Session 10: Description of

Antimalarial Drugs
: Indications of Antimalarial Drugs
• The indications of antimalarial drugs depends on the stage of disease and are classified as
follows:
• Drugs that eliminate developing or dormant liver forms of malaria parasite are called tissue
schizonticides
• Those that act on erythrocytes stage of malarial parasites are blood schizonticides
• Those that kill sexual stages of malaria parasites and prevent transmission to mosquitoes
are gametocides
• No one available agent can reliably affect a radical cure, that is, eliminate both hepatic and
erythrocytic stages of malaria parasite
• Few available agents are causal prophylactic drugs, that is, capable of preventing
erythrocytic malaria infection
• However, all effective malaria chemoprophylactic agents kill erythrocytic parasites before
they increase sufficiently in number to cause clinical disease
• The indications of different antimalaria drugs:
• Chloroquine
• Is a highly effective blood schizonticide
• It is also moderately effective against gametocytes of P. vivax, P. ovale, and P. malariae
but not against those of p falciparum
• Chloroquine is not active against liver stage parasites
• But its utility against p falciparum has been seriously compromised by drug resistance

• Amodiaquine
• Amodiaquine is closely related to chloroquine, and it probably shares mechanisms of
action and resistance with that drug
• Quinine & Quinidine
• Quinine is a rapidly acting, highly effective blood schizonticide against the four species of
human malaria parasites
• The drug is gametocidal against P. vivax and P. ovale but not P. falciparum
• It is not active against liver stage parasites.
• The mechanism of action of quinine is unknown
• Artemisinin and its derivatives
• Are very rapidly acting blood schizonticides against all human malaria parasites
• Artemisinins have no effect on hepatic stages of malaria parasites
• Artemisininsin particular artesunate and artemether are playing an increasingly important
role in the treatment of multidrug-resistant p falciparum malaria
• They are the only drugs reliably effective against quinine resistant strains
• The most important of these analogs are:
• Artesunate (water-soluble; useful for oral, intravenous, intramuscular,
and rectal administration)
• Artemether (lipid-soluble; useful for oral, intramuscular, and rectal
administration)
• Lumefantrine
• Is an aryl alcohol related to halofantrine, is available as a fixed-dose
combination with artemether as Coartem in some countries
• Coartem is highly effective in the treatment of falciparum malaria
Contraindications of Antimalarial Drugs
• Chloroquine is contraindicated in patients with
• Psoriasis or porphyria, in whom it may precipitate acute attacks of these diseases
• It should generally not be used in those with retinal or visual field abnormalities or
myopathy.
• Quinine (or quinidine)
• Should be discontinued if signs of severe cinchonism, hemolysis, or hypersensitivity occur
• It should be avoided if possible in patients with underlying visual or auditory problems
• Artemisinins
• It is contraindicated the first trimester of pregnancy if possible because teratogenicity has
been seen in animal studies, but limited inadvertent use in pregnancy has apparently not
led to fatal problems
• Is avoided in breast feeding mother whose infant is below 5kg body weight
 •Artemether & Lumefantrine
•Dosage of Artemether 20mg & Lumefantrine 120mg tablets according to weight and age

Dose, Dosage and Course of Antimalarial

Drugs
WT(Kg) AGE Day 1 Day1 Day2 Day2 Day 3 Day3
O hr 8hrs 24 hrs 36 hrs 48hrs 60hrs

5-14 3mon-3yrs 1 1 1 1 1 1

15-24 3yrs-8yrs 2 2 2 2 2 2

25-34 8yrs-12yrs 3 3 3 3 3 3

35 above 12yrs above 4 4 4 4 4 4

• Artemether & Lumefantrine
• Dosage of Artemether 20mg & Lumefantrine 120mg tablets according
to weight and age
• The first dose should be given as Direct Observed Therapy(DOT)
• The second dose should strictly be given after 8hours
• Subsequent doses could be given twice daily (morning-evening) until
completion of 6 doses
• Quinine
• Oral dose
• Adults 600 mg (salt) 8 hourly for 7 days
• Children 10mg/kg (salt) 8 hourly for 7 days
• Intravascular route
• Dilution of Quinine dihydrochloride injection (300 mg/ml) for intra-muscular use dose of
10 mg of salt/kg bodyweight (not exceeding a maximum dose of 600mg)
• Quinine should be diluted four times in water for injection to a concentration of 60
mg/ml
• Intravenous route
• Quinine dose: 10 mg/kg body weight of salt, diluted in 5-10 ml/kg body weight of 5%
dextrose or dextrose-saline and infused over 4 hours and repeated every 8 hours
Side Effects and Adverse Effects of
Antimalarial Drugs
• Quinine
• Adverse effects and side effects
• Therapeutic dosages of quinine and quinidine commonly cause tinnitus, headache, nausea, dizziness,
flushing, visual disturbances and a constellation of symptoms termed cinchonism
• Mild symptoms of cinchonism do not warrant the discontinuation of therapy
• More severe findings, often after prolonged therapy, include more marked visual and auditory
abnormalities, vomiting, diarrhoea, and abdominal pain
• Hypersensitivity reactions include skin rashes, urticaria, angioedema, and bronchospasm
• Therapeutic doses may cause hypoglycaemia through stimulation of insulin release; this is a particular
problem in severe infections and in pregnant patients, who have increased sensitivity to insulin
• Quinine can stimulate uterine contractions, especially in the third trimester
• However, this effect is mild, and quinine and quinidine remain the drugs of choice for severe falciparum
malaria even during pregnancy
• Intravenous infusions of the drugs may cause thrombophlebitis
• Chloroquine
• Adverse effects and side effects
• Pruritus is common, Nausea, vomiting, abdominal pain, headache, anorexia, malaise,
blurring of vision, and urticaria are uncommon
• Large intramuscular injections or rapid intravenous infusions of chloroquine
hydrochloride can result in severe hypotension and respiratory and cardiac arrest
• Artemisinins in particular artesunate and artemether
• Adverse effects and side effects
• The most commonly reported adverse effects have been nausea, vomiting, and diarrhea
• Irreversible neurotoxicity has been seen in animals, but only after doses much higher
than those used to treat malaria
: Interactions and Precautions of
antimalarial drugs
• Artemisinins in particular artesunate and artemether
• Interact with the following group of drugs
• Amiodarone
• Quinolone
• Antidepressants
• Imidazoles
• Antipsychotics
• Antivirals
• β-blockers
• Cimetidine
• Quinine and Quinidine
• Interact with the following drugs
• Should not be given concurrently with mefloquine
• Should be used with caution in a patient with malaria who has previously received mefloquine
chemoprophylaxis
• Absorption may be blocked by aluminium-containing antacids
• Quinine can raise plasma levels of warfarin and digoxin
• Do not give concurrent with anti psychotics
• Precaution
• Severe hypotension can follow too-rapid intravenous infusions of quinine or Quinidine
• It must be used with great caution in those with underlying cardiac abnormalities
• Dosage must be reduced in renal insufficiency
• Chloroquine
• Interaction
• The antidiarrheal agent kaolin and calcium- and magnesium-
containing antacids interfere with the absorption of chloroquine and
should not be co administered with the drug
• Precaution
• Chloroquine should be used with caution in patients with a history of
liver disease or neurologic or hematologic disorders