This document discusses antimalarial drugs, including their classification, mechanisms of action, pharmacokinetics, clinical uses, and adverse effects. The main classes of antimalarial drugs are tissue schizonticides, blood schizonticides, and gametocides. Key drugs discussed include chloroquine, mefloquine, quinine, proguanil, pyrimethamine, primaquine, and artemisinin derivatives. The document also covers antimalarial drug combinations such as sulfadoxine-pyrimethamine and artemisinin-based combination therapies.

1. ANTIMALARIAL DRUGS
Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam

2. 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

3. Symptoms of Malaria

4. Classification of Antimalarial Drugs

5. Objectives and use of Antimalarial Drugs
The aims of using drugs in relation to malarial infection are;
1. To prevent clinical attack of malaria (prophylactic)
2. To treat clinical attack of malaria (clinical curative)
3. To completely eradicate the parasite from the patient’s body (radical
curative)
4. To cutdown human to mosquito transmission (gametocidal)

6. Life Cycle of the malarial parasite, Plasmodium falciparum

7. 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

8. 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

9. Primaquine – for all species of malaria but not used due to its toxic
potential
Proguanil- primarily for 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

10. Fast acting high efficacy drugs: Chloroquine, quinine, mefloquine,
halofantrine, artemisinin Used singly to 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
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

11. 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

12. 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

13. Chloroquine- Mechanism of action
The parasite digests the host cell’s hemoglobin to obtain essential
amino acids
↓
The process releases 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

14. Mechanism of Chloroquine

15. Pharmacokinetics
Rapidly and completely absorbed from GI tract
Substantial amount is deposited in erythrocytes, liver, spleen, kidney,
lung, melanin containing tissues and leukocytes
Slow release 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

16. 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

17. 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
Mechanism of action
Like CQ, it accumulates in infected RBCs, binds to heme and this
complex damages the parasite’s membrane

18. 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
tissues and its continuous circulation through the enterohepatic and
enterogastric systems
Its major excretory route is feces

19. 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, and in cardiac
conduction defects
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

20. QUININE
Quinine is a l-isomer of alkaloid obtained from cinchona bark and
quinidine (antiarrhythmic) is its d-isomer
An effective erythrocytic schizontocide as suppressive and used to
prevent or terminate attacks of vivax, ovale, malariae, sensitive
falciparum
Moderately effective against hepatic form (pre- exoerythrocyte and
gametocytes)
Mechanism of action
Like CQ it is a weak base, and acts by inhibiting polymerization of
heme to hemozoin

21. 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
Rapid i.v. injection
 Hypotension and cardiac arrhythmias
 Can cause profused hypoglycemia

22. Pregnancy
 Causes abortion in early pregnancy by stimulating myometrium and
premature labor by stimulating uterus
 Hypoglycaemia
Clinical uses
Malarial attacks
 Uncomplicated resistant falciparum
 Complicated and severe malaria including cerebral malaria
Is not highly active, adjunctive therapy with doxycycline, tetracycline
and clindamycin is needed

23. 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 plasmodial
DHFRase 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

24. 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

25. 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 resistant to
chloroquine
Adverse effects
•Mild GIT upset • Megaloblastic anemia, bone marrow depletion •
Rashes, urticaria, serum sickness, drug fever • Exfoliative dermatitis,
Stevens Johnson syndrome • Nephrotoxicity

26. 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

27. 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)

28. ARTEMISININ
ARTEMISININ DERIVATIVES
Artesunate
Artemether
Arteether

29. 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

30. 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