What Are the Pros and Cons of Taking Quinine for Malaria?

Quinine, commonly known as cinchona cream, is the main alkaloid in the bark of the Rubiaceae family of cinchona and its genus, chemically known as cinchona. In 1820, PJ Pertier and JB Carpentou first produced pure products. It was a theobromine and 4-methoxyquinoline antimalarial agent and a fast blood schizont killer.

Chinese name:

Chinese alias: Cinchona cream; Cinchona base; Guining; Cinchona base;

English name: quinine

English alias: Chinin; Cinchonan-9-ol, 6'-methoxy-, (8, 9R)-; Cinchonan-9-ol, 6'-methoxy-, (8alpha, 9R)-; Kinin; Kinidin-d3; Quinina ; (R)-(6-Methoxyquinolin-4-yl) ((1R, 2R, 4R, 5S) -5-vinylquinuclidin-2-yl) methanol; QUININE; chinine; Pitayin-d3; Quineine; Quinie;

CAS number: 130-95-0

MDL number: MFCD00198096

EINECS number: 205-003-2

RTECS number: VA6020000

BRN number: 91867

PubChem number: 24848751

Molecular formula: C ₂₀ H ₂₄ N ₂ O ₂

Structural formula:

Malaria was once an epidemic disease in tropical and subtropical regions and has claimed thousands of lives. Indians in South America have discovered that the bark of the cinchona tree can cure malaria. They peeled the bark and dried it into powder to treat malaria. The Indians strictly guarded the secrets of the "Cinchona", stipulating that if anyone leaked the secret of this medicine to foreigners, they would be severely punished.

It is said that in the 17th century, an Earl of Spain brought his beloved wife, Ena, to Lima, Peru. Unfortunately, his wife contracted malaria, and an Indian girl took care of her. Seeing her condition was getting worse, she decided to treat her quietly. The count counted everything she did quietly. He thought that the Indian girl was going to murder his wife and punish her. She had to tell the secret of the "golden tree". After Ena healed, the Spaniards returned to Europe with this bark.

At the end of the 17th century, quinine was introduced into China from Europe and was once called "Cinchona Cream", which was a very rare medicine at that time. Later, Swedish scientist Linaius conducted a careful study of the bark of this plant, and extracted the effective ingredients, named "quinine". The word "quinine" means bark in Peruvian script. With the increase in the medical demand for quinine, it is hoped that this natural medicine can be manufactured artificially. Huffman, a British chemist, imagined that quinine could be made from a derivative of kerosene, with no success. It was not until 1945 that quinine was artificially synthesized ^[1]

Quinine pharmacological action

This medicine is a quinoline derivative, which has a strong killing effect on the erythrocytic schizonts of various plasmodium parasites. The drug can combine with the DNA of Plasmodium to form a complex, inhibit the replication of DNA and the transcription of RNA, thereby inhibiting the protein synthesis of the protozoa, but its effect is weaker than that of chloroquine. This medicine can also reduce the oxygen consumption of Plasmodium, inhibit the phosphorylase in Plasmodium and interfere with its glucose metabolism. The drug also causes agglutination of malaria pigment, but it develops slowly and rarely forms large clumps. In blood, a certain concentration of this drug can cause premature rupture of parasitic red blood cells, thereby preventing schizont from maturing. This medicine is not effective in the infrared phase and cannot cure benign malaria. Long course of treatment can cure malaria, but it has no direct effect on the gametophyte of malaria, so it cannot be interrupted. In addition, the drug has an inhibitory effect on the myocardium, which can prolong the refractory period, slow down conduction, and weaken its contractile force. It has a weak excitatory effect on the pregnant uterus. ^[2]

Quinine pharmacokinetics

Oral absorption is rapid and complete, and the plasma concentration reaches a peak within 1 to 3 hours. The drug is distributed in systemic tissues after absorption, with the highest concentration in the liver, followed by lung, kidney, and spleen, and the least in skeletal muscle and nerve tissue, with a protein binding rate of about 70%. The drug is oxidized and decomposed in the liver, and its metabolites and a small amount of the original drug (about 10%) are excreted by the kidney. It appears in the urine 15 minutes after taking the drug and is almost completely discharged after 24 hours. The half-life is 8.5h.

Quinine indications

For the prevention and treatment of chloroquine-resistant malaria, cerebral malaria, vivax, etc. ^[2]

Quinine contraindications

Disabled by pregnant women, quinine has a oxytocin effect, can cause fetal hearing damage and congenital defects of the central nervous system and limbs through the placenta. Use with caution in lactating women.
It should be used with caution in patients with asthma, atrial fibrillation and other serious heart diseases, glucose-6-phosphate dehydrogenase deficiency, myasthenia gravis, and optic neuritis.
Cardiomyopathy and pregnant women are prohibited. ^[2]

Quinine usage and dosage

Adults: (1) Oral administration: Treatment of chloroquine-resistant malaria: use quinine sulfate, 300-600 mg each time, 3 times a day for 7 days; control the symptoms of vivax malaria: this drug is no longer the first choice. If necessary, take quinine bisulfate, 480 mg each time on the first day, 360 mg each time from the second day, 3 times a day for 7 days. (2) Intravenous infusion: Severe (such as cerebral malaria) in chloroquine-resistant malaria: Quinine dihydrochloride can be added to 500ml sodium chloride injection at 5-10mg / kg (maximum amount 500mg). Repeat after 12h. After the condition improved, changed to oral.
Children: (1) Oral administration: treatment of chloroquine-resistant malaria: use quinine sulfate for 10 days. Take 2 to 3 times a day, and the daily doses are based on age: 100 200mg for those under 1 year old; 200 300mg for those 1-3 years old; 300 500mg for 4 6 years old; 500 for 7 11 years old 1000mg. (2) Intravenous drip: severe (such as cerebral malaria) in chloroquine-resistant malaria: same as adults. ^[2]

Quinine adverse reactions

Quinine drinks Quinine daily dosage of more than 1g or long-term use often causes cinchona response, which is similar to the salicylic acid response. It has symptoms such as tinnitus, headache, nausea, vomiting, and vision and hearing loss. In severe cases, temporary deafness occurs. It can often recover after stopping the drug; When the dose is greater than 4g within 24 hours, it can directly damage the nerve tissue and constrict the retinal blood vessels, resulting in reduced visual field, diplopia, amblyopia, etc. In case of large doses of poisoning, in addition to the above-mentioned reaction, due to the inhibition of myocardium , Dilation of peripheral blood vessels caused a sudden drop in blood pressure, slower and shallower breathing, fever, irritability, delirium, etc., and most died of respiratory paralysis; Quinine fatal amount is about 8g; A few patients are highly sensitive to quinine, a small amount is Can cause severe cinchona response; A small number of patients with falciparum can cause acute hemolysis (black urine fever) death with a small amount of quinine; quinine can also cause rash, itching, asthma, etc.

Leukopenia, headache, dizziness, tinnitus, can cause gastrointestinal reactions: nausea and vomiting, loss of appetite, bloating, diarrhea. Vision is blurred (double vision), and hearing is reduced. Specific cases of acute hemolysis, angioedema, bronchial asthma. When the dose is too large, cardiogenic collapse, tachycardia, dyspnea, and pregnancy may cause miscarriage. Photosensitivity. Breathing is difficult in severe overdose and death.

[Cardiovascular system] Long-term use of normal amount or excessive amount in highly sensitive people, QRS broadening, ST prolongation, T wave changes, conduction disturbances or ventricular tachycardia can be seen on the ECG. Severe poisoning can occur with circulatory collapse.

[Respiratory system] Allergic asthma can occur, and quinine poisoning can cause respiratory depression.

[Nervous System] Headache, tinnitus, dizziness can occur, and poisoning can cause convulsions and coma. Myopathy can also occur.

[Digestive system] Nausea is common, and excessive pain can cause abdominal pain and diarrhea. Granulomatous hepatitis occurred in one case, and manifested as fever, nausea, vomiting, and polyarticular pain.

[Urinary system] Renal failure can occur when quinine is poisoned, possibly due to circulatory failure.

[Hematopoietic system] Thrombocytopenia can occur, and even sensitive people can have thrombocytopenia, thrombocytopenic purpura, or acute intravascular hemolysis with renal damage or renal failure. Hemolytic anemia can occur during quinine treatment, the so-called black water fever. Granulocytopenia can occur in individual cases.

[Endocrinology, Metabolism] Quinine can reduce blood sugar, even hypoglycemia, and increase blood insulin concentration.

[Special organs] Black haze is the most serious adverse reaction. The most obvious symptoms are reduced vision and vision loss, which can be recovered after stopping the drug. Early application of stellate ganglion closure is effective in treating dark haze. In acute quinine poisoning, pupil dilation first occurs, and there is a response to light. In some cases, pupils may show peristaltic motion, and then vision is completely lost. Most patients are transient and a few are permanently blind. Tinnitus is common in quinine overdose, and continuous long-term application can cause permanent hearing impairment.

[Skin] Quinine rash is a manifestation of allergic reactions. Some people are allergic to sunlight. Topical application of quinine can cause contact dermatitis and photosensitivity.

Quinine precautions

1. Use with caution: (1) lactating women; (2) asthma patients; (3) patients with atrial fibrillation and other severe heart diseases; (4) patients with glucose-6-phosphate dehydrogenase deficiency; (5) myasthenia gravis Patients; (6) patients with optic neuritis.

2. The effect of drugs on test values or diagnosis: can interfere with the determination of 17-hydroxysteroids.

3. Because the effect of the interaction between malaria and chronic liver disease on the plasma free quinine concentration cannot be predicted, patients with liver disease should be particularly careful in using this drug, and the ECG should be closely monitored to check for the extension of the QT interval.

4. When treating severe malaria in children, it is recommended to monitor blood concentrations. ^[2]

Quinine interaction

Urine basifying drugs, such as sodium bicarbonate, can increase reabsorption of the drug by renal tubules, leading to an increase in blood concentration and toxicity of the drug.
Quinidine is used in combination with this drug to increase cinchona response.
Cimetidine can slow the excretion of this drug, extend the half-life by 49%, and thus increase the toxicity.
Combining this medicine with buclizine, syclizine, meclizine, phenothiazines, thioxanthenes, and trimethofenzamide can cause tinnitus and dizziness.
In combination with cardiac glycoside, the concentration of cardiac glycoside in plasma of some patients is significantly increased (such as the blood concentration of digoxin increased by 60%), which is prone to toxic reactions.
Hypoglycemic drugs combined with this drug can cause severe hypoglycemia.
Muscle relaxants (such as succinylcholine, cylindricin, etc.) in combination with this drug can cause respiratory depression.
Vitamin K can increase the absorption of this medicine.
Combined with nifedipine (nifedipine), the concentration of the free drug increases.
This medicine can reduce the metabolism rate of flucarney by up to 19%.
Rifampicin can reduce the blood concentration and efficacy of this drug.
Antacids and aluminum-containing preparations can delay or reduce the absorption of this medicine.
Anticoagulant combined with this medicine can enhance anticoagulant effect. ^[2]

Clinical manifestations of quinine poisoning

1. Common oral adverse reactions include headache, dizziness, dizziness, loss of appetite, nausea, vomiting, abdominal pain, diarrhea, pruritus, rash, tinnitus, and irritability. Long-term application of normal or excessive amounts may cause more severe cardiac reactions. On the electrocardiogram, QRS wave widening, QT prolongation, T wave change, conduction disturbance or ventricular tachycardia may occur. Cyclic collapse may occur in severe cases. Renal failure may be caused by circulatory failure.

2. When intoxicated in large doses or administered intravenously, due to myocardial depression and peripheral vasodilation, blood pressure can drop suddenly, breathing becomes slower and shallower, fever, irritability, or delirium.

3. Cinchona poisoning syndrome: A small number of patients are allergic to this product, and a small amount can cause this syndrome: tinnitus, headache, dizziness, visual impairment, and dizziness syndrome. Severe cases can cause cardiac conduction disorders, ventricular tachycardia, abdominal pain, diarrhea, respiratory depression, renal dysfunction, and temporary deafness.

4. Quinine Hemon is the most serious adverse reaction. The pupils dilate first and reflections of light are present. The most obvious manifestation is reduced vision and even vision loss. Fundus examination showed narrowing of the arteries, which generally recovered after stopping the drug, and a few patients were permanently blind.

5, a small number of patients with falciparum use of this product can occur acute intravascular hemolysis, black urine fever with renal impairment or renal failure.

6, granulocytopenia or thrombocytopenia occurred in individual patients. Rare anaphylactic shock occurs. It has the effect of stimulating the uterine wall and causing miscarriage of pregnant women.

7, toxic amblyopia is that the human body absorbs foreign toxic substances to degeneration of the optic nerve fibers, causing power disorders. The clinical manifestations of toxic amblyopia are well known, but little is known about the pathogenesis of toxic optic neuropathy. Generally, it occurs in both eyes, and it often invades the optic nerve or retinal ganglion cell layer below the optic cross, so there is no blindness visual field change. ^[2]

Quinine poisoning measures

1. Patients with abnormal electrocardiogram or cinchona syndrome should stop the drug immediately and be given symptomatic supportive treatment.

2. In addition to drug withdrawal in the early stages of Heimeng, stellate nerve closure can be applied.

3, intravascular hemolysis, black urine fever, immediately discontinued. Absolute bed rest, intravenous injection of glucose and low-molecular glycans to improve microcirculation; 250-500ml intravenous drip of 5% sodium bicarbonate to prevent renal tubular obstruction; application of adrenocortical hormone to control hemolysis; severe anemia can be transfused as appropriate. Patients with acute renal failure should be treated accordingly.

4. After oral quinine is completely absorbed and distributed to the tissue, it can be effectively purified by hemoperfusion treatment. Renal failure can be hemodialysis or peritoneal dialysis. ^[2]

Quinine Expert Reviews

This product was once an antimalarial drug to control the symptoms of malaria, but because of its weak effect and many adverse reactions, it is not often used as an antimalarial drug. It is only used for patients with malignant malaria that are resistant to chloroquine and is also used at night. Seizures of the gastrocnemius muscle. Because quinine is better absorbed orally, it is usually administered orally, and it is administered intravenously only to rescue patients with cerebral malaria. ^[2]