Quinine

Quinine is an active ingredient that acts against parasites (antiparasitic), has a muscle relaxing (muscle relaxant) and antipyretic (antipyretic) effect and belongs to the group of antimalarials. Quinine also has a mild analgesic effect. It is used to treat acute malaria attacks and calf cramps of unknown cause (idiopathic). Malaria is transmitted by parasites that enter the body through mosquito bites. Malaria is widespread in Africa, South America and South Asia. Quinine should not be taken to prevent malaria.

Quinine is also used in very small quantities as a bittering agent, for example in tonic water. Quinine is an alkaloid derivative obtained from the bark of the quinine tree. This group of alkaloids is very popular in medicine and is often used for pain therapy. The best-known representatives are morphine, opium, heroin and nicotine. The alkaloids are mainly found in plants. In pharmacy, a derivative is a derivative that is chemically related to a group or another active substance.

Quinine is controversial as a remedy for calf cramps and is therefore not approved in all countries.

Quinine is used against infections caused by Plasmodium, the pathogen that causes malaria. It is effective against the schizonts of Plasmodium. Schizonts are the asexual developmental stage of the Plasmodium pathogen. The malaria pathogens grow in the red blood cells (erythrocytes) and gain energy by breaking down the hemoglobin, the red blood pigment in the blood. This breakdown produces ferriprotoporphyrin IX (FPPIX), which is toxic to the malaria pathogen. FPPIX is converted to non-toxic haemozoin by the malaria pathogen. Quinine prevents this conversion to haemozoin. This increases the number (accumulates) of FPPIX and leads to the death of the pathogens. Quinine is effective against all Plasmodium species and, compared to other drugs, has little resistance.

Quinine is also effective against calf cramps of unexplained cause (idiopathic) by prolonging the refractory period, i.e. the time a cell needs before it can transmit a stimulus again, in the muscle. This reduces the excitability of the cell to stimuli and prevents overexcitation (cramps). In addition, quinine influences the distribution of calcium in the muscle fiber, which in turn increases the stimulus threshold for a muscle reaction. A stronger electrical impulse is therefore required to trigger a muscle reaction.

Quinine is also used as an additive in medicines to combat flu-like infections, as it has both a local anaesthetic and antipyretic effect.

Due to the increasing resistance of pathogens to the more effective and less toxic chloroquine, quinine is being used more frequently again nowadays.

Due to its bitter taste, quinine is used in small quantities in the food industry.

Quinine is broken down almost exclusively via the liver, more precisely via the cytochrome P450 enzymes (mainly via CYP3A4) and excreted via the kidneys. Between 10% and 20% are excreted unchanged by the kidneys (renal). Quinine is 76% - 88% bound to plasma proteins. The half-life of quinine, i.e. the time it takes for half of the drug to be excreted, is approximately 18 hours.

Always take quinine exactly as described in the package leaflet or as advised by your doctor.

The usual dose for the treatment of malaria is 648 mg in tablet form, every 8 hours for 7 days.

The recommended dose for the treatment of calf cramps is 200-400 mg per day. It may take up to 4 weeks for the number of calf cramps to decrease. The need for treatment should be reviewed every 3 months in consultation with the doctor.

Taking excessive doses of quinine can lead to quinine poisoning with the following symptoms:

• Dizziness
• vomiting
• ringing in the ears
• visual disturbances
• Damage to the optic nerve up to and including blindness
• States of agitation
• cyanosis
• Cardiac death due to cardiac arrhythmia (long QT syndrome)
• Death due to respiratory paralysis

The lethal dose of quinine is 8-10 g!

Quinine poisoning can be treated with activated charcoal, sodium sulphate and suitable benzodiazepines such as diazepam.

The following side effects may occur:

Very common:

• Abdominal and stomach cramps
• diarrhea
• Nausea and vomiting

Occasional:

• Agranulocytosis (reduced number of granulocytes (part of the white blood cells))
• Leukopenia (reduced number of leukocytes (part of the white blood cells))
• Thrombocytopenia (reduced number of platelets)
• Black or bloody stools
• Blood in the urine
• Hypoglycemia (low blood sugar)

Rarely:

• Hemolytic-uremic syndrome
• Restriction of kidney function
• Fever and chills
• Increased sweating
• muscle pain
• Hypoprothrombinemia (coagulation disorder)
• Hypersensitivity reactions
• Visual disturbances such as color perception disorders, double vision or night blindness
• Tinnitus (unwanted ringing in the ears, usually whistling)
• Dizziness

Very rare:

• Thrombopenic purpura (blood clotting disorder) - this is an indication of a quinine allergy

Medicines which by themselves frequently cause undesirable cardiac arrhythmias must not be combined with quinine.

These include

• Drugs for the treatment of cardiac arr hythmias such as class Ia and III antiarrhythmics
• drugs for the treatment of mental illnesses such as neuroleptics, tricyclic and tetracyclic antidepressants
• certain antibiotics (macrolide antibiotics, fluoroquinolones, imidazole antifungals)
• antimalarials
• Drugs for chemotherapy (arsenic trioxide)
• Medication for the treatment of allergies (non-sedating antihistamines)
• strong painkillers (opioids)

The effect of the following medicines can be enhanced by quinine:

• Digitalis preparations
• muscle relaxants (muscle relaxants)
• Medication to thin the blood (anticoagulants)

Drugs taken to neutralize stomach acid (antacids) can reduce the absorption of quinine in the intestine.

If taken at the same time as other quinine-containing medicines, the effects of the two may be mutually enhanced.

Urinary alkalinizing drugs and cimetidine can prolong the excretion of quinine.

Quinine must not be taken in the following cases:

• if you are allergic to quinine
• during pregnancy and breastfeeding
• in the case of cardiac arrhythmia, especially if the heartbeat slows down or if the QT is prolonged
• if you are also taking medication that promotes the development of cardiac arrhythmia
• in the case of glucose-6-phosphate dehydrogenase deficiency
• muscle weakness (myasthenia gravis)
• for ringing in the ears (tinnitus)
• damage to the optic nerve
• for severe heart failure (cardiac insufficiency)
• for disorders of the salt balance in the body

Quinine should not be used to treat calf cramps under the age of 18, as no data are available on its use.

For the treatment of malaria, quinine can be used from the age of 16.

According to the package inserts of various medicines, the following applies to quinine:

Quinine must not be taken during pregnancy as it can cause serious malformations in the unborn child.

Quinine must not be taken during breastfeeding as it passes into breast milk.

In the case of malaria, however, treatment is preferable as there are no alternative active ingredients.

The Pharmacovigilance and Advisory Center for Embryonal Toxicology at Charité-Universitätsmedizin (www.embryotox.de) therefore recommends

Pregnancy

In the first trimester of pregnancy, there are several reports of malformations following quinine ingestion. The malformations include deafness and visual disturbances. However, these reports are based on a much higher dose than is usual today.

In the 2nd and 3rd trimester of pregnancy, quinine can trigger contractions and lead to severe hypoglycemia in the mother.

However, because malaria therapy is preferable, quinine is usually administered in combination with clindamycin in the 1st trimester of pregnancy. In the 2nd & 3rd trimester of pregnancy, artemisinin derivatives are administered in combination with other active substances. Quinine should not be used to treat calf cramps. Excessive and regular consumption of drinks containing quinine (e.g. tonic water) should also be avoided.

Breastfeeding

Although there are few reports on the use of quinine during breastfeeding (30 published studies), an increased risk for the newborn is not assumed. Malaria therapy is also to be preferred during breastfeeding. Breastfeeding may continue if treatment is usually short-term.

Quinine has been known as a cure for malaria for several centuries. It was already being used before 1633. Quinine is a natural ingredient found in the bark of the cinchona tree. The indigenous peoples of South America already used quinine as a fever-reducing medicine.