Quinine

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Chapter: Essential pharmacology : Antimalarial Drugs

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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