Quinine hydrochloride: formula, instructions for use, effectiveness

Formula "Quinine hydrochloride"

The drug is an organic substance of plant origin, the main component of which is quinine, a universal poison (extracted from the bark of the cinchona tree).

Before a medicinal product goes on sale, a quantitative determination of quinine hydrochloride in terms of dry matter (99%) is mandatory. The composition of the medicine can be visually represented in the form of a formula (see photo below).

The name of the drug “Quinine hydrochloride” in Latin is Chininum, in international practice it is Quinine hydrochloride.

Release form and scope of application

The drug "Quinine" (simplified form of the name) is available in the form of:

• crystalline powder (taken internally and used externally);
• solution in ampoules (administered intravenously);
• in tablets (taken orally).

The drug dissolves in water, alcohol, glycerin, has no distinctive odor, and the taste is concentrated bitterness.

Quinine hydrochloride, as medical practice shows, is used not only in the fight against malaria, but also as:

• antipyretic for pneumonia, typhoid fever, articular rheumatism, smallpox;
• a substance that improves digestion for diphtheria, tuberculosis, typhoid, pleurisy;
• anticonvulsant during epileptic seizures, chorea;
• sedative for neuralgia;
• antimycotic medicine for whooping cough;
• antiparasitic agent for intestinal infectious diseases;
• antimicrobial substance for colds, flu;
• effective remedy against hair loss;
• wound healing agent for external use.

In addition, the drug “Quinine hydrochloride” is applicable in obstetrics, oncology and cardiology. The versatility of this medicine is so wide that it is almost impossible to completely abandon its use in modern medicine.

If today quinine can be replaced with other drugs in the treatment of simple forms of malaria, then in other cases without its use it is not possible to effectively fight diseases. The use of Quinine hydrochloride in cases of chemoresistance to new generation drugs is the only method of saving human life.

Indications for use

For what diseases is quinine prescribed?

1. Now it is prescribed for the development of malaria that is not treatable with other drugs.
2. Analgin-Quinine tablets are used to get rid of headaches. In this combination, the medicine works better, affecting many causes of pain. Plus, these are two drugs in one - with an antipyretic and analgesic effect.
3. In gynecology, quinine salts were used to enhance or induce labor and to contract the uterus.
4. Previously, it was used in cardiology to correct various heart rhythm disturbances: with extrasystole (extraordinary contractions of the heart muscle), to reduce attacks of tachycardia (rapid heartbeat).
5. As a sedative for neuralgia and neuroses.
6. In gastroenterology, quinine tablets were used to stimulate the secretion of the gastric glands.

Today, quinine is gradually being forgotten, since there are many analogues with fewer side effects. But even now it remains a backup option for all the above-mentioned conditions and diseases.

Pharmacological properties of the drug and its effectiveness

The widespread use of this drug in medicine is explained by the property of quinine to stimulate the viability of a living organism at the cellular level, increase its resistance to various diseases, and stimulate immune reserves. It is quickly absorbed into the gastrointestinal tract and begins to act within half an hour after administration.

The drug has an irreversible effect:

• on metabolic intramuscular processes that help relax the muscles of the patient’s body;
• on the excitability of nerve endings;
• to thermoregulatory centers;
• to reduce the excitability of the heart muscles;
• to stimulate labor in women.

The effectiveness of quinine against protozoal infection, which results in malaria, is high. The toxic substance has a gametocidal effect on plasmodia and inhibits the reproduction of single-celled microorganisms.

Contraindications

When prescribing quinine, you must carefully read the instructions, because the medicine is contraindicated for certain diseases.

1. Quinine is not prescribed for the prevention of malaria; in this case, it is absolutely ineffective.
2. It is contraindicated for diseases of the inner and middle ear.
3. If you develop an allergy to the previous administration.
4. If there are liver and kidney dysfunctions. Especially, older people should refrain from using the medicine.
5. Do not use during pregnancy or breastfeeding, since the alkaloid quinine easily penetrates the placenta and into the mother's breast milk. This can harm the baby, unless its prescription is necessary for health reasons.
6. It is not prescribed to people with congenital heart diseases, so as not to provoke rhythm disturbances.
7. In case of severe liver and kidney diseases, it is better to replace it with another medicine.

Now in medicine, quinine is used only by infectious disease specialists for severe forms of malaria, which cannot be treated with other safer analogues. Gynecology has already abandoned it. But several decades ago it was an almost ideal drug for the correction and treatment of many diseases.

Dosage

Since the drug “Quinine hydrochloride” is intended to a greater extent to combat malarial infections - Plasmodium vivax, Plasmodium malaria, Plasmodium falciparum, the instructions for this medicinal product contain only recommendations for taking the latter when the corresponding symptoms appear. The dosage of the medicine for other purposes is strictly controlled by the attending physician on an individual basis, assessing the pros and cons of its use.

Thus, for manifestations of malaria, the drug is prescribed orally in a dose of 0.25-0.5 grams, the daily dose should not exceed 1 gram per day. You can take quinine capsules, tablets and powder. In case of complex disease, the drug is prescribed intramuscularly or subcutaneously.

It is permissible to increase the dosage of the drug for tropical malaria. In this case, the dose threshold should not exceed 1.5 grams of the medicinal product per day.

Theory of action

The reason why quinine helps to lower the temperature in some febrile diseases, especially malaria, is now more or less understood.

In view of the fact that a decrease in temperature under the influence of quinine, as experiments on feverish animals show, also occurs when the animals are wrapped in cotton wool, and, consequently, when heat transfer from the skin is very difficult, it must be recognized that the alkaloid acts directly on a decrease in the heat-generating ability of the body, and not an increase in heat transfer from the skin. Moreover, sweating, as mentioned above, even stops completely when taking the medicine.

This is also supported by the fact that under the influence of quinine, nitrogen metabolism in the body decreases. Experiments of one scientist (Kerner) on himself show that the excretion of nitrogen in the urine, even with small doses of the alkaloid, is noticeably reduced. After a single daily dose of 0.93-1.24 g, nitrogen excretion, according to Kerner, decreases by 25%. This is explained by the fact that the proteins of the cells and tissues of our body, from contact and combination with quinine, become more resistant to oxygen, as a result of which they (the proteins) are more difficult to oxidize and decompose.

As for the effect of quinine in malaria, it has now been established that the substance directly kills malaria parasites - plasmodium, which causes fever. If you examine the blood of a malaria patient under a microscope after taking the drug, you will notice that plasmodia after some time lose their mobility and die.

Thus, quinine eliminates parasites from the blood of malaria patients; therefore, it acts here in the same way as during the processes of rotting and fermentation, which was discussed above.

Possible side effects

The drug containing quinine is not intended for independent use. When using it, precautions should be taken. It should be noted that even mandatory testing of the authenticity of “Quinine hydrochloride” in laboratory conditions before using it in medical practice does not guarantee the absence of side effects after taking it from the vital systems of the patient’s body.

Side effects of quinine include:

• allergic reaction;
• disruption of the functioning of the digestive system;
• decrease in blood glucose to a critical level;
• stimulation of contractile activity of the uterus;
• renal failure;
• hives;
• intense feverish state;
• decreased blood pressure;
• visual and hearing impairment;
• speech disorders;
• dizziness and headache;
• insomnia;
• violation of muscle contractile function.

Too high doses of the drug can cause death. Before taking quinine, each patient should undergo a sensitivity test to the components of the drug.

Physiological action of quinine

There is no commercially available pure alkaloid; there are only its salts, of which quinine sulfate and hydrochloride are, as mentioned above, most widely used in medical practice.

As for the question of which of these two compounds is more effective, then, according to Professor Binz, preference should be given to the hydrochloride, as it contains more active substance than sulfate, and therefore has a better effect than the latter. When starting to consider the physiological effect of the cinchona alkaloid, it should be noted that everything said below applies exclusively to its salts, namely hydrochloride and sulfate.

Experiments show that cinchona has a retarding effect on fermentation and putrefactive processes. According to the observations of Professor Binz, it is enough to add a certain amount of 0.2% solution of quinine hydrochloride or sulfate to the medium subject to decay to prevent putrefactive decomposition. The substance has the same effect on many fermentation processes, especially alcoholic fermentation and the formation of lactic and butyric acids in sugar.

The anti-rotten and anti-fermentation properties of quinine can be explained only by the harmful effect of this alkaloid on lower organisms that cause rotting and fermentation processes: bacteria and yeast.

Rossbach claims that even a weak solution (0.2%) of cinchona peel extract has a more toxic effect on lower organisms than alkaloids such as atropine and morphine.

As for the physiological effect of quinine on the body of higher animals, the numerous observations made in this direction boil down to the following.

The quinine solution is not absorbed through intact skin, but is very easily absorbed through all mucous membranes, as well as through wounds and subcutaneous injections.

In the stomach, due to the presence of hydrochloric acid in the digestive juice, the drug in question, taken in powder form, dissolves very easily and is absorbed through the mucous membrane into the blood. Quinine sulfate and hydrochloride are more difficult to dissolve in the intestines, since the bile secreted by the liver forms poorly soluble bile salts with it. But the majority of the drug taken orally is absorbed through the gastric mucosa and enters the blood.

The reverse excretion of quinine from the body occurs mainly in the urine. Just 10 minutes after administration, the substance begins to be excreted in the urine, and this excretion continues for 12 hours, and after this period, not even traces of the drug taken remain in the body. Professor Manasein’s observation is worthy of note that quinine lingers longer in the body of feverish patients than in the body of healthy people. In the first, with the help of very sensitive reagents, it is possible to determine traces of the drug in the urine even after two or three days after administration.

Effect on the digestive organs

Due to its bitter taste, quinine, even in strong dilution (1:10,000), affects the endings of the taste nerves in the mouth, as a result of which salivation increases. The bitter taste lingers in the mouth for a long time and does not go away soon after rinsing the mouth with water.

Increased salivation and retention in the mouth occur if the medicine is taken in the form of powders (not in wafers).

According to some authors, repeated doses of quinine cause an increased feeling of hunger and an increase in digestive ability. Others, in particular Nothnagel, deny the direct effect of the alkaloid on increasing appetite and explain the observations of the above authors by the fact that with the elimination, under the influence of the drug, of high fever and painful conditions, the appetite and digestion that disappeared due to extreme heat can be restored by themselves. Thus, quinine has only an indirect effect on appetite and digestion.

Effect on blood

When large doses of quinine hydrochloride or sulfate are introduced into the body, red blood cells (erythrocytes) increase in volume, since under the influence of the drug the hemoglobin in the blood binds to a large amount of oxygen.

White blood cells - leukocytes, like the bacteria, ciliates and other lower animals mentioned above, lose their characteristic mobility from the action of even very small amounts of a weak solution of quinine.

Experiments with subcutaneous injection of quinine into the body of cold-blooded animals show that the release of white blood cells (leukocytes) from the blood vessels and the formation of pus stop when even a weak solution of the drug is administered, and the process of pus formation stops due to dysfunction of the cells themselves.

The spleen (the main source of formation of blood cells) shrinks under the influence of the drug and becomes dense and hard, if before it was flabby and sluggish.

Effect on the heart

As for the effect of quinine on the activity of the heart (blood circulation), then, like other alkaloids, the drug in question causes an increase in heart rate and an increase in blood pressure, but to a much lesser extent than, for example, morphine. The above applies to average doses of the drug (from 0.31 to 0.62 g). On the contrary, large doses (from 1.24 to 1.86 g) slow and weaken cardiac activity in both healthy and febrile people.

When high doses of an alkaloid are administered orally, the weakly pulsating heart stops beating altogether, and death occurs. From this it is easy to conclude that quinine is far from a safe drug that can be taken in any quantity without first consulting a doctor.

Effect on body temperature

In completely healthy (not febrile) people and animals, body temperature, under the influence of quinine hydrochloride or sulfate, undergoes very slight fluctuations. Even after large doses (1.24 to 1.86 g) of this alkaloid, body temperature in healthy people decreases by only a few tenths (0.5-0.6 °) of a degree, but it is worth noting the fact that sweating in healthy people , under the influence of large doses of the drug, decreases or even stops altogether, despite the summer heat. Cinchona has a different effect on body temperature in feverish people.

Observations by various authors show that not all febrile diseases have the same antipyretic effect on body temperature. In one series of such diseases, a medicinal substance is capable of lowering the temperature by 2-3 or more degrees, while in another it only slightly lowers the temperature, and sometimes even has no effect on it at all.

Let us consider separately the effect of hydrochloric acid and sulphate of quinine on each of the mentioned groups of febrile diseases:

1. For fever caused by putrefactive blood poisoning (sepsis), according to Binz, Manasein and other competent authors, the substance causes an improvement in the general condition of the body and a decrease in temperature, but such an improvement occurs only after excessively large doses, often threatening the patient’s life. However, one cannot expect great success from this medicine in case of putrefactive blood poisoning, since no one has yet managed to cure at least one case of sepsis with large doses of the drug.
2. In case of erysipelas, the effect of quinine on fever, according to many researchers, is very insignificant.
3. Also, the effect of the alkaloid on fever in acute forms of articular rheumatism is extremely negligible.
4. In relapsing fever, quinine also has almost no effect on fever.
5. In smallpox and other febrile rash diseases, the substance has a beneficial effect only in some cases, but not always.
6. The drug works successfully on mild forms of puerperal fever, but severe cases are not cured.
7. With typhoid fever, the temperature, under the influence of large doses, decreases in many cases, but not in all.
8. For lobar pneumonia (pneumonia) and other purulent-necrotic lung diseases, large doses of quinine have a strong antipyretic effect; however, no one has yet observed inhibition of further development of the inflammatory process.

Quinine for malaria

All researchers unanimously agree that quinine is the most effective remedy for malaria (swamp fever, intermittent fever). All cases of disease respond to a greater or lesser extent to the action of the alkaloid, and no other antipyretic agent exhibits such an effective effect. But the drug has such a beneficial effect on malaria only in large dosages (from 0.93 to 1.86 g per dose); at lower doses no significant decrease in temperature is noticeable.

The antipyretic effect of quinine continues until it is completely eliminated from the body, that is, at least 12 hours.

From everything that has been said about the antipyretic effect of quinine sulfate or hydrochloride in various febrile diseases, it is easy to see that the substance, although it lowers the temperature in many diseases of an inflammatory nature, is most effective and, so to speak, specific, in only one disease, namely malaria.

Effect on the nervous system

Not all people are equally sensitive to quinine. Some tolerate relatively large doses of this alkaloid, without noticeable disturbance from the nervous system; others, on the contrary, are so sensitive to the drug that it is enough to take 0.93-1.24 g of this substance for neurological symptoms to immediately appear.

In such subjects, after taking a more or less significant dose of quinine, there is at first a significant improvement in well-being, but this condition is soon replaced by decreased sensitivity, tinnitus and confusion. The tinnitus gets worse, the acuity of hearing becomes dull, and sometimes various auditory hallucinations appear. The pupils dilate slightly, and the field of vision seems as if in a fog.

Severe quinine intoxication in most cases is accompanied by severe headache, dizziness and a feeling of strong pulsation of the carotid arteries; patients feel apathetic, drowsy and feel some kind of weakness throughout the body. All these phenomena disappear, however, after a few hours, if, of course, further intake of quinine hydrochloride or sulfate is stopped, but tinnitus and headache remain for a longer time.

If a dose of cinchona alkaloid of 1.866 or 3.732 g was initially taken, or the above doses were continued to be given to the patient, despite the appearance of neurological symptoms, then the attacks of cinchona intoxication reach even greater intensity:

• the gait becomes shaky, unsteady,
• delirium appears, a confusion of ideas appears,
• in very serious cases it even comes to: speech disorders,
• complete muteness,
• deafness.

But even in these cases, with the cessation of taking quinine, recovery soon occurs, only deafness and visual impairment can sometimes last for a very long time, even for years.

With even larger doses (7.464-11.196 g), general paralysis and convulsions can occur, usually ending in death.

All of these phenomena of quinine intoxication are explained by the fact that quinine, like other alkaloids, has a direct effect on brain cells.

Effect on skin

With long-term use of quinine, many patients may develop various skin rashes in the form of pinpoint redness (roseola), scarlet spots, and sometimes even eczema.

There is also a cessation of sweating in the hot season, even in people engaged in physical labor.

Symptoms and treatment for overdose

If the recommendations are not followed according to the introduced standards of the drug, cases of overdose are possible. The patient's critical condition may be accompanied by the following symptoms:

• headache;
• blood pressure surges;
• physical weakness;
• labored breathing;
• sudden loss of vision;
• convulsive muscle contraction;
• heart failure.

First aid in case of overdose primarily comes down to flushing the gastrointestinal tract; in case of cardiac arrest, specialists resort to resuscitation measures.

What can replace the drug?

Synonyms for the drug “Quinine hydrochloride” are:

• "Quinine dihydrochloride";
• "Quinine sulfate";
• "Chinna tincture";
• “Alcohol cinchona tincture”;
• "Water cinchona tincture."

Analog drugs, which are often used in medical practice as an alternative to drugs with quinine, belonging to the group of antimalarials:

• "Delagil";
• "Plaquenil";
• "Immard";
• "Hydroxychloroquine."

Since quinine is a toxic substance, today pharmacies dispense the drug “Quinine hydrochloride” by prescription. Due to the filling of the pharmaceutical market with new antimalarial drugs, the share of drugs containing quinine is constantly decreasing, although their effectiveness has long been proven and confirmed.