Isoniazid

Isoniazid is one of the most effective drugs for fighting the pathogens of a serious disease like tuberculosis, regardless of the form and location of the latter. But tuberculosis is considered one of the most common infectious diseases in the world, which affects both animals and humans. And the disease can be infected in various ways: airborne during verbal communication with a sick person or being with him in close proximity, while eating meat affected by an animal or contaminated food, by direct contact with a bacterial infection, in utero.

If there is no vaccination or vaccination without taking contraindications into account, getting tuberculosis will not be difficult, but getting rid of it is much more difficult. That's where Isoniazid comes to the rescue.

[1], [2], [3], [4], [5],

Indications Isoniazid

In most cases, tuberculosis covers the respiratory system, preferring lungs, bronchi, pleura.

Isoniazit treatment is indicated for any active form of pulmonary tuberculosis: dissiminated, miliary, focal, infiltrative, cavernous, fibrous-cavernous, cirrhotic, with caseous pneumonia and tuberculosis (caseous tuberculosis).

Slightly less often, tuberculosis affects joints and bones in the spine. In some cases, doctors diagnose other types of tuberculosis affecting the gastrointestinal tract (mainly the small intestine and the "blind" gut), the genitourinary system (kidneys, urinary tract, genital organs), the brain and the central nervous system (the brain itself and the spinal cord, the hard membrane of the brain, when it is said that tuberculous meningitis develops), eyes, skin, lymph nodes. In these cases, therapy with this drug may also be prescribed.

Indications for the use of the drug "Isoniazid" are considered various forms in which tuberculosis can occur. It can be both primary (during infection into the body) and secondary (complication of already existing pathology) infection, acute and chronic active form of pathology, open and closed tuberculosis.

Isoniazid is used for preventive purposes:

• To prevent the disease in people who had to contact active TB patients with patients,
• If there is a positive reaction to tuberculin in the form of redness and densification after grafting larger than 5 mm, and the x-ray confirms the presence of a non-progressive process,
• If the response to a tuberculosis test in children under 4 years old is greater than 1 cm and there is a possibility of further development of the inflammatory process in the lungs or other organs.

For the treatment of tuberculosis, the drug is most often prescribed as part of complex therapy. If there is a mixed infection, antibiotics and other medicines are added to anti-tuberculosis drugs.

Sometimes Isoniazid is used for other purposes, for example, for the destruction of dogs. This is due to the fact that in high dosages the preparation has a high toxic effect.

[6], [7], [8],

Release form

The main active substance of the preparation "Isoniaad" is a white powder with a bitter aftertaste and the same name, which has a selective effect on the bacteria that cause tuberculosis.

There are following forms of release of the anti-TB medication Isoniazid:

• Tablets with a dosage of 100. 200 and 300 mg
• 10% isoniazid solution in ampoules (volume 5 ml)
• Substance-powder for the preparation of solution.

Tablets with a different dosage containing isoniazid plus auxiliary substances (surfactant polysorbate 80, calcium stearate, crospovidone, tablet dissolving potato, potato starch) are packaged in 10 pieces in blisters that can be placed in cardboard boxes (5 to 100 blisters each ).

On sale it is possible to meet and tablets "Izoniazid" in a glass dark jar (the number of tablets - 100 pcs.).

The injection solution contains 500 mg of the active ingredient. In the role of excipient is water for injection. Produced in cardboard boxes of 10 ampoules each.

Powder for the preparation of the solution is not intended for home use. It is packed in large polyethylene bags. The net weight of the bag with powder is 25 or 50 kg.

In the pharmacy you can buy tablets and injections. But for this you need a prescription from the doctor with his signature and stamp, as well as the stamp of the medical and preventive institution.

[9], [10], [11], [12], [13]

Pharmacodynamics

"Isoniazid" is a popular remedy for tuberculosis based on the isonicotinic acid derivative.

The culprit for the development of various forms and types of tuberculosis is mycobacterium (Mycobacterium tuberculosis). It is with respect to this type of bacteria that the active substance of the drug shows bactericidal action, while it belongs to other microorganisms neutrally. Chemotherapeutic action against other infectious agents is poorly expressed.

Isoniazid pays particular attention to mycobacteria, which are in a state of active reproduction, which occurs by dividing cells. It is assumed that the drug negatively affects the synthesis of mycolic acids, which are constituents of the bacterial cell wall, as a result of which microorganisms perish.

[14], [15], [16], [17], [18]

Pharmacokinetics

Isoniazid is characterized by almost complete absorption after ingestion in the digestive tract with peroral administration. It easily falls into all kinds of tissues and body fluids, and also has a unique ability to penetrate the protective (hematoencephalic) barrier of the brain, having a bactericidal effect against bacteria that enter the brain.

Before reaching the maximum concentration of the drug in the blood plasma should pass from 1 to 4 hours tablets, and its effect on pathogenic microorganisms after a single dose can last from 6 to 24 hours.

Metabolized isoniazid in the liver by acetylation, In this case, inactive substances are formed. The drug is excreted from the body mainly by the kidneys. The half-life of the drug is:

• with rapid metabolism, which is a physiological feature of patients, from half an hour to an hour and a half,
• at a slow one - on the order of 2-5 hours,
• severe renal impairment can reach 6 and even 7 hours.

[19], [20], [21], [22], [23], [24]

Dosing and administration

The introduction of the preparation "Isoniazid" can be carried out in various ways:

• oral (tablets for internal administration),
• intravenously
• intramuscularly
• by inhalation
• intracavernous method, when the solution is delivered directly to the affected area, where necrotic processes are observed.

Selection of an effective method is handled by the attending physician. He also determines the effective dose of the drug, as well as the duration of the therapeutic course, based on the severity of the disease, the condition and age of the patient.

The purpose and correction of the dose of the drug is carried out taking into account the characteristics of the patient's organism, due to the rapid or slow removal of isoniazid through the blood and urine, in connection with which it may be necessary to increase the dosage or the frequency of reception.

Dosage also depends on the method of administration of the drug and is calculated based on the patient's body weight.

Treatment with tablets for oral administration. The recommended average daily dose for adult patients is 15 mg per kilogram of body weight. With this dosage, the drug should be taken once every 2-3 days. Sometimes prescribed daily intake of tablets in a maximum daily dosage of 300 mg.

For children, an effective daily dose can vary from 20 to 40 mg per kg of body weight, provided that the drug is taken 2 or 3 times a week. If the medicine is taken daily, the daily dose will be 10-20 mg.

The frequency of admission will depend on the rate of metabolism of isoniazid in the liver. The course of treatment is quite long, it can reach 6 months.

Prevention of tuberculosis is carried out only with the help of tablets. The recommended daily dose is 5-10 mg per 1 kg of the patient's weight. Tablets are taken once or twice a day.

If with active forms of tuberculosis the patient can not use oral means, for example, in connection with gastrointestinal pathologies, he is prescribed intravenous or intramuscular injections. Injection method of drug administration is recommended for the treatment of adult patients with different types and forms of tuberculosis, but it is not excluded in the therapy of small patients.

The effective single dose for intramuscular administration for adults is 5 mg per 1 kg of body weight. The injections should be done once a day.

Another treatment regimen is possible, when injections are done once every 2-3 days. Then a single dose is already 15 mg per kilogram of the patient's weight.

For children, an effective single dose will be from 20 to 40 mg per kilogram of weight (for the regimen once every 2-3 days) and 10 to 20 mg (for daily intake once a day).

Intravenous injection of the drug "Isoniazid" is indicated in the prevalent forms of pulmonary tuberculosis with an increased level of infectiousness. The daily dosage for adults is 10-15 mg per 1 kg of body weight. After the administration of the drug, the patient is recommended to stay in bed for about 1-1 ½ hours.

For intra-cavernous injection with forms of pulmonary tuberculosis with the formation of necrotic sites, and also as preparation for surgery, the same 10% solution of the drug is used as for intravenous and / or injections. The effective dosage is 10-15 mg per kilogram of body weight of the patient.

Inhalation 10% solution is done daily. The daily dose at the same time will be 5-10 mg per 1 kg of weight. The daily dose is sometimes recommended to be divided into 2 divided doses.

In order to reduce the manifestations of side effects, in parallel with the introduction of "Isoniazid" is carried out therapy "Pyridoxine" (60-100 mg) and glutamic acid (1-1.5 g per day).

The course of treatment usually lasts from 1month to six months, preventive course - about 2 months.

[31], [32], [33], [34], [35], [36], [37]

Use Isoniazid during pregnancy

Use of the preparation "Izoniazid" during pregnancy means taking the medicine in a limited dosage (no more than 10 mg per 1 kg of the body weight of the future mother) and strictly according to the doctor's indications. Exceeding the dose is fraught with intoxication of the fetus in the womb, the consequences of which can be the most diverse, but unambiguously unpleasant.

Contraindications

It is forbidden to conduct tuberculosis therapy with Isoniazid if the patient has the following pathologies:

• Expressed forms of arteriosclerosis of vessels, in which the deposition of harmful cholesterol in the lumen of the arteries is observed
• Various serious liver pathologies, including cases of toxic hepatitis occurring earlier
• Severe renal insufficiency
• The presence in the patient's history of convulsive seizures or epilepsy
• Children's spinal paralysis, known to many as polio

The dosage of the drug is limited in such diseases as

• Hypertension (stably high blood pressure values) 2 and 3 stages
• CHD
• Bronchial asthma
• Destruction (cirrhosis) of the liver
• Acute stage of eczema
• Various pathologies of the visual and peripheral nerves
• Psoriasis
• Common atherosclerosis
• Myxedema, or mucus edema, which is the last stage of thyroid insufficiency
• And also at the stage of decompensated pulmonary heart.

Do not use the drug as a solution for injection with inflammation of the wall of venous vessels (phlebitis).

The drug is not administered if the patient has a hypersensitivity to its individual components.

Pregnancy and children's age are not contraindications to the use of an antituberculous drug.  

[25], [26], [27], [28],

Side effects Isoniazid

Therapy with Isoniazid is not always cloudless. Sometimes there are various side effects on the part of the organs and systems of the body.

Cardiovascular system can respond to the introduction of the drug:

• increased blood pressure, including pulmonary pressure,
• heart pains,
• increased heart rate,
• symptoms of angina pectoris,
• strengthening of ischemic processes in the cardiac muscle.

The nervous system can give its symptoms in the form of:

• intoxication psychosis,
• generalized convulsive seizures, characteristic of epilepsy,
• tingling and numbness of various parts of the body, paralysis of the limbs,
• pain in the head and dizziness,
• multiple lesions of nerves due to intoxication with the use of large doses of the drug,
• inflammation or decreased function of the optic nerve,
• organic brain damage of non-inflammatory nature, called encephalopathy,
• increased excitability,
• irritability and insomnia,
• peripheral nerve congestion
• temporary partial memory loss, etc.

From the gastrointestinal tract can expect the following unpleasant effects:

• nausea accompanied by vomiting,
• dryness of the mucous membranes of the mouth,
• Hepatitis, caused by the toxic effect of the drug,
• increased activity of some enzymes (ALT and AST) and increased production of bilirubin,
• the initial symptomatology of developing hepatitis,

Genitourinary system will remind you:

• rare cases of menorrhagia (profuse menstruation) in women,
• dysmenorrhea (severe soreness accompanying menstrual flow),
• increase and swelling of the mammary glands in women and men.

There are also various changes in the composition and properties of blood, skin allergic reactions, fever, short-term muscle spasms, manifested in the form of twitching, inflammation of the venous wall with intravenous administration, muscle weakness, etc.

[29], [30],

Overdose

The phenomenon of an overdose of Isoniazid may occur if the therapy is performed at high dosages, most often through the patient's own fault, who believes that increased doses will accelerate recovery.

Single intake of large doses can cause the development of such pathologies as:

• metabolic acidosis (increased acidity of the body),
• severe epileptic seizures,
• coma.

Light intoxication will make itself felt after half an hour after taking the drug in the form of increased heart rate, nausea and vomiting, dizziness and speech disorders.

In the case of acute intoxication (20 mg or more per 1 kg of weight), its manifestations will be immediately apparent in the form of epileptic seizures.

In this case, the following reactions are observed: an increase in body temperature, a drop in blood pressure, the appearance of acetone in the urine, an increase in blood sugar and urine, kidney failure, psychosis, ataxia, hallucinations.

In severe cases coma occurs for a period of 1 to 1.5 days.

With prolonged therapy at maximum doses, a chronic overdose occurs, which leads to a decrease in the number of active hepatocytes. First it manifests itself in the form of an increase in the parameters of AST and ALT, and then in some cases it is diagnosed the development of hepatitis that affects the liver.

It is not excluded also against the background of treatment with increased doses and the appearance of other pathologies. For example, optic neuritis with impaired visual perception or polyneuropathy as a result of peripheral nerve damage. There is a polyneuropathy loss of sensitivity of hands and feet, muscle weakness, ataxia.

With mild intoxication, it may only be necessary to adjust the dose of the drug and wash the stomach with the subsequent intake of activated carbon. The development of medicinal hepatitis requires the withdrawal of the medicine.

If the effects of intoxication are clearly expressed and accompanied by convulsive seizures, a disturbance in the metabolism of acids, coma, intravenous sodium bicarbonate is used as a first aid. To remove the remains of isoniazid from the gastrointestinal tract, reception of enterosorbents, in particular activated charcoal, is shown.

Neurological symptoms require other treatment. To reduce it, use "Pyridoxine" (both for prevention and treatment of overdose) and benzodiazepines ("Diazepam"). "Pyridoxine" is administered in the same dosage as isoniazid. If the dosage of Isoniazid was not determined, the dose of "Pyridoxine" for adults will be from 5 to 10 mg (for children - at the rate of 80 mg per 1 kg of body weight).

[38], [39], [40], [41], [42]

Interactions with other drugs

Parallel administration of Paracetamol, Enflurane and Rifampicin with isoniazid therapy can increase the toxic effects of these drugs on the liver, which increases the risk of developing hepatitis. This combination is especially dangerous for patients with various liver pathologies.

But ethanol is able to accelerate metabolism and increase the hepatotoxicity of isoniazid itself. They are able to accelerate metabolism and reduce the concentration of isoniazid in the blood and glucocorticosteroids.

"Isoniazid" reduces the metabolism of "Theophylline", "Ethosuximide", "Phenytoin", "Carbamazepine", "Alfentanil", benzodiazepines, coumarin or indanedione derivatives and anticoagulants of indirect action, as a result of which their concentration in the blood and therapeutic effect can significantly increase. This increases the toxic effect of drugs.

The intake of "Isoniazid" along with other drugs from tuberculosis ("Cycloseril", etc.) causes mutual reinforcement of their actions. Strengthens the central action of isoniazid and an agent for the treatment of alcohol dependence "Disulfiram."

"Isoniazid" is able to reduce the concentration to the blood plasma "Ketoconazole" and increase the content of valproic acid in the blood, which requires dose adjustment.

With oral administration, antacids to reduce the acidity of gastric juice can reduce the absorption of isoniazid.

"Pyridoxine", "Diazepam", "Thiamin" and glutamic acid can reduce the neurotoxic effect of isoniazid.

[43], [44], [45], [46], [47], [48], [49]

Storage conditions

So the tablets and ukuporenny in jars of dark glass powder can be stored at room temperature (not above 25 degrees) and preferably away from the light.

But ampoules with a solution require maintaining the storage temperature no higher than 10 degrees. Keep them also recommended away from sunlight. 

Solutions prepared from powder are also stored at temperatures up to 10 degrees. 

[50], [51], [52], [53], [54], [55],

Shelf life

Tablets shelf life of 6 years, provided that they are properly stored.

Ampoule shelf life is 2 years, provided it is properly stored.

The solution period of freshly prepared Isoniazid solutions is only 1-2 days.

[56], [57],