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

The effects of nitroglycerin are due to its ability to release from its molecule nitric oxide, which is a natural endothelial relaxing factor. Nitric oxide increases the intracellular concentration of cyclic guanosine monophosphatase, which prevents the penetration of calcium ions into the smooth muscle cells and causes their relaxation. Relaxation of the smooth muscles of the vascular wall causes vasodilation, which reduces the venous return to the heart (preload) and resistance to a large circulation (postload).This reduces the work of the heart and the need for myocardium in oxygen. Expansion of the coronary vessels improves coronary blood flow and promotes its redistribution in the area with reduced blood circulation, which increases the delivery of oxygen to the myocardium.

Reduction of venous return leads to a decrease in filling pressure, an improvement in the blood supply of the subendocardial layers, a decrease in pressure in the small circle of circulation and a regression of symptoms in pulmonary edema. Nitroglycerine has a central inhibitory effect on sympathetic vascular tone, inhibiting the vascular component of the formation of pain syndrome. Nitroglycerine smooth muscle cells of bronchi, urinary tract, gall bladder, bile duct, esophagus, small and large intestine, as well as their sphincters.

The action of nitroglycerin with sublingual application begins quickly, the effect develops within 1-1.5 minutes and lasts about 30 minutes.

Pharmacokinetics:

Nitroglycerin spray is quickly and completely absorbed from the oral cavity into the systemic circulation. Bioavailability is 100% with sublingual admission, since the "primary" hepatic degradation of the drug is excluded. The maximum concentration in the blood plasma is reached after 4 minutes.The connection with plasma proteins is 60%. Rapidly metabolized with the participation of nitrate reductase, 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 25-30 l / min. After taking the drug under the tongue, the elimination half-life from the blood plasma is 2.5-4.4 minutes. Circulating nitroglycerine is firmly connected with erythrocytes and accumulates in the walls of the vessels. The main way to excrete nitroglycerin is the extraction of metabolites with urine; less than 1% of the dose is released unchanged.

Indications:

Angina pectoris (relief and prevention of seizures, including before physical exertion).

Contraindications:

Hypersensitivity to nitrates; collapse; shock; age under 18 years (lack of sufficient clinical data); simultaneous use of phosphodiesterase inhibitors of the fifth type of PDE-5 (including sildenafil, vardenafil, tadalafil and other PDE-5 inhibitors); severe arterial hypotension (systolic blood pressure below 90 mm Hg); cardiogenic shock (unless measures are taken to maintain the end diastolic pressure); angina pectoris,the hypertrophic obstructive cardiomyopathy; constrictive pericarditis; tamponade of the pericardium; acute myocardial infarction and chronic heart failure with low filling pressure of the left ventricle; severe stenosis of the aortic and / or mitral valve, primary pulmonary hypertension (since hyperemia of insufficiently ventilated alveolar zones can lead to hypoxia), any condition associated with increased intracranial pressure.

Carefully:

Use with caution in orthostatic hypotension, hemorrhagic stroke, severe renal and / or hepatic insufficiency, thyrotoxicosis, alcohol abuse, epilepsy, craniocerebral trauma, occlusive glaucoma (risk of increasing intraocular pressure), migraine, severe anemia; special attention and observation is required in the treatment of patients prone to developing orthostatic hypotension, as well as with increased intracranial pressure.

Pregnancy and lactation:

The use of nitroglycerin during pregnancy and during breastfeeding requires careful comparison of risk and benefit and should be performed under strict medicalobservation.

Isolation of nitroglycerin in breast milk is not established.

Dosing and Administration:

The drug is recommended to use as directed by the doctor to avoid complications.

At the first signs of an attack of angina, depending on the severity, enter Nitroglycerine as follows: preferably in the "sitting" position 0.4-0.8 mg (1-2 doses) by pressing the dosing valve is applied to or under the tongue, with respiratory arrest at intervals of 30 seconds; then close your mouth for a few seconds. If necessary, re-administration, but not more than 1.2 mg (3 doses) for 15 minutes.

If necessary, to stop the attack, angina pectoris is repeated again at 5-minute intervals.

If after receiving three metered doses within 15 minutes of relief did not come, you need a doctor's consultation.

For preventive purposes 1 dose is administered 5-10 minutes before the expected load or stress.

Before use, do not shake the package, keep it on spraying vertically, directly in front of you. After each spraying, close the mouth, do not swallow at once.

The highest single dose: 3 doses.

Each press on the dosing valve releases one dose (0.4 mg nitroglycerin) in the form of a spray from the balloon. Do not inhale the spray.

Before the first use of the balloon, you should fill the dosing pump by removing the protective cap and pressing the dosing valve several times until the spray appears. After prolonged non-use of the cylinder, it may be necessary to re-fill the pump.

Side effects:

From the cardiovascular system: dizziness, headache, tachycardia, fever, lowering blood pressure; rarely (especially with an overdose) - orthostatic collapse, cyanosis, due to a pronounced decrease in blood pressure, the drug can enhance the symptoms of angina pectoris (a paradoxical reaction to nitrates). Sometimes there is a collapse with bradyarrhythmia and loss of consciousness.

From the digestive system: dryness of the oral mucosa; rarely - nausea, vomiting, abdominal pain.

From the central nervous system: weakness; rarely - anxiety, psychotic reactions, inhibition, disorientation.

Allergic reactions: rarely - skin rash, itching, exfoliative dermatitis.

Local reactions: hyperemia of the skin, burning under the tongue.

Other: rarely - blurred vision, hypothermia, methemoglobinemia.

Overdose:

Symptoms: headache, lowering blood pressure, orthostatic hypotension, reflex tachycardia, dizziness, redness of the face, vomiting and diarrhea, asthenia, increased drowsiness, a feeling of heat.

Extremely high doses (more than 20 mg / kg) lead to methemoglobinemia, cyanosis, dyspnea and tachypnea, orthostatic collapse.

Treatment:

In mild cases - transfer of the patient to the "lying" position with raised legs.

In severe cases of overdose, general methods of treatment of intoxication and shock should be used (replenishment of the volume of circulating blood, norepinephrine and / or dopamine).

The use of epinephrine is contraindicated.

With the development of methemoglobinemia, the following antidotes and treatment methods can be used:

1. Vitamin C - 1 g in the form of sodium salt inside or intravenously.

2. Oxygenotherapy, hemodialysis, blood transfusion (exchange).

Interaction:

Other vasodilators and antihypertensives (beta-blockers, slow calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors), neuroleptics, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, fifth type phosphodiesterase inhibitors (including sildenafil and other PDE-5 inhibitors), procainamide and ethanol can enhance the hypotensive effect of nitroglycerin.

Nitroglycerin increases the effect of dihydroergotamine and reduces the effectiveness of heparin, nitroglycerine increases the concentration of dihydroergotamine in the serum, thereby enhancing its effect.

The intake of acetylsalicylic acid increases the level of nitroglycerin in the blood and strengthens its effect.

Nitroglycerin spray increases the excretion of catecholamines and vanillin-mandelic acid in the urine.

Special instructions:

The sensitivity to nitrates in different patients can vary greatly, which should be considered when choosing a dosage.

Increasing the dose may cause tolerance to the drug (addictive).

The drug contains alcohol, which is important for patients with impaired liver function, alcohol abuse, epilepsy, craniocerebral trauma and other diseases of the central nervous system, as well as pregnant women and children.

Nitroglycerin can enhance the effects of other drugs.

If blurred vision or dry mouth is retained or severely expressed, treatment should be discontinued.

The use of alcoholic beverages during the use of the drug is strictly prohibited.

Indication of the features of the drug during the first admission or when it is withdrawn:

There is no information.

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

During the treatment period it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Spray dosed sublingual, 0.4 mg / dose.

Packaging:

Vials or cylinders, polymer, metal or glass, containing 10 ml of a 1% solution of nitroglycerin, equipped with mechanical dosing pumps (200 doses are contained in the vial or bottle, 1 dose contains 0.4 mg of nitroglycerin).

Bottle (balloon) in a pack of cardboard along with instructions for use.

Storage conditions:

In the dark place at a temperature of no higher than 15 ° C, away from fire.

Keep out of the reach of children.

Shelf life:

2 years

Do not use after the time specified on the package.

Terms of leave from pharmacies:Without recipe

Registration number:LP-001009

Date of registration:18.10.2011

Date of cancellation:2016-10-18

The owner of the registration certificate:SAMARAHEDPROM, JSC SAMARAHEDPROM, JSC Russia

Manufacturer: & nbsp

SAMARAHEDPROM, JSC Russia

Representation: & nbspSAMARAHEDPROM, JSCSAMARAHEDPROM, JSC

Information update date: & nbsp10.03.2016

Illustrated instructions

Instructions

Nitroglycerine (Nitroglycerin)