Organic nitrates: pharmacology, composition, use in medicine, instructions for use, indications and contraindications. Indications for use and dosing of nitrates Nitrates in cardiology

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Nitroglycerin and its derivatives.

Isosorbide di- and mononitrate and their derivatives.

Organic nitrates have a powerful dilating effect on coronary vessels subject to initially impaired vasomotor vascular tone. In this situation, their effect can be called similar to the effect of the recently discovered endogenous relaxation factor of endothelial origin. Along with this, organic nitrates have antiplatelet activity (activation of prostacyclin), which improves coronary circulation.

In the antianginal and antiischemic effect of organic nitrates, the most importance belongs to their peripheral vasodilatory effect, especially on the venous circulation, which leads to a decrease in preload on the myocardium. They also affect (to a lesser extent) the arterial bed, which is accompanied by a decrease in myocardial afterload, which provides both an increase in supply and a decrease in myocardial oxygen demand.

Indications for the use of nitrates:

• relief (only individual dosage forms) and prevention of angina attacks,
• treatment of patients with acute myocardial infarction (without severe hypotension);
• therapy of acute and chronic heart failure (without severe hypotension).

Contraindications to the use of nitrites:

• poor individual tolerability of IG due to increased sensitivity to nitrates (headache, hypotension, tachycardia);
• pronounced hypotension, collapse, postural hypotension (systolic blood pressure below 100 mm Hg, diastolic blood pressure below 60 mm Hg);
• allergic reaction to nitrates;
• ischemic strokes, increased intracranial pressure, cerebral ischemia (for intravenous administration);
• cardiac tamponade (for intravenous administration);
• severe anemia;
• toxic pulmonary edema;
• severe aortic stenosis (decrease in the filling of the left ventricle - rare hypotension is possible);
• angle-closure glaucoma;
• the presence of a paradoxical action of nitrates - an attack of angina pectoris, myocardial ischemia up to the development of myocardial infarction and sudden death.

Side effects:

• headache or feeling of "bursting" of the head, noise in the head. facial flushing, dizziness, palpitations, hypotension;
• tachycardia (reflex), burning of the oral mucosa (with sublingual intake), nausea, vomiting;
• methemoglobinemia (with frequent and prolonged use);
• paradoxical effects - (see above).

Risk factors for side effects:

• simultaneous administration of drugs with pronounced gynotensive properties, other drugs with a synergistic effect in relation to hypotensive and vasodilating effects;
• taking several tablets for the first time at the same time or sequentially in a short period of time;
• appointment of nitrates to patients with hypertrophic cardiomyopathy;
• the use of nitrates while taking alcohol, diuretics, high temperature environment(bath, sauna, hot shower).

Tolerance (addiction) to nitrates

An important feature of nitrates is the possibility of developing tolerance, early negative aftereffect syndrome and withdrawal syndrome (rebound).

Tolerance or addiction is manifested by a decrease in the duration and severity of the effect of nitrates with regular use, or the need to use a larger and larger dose to achieve the same effect. Tachyphylaxis is a special case of its rapid development (even after taking the first dose).

Possible mechanisms for the development of tolerance to nitrates:

• depletion of sulfhydryl groups necessary for their interaction with receptors of vascular smooth muscle cells;
• stimulation of endogenous vasocostrictor reactions of the body (mediators - renin, angiotensin, catecholamines, etc.);
• change in density and decrease in the affinity of receptors for nitrates on the membrane of vascular smooth muscle cells;
• balanced arterial and venous hemodynamic effect, which consists in the need for equal intensity dilatation of veins and arteries.

Increasing the dose of the drug, as a rule, gives a temporary effect due to the high likelihood of developing tolerance to an increased dose of the drug.

To prevent the emergence of tolerance, several methods are used:

• intermittent intake of nitrates during the day so that the free period from their entry into the blood is 10-12 hours, while, however, it is impossible to provide an effect with frequent angina attacks, there is a possibility of a “negative aftereffect syndrome” during a break in taking the medicine when the patient performs physical activity;
• alternation during the day of taking nitrate and a calcium antagonist (for example, isosorbide dinitrate and nifedipine);
• use together with nitrates when signs of tolerance appear “correctors” - donators of SH-groups (methioiin, N-acetylcysteine, fluimucil), angiotensin-converting enzyme inhibitors (captopril, perindopril), diuretics.

Early Negative Aftereffect Syndrome manifests itself in exacerbation of overt and asymptomatic ischemia after taking a single dose of nitrate, and the withdrawal syndrome (rebound) is an increase in blood pressure above baseline levels, the appearance or increase in angina attacks up to the development of myocardial infarction, episodes of painless myocardial ischemia during exercise and at rest.

The most important in the group are three drugs: nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate.

Nitroglycerin (NG)

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Nitroglycerin (NG)

Has a specific antispasmodic (myotropic) effect on smooth muscles vascular wall. The drug is predominantly a venous dilator, causing a decrease in venous return of blood to the heart (preload). To a lesser extent, NG acts on the arterial bed (on large arteries), reducing afterload. The drug reduces the resistance of the coronary arteries and increases blood flow in them, has a relatively stable direct effect on collaterals, leading to an increase in retrograde blood flow due to the expansion and increase in the number of functioning collaterals. An important property of NG is its ability to redistribute coronary blood flow towards a better blood supply to the ischemic area of ​​the myocardium, in particular, subendocardial regions. NG has antiaggregatory properties against platelets.

NG can be absorbed when applied to the skin in the form of an oily solution, in special transdermal dosage forms ah (ointments, patches, disks).

The interaction of NG with other drugs can be synergistic and antagonistic. The synergistic effect is manifested by an increase in the hypotensive and systemic vasodilatory effects (hypothetical, antiadrenergic drugs, diuretics, vasodilators, calcium antagonists, beta-adrenergic agonists, ethyl alcohol, procainamide, quinidine sulfate), as well as an increase in the antianginal effect (SH-group donators, angiotensin-converting enzyme inhibitors). , salicylates). Antagonistic - a weakening of the vasodilating effect (carbacholine, pilocarpine, alpha-adrenergic agonists, histamine, bee and snake venoms, excessive insolation, angiotheisin, pituitrin, corticosteroids, stimulants of the central nervous system and autonomic ganglia, blockers of M-cholinergic receptors), as well as a weakening of the antianginal effect due to the development of cross tolerance to NG due to regular and long-term use of isosorbide dinitrate and prolonged forms of NG in the form of patches.

Sublngvalpy forms of NG

The general indication for their reception is the relief of an attack of angina pectoris.

NG tablets for sublingual administration (nitroglycerin, angibid, angiolingval, angiosed, angorin, glycerol trinitrate, myoglyceria, nitrangin, nitrocardiol, nitroglia, nitromint, nigrol, nitrostat, trinitrine, trinitroglycerin, trinitrol, etc.) dissolve quickly in the oral cavity, have a high bioavailability, dosing accuracy. The pronounced effect begins after 1 minute and reaches a maximum after 4-6 minutes. In 9% of patients, in the first minutes after taking NG, a sharp decrease in systolic and diastolic blood pressure can be observed with a simultaneous increase in heart rate. The antianginal effect may not coincide with the disappearance of myocardial ischemia, which may persist after the relief of a painful attack (painless form of ischemia).

In addition to tablet forms, a solution of NG in alcohol is used (the stopping effect of 2-4 drops corresponds to the effect of one table of NG) and a solution of NG in oil in capsules (the capsule is crushed with the front teeth so that its contents fall under the tongue).

Inhaled forms of NG include aerosol and cigarettes.

An aerosol jet with NG (nitroglycerin aerosol, nitrolingual spray, etc.) is directed into the open mouth under the tongue by pressing the canister valve (one or two times), which corresponds to 0.2-0.4 mg or 0.4-0.8 mg of NG depending on the dose size at one pressing of the valve. Features of the application are: faster hemodiamic effect (on average after 30-60 s) compared with subligual administration of tablets; a great danger of overdose (the patient can press the valve several times); the possibility of aerosol entering the atmosphere in a closed room (dangerous for people around who do not tolerate NG).

Dosage forms of NG for oral administration

A common indication for this group of drugs is both the prevention and relief of angina attacks.

They are tablets or capsules of prolonged action and are usually produced in two forms depending on the dosage: small (mite) and large (forte).

Low-dose dosage forms include nitrong mite, nitropek-retard, sustak mite, nitrogranulolong, nitretspofa, nitro-mac. They are better tolerated by patients than sublingual forms of NG. The hemodynamic effect lasts an average of 0.5 hours.

Dosage forms with a higher dosage include nitrogranulong, sustak forte, nitrong forte, sustonite forte, nitrocor, nitro-mac retard, gilustenone, nitromyit. The hemodynamic effect after taking 6.4-13.0 mg begins after 2-5 minutes. Its duration is 5-6 hours. The antianginal effect occurs in 20-45 minutes, the most pronounced effect lasts 45-120 minutes, its total duration is 2-6 hours.

The drugs are prescribed and a single dose of 1-2 tablets several times a day. It is important to remember that tablets and capsules should not be chewed to stop an attack of angina pectoris, because. an excessive amount of NG from microcapsules destroyed in this way, entering the oral cavity, can cause dangerous side effects.

Transdermal forms of nitroglycerin

Available in two dosage forms: ointments; patches (discs).

Ointment with 2% oil solution NG (nitro, nitrobid, nitrong) is used to prevent angina attacks in patients with angina pectoris of exertion and rest with frequent attacks, especially at night. This is a difficult-to-dose dosage form, leaves oil marks on clothes, and often causes skin irritation at the site of application. The antianginal effect occurs in 15-60 minutes, the peak of action is in 30-120 minutes, and its duration is 3-4 hours (rarely 6-8 hours).

Usually the ointment is applied in an amount of 7.5-30 mg per chest front. It is squeezed out of the tube onto a special film with divisions: 12.5 mm long (corresponding to 7.5 mg), maximum length 50 mm (30 mg). It is better to apply the ointment in the morning or at night, after cleansing the skin. To avoid irritation, you need to change the place of application.

Plasters and discs are special transdermal systems for the slow release of drugs - demonite, nitroderm TTS, pitrodisk, pitrodur. transderm-nitro. Their maximum anti-ischemic effect is significantly lower than that of NG tablets for sublngvalpo administration. The use of patches and discs can lead not only to the development of tolerance to NG, but even cause tachyphylaxis (the development of tolerance to the first dose - after 8-10 hours), including the development of cross-tolerance to NG for sublingual administration. Ambient temperature and physical activity can affect the kinetics of NG - with local warming, the concentration of NG in the blood plasma increases by 2-3 times, and decreases with cooling.

Buccal forms of nitroglycerin

They are used in the form of two main various forms: plates (trinitrolonne) and booklet tablets (susadrip, suscard, sustabuccal, nitrocard, etc.). placed on the oral mucosa. After their adhesion, NG gradually penetrates into the blood without being metabolized during the first passage through the liver. The effectiveness of buccal formulations may be equivalent to intravenous administration of NG, given a small delay in the onset of action (by 1 min). Buccal forms of NG are the only ones that are able to stop an angina attack as quickly as NG when taken sublingually.

Trinitrolong

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Able to stop an attack of angina pectoris after 1.5 minutes, the duration of antianginal and anti-ischemic effects is 3-5 hours. Intermittent administration of the drug during the day (1-2 times) avoids the development of tolerance to NG. One of the features of the drug is the possibility of its use in patients with myocardial infarction when intravenous forms of NG are unavailable.

The plate is glued to the mucous membrane of the upper gums above the canine, or small molars, or incisors on the right or left, preferably after eating hot food. After application, the plate should not be moved to the side, it should not be chewed or swallowed. The dose of the drug is selected individually depending on the time of resorption of the plate: a plate with 1 mg - with resorption within 1-1.5 hours; with 2 mg - with resorption in 2-3 hours; from 3-4 mg - with resorption up to 6 hours. Two plates can be applied, while the total dose should correspond to the required one. If it is necessary to increase physical activity (speed up the step), it is enough for the patient to lick the plate with the tip of the tongue 2-3 times (without trying to move it). This technique is used if the attack did not stop with the application of one plate. To prevent attacks, the plate can be glued to the upper gum 1-2 minutes before the expected physical or emotional stress. If the load turned out to be short and the plate has not yet resolved, it can be removed.

Susadrin

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Tablets-booklets. The onset of the hemodynamic and antianginal effect occurs 3 minutes after application, the effect persists for 5 hours (during the period of resorption of the booklets).

Internal forms

Proprietary names: nirmin, i.v. nitro-bid, i.v. nitrostat, nitronal, nitro, i.v. nitro-mac, 1%, NG solution in alcohol for i.v. administration, perlinganite, etc. After i.v. administration NG the onset of the effect occurs after 2-5 minutes, the half-life due to the rapid metabolism of the drug in the blood is 1-2-3 minutes.

Indications for IV ifusion NG: elimination of anginal attack in acute myocardial infarction, unstable angina pectoris, relief of coronary spasm during coronary angiography, heart failure with some heart defects.

Infusion solution is prepared by diluting 50-100 mg of the contents of the amp. or vials in 500 ml of 5% glucose solution or 0.9% sodium chloride solution. The initial infusion rate is 5-10 mcg / min or 20-30 mcg / min, depending on the patient's condition. Every 3-5-10 minutes the infusion rate can be changed by 10 µg/min. The dose is titrated to reduce systolic LD by 10-20% (not less than 90 mm Hg. Art.) or 10 mm Hg. Art. or until the wedge pressure of the pulmonary capillaries is reduced by 20-30%. The maximum infusion rate is 150-200 mcg/min, the optimal one is 40-60 mcg/min. With a duration of continuous IV infusion of NG over 48 hours, the risk of developing tolerance to NG increases.

Contraindications for IV forms of NG are hypotension or uncorrected hypovolemia; pericardial constriction, cardiac tamponade, severe aortic or mitral stenosis (when it is necessary to maintain filling pressure or left ventricular volume); inadequate cerebral perfusion.

Isosorbide dinitrate (ID)

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In addition to the properties characteristic of NG, it has a selective dilating effect on the mesenteric and other capacitive veins, does not change or slightly increases the heart rate. Systemic vascular peripheral resistance does not change due to reflex sympathetic activation, pulmonary vascular resistance decreases. As well as other nitrates.

ID does not have its own inotropic and chropotron effects. Improvement in the systolic function of the heart is due to a decrease in preload, reflex stimulation of the sympathetic nervous system. In patients with coronary heart disease, improvement in systolic function occurs due to a decrease in myocardial oxygen demand, a decrease in preload, and an improvement in perfusion of subendocardial myocardium.

The drug is available in almost all possible dosage forms.

ID for sublingual intake has a pronounced hemodynamic and antianginal effect, which occurs no earlier than after 3-4 minutes, the maximum effect is observed from the 15th minute and later, the total duration of action is 45-120 minutes. The onset of action of ID for chewing is within 10 minutes, but not earlier than 3-4 minutes, the peak of action is 25 minutes. after taking.

Antianginal and antiischemic aerosol id effects(iso-mac spray, isoket sirey, dynamant spray, etc.) occur after inhalation of two doses (2.5 mg) after 2-6 minutes, the duration of the effect is 60 minutes. At the first application, you need to press the valve several times until a uniform cloud of spray appears, later you can immediately direct the jet into the oral cavity. The can must be held vertically, directing the aerosol jet to the inner surface of the cheek and holding the breath (not swallowing). To stop an attack of angina pectoris, one, two, less often three doses in a row with an interval of about 30 seconds are required.

regular ID pills have average duration anti-ischemic effect 4 hours. Anti-anginal effect is recorded longer than anti-ischemic. With long-term regular intake, the stationary level of ID concentration in blood plasma increases, which, apparently, is associated with the accumulation of metabolites. The drugs are used 10-20 mg 2 to 6 times a day. In severe cases, a single dose is increased to 30-40 mg. To prevent the development of tolerance to ID, one should strive to prescribe the minimum effective dose, if possible, only 30 minutes before the expected physical activity, preferably no more than 2-3 times a day.

At sustained action ID(isoket retard, cardiquet retard, iso-mac retard, isosorb retard, sorbitrate, isordyl tembides, dilartrat-SR) after taking 40 mg of the drug, the anti-ischemic effect is recorded after 1 hour, the maximum effect - after 2 hours, the total duration of the antianginal and anti-ischemic effect - around 8 o'clock

Transdermal form of ID(iso-mac TD siray) is used after washing in the morning or, if necessary, in the evening, one or two doses (30-60 mg ID), followed by rubbing the drug on the skin with the tailbones of the fingers. Its action lasts about 16 hours.

Isoket cream, as a rule, is applied before bedtime (with frequent attacks of angina pectoris in the morning and at bedtime). Two single doses of cream (500 mg of cream correspond to 50 mi ID) are rubbed into the skin of the chest, inner surface of the forearm or abdomen. The minimum surface for its application corresponds to; two palms. The effect of coxpanyatsya about 12 hours.

Buccal form of ID(dinitrosorbilong) biosoluble plates, the application of which in doses of 20 and 40 mg allows for a continuous, uniform and prolonged (about 10 hours) intake of the drug into the blood.

Isosorbide dinitrate for infusion(dinit, isodinite, nzoketidr) diluted in 0,9% solution of sodium chloride or 5% solution of glucose, administered at an initial rate of 3-4 drops per minute (at an ID concentration of 100 µg/ml) or 1-2 drops (at an ID concentration of 200 µg/ml). The rate of administration can be increased every 5-15 minutes by 2-3 drops, depending on the tolerance of the drug when monitoring blood pressure, heart rate, ECG and diuresis. Duration of administration - from several hours to several days. The cessation of the infusion should be gradual, with the transition to sublingual or oral administration of ID.

Isosorbide-5-mononitrate (isosorbide, isomochat, mopish), monizol, monocyte, and op.)

The antianginal effect occurs 30-45 minutes after ingestion, the maximum anti-ischemic effect develops after 45-60 minutes. Its duration for isomopath is 2-6 hours, for monizid and monocyte - 4-7 hours. Application can be started with a trial dose for tolerance - 10 mg 1 time per day. Therapeutic dose - 20 mg. 2 times a day with an interval of 7 hours or as needed before exercise. The dose can be increased to 20 mg 3 times a day, then up to 40 mg 2-3 and even 4 times a day.

Long-acting drugs(elantan retard, efox dong 50; olicard retard, ismo retard, imdur, etc.) have an average duration of the antianginal effect of a single dose of 10-14 hours. Apply 1 table. once a day, if necessary - up to 2 tablets. The drug should not be chewed or attempted to dissolve.

International name:

Dosage form:

Pharmachologic effect:

Indications:

Deposit 10

International name: Nitroglycerin (Nitroglycerin)

Dosage form: sublingual metered aerosol, sublingual drops, sublingual capsules, prolonged-release capsules, concentrate for solution for infusion, films for sticking on the gums, sublingual dosed spray, sublingual tablets, t

Pharmachologic effect: Venodilator from the group of nitrates. Nitrates are able to release nitric oxide from their molecule, which is a natural endothelial ...

Indications: IHD: angina pectoris (treatment, prevention), myocardial infarction (rehabilitation). For intravenous administration - acute myocardial infarction (including complicated by acute ...

Deposit 5

International name: Nitroglycerin (Nitroglycerin)

Dosage form: sublingual metered aerosol, sublingual drops, sublingual capsules, prolonged-release capsules, concentrate for solution for infusion, films for sticking on the gums, sublingual dosed spray, sublingual tablets, t

Pharmachologic effect: Venodilator from the group of nitrates. Nitrates are able to release nitric oxide from their molecule, which is a natural endothelial ...

Indications: IHD: angina pectoris (treatment, prevention), myocardial infarction (rehabilitation). For intravenous administration - acute myocardial infarction (including complicated by acute ...

Dilkoran 80

International name: Pentaerythrityl tetranitrate (Pentaerithrityl tetranitrate)

Dosage form: tablets

Pharmachologic effect: Venous vasodilator, has an antianginal effect. Stimulates the formation of nitric oxide in the wall of blood vessels, which is an endothelial ...

Indications: IHD, angina pectoris (prevention, including in the post-infarction period); CHF (as part of complex therapy).

Dinite

International name:

Dosage form:

Pharmachologic effect:

Indications:

Dinitrosorbilong

International name: Isosorbide dinitrate (Isosorbide dinitrate)

Dosage form: sublingual metered aerosol, capsules of prolonged action, concentrate for solution for infusion, films for sticking on the gums, sublingual metered spray, tablets, tablets of prolonged action, transdermal

Pharmachologic effect: Peripheral vasodilator with a predominant effect on venous vessels. Stimulates the formation of "first pass" nitric oxide (endothelial...

Indications: Angina pectoris (stopping and prevention, including unstable angina), acute myocardial infarction (including complicated by acute left ventricular ...

ditrate

International name: Isosorbide dinitrate (Isosorbide dinitrate)

Dosage form: sublingual metered aerosol, capsules of prolonged action, concentrate for solution for infusion, films for sticking on the gums, sublingual metered spray, tablets, tablets of prolonged action, transdermal

Pharmachologic effect: Peripheral vasodilator with a predominant effect on venous vessels. Stimulates the formation of "first pass" nitric oxide (endothelial...

Indications: Angina pectoris (stopping and prevention, including unstable angina), acute myocardial infarction (including complicated by acute left ventricular ...

From 5 mono-Ratiopharm

International name: Isosorbide mononitrate (Isosorbide mononitrate)

Dosage form: long-acting capsules, tablets, long-acting tablets

Pharmachologic effect: Peripheral vasodilator with a predominant effect on venous vessels. Stimulates the formation of nitric oxide (endothelial relaxing...

Peculiarities: one of the most "ancient" groups medicines: Nitroglycerin has been used in heart disease since the 19th century. The effect of nitrates on coronary disease heart is due to vasodilation and the associated restructuring of blood circulation. They are produced in various dosage forms: tablets and capsules for sublingual administration, tablets for oral administration, sprays, solutions, etc. Depending on the type of drug and the form of release, they are prescribed for the treatment or prevention of angina attacks and myocardial infarction.

Most Common Side Effects: headache, usually occurring in the first days of treatment, increased heart rate, decreased blood pressure, dizziness, weakness.

Main contraindications: hemorrhagic stroke, increased intracranial pressure, glaucoma, severe anemia, thyrotoxicosis, hypotension, pregnancy, lactation, individual intolerance.

Important information for the patient:

Short-acting nitroglycerin preparations should be used in a sitting position, especially at the beginning of treatment. This is due to the possible development of dizziness.

Long-term constant intake of nitrates can lead to the so-called tolerance, that is, the body's insensitivity to the drug. This condition is reversible, it is only important to take a break in taking these drugs for a while. On how to maintain normal health during the period of "rest" from nitrates, it is necessary to consult a doctor.

When you first take nitrates, you need to be prepared for the onset of a headache. It appears very often, but after 2-5 days of admission it decreases or disappears altogether.

Unopened vials of nitroglycerin tablets should not be stored for more than one month.

From interaction with air, tablets lose their medicinal properties. Capsules and especially aerosols are more reliable in this regard.

During treatment with nitrates, you can not take many medicines designed to improve the sexual function of men. If you need to take such drugs, you need to consult a specialist.

Remember, self-medication is life-threatening, consult a doctor for advice on the use of any medications.

Neurotropic agents

Means that depress SDC: clonidine, methyldopa, guanfacine

Ganglioblockers: azamethonium, trepyrium

Sympatholytics: reserpine, guanfacine

Adrenoblockers: phentolamine (α 1 - and α 2 - AB), prazosin(α 1 -AB), labetalol (α, β-AB)

Beta-agonists: nonahlazine

Myotropic agents

• Phosphodiesterase inhibitors: papaverine, aminophylline, etc.

  Substances with an adenosine mechanism of action: dipyridamole

  Donors NO: nitroglycerin, sodium nitroprusside, etc..

  Ca 2+ channel blockers: verapamil etc.

  Activators of K + -channels: minoxidil, diazoxide

  Miscellaneous means: magnesium sulfate, bendazole

Means affecting the RAAS:enalapril, losartan, etc.

Substances of mixed action:nitrates, magnesium sulfate

Direction of action.

affecting regional blood circulation (used for ischemic heart disease, spasms of the vessels of the brain, limbs)

affecting the systemic circulation (antihypertensive drugs).

Means used in ischemic heart disease (Antianginal drugs)

IHD is an acute or chronic lesion of the heart muscle due to a mismatch between myocardial oxygen demand and the possibilities of its blood supply.

Clinically, angina pectoris is characterized by the episodic appearance of paroxysmal pain, discomfort or pressure, constriction in the region of the heart. Pain can spread to the left arm, shoulder, under the left shoulder blade. The attack may be accompanied by shortness of breath, nausea, vomiting, dizziness.

Principles of treatment of angina pectoris

Increased oxygen delivery to the heart- coronary anatomy.

Decreased oxygen demand of the heart. They use drugs that reduce the work of the heart and the rhythm of heart contractions.

Decreased blood clotting:

antiplatelet agents: aspirin, ticlid, clopidogrel

anticoagulants: heparin, warfarin.

Improving the metabolism of the heart muscle, increasing the resistance of the heart to hypoxia- cardioprotectors (means of metabolic protection): trimetazidine, mildronate, riboxin

Carrying out etiotropic therapy - special lipid-lowering drugs colestipol, clofibrate, lovastatin, lipostabil, etc.

6) Reducing neuropsychic stress - psychosedative drugs.

Classification by the nature of the action

1. Drugs that dilate coronary vessels and reduce myocardial oxygen demand: nitrates, calcium antagonists, amiodarone, nicorandil

   Means that dilate the coronary vessels (coronary medicines): dipyridamole

   Drugs that reduce myocardial oxygen demand: β-blockers.

   Means that improve myocardial metabolism:means of metabolic therapy - cocarboxylase, riboxin, trimetazidine, etc.

Classification for use in angina pectoris

Remedies for the relief of angina attacks:nitroglycerine.

Means for the prevention of angina attacks:all other substances.

organic nitrates.

Nitroglycerin preparations:

BUT) short action–nitroglycerine in tablets for sublingual use; in capsules with oil solution nitroglycerin; alcohol solution of nitroglycerin (used under the tongue on a piece of sugar); aerosol form nitromint-aerosol(s.d. 0.4 mg), nitrosprey(aerosol forms are better stored, cause effect faster), drugs for injection nitro and nitro poppy.

B) prolonged action- sustak, nitrong, nitroderm patch, 2% nitro ointment, trinitrolong films.

2) Preparations of isosorbide dinitrate: isodinite, nitrosorbide (short-acting); isosorb retard, cardonite retard (long-acting).

3) Preparations of isosorbide-5-mononitrate– have 100% bioavailability , practically not destroyed in the liver, long-acting (appointed 1-2 times a day ) : isosorbide mononitrate, mono poppy, monocinque (effective for angina pectoris of any severity, with heart failure, safe).

4 ).Nitrate-like compounds: molsidomine

mechanism of antianginal action of nitroglycerin

It has a mixed mixed effect: it has neurotropic and myotropic effects.

Neurotropic action is associated with the ability to reflexively block the central and peripheral links of coronary reflexes, which leads to vasodilation.

Myotropic action : nitroglycerin and other nitrates interact with SH-groups of cysteine ​​in the vascular endothelium, nitrosocysteine ​​and nitric oxide NO (endothelial muscle relaxant factor) are formed. NO activates cytosolic guanylate cyclase and increases the content of cGMP in smooth muscle cells. cGMP activates protein kinase G and calcium ATPase, which promotes the transfer of calcium ions from the cytoplasm to the SPR, the vessels expand (to a greater extent acts on the veins).

The expansion of the veins leads to a decrease in venous return and a decrease in the preload on the heart. The expansion of the arteries reduces the peripheral resistance to blood flow, reduces afterload. The tension of the muscles of the ventricles of the heart decreases, and the need for oxygen in the heart decreases.

Nitroglycerin increases the delivery of oxygen to the heart, as it expands the large coronary vessels, and redistributes blood from the epicardium to the endocardium, from healthy areas of the heart to ischemic ones. It reduces the diastolic tension of the ventricles and improves the blood supply to the subendocardial part of the myocardium. In addition, nitrates increase the formation of prostacyclin and reduce the synthesis of thromboxane, which reduces platelet adhesion and aggregation and improves microcirculation.

Nitrates dilate the vessels of the upper half of the body.

Short-acting nitrates when applied sublingually cause a rapid onset of effect within 1-2 minutes, but act within 30 minutes, therefore they are used only to stop an angina attack.

Side effects of nitroglycerin: arterial hypotension and reflex tachycardia; headache (associated with cerebral hypoxia and increased intracranial pressure); tolerance (occurs 1.5-2 months after continuous use of nitroglycerin and is associated with a deficiency of SH-groups). Donators of SH-groups (unithiol, ACC, methionine) are prescribed to increase sensitivity to the drug.

Long-acting drugs are used to prevent angina attacks.

Sustak and sustonitis- made by microencapsulation: part of the nitroglycerin is released immediately and acts after 10-15 minutes from the moment of administration, and the rest is released gradually and evenly and acts from 4-5 hours (sustac) to 10-12 hours (sustonitis). The tablets are swallowed whole, not broken or chewed.

Nitrong- contains granules from which nitroglycerin is released in the intestines for a long time . The action starts in an hour and lasts 8-10 hours.

Trinitrolong - nitroglycerin as part of a film that sticks to the gum: the concentration of nitroglycerin is determined in the blood after 2 minutes, the activity persists for 4-6 hours. It is used for the prevention and relief of angina attacks.

Transdermal systems (plasters, discs, ointments), provide a uniform flow of nitroglycerin through the skin during the day. They are used in patients with nocturnal angina pectoris, with a combination of angina pectoris with heart failure. To transdermal forms of nitroglycerin, addiction develops faster.

Nitro ointment - applied to the skin in the chest area. Dosed: 0.5 cm = 3 mg of nitroglycerin, effect after 30-40 minutes, duration 5 hours.

The effectiveness of other nitrates is somewhat less than that of long-acting nitroglycerin preparations. When taken orally, the action develops after 30 minutes and lasts from 2 to 12 hours. They bind to plasma proteins.

During treatment severe forms angina pectoris, nitrates are usually combined with beta-blockers or calcium antagonists (verapamil, diltiazem).

Nitrates are prescribed for angina, heart failure, acute myocardial infarction, pulmonary edema.

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Contraindications

Individual intolerance (allergy, hypersensitivity), hypertrophic obstructive cardiomyopathy, arterial hypotension, acute myocardial infarction involving the pancreas, pronounced tachycardia or bradycardia in acute myocardial infarction, uncorrected hypovolemia, recent use of phosphodiesterase-5 inhibitors (at least 24 hours after taking sildenafil or vardenafil, as at least 48 hours after taking tadalafil). Relative contraindications include cor pulmonale and arterial hypoxemia, cardiac tamponade, constrictive pericarditis, severe mitral stenosis, severe aortic stenosis, severe anemia, intracranial hemorrhage or a recent head injury.

Side effects

The main side effect is headache. Since tolerance to the vasodilatory action of nitrates in the arterial vascular bed occurs faster than in the venous, with continued treatment, headache may decrease or disappear without loss of antianginal effect. headache is often relieved while taking acetylsalicylic acid. Possible redness of the face.

most serious side effect arterial hypotension occurs. Its occurrence is facilitated by normal or reduced filling pressure of the ventricles of the heart, hypovolemia, the use of other vasodilators, being in an upright position, and drinking alcohol. Sometimes a decrease in blood pressure is noted when taking nitrates before meals or shortly after it. To eliminate arterial hypotension, it is usually enough to move to a horizontal position; in more severe cases, it may be necessary to give the legs an elevated position, as well as intravenous administration fluids and short-term infusion of vasopressor drugs.

Reflex activation of the sympathetic nervous system may exacerbate myocardial ischemia. This effect is counteracted by the simultaneous use of β-blockers. It is also possible the occurrence of severe bradycardia, possibly associated with the activation of the Bezold-Jarisch reflex. A decrease in RV filling pressure involved in the MI zone can lead to a pronounced decrease in cardiac output. A similar complication may occur with impaired diastolic filling of the ventricles of the heart (cardiac tamponade, constrictive pericarditis, severe mitral stenosis). The use of nitrates in hypertrophic obstructive cardiomyopathy contributes to aggravation of LV outflow tract obstruction, worsening of mitral regurgitation, and sometimes leads to syncope. With severe stenosis of the aortic mouth, there is a risk of fainting and worsening of angina pectoris.

The use of sublingual dosage forms may contribute to bad breath. Sometimes there is blurred vision, dry mouth.

Expansion of arterioles in the vessels of the pulmonary circulation in some cases leads to an aggravation of ventilation-perfusion disorders and an increase in hypoxemia in patients with lung diseases. At acute pathology in the cranial cavity (hemorrhage, recent head injury), nitrates may increase intracranial pressure. In patients with glaucoma, intraocular pressure may increase.

With prolonged use of high doses of nitrates, in rare cases, pronounced methemoglobinemia occurs due to the oxidation of Hb. Its risk is increased with severe violation liver functions. To treat this complication, intravenous administration of methylene blue (1-2 mg/kg over 5 minutes) is prescribed.

Clinically Significant Interactions

The combination with β-blockers and / or blockers of slow calcium channels increases the antianginal effect.

Simultaneous use of β-blockers and vasodilators (blockers of slow calcium channels, ACE inhibitors) increases the risk of arterial hypotension. The simultaneous administration of nitrates and arterial vasodilators may contribute to the reflex activation of the sympathetic nervous system and the occurrence of tachycardia. β-blockers prevent the occurrence of reflex tachycardia in response to the vasodilating effect of nitrates and increase their antianginal effect.