Antimalarials

Malaria is a protozoal infection caused by genus

plasmodium and transmitted to man by the
infected female anapheles mosquito.

The species of malarial parasites are

plasmodium vivax, plasmodium
ovale,plasmodium malariae.
• Chloroquine
• Amodiaquine
• Piperaquine
• Primaquine
• Tafenoquine
• Mefloquine
• Quinine and quinidine
Chloroquine

 Chloroquine is a 4-aminoquinoline
 It is very effective
 Rapidly acting blood schizontocide against
P.vivax, P.ovale, P.malariae.
 It has no activity against liver forms
MOA
chloroquine is a basic drug, which is taken up
by the acidic food vacuoles of susceptible
plasmodia

Inhibits the conversion of haemo to hemozoin.

The “drug-haeme” complex is toxic

Kills the parasite.

Haemoglobin haeme(toxic) hemozoin(non-
toxic.

Chloroquine concentrated in acidic vacuole

of parasite binds to haeme
drug-haeme complex damages
plasmodial membrane
p.K
 Orally, parenteral
 Well absorbed after oral and parenteral
administration .
 It rapidly distributed to tissues
 It get concentrated in liver, spleen, kidney,
lungs, skin etc.
 Metabolized in the liver
 Excreted in urine.
A.E and contraindication.
 Nausea
 Vomiting ,
 Skin rashes
 Itching
 Headche
 Visual disturbances
 Hypotension
 Confusion
 Cardiac arrhythmias,
 Convulsions
 Cardiac arrest
 Rheumatoid arthritis
 Irrevesible retinopathy
 Ototoxicity
 Myopathy
 Cardiomyopathy
 Neuropathy
 Psychiatric disturbances

Should be avoided in epileptics.

Safe in pregnancy.
Uses

1. Malaria
 Chloroquine is the drug of choice for the
treatment of acute attackof malaria caused by
P.vivax, P.ovale, P.malariae
 Fever resolves within24-48 hrs.
 Blood smear become negative within 2-3 days.

2. Chemoprophylactic agent for all types of

malaria.
2. Amoebiasis
3. Lepra reaction
4. Rheumatoid arthritis
5. Autoimmune disorder.
Amodiaquine
It is not used for prophylaxis of malaria owing to
its toxicities that id agranulocytosis and
hepatotoxicity.
Quinine and quinidine
MOA same as choloroquine

Pharmacological actions
1. Antimalarial actions :
 Quinine is a highly effective blood
schizontocide against all the four sps. Of
plasmodia.
 It has gametocidal activity against P.vivax
 It has no activity on hepatic forms.
• GIT: Being bitter, quinine reflexly increases gastric acid
secretion.
• CVS: Quinine directly depresses the myocardium and can
cause hypotension.
• Skeletal muscle: quinine directly depresses the skeletal
muscle contraction.
• CNS: quinine causes disturbances of hearing and vision. It
also has mild analgesic and antipyretic effect.
• Local action: loca anaesthetic effect, orally causes gi
ittiration with nausea, vomiting and abdominal discomfort.
• i.Mly causes local pain and necrosis..i.vnly causes
thrombophlebitis.
P.K
i.m,i.v
Quinine is readily absorbed from the gut
Well distributed in the body
Liver
Urine
A.E
 Cinchonism (tinnitus, deafness, visual
disturbances, hdche, nausea, vomiting
 Hypoglyceamia
 Hypotension
 Black water fever, a hypersensitivity reaction
to quinine , is characterised by haemolysis,
haemoglobinaemia, and haemoglobinuria
leading to renal failure.
Uses
1. Malaria : quinine is effective for treatment of
acute attack of chloroquine resistant P.
falciparum malaria.

2. Nocturnal leg cramps:

Quinine is not used for chemoprophylaxis of

malaria because of its toxicity.
Mefloquine
antifolates

• They are pyrimethamine, sulphadoxine,

sulphones (dapsone) and proguanil.
MOA
PABA

• Sulphadoxine - Folate synthetase

• Dapsone

Dihydrofolic acid

• Pyrimethamine -
folate reductase
• Proguanil

Tetrahydrofolic acid
P.K
 Oral
 Binds to plasma proteins
 Accumulates in liver,kidney, lungs and spleen.
 It has a long plasma half life
 Excreted in urine.

a.E
Skin rashes, urticaria, megaloblastic anaemia
Teratogenic effect.
Proguanil

a.e:
Nausea, vomiting, diarrhoea, abdominal pain,
haematuria and skin rashes.
Artemisinin and its derivatives
• They are highly effective against erythrocytic
stages of all plasmodia.
• They are highly potent, rapid acting, produce
faster clinical cure
• Parasite clearance than othr antimalarial
parasite.
MOA
In the acid vacuole of parasite, cleavage of
endoperoxide bridge of artemisinin compounds
by haeme iron.

Free radicals generated

Damage to proteins and lipid peroxidation.

Death of parasite
p.K
 Oral, i.v, rectal ,i.m
 Metabolozed to active metabolite,
digydroartemisinin.
A.E
GI
Netropaenia
Prolongation of QT interval.