Quinine, an alkaloid obtained from the bark of cinchona tree and the levorotatory isomer of quinidine, is an antimalarial agent. Its chemical formula is 6'-methoxycinchonan-9-ol and its molecular formula is C₂₀H₂₄N₂O₂.H₂O.

Quinine is a blood schizonticidal agent and is active against the asexual erythrocytic forms of P. falciparum, P. malariae, P. ovale and P. vivax. The drug is not active against sporozoites or preerythrocytic or exoerythrocytic forms of plasmodia. Quinine is also gametocytocidal for P. malariae and P. vivax, but has no direct activity against the gametocytes of P. falciparum.

Quinine, a cinchona alkaloid, acts primarily as a blood schizonticide. Its antimalarial action is unclear. It was once believed to be due to the intercalation of the quinoline moiety into the DNA of the parasite, thereby reducing the effectiveness of DNA to act as a template, as well as depression of the oxygen uptake and carbohydrate metabolism of plasmodia. More recently it is thought that pH elevation in intracellular organelles of the parasites by quinine plays a role in the mechanism.

Quinine is known to accumulate in the acid food vacuoles of malarial parasites and may inhibit the parasite enzyme hemepolymerase. This enzyme allows the incorporation of heme, which is toxic to the parasite, into insoluble (and apparently inert) crystalline material hemozoin.

Because quinine is active only against the asexual erythrocytic forms of plasmodia, the drug cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria and cannot provide a radical cure in malaria caused by these species since they have exoerythrocytic stages. Therefore, primaquine phosphate may be indicated in conjunction with quinine if the drug is used for treatment of P. vivax malaria..

Quinine is readily absorbed orally, mainly from the upper small intestine. Bioavailability is approximately 80% in healthy subjects. Absorption is almost complete, even in patients with marked diarrhoea. Quinine is ~ 70% to 85% protein bound.

Quinine is widely distributed into body tissues. Small amounts of the drug are distributed into bile and saliva.

The cinchona alkaloids are primary metabolized in the liver. 5% is excreted unaltered in the urine. There is no accumulation in the body upon continued administration.

The plasma elimination half life of quinine reportedly averages 8 - 21 hours in adults with malaria and 7 - 12 hours in healthy or convalescing adults. In children 1 - 12 years of age, the plasma elimination half life of quinine reportedly averages 11 - 12 hours in those with malaria and 6 hours in those convalescing from the disease.

Quinine is extensively metabolized, mainly in the liver (> 80%). The metabolites are excreted in the urine, mainly as hydroxy derivatives; small amounts also appear in the feces, gastric juice, bile and saliva. Renal excretion of quinine is twice as rapid when the urine is acidic as when it is alkaline; greater tubular reabsorption of the alkaloidal base occurs in an alkaline medium.

The pharmacokinetics of quinine are affected by malarial infection, with volume of distribution and systemic clearance decreasing. Also, protein binding increases to > 90% in patients with cerebral malaria, in pregnant patients and in children.

Quinine is indicated for the treatment of chloroquine resistant falciparum malaria, either alone, with pyrimethamine and a sulfonamide, or with a tetracycline. It is also considered alternative therapy for chloroquine sensitive strains of P. falciparum, P. malariae, P. ovale and P. vivax.

Quinine is contraindicated in patients hypersensitivity to quinine, in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, optic neuritis, tinnitus, history of black water fever and thrombocytopenic purpura (associated with previous quinine ingestion), pregnancy

Because thrombocytopenic purpura may occur during therapy with quinine in highly sensitive patients, a history of this adverse hematologic effect with previous administration of quinine is also a contraindication for use of the drug.

Cinchonism - Repeated doses or overdose of quinine may precipitate cinchonism. The mildest symptoms include tinnitus, headache, and nausea and slightly disturbed vision, which usually subside rapidly upon discontinuation of the drug. When quinine is continued or after large single doses, symptoms also involve the GI tract, the nervous and cardiovascular systems and the skin.

Patients should be warned to discontinue the drug and contact a physician if tinnitus, hearing loss, rash or visual disturbances occur during quinine therapy.

Tinnitus and impaired hearing - These may occur at plasma quinine concentrations > 10 mcg/ml, a level not normally attained with quinine 260 to 520mg/day. In a hypersensitive patient, as little as 300mg may produce tinnitus.

Hemolysis (with the potential for hemolytic anemia) - This has been associated with G-6-PD deficiency in patients taking quinine. Stop therapy immediately if hemolysis appears.

Cardiac disease - Use with caution in patients with cardiac arrhythmias; quinine has quinidine like activity. In patients with atrial fibrillation, quinine use requires the same precautions as those for quinidine. May cause cardiotoxicity. Rapid IV administration of quinine dihydrochloride has resulted in severe hypotension, arrhythmias and acute circulatory failure.

Hypersensitivity reactions - Discontinue quinine if there is any evidence of hypersensitivity. Cutaneous flushing, pruritus, skin rashes, fever, gastric distress, dyspnea, ringing in the ears and visual impairment may occur, particularly with only small doses of quinine. Extreme flushing of the skin accompanied by intense, generalized pruritus is most common. Hemoglobinuria and asthma are idiosyncratic.

Quinine should be avoided in patients with myasthenia gravis as it may aggravate their condition.

It is important that when quinine is given intravenously it should be given by slow infusion and the patient observed closely for signs of cardiotoxicity.

Blood glucose concentrations should also be monitored. Both the disease itself and the administration of quinine may promote insulin secretion and induce hypoglycemia.

Aluminum containing antacids may delay or decrease absorption of concurrent quinine

Cimetidine may reduce quinine's oral clearance and increase its elimination half life.

Do not use mefloquine concurrently with quinine. If these agents are to be used in the initial treatment of severe malaria, delay mefloquine administration > 12 hours after the last dose of quinine. ECG abnormalities or cardiac arrest may occur. The risk of convulsions may also be increased with coadminstration.

Rifamycins, potent inducers of hepatic microsomal enzymes, increased the hepatic clearance of quinine. Enzyme induction can persist for several days following discontinuation of the rifamycin.

Urinary alkanizers administered concurrently with quinine may increase quinine blood levels with potential for toxicity.

Quinine may depress the hepatic enzyme system that synthesizes the vitamin K-dependent clotting factors and thus may enhance the action of warfarin and other oral anticoagulants.

Digoxin, serum concentrations may be increased by concurrent quinine. Monitor digoxin levels periodically.

Quinine may potentiate the effects of neuromuscular blocking agents, particularly pancuronium, succinylcholine and tubocurarine, which may result in respiratory difficulties.

Although increases in plasma concentrations of astemizole and its desmethyl metabolite also occurred in patients receiving astemizole concomitantly with food products containing quinine (e.g. tonic water), such increases were small and were not associated with clinically or statistically significant prolongation of the QT interval when consumption was limited to approximately 1 liter of tonic water a day (about 80mg of quinine sulphate).

Although interactions between terfenadine and quinine have not been reported to date, specific drug interaction studies have not been reported to date, specific drug interaction studies have not been performed to rule out the possibility of a clinically important interaction and concerns have existed that terfenadine may interact with quinine in a similar fashion to astemizole since both antihistamines undergo metabolism via hepatic microsomal enzymes and have been reported to produce similar cardiac effects. During postmarketing surveillance, adverse cardiac effects that included cardiac arrest, ventricular tachycardia, syncope and cardiac torsades de pointes were reported in atleast one patient receiving terfenadine and quinine as components of multiple-drug therapy.

Cinchona alkaloids, including quinine, reportedly may depress the hepatic synthesis of vitamin-K dependent coagulation factors and the resulting hypoprothombinemic effect may enhance the caution of warfarin and other oral anticoagulants. Quinine reportedly may interfere with the anticoagulant action of heparin; however, the clinical importance of this effect is unclear.

There is an increased risk of inducing ventricular arrhythmias if quinine is given together with halofantrine or other arrythmogenic drugs such as amiodarone, cisapride and the antipsychotic pimozide.

As quinine stimulates the release of insulin from islet cells, diabetic control may be compromised.

Elevated values for urinary 17-ketogenic steroids may occur with the Zimmerman method.

Cardiovascular - Anginal symptoms, conduction disturbances, ventricular tachycardia, severe hypotension, arrhythmias and acute circulatory failure.

CNS - Tinnitus, deafness, vertigo, headache, fever, apprehension, restlessness, confusion, syncope, excitement, delirium, hypothermia, convulsions, dizziness.

GI - Nausea, vomiting, epigastric pain, hepatitis, GI disturbance.

Hematologic - Acute hemolysis, hemolytic anemia, thrombocytopenic purpura, agranulocytosis, hypoprothrombinemia .

Hypersensitivity - Cutaneous rashes (urticarial, papular, scarlatinal), pruritus, flushing, sweating, facial edema, asthmatic symptoms.

Ophthalmic - Visual disturbances, including disturbed color vision and perception; photophobia, blurred vision with scotomata, night blindness, amblyopia, diplopia, diminished visual fields, mydriasis, optic atrophy .

Miscellaneous - Cinchonism, vasculitis, hypoglycemia, lichenoid photosensitivity, granulomatous hepatitis, hepatocellular cholestatic hepatotoxicity, renal failure associated with coagulopathy and quinine-dependent antibodies.

Intramuscular injections of quinine can be irritant and have caused pain, focal necrosis, and abscess formation; tetanus have developed in some patients.

Quinine can be given by the oral, intravenous or intramuscular routes.

Quinine should be given orally for the treatment of uncomplicated multidrug resistant falciparum malaria and to complete the treatment of patients with severe or complicated malaria who are initially treated parenterally. If part or all of a dose is vomited within 1 hour, the same amount must be readministered immediately. It is administered parenterally to patients with severe or complicated malaria who cannot take drugs by mouth because of coma, convulsions or vomiting.

Areas where parasites are sensitive to quinine: Quinine, 8 mg of base per kg three times daily for 7 days.

Areas where parasites are sensitive to both sulfa drug-pyrimethamine and quinine, and where adherence may be a problem: Quinine, 8 mg of base per kg three times daily for 3 days plus Sulfadoxine 1 500 mg or sulfalene 1500 mg plus pyrimethamine 75 mg given on the first day of quinine treatment.

Areas with marked decrease in susceptibility of P. falciparum to quinine: Quinine 8 mg of base per kg three times daily for 7 days plus doxycycline 100 mg of salt daily for 7 days (not in children under 8 years of age and not during pregnancy); a pharmacologically superior regimen would include a loading dose of 200 mg of doxycycline followed by 100 mg daily for 6 days. Or Tetracycline 250 mg four times daily for 7 days (not in children under 8 years of age and not in pregnancy). Or Clindamycin 300 mg four times daily for 5 days (not contraindicated in children and pregnancy).

Intravenous administration - An initial dose of 16.4mg (equivalent to 20mg of dihydrochloride)/Kg is infused over 4 hours followed by 8.2mg (equivalent to 10mg of dihydrochloride)/Kg every 8 hours in adults and every 12 hours in children. The initial dose should be halved if the patient has received quinine, quinidine or mefloquine during the previous 12-24 hours. The maintenance dose should be reduced threefold in patients with impaired renal function.

Where facilities for intravenous infusion does not exist, quinine can be administered intramuscularly in the same dosage. The required dose should be divided equally between two sites, one in each anterior thigh.

Whenever parenteral quinine is used, oral treatment should be resumed as soon as the patient is able to take it, and continued for the completion of the course.

Symptoms : The more common signs and symptoms are tinnitus, dizziness, skin rash and GI disturbance (intestinal cramping). With higher doses, cardiovascular and CNS effects may occur, including headache, fever, vomiting, apprehension, confusion, and convulsions

Fatalities with quinine have occurred from single oral doses of 2 to 8g; a single fatality reported with a dose of 1.5g may reflect an idiosyncratic effect. Several cases of blindness following large overdoses of quinine, with partial recovery of vision in each instances have been reported .

Treatment : Employ gastric lavage or induce emesis. Support blood pressure and maintain renal function; provide mechanical ventilation if needed. Use sedatives, oxygen and other supportive measures as necessary. Maintain fluid and electrolyte balance with IV fluids.

Urinary acidification will promote renal excretion of quinine; however, in the presence of hemoglobinuria, acidification of the urine may augment renal blockade. Quinine is readily dialyzable by hemodialysis or hemoperfusion.

Angioedema or asthma may require epinephrine, corticosteroids or antihistamines.

In the acute phase of toxic amaurosis caused by quinine, IV vasodilators may have a salutory effect. Stellate block also has been used effectively for quinine associated blindness. Residual visual impairment occasionally yields to vasodilators.

Store in cool dry dark place.

Cinkona 600 - 10 x 10's
Cinkona 300 - 10 x 6's
Cinkona 100 - 10 x 10's
Cinkona Suspension - 30 x 60ml
Cinkona Injection - 5 x 2ml