Review of Pharmacology - 9E (2015)

Chemotherapy B: Antimicrobials for Specific Conditions
Antifolate Drugs
These include pyrimethamine, proguanil, sulfadoxine and dapsone. Proguanil is a prodrug and is
activated to form cycloguanil. Pyrimethamine and cycloguanil act by inhibiting DHFRase.
Pyrimethamine plus sulfadoxine act through sequential blockade. These are slow acting blood
schizonticides that are active against chloroquine resistant P. falciparum infections. Proguanil
plus atovaquone can be used for treatment as well as chemoprophylaxis of chloroquine
resistant malaria.
Atovaquone
It is a rapidly acting blood schizonticide that acts by collapsing the parasite’s membrane.
Proguanil potentiates its antimalarial action. It can also be used for Pneumocystis jiroveci
pneumonia and Toxoplasma gondii infections.
Fast acting Erythrocytic
schizonticidal drugs
M – Mefloquine
A – Atovaquone
C – Chloroquine (and
amiodiaquine and
piperaquine)
H – Halofantrine (and lumefant
rine)
A – Artemisinins
R – Res-Q (Quinine)
Artemisinin Derivatives
Artemisinin, dihydroartemisinin, artesunate, artemether and arteether are the compounds
obtained from a Chinese herb Artemisia annua. Artemisinin is a prodrug and is activated in
the body to dihydroartemisinin. These drugs generate highly active free radicals that damage
parasite membranes. These drugs are the fastest acting drugs against malaria. Artesunate has
a very short half life and can be given i.v. These can be used for the treatment of multidrug
resistant malaria as well as serious forms like cerebral malaria. Artemisinin derivatives are
not indicated for chemoprophylaxis of malaria. It can rarely cause QT prolongation.
Halofantrine and Lumefantrine
Halofantrine has erratic oral bioavailability and can cause potentially serious cardiotoxicity
(even more if combined with mefloquine). Due to these reasons, it is not recommended
for chemoprophylaxis of malaria. Use of this drug is reserved for treatment of multidrug
resistant malaria. Lumefantrine is a new drug similar to halofantrine and is always used
along with artemether. Its absorption markedly increases with fatty food.
Other drugs
Other antimalarial drugs include doxycycline, amodiaquine, mepacrine and pyronaridine etc.
Mepacrine is most concentrated in collagen.
Males and Non-pregnant
Females
Treatment of Uncomplicated Malaria
P. vivax Chloroquine (3 days) +
Primaquine (14 days)
P. falciparum Artesunate (3 days) +
Primaquine (single dose)
Mixed (P. vivax +
P. falciparum)
Artesunate (3 days)
+ Sulfadoxine/Pyrimethamine
(1 day) +
Primaquine (14 days)
Pregnancy 1st
tri mes ter
Chloroquine (3
days)
Quinine
Quinine
Pregnancy 2nd and 3rd
trimester
Chloroquine (3 days)
Artesunate (3 days) + Sulfadoxine/
Pyrimethamine (1 day)
Artesunate (3 days) + Sulfadoxine/
Pyrimethamine (1 day)
Artemisinins are the fastest
acting drugs against malaria.
Remarks
Primaquine is contra-indicated in
pregnancy, infants and patients
with G-6-PD deficiency
Primaquine is used for killing the
gametes here
Primaquine is given for 14 days to
prevent relapse (for radical cure)
Chemotherapy B: General Antimicrobials Pharmacology for Specific Conditions
Suspected malaria
but parasitological
diagnosis is not
possible
Treatment of
Severe or complicated
malaria
Full course of chloroquine, till the results of microscopy are received. Once the parasitological diagnosis is available,
appropriate treatment as per the species (as given above)
Parenteral artemisinin
derivative (minimum 24
hours) followed by Oral
ACT
(3 days)
Parenteral quinine
(minimum
24 hours) +
oral quinine +
clindamycin (for
7 days)
Parenteral artemisinin derivative
(minimum 24 hours) followed by
Oral ACT
(3 days)
Artemisinin derivatives include:
• Artesunate (i.v. or i.m.)
• Artemether (i.m.)
• Arteether (i.m.)
– Arteether is not recommended
for children
– Doxycycline is contra indicated
in pregnant women and children
under 8 years of age
Contd...
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