Transcript Antimalarial Drugs Malaria

Malaria
 Endemic in most tropical countries.
USE OF ANTIMALARIAL DRUGS
 The aims of using drugs in relation to malarial infection
are:
1. To prevent clinical attack of malaria (private
prophylaxis).
2. To treat and completely eradicate the parasite from the
patient’s body (Clinical cure).
3. To cutdown human-to-mosquito transmission (public
prophylaxis ).
The life cycle of malarial
parasite in man.
Antimalarials that act on
erythrocytic schizogony are
called erythrocytic (blood)
schizontocides
Those that act on
preerythrocytic as well as
exoerythrocytic (P. vivax)
stages in liver are called
tissue schizontocides
Those which kill gametocytes
in blood are called
gametocides.
Comparative properties of
antimalarial drugs
Private prophylaxis
Causal prophylaxis
 The preerythrocytic phase (in liver) is the target for
this purpose.
 Primaquine is a causal prophylactic for all species of
malaria, but has not been used in mass programmes,
because of its toxic potential.
 Proguanil is a causal prophylactic, primarily for P.f.,
but rapid development of resistance when used alone.
 A combined formulation of atovaquone (250 mg) + proguanil (100 mg) is commonly used
as a prophylactic by Americans and other western travellers visiting malaria endemic
areas
Private prophylaxis
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Suppressive prophylaxis
The schizontocides which suppress the erythrocytic phase and
thus attacks of malarial fever can be used as prophylactics.
Though the exoerythrocytic phase in case of vivax and other
relapsing malarias continues, clinical disease does not appear.
Chloroquine (CQ) In travellers, start one week before and
continue till one month after return from endemic area.
However, it can be used as a prophylactic only in areas with CQsensitive P.f. (Mexico, Argentina, etc.)
Mefloquine- started 1–2 weeks before and taken weekly till 4
weeks after return from CQ-resistant P.f. area, except
mefloquine-resistant P.f. areas (Myanmar, Thailand,Cambodia,
India).
Doxycycline -100 mg daily starting day before travel and taken
till 4 weeks after return. Use for short-term (maximum 6 weeks)
visitors and those unable to take mefloquine.
Chemoprophylaxis of malaria
Chemoprophylaxis of malaria should be limited to
short-term use in special risk groups, such as :
Nonimmune travellers,
Nonimmune persons living in endemic areas for fixed
periods (army units, labour forces),
Infants, children and pregnant women (falciparum
malaria has serious consequences in the pregnant).
 Intermittent preventive therapy in the form of one dose pyrimethamine (75 mg) +
sulfadoxine (1500 mg) each is 2nd and 3rd trimester (gap not < 1 month) is recommended
by WHO only in areas with high P.f. endemicity (P.f. >30%) for pregnant women.
Clinical cure
High-efficacy drugs:
Low-efficacy drugs:
 Artemisinin,
 Proguanil
 CQ,
 Pyrimethamine
 Amodiaquine
 Sulfonamides
 Quinine
 Tetracyclines
 Mefloquine
 Clindamycin
 Halofantrine
 Lumefantrine
 Atovaquone.
The erythrocytic schizontocides are used to terminate an
episode of malarial fever.
The erythrocytic schizontocides are radical curatives for
falciparum, but not for vivax or ovale malaria.
Severe and complicated falciparum malaria
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Hyperpyrexia
Fluid and electrolyte imbalance,
Acidosis,
hypoglycaemia,
1) Quinine
prostration,
Quinine + clindamycin
2)Artemisinin-based therapy (ACT):
Cardiovascular collapse,
Artesunate
severe anaemia,
Artemether
spontaneous bleeding,
Arteether
pulmonary edema,
haemoglobinuria,
renal failure
 Parenteral (i.m./i.v.) drugs have to be used
Chloroquine
1) CQ causes rapid fever clearance and disappearance of
parasitaemia in patients of malaria caused by all
P.ovale and P.malariae, most P.vivax
 It is the drug of choice for clinical cure of vivax, ovale
and malariae malaria.
2) Extraintestinal amoebiasis
3) Rheumatoid arthritis
Mefloquine
 Mefloquine is an effective drug to treat for multi-resistant
P. falciparum.
 To limit the spread of MQ-resistance, current
recommendation is to use it only in combination with
artesunate
 For prophylaxis of malaria among travellers to areas with
multidrug resistance;
 It is not recommended for prophylaxis in residents of the
endemic area.
Quinine
 Quinine is used orally for uncomplicated CQ-resistant
malaria, and i.v. for complicated/cerebral malaria.
 - Uncomplicated resistant falciparum malaria
 - Complicated and severe malaria including cerebral
malaria
 Drug of choice for falciparum malaria
ARTEMISININ DERIVATIVES
 Artemisinin is the active substanse of Artemisia annua
(wormwood).
 Active against P.falciparum resistant to all other
antimalarial drugs
Artemisinin derivatives (Artemisinins):
Artemether
Artesunate
Arteether
Arterolane
Use:
Uncomplicated falciparum malaria
Severe and complicated falciparum malaria
Proguanil (Chloroguanide)
 It is a relatively slow-acting erythrocytic schizontocide for
both P.f. and P.v.
 Its combination with atovaquone is commonly used in
Thailand, USA and some other countries as a fast-acting
erythrocytic schizontocide for treatment of multidrug
resistant falciparum malaria.
 Atovaquone-proguanil is also used by western travellers as
a causal prophylactic while visiting CQresistant/multidrugresistant P.f. endemic areas.
Sulfonamides-pyrimethamine
 Sulfadoxine 500mg + pyrimethamine 25mg tab: FANCIDAR
 The major importance of this combination is due to its
efficacy against CQ-resistant P.falciparum.
Primaquine
 Active against the preerythrocytic stage of P. falciparum
 Marked effect on primary as well as secondary hepatic
phases of the malarial parasite.
 It is highly active against gametocytes and hypnozoites.
Tetracycline and Doxycycline
 These antibiotics have weak erythrocytic
schizontocidal action against all plasmodial species
including CQ, MQ and S/P resistant P. falciparum.
 Tetracyclines are never used alone to treat malaria, but
only in combination with quinine or artesunate to
treat mefloquine/chloroquine/S/P-resistant
falciparum malaria
 100 mg/day is used as a 2nd line prophylactic for shortterm travellers to CQ-resistant P. falciparum areas.
 Tetracyclines are not to be given to children and
pregnant women