations. 3. These drugs act on different life stages of the malaria parasite and are used for prevention, treatment, radical cure, and blocking transmission to mosquitoes. Adverse effects and mechanisms of action are described for major antimal

1. GRACE COLLEGE OF PHARMACY,PALAKKAD
APPROVED BY PCI,GOVERNMENT OF KERALA AFFLIATED TO KERALA UNIVERSITY OF HEALTH SCIENCES
ANTI-MALARIAL DRUGS
Prepared by:
Mr. GOKUL J SIDDHARTH
RESEARCH SCHOLAR
gokulsiddu@gmail.com

2. ANTIMALARIAL DRUGS

3. ANTIMALARIAL DRUGS
• These are drugs used for prophylaxis, treatment and
prevention of relapses of malaria
• malaria is an acute infectious disease caused by four
species of the protozoal genus Plasmodium
• Plasmodium species which infect humans
1. Plasmodium vivax (tertian)
2. Plasmodium ovale (tertian)
3. Plasmodium falciparum (tertian): Most dangerous species
4. Plasmodium malariae (quartan)
• The parasite is transmitted to human through the bite of a
female Anopheles mosquito

4. SYMPTOMS OF MALARIA

5. CLASSIFICATION OF ANTIMALARIAL DRUGS

6. OBJECTIVES AND USE OF ANTIMALARIAL
DRUGS
• The aims of using drugs in relation to malarial infection
are;
• To prevent clinical attack of malaria (prophylactic)
• To treat clinical attack of malaria (clinical curative)
• To completely eradicate the parasite from the patient’s
body (radical curative)
• To cutdown human to mosquito transmission
(gametocidal)

7. LIFE CYCLE OF THE MALARIAL PARASITE,
PLASMODIUM FALCIPARUM

8. DRUGS USED IN MALARIA
• Tissue schizonticides- drugs eliminating developing
or dormant liver forms
• Blood schizonticides- drugs acting on
erythrocytic parasites
• Gametocides- drugs that kill sexual stages and
prevent transmission to mosquitoes

9. FORMS OF ANTIMALARIAL DRUGS
Clinically malarial infections can be controlled by the drugs
used in following ways:
1. Causal prophylaxis
2. Suppressive prophylaxis
3. Clinical cure
4. Radical cure
5. Gametocidal
1.Causal prophylaxis
• Drugs prevent the maturation of or destroy the
sporozoites within the infected hepatic cell- thus prevent
erythrocytic invasion

10. • Primaquine – for all species of malaria but not used due to
its toxic potential
• Proguanil-primarilyfor P. falciparum and not
effective against P. vivax (weak activity), rapid
development of resistance
2. Suppressive prophylaxis
• Schizontocides inhibit erythrocyte phase and prevent the
rupture of the infected erythrocytes, lead to freedom from
rigors and pyrexia
• Includes quinine, chloroquine, proguanil,
pyrimethamine, artemicinin and tetracycline
3. Clinical cure
• Erythrocytic schizontocides are used to terminate
episodes of malarial fever

11. • Fast acting high efficacy drugs: Chloroquine, quinine,
mefloquine, halofantrine, artemisinin Used
singlyto treat malaria fever o Faster acting, preferably
used in falciparum malaria where delayed treatment may lead
to death even if parasites are clear from blood
• Slow acting low efficacy drugs: Proguanil,
pyrimethamine, sulfonamides, tetracyclines- Used only in
combination
4. Radical cure
• Drug attack exoerythrocytic stage (hypnozoites) given
with clinical curative for the total eradication of the
parasite from the patient’s body.

12. • Radical cure of the P. falciparum malaria can be
achieved by suppressives only
• For radical cure of P.vivax infection, primaquine and
proguanil are effective
5. Gametocial
• Removal of male and female gametes of Plasmodia
formed in the patient’s blood
• It has no benefit for treated patient
• Primaquine and artemisinins are highly effective against
gametocytes of all species.

13. CHLOROQUINE (CQ)
• Rapidly acting erythrocytic schizontocide against
all species of Plasmodia
• Drug of choice for treating acute attacks caused by
sensitive strains of P. vivax or P. falciparum
• Controls most clinical attack in 1-2days with
disappearance of parasite from peripheral blood in 1- 3days
• No effect on exo- erythrocytic phase
• Neither prevent primary infection nor relapse in P.
vivax and P.ovale
• Drug of choice for use in pregnancy, prophylaxis

14. Chloroquine- mechanism of action
• The parasite digests the host cell’s hemoglobin to
obtain essential amino acids
• The processreleases large amounts of heme, which
is toxic to the parasite
• To protect itself the parasite ordinarily polymerizes
the heme to nontoxic hemozoin, which is sequestered in
the parasite’s food vacuole Cholroquine prevents the
polymerization to hemozoin
• The accumulation of heme results in lysis of both the parasite
and the red blood cell

16. Pharmacokinetics
• Rapidly and completely absorbed from GI tract
• Substantial amount is deposited in erythrocytes, liver, spleen,
kidney, lung, melanin containing tissues and leukocytes
• Slowrelease from these sites helps in maintaining
the therapeutic plasma levels – when used for prophylaxis,
it is administered just once a week
• Also crosses the blood- brain barrier and traverses the placenta
Excreted predominantly in the urine
Uses
• Extraintestinal amoebiasis • Rheumatoid arthritis •
Discoid lupus erythematosus • Lepra reaction •
Photogenic reactions • Infectious mononucleosis

17. Adverse effects
• CNS- mild headache, confusion, psychosis,
convulsion, impaired hearing
• Eye (with high dose)- loss of vision due to retinal damage,
reversible corneal damage
• GIT- Nausea, vomiting, anorexia, epigastric pain,
diarrhea( can be minimized by taking with meal)
• Skin- uncontrolled itching, urticaria, exfoliative dermatitis
Parenteral administration- Hypotension, cardiac
arrhythmias, cardiac depression

18. Contraindications
• Patient with psoriasis, porphyria
• In dermatitis, liver damage, alcoholism,
neurological, retinal and hematological diseases
MEFLOQUINE (MQ)
• Fast acting erythrocytic (blood) schizontocide but slower
than CQ or quinine
• Effective against CQ-sensitive as well as resistant
Plasmodia Efficacious suppressive prophylactic for multi-
resistant P. falciparum

19. Mechanism of action
• Like CQ, it accumulates in infected RBCs, binds to
heme and this complex damages the parasite’s membrane
• However recent evidence suggests that the site of action of
MQ is in the parasitic cytosol rather than in the acidic vacuole
Pharmacokinetics
• Prolonged absorption after oral ingestion
• It is highly plasma protein bound and concentrated in the
liver, lung and intestines
• Extensive metabolism occurs in liver and is primarily secreted
in bile It has a long half life (17days) due to
its concentration in various

20. tissues and its continuous circulation through the
enterohepatic and enterogastric systems
• Its major excretory route is feces
Adverse effects
• MQ is bitter in taste
• At high doses: Nausea, vomiting, diarrhea,
abdominal pain, bradycardia o Ataxia, hallucinations,
depression
• MQ is safe in pregnancy
• Rare events of toxicity are seen Contraindications
• In patients with anxiety, depression, psychosis,
andin cardiac conduction defects

21. Drug interactions
• Cardiac arrests are possible if MQ is taken concurrently
with quinine or quinidine Uses
• Effective for multidrug resistant P. falciparum
• However its use is restricted due to its toxicity, cost and
long half life
QUININE
• Quinine is a l-isomer of alkaloid obtained from
cinchona bark and quinidine (antiarrhythmic) is its d- isomer
• An effective erythrocyticschizontocide as
suppressive and used to prevent or terminate
attacks of vivax, ovale, malariae, sensitive
falciparum
• Moderately effective against hepatic form (pre-
exoerythrocyte and gametocytes)

22. Mechanism of action
• Like CQ it is a weak base, and acts by inhibiting
polymerization of heme to hemozoin
• Free heme or heme-quinine complex damages
parasite’s membrane and kills it
Pharmacokinetics
• Well absorbed from GI tract, even in patients with
diarrhea Metabolized in liver and excreted in urine
Adverse effects
• Cinchonism
• Higher dose symptoms include nausea, vomiting,
tinnitus, vertigo, headache, mental confusion, difficulty
in hearing and visual defects, diarrhea,
flushing

23. • Rapid i.v. injection
• Hypotension and cardiac arrhythmias
• Can cause profused hypoglycemia
• Pregnancy
• Hypoglycaemia
• Causes abortion in early pregnancy by stimulating
myometrium and premature labor by stimulating uterus
Clinical uses
• Malarial attacks
• Uncomplicated resistant falciparum Complicated and severe
malaria including cerebral malariaIs not highly active,
adjunctive therapy with doxycycline, tetracycline and
clindamycin is needed

24. • PROGUANIL (CHLOROGUANIDE)
• Slow acting erythrocytic schizontocide
• Cyclized in body to a triazine derivative (cycloguanil)
• Cycloguanil inhibits plasmodial dihydrofolate reductase
(DHFRase) Resistance developed due to
mutational changes in the plasmodialDHFRase enzyme
• Slow but adequate absorption from the gut
• Partly metabolized and excreted in urine
• Half life 16-20 hour ; noncumulative
Adverse effects
• Mild abdominal upset, vomiting, occasional stomatitis,
haematuria, rashes and transient loss of hair

25. PYRIMETHAMINE
• Slow acting erythrocytic schizontocide
• Direct inhibitor of plasmodial dihydrofolate reductase
(DHFRase) Conversion of dihydrofolic acid to tetrafolic acid is
inhibited
• High doses inhibits Toxoplasma gondii
• Resistance develops by mutation in DHFRase enzyme
Adverse effects
• Occasional nausea and rashes
• Folate deficiency rare
• Megaloblastic anaemia and granulocytopenia with higher
dose
• Can be treated with folinic acid
• Combined with a sulfonamide (S/P) or dapsone for
treatment of falciparum malaria

26. SULFONAMIDE-PYRIMETHAMINE(S/P)
• Sulphadoxine is a sulfonamide thus competes with para–
amino benzoic acid – inhibits the formation of dihydropteric
acid
• Pyrimethamine inhibits DHFRase enzyme as a
result of which conversion of dihydrofolic acid to
tetrahydrofolic acid is blocked – thus inhibits DNA
synthesis
• Effective blood schizontocide against Plasmodium
falciparum Treatment and prophylaxis of
falciparum malaria resistantto chloroquine
Adverse effects
• Mild GIT upset • Megaloblastic anemia, bone marrow
depletion • Rashes, urticaria, serum sickness,
drug fever • Exfoliative dermatitis, Stevens Johnson
syndrome • Nephrotoxicity

27. PRIMAQUINE
• Poor erythrocytic schizontocide
• Has marked effect on primary and secondary
hepatic phases of malarial parasite
• Highly active against gametocytes and hypnozoites
Mechanism of action
• Intermediate act as oxidant that are responsible for the
schizontocial action
Pharmacokinetics
• Readily absorbed after oral absorption
• Oxidized in liver with a plasma half life of 3-6
hours
• Excreted in urine within 24 hour
• Not a cumulative drug

28. Adverse effects
• Abdominal pain, gastrointestinal upset, weakness or
uneasiness chest Leucopenia (high dose)
• Hemolysis
• Methaemoglobinaemia
• Tachypnoea
• Cyanosis
Clinical uses
• Radical cure of relapsing malaria (P.ovale and P.vivax)
• Single 45mg dose given with curative dose of
chloroquine to kill gametes (P. falciparum)

29. ARTEMISININ

30. ARTEMISININ- BASED COMBINATION THERAPY
• Artesunate- sulfadoxine+ pyrimethamine (AS- S/P)
• Artesunate- mefloquine (AS/MQ)
• Artesunate- amodiaquine (AS/AQ)
• Artemether-lumefantrine
• Dihydroartemisinin (DHA)- piperaquine
• Arterolane- piperaquine
• Artesunate- pyronaridine

31. ATOVAQUONE
• Synthetic naphthaquinone
• Rapidly acting erythrocytic schizontocide as well as active
against pre erythrocytic stage of P. falciparum and other
plasmodia
• Pneumocystis jiroveci and Toxoplasma gondii are also
susceptible to atovaquone.
• It collapses plasmodial mitochondrial membranes and
interferes with ATP production
• Proguanil potentiates its antimalarial action
Side effects
• Diarrhoea, vomiting, headache, rashes, fever

32. REFERANCE
KD Tripathi Essential of Medical Pharmacology
7th Edition Page no:
©2013,KD Tripathi