Quinine is the levo rotatory alkaloid obtained from cinchona bark. Its disomer quinidine is used as an antiarrhythmic (and for malaria in some countries).
QUININE
Quinine is the levo
rotatory alkaloid obtained from cinchona bark. Its disomer quinidine is used as an antiarrhythmic (and for malaria in
some countries).
Quinine is an erythrocytic
schizontocide for all species of plasmodia; less effective and more toxic than
chloroquine. Resurgence of interest in quinine is due to the fact that most
chloroquine and multi-drug-resistant strains of P. falciparum still respond to it. However, even quinine-resistance
has been described in certain parts of Southeast Asia and Brazil where quinine
+ tetracycline has been the standard treatment of complicated malaria. Quinine-resistance
has been encountered sporadically in India, particularly along Myanmar border
where in a sample study 6% falciparum malaria cases did not respond
sequentially to chloroquine, S/P and quinine. There is partial cross resistance
between quinine and mefloquine, but many mefloquine-resistant cases respond to
quinine. Though effective in terminating an acute attack of falciparum malaria,
it may not prevent recrudescence — indicating incomplete clearance of the
parasites.
Quinine has no effect
on pre-erythrocytic stage and on hypnozoites of relapsing malaria, but kills
vivax gametes. Like chloroquine, it is a weak base: gets concentrated in the
acidic vacuoles of the blood schizonts and causes pigment changes; inhibits
polymerization of haeme to hemozoin; free haeme or haemequinine complex damages
parasite membranes and kills it. However, the exact mechanism of action is not
known.
Quinine Has Many Other
Actions:
1. Local irritant and anaesthetic Quinine is intensely
bitter and irritant. Orally it causes nausea, vomiting, epigastric discomfort.
Injections can cause pain and local necrosis in the muscle and thrombosis in
the vein. Local inflammation may be followed by fibrosis.
2. Systemic actions Gastric secretion is
increased. Quinine is a weak analgesic and antipyretic; affects hearing and
vision at higher doses. Cardiodepressant, antiarrhythmic and hypotensive
actions are similar to quinidine (see
Ch. No. 38). Rapid i.v. injection can produce marked fall in BP and
cardiovascular collapse.
Quinine directly
decreases contractile power of the muscle fibre. It stimulates the myometrium
and can cause abortion in early pregnancy. However, it is not a dependable
abortifacient. Blood sugar is slightly lowered due to release of insulin from
the pancreas. Rapid i.v. injection of quinine has caused hypoglycaemia.
Pharmacokinetics
Quinine is rapidly and completely absorbed
orally. It is 70% bound to plasma proteins, especially α1 acid glycoprotein.
Such binding increases during acute malarial infection. CSF concentrations are
low. A large fraction of the dose is metabolized in the liver by CYP3A4 and
excreted in urine with a t½ of 10–12 hours. Quinine is noncumulative.
Adverse Effects
Toxicity of quinine is high and dose related; 8–10 g
taken in a single dose may be fatal.
Cinchonism: A large single dose or higher therapeutic
doses taken for a few days produce a syndrome called cinchonism. It consists of
ringing in ears, nausea, vomiting (due to both gastric irritation and CTZ
stimulation), headache, mental confusion, vertigo, difficulty in hearing and
visual defects (due to direct neurotoxicity as well as constriction of retinal
and auditory vessels). Diarrhoea, flushing and marked perspiration may also
appear. The syndrome subsides completely if the drug is stopped.
Poisoning with still higher doses results in the above symptoms
in an exaggerated form. In addition, delirium, fever, tachypnoea followed by
respiratory depression, marked weakness and prostration can occur. Hypotension,
cardiac arrhythmias develop only on rapid i.v. injection — the patient may die.
Few individuals are idiosyncratic/hypersensitive to quinine;
cinchonism may appear after a single therapeutic dose. Purpura, rashes,
itching, angioedema of face and bronchoconstriction may also develop.
Quinine occasionally causes haemolysis, especially in pregnant
women and in patients of falciparum malaria, resulting in haemoglobinuria
(black water fever) and kidney damage.
During pregnancy it should be used only for life-threatening
infection, with special care to prevent hypoglycaemia.
Uses
1. Malaria Quinine is used orally
for uncomplicated chloroquine-resistant malaria, and i.v. for
complicated/cerebral malaria (chloroquine-sensitive or resistant).
· Uncomplicated resistant falciparum malaria: Quinine may be used
orally as an alternative to S/PACT in uncomplicated chloroquine-resistant
falciparum malaria. It acts more rapidly than S/P alone. The 7 day quinine + doxycycline
regimen is the 2nd line treatment of chloroquine-resistant malaria (both
falciparum and vivax) under NVBDCP. Certain chloroquine-resistant strains are
also resistant to S/P, but respond to quinine.
· Complicated and severe malaria including cerebral
malaria: Quinine (i.v.) has been used as the drug of choice for cerebral malaria (falciparum malaria with impaired
consciousness) and other forms of complicated malaria. However, some recent
studies indicate that parenteral artemisinins are faster acting, more effective,
better tolerated and more conveniently administered. Many experts now prefer
i.v./i.m. artesunate/artemether/ arteether over quinine for severe malaria. The
dosage and schedule for i.v. infusion of quinine for severe malaria is given in
the box on p. 784. Hypoglycaemia due to hyperinsulinemia is the most important
side effect: can be prevented by 5% dextrose infusion.
Supportive treatment —
cooling for fever, i.v. diazepam for convulsions, correction of fluid and
electrolyte balance and acidosis is of vital importance. Corticosteroids have
been used but are of no benefit; may be harmful — avoid them.
2. Nocturnal muscle
cramps: a single tablet of quinine (300 mg) at bed time affords benefit in some
but not all cases. It is also effective in myotonia congenita.
3. Diagnosis of
myasthenia gravis: a single dose of quinine precipitates weakness in myasthenia
gravis. However, this provocative test is dangerous — not recommended.
4. Varicose veins:
injected along with urethane, it causes thrombosis and fibrosis of the varicose
vein mass.
REZQ, QSET, QUINARSOL
100, 300, 600 mg tab, 600 mg/2 ml inj.
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