Antimalarial drug
Antimalarial drugs are designed to prevent or cure
alaria. Some
antimalarial agents, particularly
chloroquine and
hydroxychloroquine, are also used in the treatment of
rheumatoid arthritis and
lupus associated arthritis. There are many of these drugs currently on the
market. uinine
is the oldest and most famous anti-malarial.
Quinine
uinine
has a long history stretching from
eru, and the
discovery of the
inchona
tree, and the potential uses of its bark, to the current day and a collection of
derivatives that are still frequently used in the prevention and treatment of
malaria. Quinine is an
lkaloid
that acts as a blood
schizonticidal and weak
ametocide
against
Plasmodium vivax and
Plasmodium malariae. As an alkaloid, it is accumulated in the food
acuoles of
plasmodium species, especially
Plasmodium falciparum. It acts by inhibiting the
emozoin
biocrystallization, thus facilitating an aggregation of
cytotoxic heme. Quinine is less effective and more toxic as a blood
schizonticidal agent than
Chloroquine; however it is still very effective and widely used in the
treatment of acute cases of severe P. falciparum. It is especially useful
in areas where there is known to be a high level of resistance to Chloroquine,
efloquine
and
sulfa drug combinations with
pyrimethamine. Quinine is also used in post-exposure treatment of
individuals returning from an area where malaria is
endemic.
The treatment regimen of Quinine is complex and is determined largely by the
parasite�s level of resistance and the reason for drug therapy (i.e. acute
treatment or prophylaxis). The
World Health Organization recommendation for Quinine is 8mg/kg three times
daily for 3 days (in areas where the level of adherence is questionable) and for
7 days (where parasites are sensitive to Quinine). In areas where there is an
increased level of resistance to Quinine 8mg/kg three times daily for 7 days is
recommended, combined with
Doxycycline,
Tetracycline or
Clindamycin. Doses can be given by oral,
intravenous or
intramuscular routes. The recommended method depends on the urgency of
treatment and the available facilities (i.e. sterilised needles for IV or IM
injections).
Use of Quinine is characterised by a frequently experienced syndrome called
inchonism.
innitus (a
hearing impairment), rashes,
vertigo, nausea, vomiting and abdominal pain are the most common symptoms.
Neurological effects are experienced in some cases due to the drug�s
neurotoxic properties. These actions are mediated through the interactions
of Quinine causing a decrease in the excitability of the
otor
neuron
end plates. This often results in functional impairment of the eight
cranial nerve; resulting in confusion,
elirium
and coma. Quinine can cause
hypoglycaemia through its action of stimulating
nsulin
secretion, this occurs in therapeutic doses and therefore it is advised that
glucose levels are monitored in all patients every 4-6 hours. This effect can be
exaggerated in pregnancy and therefore additional care in administering and
monitoring the dosage is essential. Repeated or over-dosage can result in
enal
failure and death through depression of the
respiratory system.
Other Alkaloids
Quinimax and
uinidine
are the two most commonly used alkaloids related to Quinine, in the treatment or
prevention of Malaria. Quinimax is a combination of four alkaloids (namely
Quinine Quinidine Cinchoine and Cinchonidine). This combination has been shown
in several studies to be more effective than Quinine, supposedly due to a
synergistic action between the four Cinchona derivatives. Quinidine is a direct
derivative of Quinine. It is a
distereoisomer, thus having similar anti-malarial properties to the parent
compound. Quinidine is recommended only for the treatment or severe cases of
malaria.
Chloroquine
Chloroquine was until recently the most widely used anti-malarial. It was
the original prototype from which most other methods of treatment are derived.
It is also the least expensive, best tested and safest of all available drugs.
The emergence of drug resistant parasitic strains is rapidly decreasing its
effectiveness; however it is still the first-line drug of choice in most
sub-Saharan African countries. It is now suggested that it is used in
combination with other antimalarial drugs to extend it�s effective usage.
Chloroquine is a
4-aminoquinolone compound with a complicated and still unclear mechanism of
action. It is believed to reach high concentrations in the vacuoles of the
parasite, which, due to it�s alkaline nature, raises the internal
H. It controls the
conversion of toxic
heme to
hemozoin by inhibiting the
biocrystallization of
emozoin
thus poisoning the parasite through excess levels of toxicity.
Other potential mechanisms through which it may act include interfering with the
biosynthesis of parasitic
ucleic
acids, the formation of a chloroquine-haem or chloroquine-NA
complex. The most significant level of activity found is against all forms of
the schizonts (with the obvious exception of chloroquine-resistant P.
falciparum and P. vivax strains) and the
ametocytes
of P. vivax, P. malariae,
P. ovale as well as the immature gametocytes of P. falciparum.
Chloroquine also has a significant
anti-pyretic and
anti-inflammatory effect when used to treat P. vivax infections, thus
it may still remain useful even when resistance is more widespread. According to
a report on the Science and Development Network website's sub-Saharan Africa
section, there is very little drug resistance among children infected with
malaria on the island of Madagascar, but what drug resistance there is, exists
against chloroquinine.
Children and adults should receive 25mg of chloroquine per kg given over 3
days. A
pharmacokinetically superior regime, recommended by the WHO, involves giving
an initial dose of 10mg/kg followed 6-8 hours later by 5mg/kg, then 5mg/kg on
the following 2 days. For
chemoprophylaxis: 5mg/kg/week (single dose) or 10mg/kg/week divided into 6
daily doses is advised. It should be noted that chloroquine is only recommended
as a prophylactic drug in regions only affected by P. vivax and sensitive
P. falciparum strains. Chloroquine has been used in the treatment of
malaria for many years and no
abortifacient or
teratogenic effects have been reported during this time, therefore it is
considered very safe to use during pregnancy. However,
tching can occur
at intolerable level.
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