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Isordil

Isordil
Isoridil is used to prevent angina pectoris (chest pain) caused by coronary artery disease. It works fast enough to relieve the pain of an angina attack that has already begun.

Brand: Isosorbide Dinitrate

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: January 2024
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Isordil 10 mg
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Product description

Pharmacodynamics of the Isordil

Buy Isordil in Canada

Isosorbide dinitrate is a peripheral vasodilator with a predominant effect on the venous vessels. Has an antianginal effect, causes an antihypertensive effect. The mechanism of action is associated with the release of nitric oxide (an endothelial relaxing factor) in the vascular endothelium, which causes the activation of intracellular guanylate cyclase, which results in an increase in the level of cGMP (a mediator of vasodilation). The latter stimulates cGMP-dependent protein kinase, which disrupts the phosphorylation of certain proteins of smooth muscle cells, including the myosin light chain, which ultimately reduces the contractility of vascular smooth muscles and subsequently leads to their relaxation.

Acts on peripheral arteries and veins. Relaxation of the veins results in decreased venous return to the heart (preload), which decreases left ventricular filling pressure. There also occurs (albeit to a lesser extent) the expansion of arterial vessels, which is accompanied by a decrease in blood pressure, a decrease in OPSS (afterload).

A decrease in pre- and afterload leads to a decrease in oxygen consumption by the myocardium.

Promotes the redistribution of coronary blood flow in favor of the subendocardial zones, especially in atherosclerosis of the coronary arteries (mainly large). Vasodilation of collateral arteries can improve myocardial blood supply. By reducing oxygen consumption by the myocardium and improving oxygen delivery to ischemic areas, it reduces the zone of myocardial damage.

Improves hemodynamics in patients with CHF, both at rest and during exercise.

Reduces blood flow to the right atrium, helps to reduce pressure in the pulmonary circulation and regression of symptoms in pulmonary edema.

Expands the vessels of the brain, dura mater, which may be accompanied by a headache.

It also relaxes the smooth muscles of the bronchi, gastrointestinal tract, bile and urinary tract.

As with other nitrates, cross-tolerance develops. After cancellation (a break in treatment), sensitivity to it quickly recovers. In order to prevent the onset of tolerance, it is recommended to observe a daily, preferably nightly, nitrate-free interval for 8-12 hours. In most patients, such therapy is more effective than continuous treatment.

Pharmacokinetics

After spraying isosorbide dinitrate on the mucous membrane of the oral cavity, the effect appears in 1-3 minutes and lasts 90-120 minutes. Absorption is high. Bioavailability through the oral mucosa - 60%. T1/2 is 30-60 minutes.

When taken orally - absorption is high, bioavailability - 22% (the effect of the first passage through the liver), with sublingual use - 60%. Time to reach Cmax when taken orally - 1 hour, T1/2 - 4 hours.

When taken orally, long-acting dinitrate is rapidly absorbed. The relative bioavailability is> 80%. The onset of action is after 15-30 minutes, Cmax in the blood plasma is achieved after 15 minutes - 2 hours.

When administered intravenously, the effect of the first passage through the liver is absent, T1/2 - 10 minutes.

Connection with plasma proteins - 30%.

Isosorbide dinitrate is metabolized in the liver due to the participation of the glutathione-S-transferase enzyme system. The active metabolites formed during the elimination of the nitro group, isosorbide-2-mononitrate and isosorbide-5-mononitrate, have T1/2 1.5–2 and 4–6 hours, respectively.

Application of the Isordil

Isordil for pain in the heart

Treatment of coronary heart disease (prevention of angina attacks); relief of angina attacks; acute myocardial infarction; acute left ventricular failure; rehabilitation treatment after myocardial infarction (as part of combination therapy); chronic heart failure (as part of combination therapy with cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitors); angina pectoris (unstable and vasospastic).

Dosage and administration of the drug Isordil

Isordil packaging appearance

Inside, after meals, without crushing, without chewing and drinking plenty of liquid - 20 mg 2 times a day (morning and evening) or 40-60 mg 1 time a day (at the same time).

Contraindications

Hypersensitivity to isosorbide dinitrate, other nitro compounds; acute circulatory disorders (shock, vascular collapse); cardiogenic shock (if measures are not taken to maintain a sufficient final DBP); cerebral hemorrhage; traumatic brain injury; increased intraocular pressure, incl. angle-closure glaucoma; hypertrophic obstructive cardiomyopathy; constrictive pericarditis; cardiac tamponade; severe arterial hypotension (SBP <90 mm Hg, DBP <60 mm Hg); severe hypovolemia; severe anemia; severe aortic, subaortic, or mitral stenosis; concomitant use of PDE-5 inhibitors (including sildenafil, vardenafil, tadalafil), since they potentiate the antihypertensive effect of nitrates; simultaneous reception with a soluble guanylate cyclase stimulant riociguat; lactation period; age up to 18 years (efficacy and safety have not been established).

Restrictions on use

Low filling pressure of the left ventricle, incl. in acute myocardial infarction, impaired left ventricular function (for example, with left ventricular failure), it is necessary to avoid a decrease in systolic blood pressure of less than 90 mm Hg; mild to moderate aortic and / or mitral stenosis; diseases accompanied by increased intracranial pressure (until now, an increase in intracranial pressure was observed only after intravenous administration of nitroglycerin in high doses); a tendency to orthostatic disorders of vascular regulation; severe renal and / or hepatic impairment; hypothyroidism; malnutrition and malnutrition; pregnancy.

Application in pregnancy and lactation

FDA category of action on the fetus - C.

There is no data on the effect of isosorbide dinitrate on human fertility.

There have been no adequate and well-controlled clinical studies of the safety of isosorbide dinitrate in pregnancy. Reproductive toxicity studies performed on rats and rabbits at doses reaching maternal toxicity levels showed no evidence of fetal harm from isosorbide dinitrate.

The use of isosorbide dinitrate during pregnancy is possible only strictly according to the doctor's prescription and in the case when the intended benefit to the mother outweighs the possible risk to the fetus and / or child. At the same time, careful monitoring of the condition of the pregnant woman and the development of the fetus is carried out.

There is information about the penetration of nitrates into breast milk, but the exact content of isosorbide dinitrate in breast milk has not been determined. It was also reported about the possible risk of developing methemoglobinemia in infants, therefore, if necessary, use during lactation, breastfeeding should be discontinued.

Overdose

Symptoms: marked decrease in blood pressure with symptoms of orthostatic vasodilation, reflex tachycardia and headache. There may be pallor, increased sweating, threadlike pulse, weakness, dizziness, incl. postural, skin hyperemia, nausea, vomiting, diarrhea. In high doses (> 20 mg / kg), methemoglobinemia, cyanosis, tachypnea, dyspnea may occur due to the formation of nitrite ions due to the metabolism of isosorbide mononitrate, and anxiety, loss of consciousness and cardiac arrest are also possible. It is possible that these symptoms may be caused by an overdose of isosorbide dinitrate.

At very high doses of isosorbide dinitrate, ICP can increase, which can lead to cerebral symptoms (headache, dizziness, drowsiness). In chronic overdose, an increase in methemoglobin is detected.

Treatment: if symptoms of an overdose appear, the use of isosorbide dinitrate should be discontinued.

With a pronounced decrease in blood pressure and / or a state of shock - give the patient a horizontal position with raised legs and take measures to replenish the BCC; in exceptional cases, norepinephrine and / or dopamine infusions can be used to improve circulation.

Epinephrine administration is contraindicated!

With methemoglobinemia: ascorbic acid - 1 g orally or in the form of sodium salt i / v - 0.1-0.15 ml / kg of 1% solution up to 50 ml; oxygen therapy, hemodialysis, exchange blood transfusion.

Precautions for the substance Isosorbide dinitrate

During long-term therapy with isosorbide dinitrate, blood pressure and heart rate control is necessary, especially in the case of a gradual increase in dose. Avoid abrupt withdrawal of the drug, gradually reducing the dose. Frequent use and in high doses can cause the development of tolerance, in this case, it is recommended to cancel for 24-48 hours or after 3-6 weeks of regular use, a break for 3-5 days with replacement of isosorbide dinitrate by other antianginal agents.

Isosorbide dinitrate should not be treated in patients who have taken PDE-5 inhibitors (for example, sildenafil, tadalafil, vardenafil) immediately before its appointment. Also, interruptions in therapy with isosorbide dinitrate for taking PDE-5 inhibitors are unacceptable, since the risk of developing angina attacks and withdrawal syndrome increases. In the event of an attack of angina pectoris, fast-acting nitrates should be additionally used to stop it.

During treatment, a decrease in blood pressure and the appearance of dizziness may occur with a sharp transition from a lying or sitting position to a standing position, alcohol consumption, exercise and hot weather, as well as an increase in angina pectoris with a sharp decrease in blood pressure, the development of ischemia up to myocardial infarction and sudden death (paradoxical nitrate reactions).

Isosorbide dinitrate (in the form of extended-release dosage forms) is not used to relieve angina attacks. In acute myocardial infarction or acute heart failure, it should be used only with close clinical observation of the patient.

In the course of emergency therapy with isosorbide dinitrate (i.v. administration), it is necessary to monitor the indicators of the CVS and other vital systems and organs.

Influence on the ability to drive vehicles and other mechanisms. During the period of treatment, it is necessary to refrain from driving and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (risk of drowsiness). This effect is enhanced by alcohol.

Side effects of the substance Isorbidil

Possible side effects are listed below by body systems and frequency of occurrence (WHO classification): very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000,> 1/100); rarely (≥1 / 10000, <1/1000); very rare (<1/10000); frequency unknown (frequency cannot be estimated from available data).

From the side of the central nervous system: very often - headache (nitrate) at the beginning of treatment; often - drowsiness, light dizziness; the frequency is unknown - blurred vision, lethargy (especially at the beginning of treatment), cerebral ischemia (when sprayed on the oral mucosa).

From the CVS: often - tachycardia, orthostatic hypotension; infrequently - a paradoxical increase in angina attacks, collapse (sometimes accompanied by bradyarrhythmia and fainting - when sprayed onto the oral mucosa and intravenously); very rarely - a pronounced decrease in blood pressure.

From the digestive tract: infrequently - nausea, vomiting; very rarely - heartburn.

On the part of the skin and subcutaneous tissues: infrequently - allergic skin reactions (including rash), flushing of the skin of the face; very rarely - angioedema, Stevens-Johnson syndrome; frequency unknown - exfoliative dermatitis.

General disorders and disorders at the injection site: often - asthenia, burning of the tongue (when sprayed on the mucous membrane of the oral cavity); frequency unknown - dryness of the oral mucosa (when sprayed on the oral mucosa).

Others: development of tolerance (including cross-over to other nitrates). To prevent the development of tolerance, continuous use of high doses should be avoided.

For organic nitrates, cases of severe arterial hypotension were noted, accompanied by nausea, vomiting, anxiety, pallor and increased sweating.

Long-term use of isosorbide dinitrate can cause transient hypoxemia due to a relative redistribution of blood flow to hypoventilated alveolar areas (in patients with coronary artery disease, it can lead to myocardial hypoxia).