Nitroglycerin - instructions for use, dose, side effects, contraindications

Bazodilating agent from the group of nitrates. Nitrates are able to release from their molecule nitric oxide, which is a natural endothelial relaxing factor - a mediator of the direct activation of guanylate cyclase. An increase in the concentration of cyclic guanosine monophosphate results in the relaxation of smooth muscle fibers, predominantly venules and veins.

Has antianginal and spasmolytic effect, relaxes the smooth muscles of the vascular walls, bronchi, gastrointestinal tract, bile ducts, ureters.With intravenous administration, a rapid decrease in preload on the heart is caused by the widening of the peripheral veins. Reduces the flow of blood to the right atrium, helps to reduce pressure in the small circle of blood circulation and regression of symptoms with pulmonary edema; reduces postnagruzku, the need for myocardium in oxygen (due to reduced preload, postnagruzki and stress of the walls of the ventricles due to a decrease in the volume of the heart). Promotes the redistribution of coronary blood flow to the zones of the ischemic myocardium. Has a central inhibitory effect on the symptomatic vascular tone, inhibiting the vascular component of the pain syndrome. Causes the expansion of cerebral vessels, which explains the headache when taking the drug.

Pharmacokinetics:

Getting into the systemic bloodstream, 60% binds to blood plasma proteins. It has high lipophilicity, has a large volume of distribution (3.3-1.2 l / kg). Rapidly metabolized in the liver by glutathione reductase, which affects organic nitrates, with the formation of di- and mononitrates (only isosorbide-5-mononitrate is active), the final metabolite is glycerin. It is excreted by the kidneys in the form of metabolites.The total ground clearance is 30-78 l / min, half-life - 1-3 minutes.

Indications:

- Acute myocardial infarction, incl. complicated by acute left ventricular failure;

- severe forms of angina, incl. unstable and postinfarction angina;

- pulmonary edema, acute heart failure, incl. against a background of hypertensive crisis;

- controlled arterial hypotension during surgical interventions to reduce bleeding in the operating field.

Contraindications:

- Hypersensitivity to the active substance, other organic nitrates or excipients;

- Acute circulatory disturbance (shock, vascular collapse);

- cardiogenic shock (if no measures are taken to maintain the end diastolic pressure);

- severe arterial hypotension (systolic blood pressure (BP) below 90 mm Hg);

- severe hypovolemia;

- severe anemia;

- hypertrophic obstructive cardiomyopathy;

- constrictive pericarditis;

- cardiac tamponade;

- simultaneous administration of inhibitors of phosphodiesterase-5 (including sildenafil, vardenafil, tadalafil);

- age under 18 years (effectiveness and safety not established);

- craniocerebral trauma;

- Isolated mitral stenosis, aortic stenosis, subaortic stenosis;

- toxic pulmonary edema;

- intracranial hypertension;

- Hemorrhage in the brain.

Carefully:

The drug should be used with extreme caution and with careful medical supervision in the following cases:

- low filling pressure of the left ventricle, incl. with acute myocardial infarction (systolic blood pressure below 90 mm Hg should be avoided);

- a violation of the function of the left ventricle (for example, with left ventricular failure);

- tendency to orthostatic disorders of vascular regulation;

- increased intraocular pressure, incl. angle-closure glaucoma;

- severe renal and / or hepatic insufficiency (risk of methaemoglobinaemia);

- thyrotoxicosis;

- diabetes;

- atherosclerosis.

Pregnancy and lactation:

The use of the drug in pregnancy is possible only if the intended benefit to the mother exceeds the possible risk to the fetus and / or child, as prescribed by the doctor and careful monitoring of the condition of the pregnant woman and development of the fetus.

There is information about the penetration of nitrates into breast milk, but the exact content of nitroglycerin in breast milk has not been determined. A possible risk of methaemoglobinemia in infants has also been reported. The decision to stop breastfeeding or stop / refuse treatment should be taken after assessing the benefits of breastfeeding and therapy for the mother.

Dosing and Administration:

Treatment should be conducted in a hospital with an individual choice of the speed of infusion of the drug. The solution is administered via an automatic dispenser or through a conventional system for intravenous infusion.

The automatic dispenser allows the introduction of even undiluted 0.1% solution with accurate dosing of the rate of administration and total dose. The introduction through a conventional system for fluid transfusion provides an accurate dose selection by counting the number of drops of the transfused liquid.

For intravenous administration the following materials are used: polyethylene, polypropylene or polytetrafluoroethylene. Infusion materials made of polyvinyl chloride or polyurethane reduce the effectiveness of the drug as a result of absorption (up to 60%), which must be compensated for by increasing the dose.

The solution is rapidly destroyed in the light, therefore the vials and the transfusion system must be screened with a lightproof material. Usually, an infusion solution with a concentration of 100 or 200 μg / ml is used: the concentrated solution is diluted with 0.9% sodium chloride solution, 5% or 10% dextrose (glucose) solution.

Dilution - see dilution table.

It is recommended to start treatment with a dose of 0.5-1.0 mg nitroglycerin per hour (8-16 μg / min), if necessary, gradually (every 3-5 minutes) increase the dose (depending on the effect and response of heart rate, central venous pressure and systolic blood pressure, which can be reduced by 10-25% of the initial, but should not be less than 90 mm Hg).

If no therapeutic effect is obtained at a rate of 20 μg / min, a further increase in the rate of administration should be 10-20 μg / min. When there is a response (in particular, a decrease in blood pressure), a further increase in the rate of infusion is not carried out or is carried out at longer intervals. The maximum dose is 8 mg of nitroglycerin in tea (133 μg / min), in rare cases 10 mg per hour (166 μg / min).

In severe angina, the dose is 2-8 mg / h (33-133 μg / min).

In hypertensive crisis with cardiac decompensation under constant control of blood pressure and heart rate (HR), infusion is carried out at a speed of 2-8 mg / h (an average of 5 mg / h).

With controlled arterial hypotension, depending on the type of anesthesia and the required level of blood pressure reduction, the dose is 2-10 μg / kg / min.

Dilution table

Number of acting matter nitroglycerin	Dilutions	5 mg	10 mg	20 mg	30 mg	40 mg	50 mg
The volume of the infusion solution to be diluted		5 ml	10 ml	20 ml	30 ML	40 ml	50 ml
The volume of the infusion solution, intended for breeding	1/10	50 ml	100 ml	200 ml	300 ml	400 ml	500 ml
	1/20	100 ml	200 ml	400 ml	600 ml	800 ml	1000 ml
	1/40	200 ml	400 ml	800 ml	1200 ml	1600 ml	2000 ml
The volume of the infusion solution obtained as a result of breeding	1/10	55 ml	110 ml	220 ml	330 ml	440 ml	550 ml
	1/20	105 ml	210 ml	420 ml	630 ml	840 ml	1050 ml
	1/40	205 ml	410 ml	820 ml	1230 ml	1640 ml	2050 ml

* - 0.9% solution of sodium chloride or 5% solution of dextrose (glucose) can be used as an infusion solution for dilution.

Infusion table

Breeding	1/10		1/20		1/40
Required speed introduction of nitroglycerin per hour	Infusion
Required speed introduction of nitroglycerin per hour	ml / hour	drops in mines	ml / hour	drops in mines	ml / hour	drops in mines
0.5 mg	5,5	2	10,5	3-4	20,5	6-7
0.75 mg	8,25	3	15,75	5	30,75	10
1.0 mg	11,0	3-4	21,0	7	41,0	13-14
1.25 mg	13,75	4-5	26,25	8-9	51,25	17
1.5 mg	16,5	5-6	31,5	10-11	61,5	20-21
2.0 mg	22,0	6-7	42,0	14	82,0	26-27
2.5 mg	27,5	9	52,5	17	102,5	34
3.0 mg	33,0	11	63	21	123,0	41
3.5 mg	38,5	12-13	73,5	24-25	143,5	47-48
4.0 mg	44,0	13	84,0	28	164,0	53
4.5 mg	49,5	14-15	94,5	31-32	184,5	59-60
5.0 mg	55,0	18	105,0	35	205	68
5.5 mg	60,5	20	115,5	38-39	225,5	74-75
6.0 mg	66,0	22	126	42	246	82
7.0 mg	77,0	25-26	147	49	287,0	95-96
8.0 mg	88,0	28-29	168,0	56	328,0	108-109
9.0 mg	99,0	31-32	189,0	63	369,0	121-122
10.0 mg	110,0	36	210	70	-	-

Side effects:

To assess the incidence of adverse events, the following criteria were used (according to the classification of the World Health Organization): Often (≥10% of prescriptions); often (≥1% and <10%); infrequently (≥0.1% and <1%); rarely (≥0.01% and <0.1%); rarely (<0,01%); frequency unknown (insufficient data to estimate the frequency of development).

From the central nervous system: Often - headache; often - drowsiness, dizziness, incl. postural.

From the gastrointestinal tract: infrequently - nausea, vomiting; rarely - ofzhoga.

From the cardiovascular system: often - tachycardia, orthostatic hypotension; infrequently - "paradoxical" enhancement of angina attacks, collapse (sometimes accompanied by bradyarrhythmia and syncope); transient hypoxemia allethe relative redistribution of blood flow to hypoventilated alatеолярные sites (at patients with an ischemic illness of heart - can lead to a hypoxia of a myocardium); rarely - cyanosis; frequency unknown - marked decrease in blood pressure, skin hyperemia.

From the skin and subcutaneous tissues: infrequently - skin allergic reactions (including rash); frequency unknown - exfoliative dermatitis.

General disorders: often - asthenia.

Other: infrequently - blurred vision; rarely - methemoglobinemia.

For organic nitrates, there have been cases of development of a marked decrease in blood pressure, accompanied by nausea, vomiting, anxiety, pallor and increased sweating.

Overdose:

Symptoms: a sharp decrease in blood pressure (less than 90 mm Hg) with orthostatic dysregulation, reflex tachycardia, a general feeling of weakness, dizziness and blocking, as well as a throbbing headache, "hot flashes" and redness of the face or upper body, nausea, vomiting and diarrhea.

When using the drug in high doses (more than 20 mg / ml), it is possible to develop methemoglobinemia, collapse, cyanosis, dyspnea and tachypnea; possibly increased intracranial pressure with cerebral symptoms.

Treatment: stopping the introduction of the drug, it is necessary to monitor the function of vital organs. When lowering the blood pressure, lower the head and lift the foot of the bed.As a rule, blood pressure is normalized within 15-20 minutes; After re-selection of the infusion rate, the administration of the drug can be resumed.

With a marked decrease in blood pressure and / or shock, the volume of circulating blood should be increased; in exceptional cases, you can make an infusion of norepinephrine (noradrenaline) and / or dopamine. Contraindicated in the use of eninephrine (adrenaline) and related substances.

With methemoglobinemia, depending on the severity level, ascorbic acid is used in the form of a sodium salt IV / 0.1-0.15 ml / kg 1% solution up to 50 ml; oxygen therapy, artificial ventilation, hemodialysis.

Interaction:

With simultaneous use with other vasodilators, antihypertensive drugs, incl. beta-blockers, slow calcium channel blockers, angiotensin-converting enzyme inhibitors, and type 5 phosphodiesterase inhibitors used to treat erectile dysfunction (for example, sildenafil), procainamide, antipsychotics, tricyclic antidepressants, monoamine oxidase inhibitors (MAO), and also ethanol, hypotensive action may be enhanced.

With the simultaneous use of the drug with dihydroergotamine, there may be an increase in the concentration of dihydroergotamine in the blood, which leads to an increase in its hypotensive effect.

With the simultaneous use of heparin and nitroglycerin, the effect of heparin is weakened. Under the control of blood coagulability indicators, a suitable dose of heparin is selected. After cessation of nitroglycerin infusion, a significant reduction in blood coagulability is possible, which may require a reduction in the dose of heparin.

Ppand simultaneous application of a solution of nitroglycerin and a tissue plasminogen activator, a decrease in the concentration in the blood and a decrease in the efficiency of the latter due to acceleration of hepatic clearance are described.

Sapropterin is a coenzyme of nitric oxide synthetase, which is important to consider, in connection with the occurrence of an increased risk of hypotension, with the simultaneous use of sapropterin with all vasodilating agents that are associated with nitric oxide, including classical donators of nitric oxide (for example, nitroglycerine, isosorbide dinitrate, isosorbide mononitrate, sodium nitroprusside, molsidomine and etc.).

Special instructions:

In order to prevent undesirable blood pressure reduction, you should individually select the rate of administration of the drug, for which it is recommended to control blood pressure and heart rate at least 3-4 times per hour during the entire time of drug administration.

When Nitroglycerin is used, redistribution of blood flow in the lungs is possible, which can lead to hypoxemia and cause transient myocardial ischemia in patients with ischemic heart disease.

After the appearance of the first signs of intolerance, the drug should not be used again.

When treating patients with type 1 diabetes, it should be noted that the solution contains about 5% glucose.

The solution is sterile, does not contain preservatives. Nitroglycerine in ampoules or vials should be opened in aseptic conditions immediately before use.

If the patient has previously been treated with organic nitrates, for example, isosorbide dinitrate, isosorbide-5 mononitrate, then large doses of nitroglycerin may be required to achieve the desired hemodynamic effect.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment and for some time afterwards, care must be taken when driving vehicles and occupying otherpotentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Concentrate for solution for infusion, 1 mg / ml.

Packaging:

To 5, 10 ml into ampoules of colorless neutral glass type I with a color fracture ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. Ampoules can additionally be applied with one, two or three colored rings and / or two-dimensionalsth barcode, and / or alphanumeric encoding or without additional color rings, a two-dimensional barcode, alphanumeric encoding.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film or without foil and without film. Or 5 ampoules are placed in a prefabricated form (gray) made of cardboard with cells for packing ampoules.

1, 2 or 10 contour squares or cardboard grams together with the instructions for use and the scarifier or knife ampoule, or without the scarifier and the ampoule knife are placed in a cardboard package.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003182

Date of registration:07.09.2015

Date of cancellation:2020-09-07

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp10.03.2016

Illustrated instructions

Instructions

Nitroglycerine (Nitroglycerin)