Pharmacodynamics and pharmacokinetics
Pharmacodynamics
The effect of the drug is due to the action of the active metabolite of molsidomine - linsidomine . This substance affects the smooth muscle layer of blood vessels, reducing their tone, and also has an antiplatelet effect. When the tone of smooth muscle elements is reduced, the volume of the vascular bed increases and the pressure in the ventricles of the heart decreases. As a result, the load on the heart decreases and the need of the heart muscle for oxygen decreases.
Also, under the influence of molsidomine, spasm of the coronary arteries decreases, their branches expand and, accordingly, blood supply to the heart muscle improves.
Pharmacokinetics
After oral administration, approximately 90% of the active substance is absorbed in the digestive tract. Bioavailability is 65%. Only 11% of molsidomine is bound to plasma proteins.
The effect begins to be felt after 20 minutes and lasts 4-6 hours. After 30-60 minutes, the concentration of the drug in the blood reaches its maximum.
A transformation occurs in the liver: molsidomine is converted enzymatically into sydnonimine 1, and sydnonimine 1 is converted non-enzymatically into linsidomine , which provides the pharmacological effect of the drug.
Molsidomine is mainly excreted from the body through urine (90-95%, of which 2% is unchanged substance) and feces (3-4%). The half-life lasts one and a half to two hours, but can increase significantly in case of liver failure (up to 7.5 hours).
Contraindications
The medicine must not be taken if:
- cardiogenic shock;
- severe hypotension ;
- glaucoma;
- acute phase of myocardial infarction , especially if blood pressure is low;
- pregnancy and lactation;
- for disorders of carbohydrate metabolism (hereditary intolerance to galactose, fructose, Lapp lactose deficiency, sucrase-isomaltase, glucose, galactose malabsorption syndrome).
Taking the drug for acute myocardial infarction is permitted only with constant monitoring by the attending physician.
Angina pectoris is a clinical syndrome manifested by discomfort or pain.
Angina is a clinical syndrome manifested by discomfort or pain in the chest of a squeezing, pressing nature, which is most often localized behind the sternum and can radiate to the left arm, neck, lower jaw, and epigastric region.
Angina-like pain may be a symptom of non-cardiac diseases or pathological conditions, including those involving the esophagus, chest or lungs. Among them, conditions that increase oxygen consumption include hyperthermia, hyperthyroidism, and intoxication with sympathomimetics. Oxygen supply is reduced by anemia, hypoxemia, pneumonia, bronchial asthma, chronic obstructive pulmonary disease, pulmonary hypertension, sleep apnea syndrome, hypercoagulation, polycythemia, leukemia, thrombocytosis.
The first and most important step in diagnosing coronary artery disease is a detailed description of the pain syndrome. Five characteristics of pain are assessed: nature, localization, duration, factors provoking and relieving pain.
Non-invasive instrumental diagnostic methods include
1. Registration of an ECG at rest. During myocardial ischemia, the ECG records changes in the final part of the ventricular complex - the ST segment and the T wave (transient horizontal or oblique decrease in the ST segment and flattening or inversion of the T wave). Sometimes there is ST segment elevation, which indicates more severe transmural myocardial ischemia. In contrast to myocardial infarction, with angina pectoris, ST segment deviations quickly return to normal after symptoms are relieved. In addition, the ECG may reveal left ventricular hypertrophy, bundle branch block, rhythm or conduction disturbances. When diagnosing stable angina, it is recommended to record a resting ECG outside of a painful attack, and also (if possible) during a painful episode.
2. Stress ECG tests. These are more sensitive and specific methods than recording an ECG at rest for identifying ischemia. Stress tests provoke myocardial ischemia by increasing myocardial oxygen demand (treadmill test, bicycle ergometry, dobutamine test) or reducing oxygen delivery to the myocardium (tests with dipyridamole and adenosine). In this case, ischemia can be detected using various methods based on specific disturbances in myocardial perfusion and metabolism, regional contractility, or taking into account ECG changes and clinical symptoms.
3. Tests with dosed physical activity. During a test with dosed physical activity, the patient performs an increasing load on a treadmill or bicycle ergometer, while the heart rate and ECG are constantly recorded at regular intervals (1–3 min), and blood pressure is monitored. In addition to recording an exercise ECG, this stress test plays an important role in identifying silent ischemia and assessing the prognosis of people with stable angina, as well as in studying the further development of the disease and the effectiveness of treatment. An exercise test is considered positive for ischemic heart disease if it reproduces the patient's typical chest pain or tightness and produces changes on the ECG characteristic of ischemia.
4. Holter monitoring (HM) ECG. In patients with coronary artery disease, the use of Holter monitoring is most justified for diagnosing silent myocardial ischemia. This is the only method that allows you to determine its severity, evaluate painful and painless ischemic ECG changes that occur at different times of the day in an outpatient setting.
With the help of CM in patients with coronary artery disease, it is possible to register the daily rhythms of ischemic activity. The use of CM makes it possible to detect myocardial ischemia in patients who are unable to perform physical stress tests (physical status, peripheral vascular disease, severe pulmonary pathology), as well as in some special conditions, for example during psycho-emotional stress.
5. Echocardiography (EchoCG). It is advisable to carry out it if there is a suspicion of valve damage or hypertrophic cardiopathy, which can cause symptoms similar to coronary artery disease, as well as to determine the function of the left ventricle. In some patients, echocardiography can reveal some consequences of coronary artery disease, such as impaired regional myocardial contractility and mitral regurgitation.
Doppler echocardiography data usually provide precise quantitative information about the presence and extent of associated lesions. For example, if we are talking about hypertrophy, we can determine whether it is concentric or asymmetric, and clarify its localization - in the area of the interventricular septum, the apex of the left ventricle or the free wall.
After carrying out diagnostic measures, an important task of the outpatient physician is to select the optimal therapy aimed at reducing the frequency of anginal attacks, preventing acute myocardial infarction, and improving the patient’s quality of life.
To prevent acute myocardial infarction, the following groups of drugs are used:
lipid-lowering (anti-atherosclerotic): statins, fibrates, nicotinic acid, PUFAs; antiplatelet: acetylsalicylic acid, clopidogrel, ticlopidine, warfarin, dipyridamole; metabolic: trimetazidine, ranagazine, L-carnitine, dichloroacetate; antianginal drugs that affect hemodynamics: organic nitrates, b-blockers and calcium antagonists. Antianginal drugs (drugs that prevent angina attacks) by preventing myocardial ischemia significantly improve the patient’s well-being and increase exercise tolerance. To optimize the treatment of patients with coronary artery disease with stable angina at the Institute of Cardiology named after. A.L. Myasnikov proposed a method of stepwise drug treatment for this category of patients on an outpatient basis. Its essence is as follows: 1) the prescription of medications is carried out in the form of 3 steps with an increasing antianginal effect by combining drugs with different mechanisms of action; 2) the stage of treatment is selected in accordance with the functional class (FC) of the patient’s angina; 3) the range of drugs used is limited to the most effective, well tolerated and accessible; 4) treatment should be carried out within the range of established single and daily doses of drugs; 5) if within a week the treatment at the chosen level is ineffective, it is necessary to move to the next, higher level; 6) if side effects associated with taking a specific drug occur, it is canceled, replacing it with another within the chosen level; 7) the duration of treatment, transitions to another stage and breaks in treatment are determined by the FC, the clinical course of the disease, the effectiveness and tolerability of treatment.
The scheme for the stepwise prescription of antianginal drugs to patients with stable angina of various FCs in an outpatient setting (B.A. Sidorenko et al., 1986) is presented in Table. 1.
To prevent attacks of angina, organic nitrates are most often prescribed as monotherapy, which have a favorable combination of vasodilating effects that help eliminate the imbalance between the myocardial oxygen supply and its oxygen demand in patients with coronary artery disease. In addition, nitrates reduce pre- and afterload of the left ventricle, vascular resistance, including coronary arteries, blood pressure, and have antiplatelet activity.
However, their use is associated with a number of negative effects. Thus, with long-term use of nitrates, it is possible to develop tolerance to them, manifested either by a shortening of the period of action of the drug or by the complete disappearance of the effect. This is due to the appearance of a deficiency of intracellular SH groups and neurohormonal activation of the renin-angiotensin system with the subsequent release of catecholamines into the blood. Cerebral symptoms are common - a sharp headache, a feeling of fullness, pulsation of the head, noise in the ears and head. Sometimes palpitations caused by reflex sinus tachycardia appear. In some patients, withdrawal syndrome is possible, accompanied by exacerbation of coronary artery disease in the form of increased frequency of angina attacks, myocardial infarction and even sudden death.
Molsidomine, instructions for use (Method and dosage)
The method of use of the medicine and its dosage depend on the purpose for which and to whom Molsidomin tablets were prescribed:
- angina attacks – 4 – 12 mg per day, taken orally after meals.
- When taken for medicinal purposes, it is first prescribed with 4-6 doses of 1-2 mg daily. Then, if necessary, the dose is increased to 2-4 mg, and the number of doses is reduced to 2-3 times a day.
- To relieve an attack of angina, the tablet is placed under the tongue.
If the patient is elderly, has renal or hepatic insufficiency and is prone to low blood pressure, treatment should begin with lower doses, which the doctor should set on an individual basis.
Note!
Description of the drug Molsikor tablet. 4mg No. 30 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Overdose
headache appears , blood pressure drops, and the pulse increases sharply.
In case of a slight overdose, it is enough to lie down with your legs raised up. If the dose taken is more than twice the usual dose, it is necessary to rinse the stomach (if the person is conscious) and carry out symptomatic therapy.
If, despite the measures taken, the symptoms intensify, you need to go to the hospital for infusion therapy.
Side effects
The following side effects are observed.
From the cardiovascular system: decreased blood pressure, orthostatic hypotension, collapse.
From the side of the central nervous system: headache that occurs at the beginning of treatment and disappears as it continues; dizziness, increased fatigue, general weakness.
From the gastrointestinal tract: anorexia, nausea, vomiting.
From the skin: facial hyperemia; allergic reactions, including skin rashes.
From the respiratory system: bronchospasm.
Interaction
When taking Molsidomin and other medications simultaneously, you need to take into account the features of their interaction:
- vasodilators , calcium antagonists, ATP inhibitors, diuretics help increase the hypotensive effect;
- acetylsalicylic acid enhances the antiplatelet effect;
- combination with Iloprost leads to a significant decrease in platelet aggregation, so in this case it is imperative to regularly check and evaluate the blood test;
- simultaneous use of Molsidomine and Sildenafil can lead to the development of irreversible arterial hypotension with life-threatening consequences, therefore this combination is strictly prohibited.
During pregnancy and lactation
Studies were conducted only on animals. No teratogenic effect was detected, but there is not enough information to date to make a definitive conclusion. Therefore, the use of Molsidomine during pregnancy is prohibited, especially in the first trimester.
The lactation period is a contraindication to Molsidomine therapy. If it is still prescribed, it is necessary to stop feeding milk for the period of treatment.
special instructions
Cautions and special measures for use. Molsidomine, as a rule, does not cause a significant decrease in blood pressure, however, caution should be exercised in patients with arterial hypotension, elderly people with reduced blood volume and patients receiving treatment with other vasodilators.
Particular attention when treating with the drug is required for patients after a hemorrhagic stroke, with impaired cerebral circulation and increased intracranial pressure, patients after a recent myocardial infarction, patients with a tendency to hypotensive reactions.
With long-term use of nitrates, it is recommended to include molsidomine in the treatment regimen to prevent the development of tolerance to them.
Patients with hepatic or renal insufficiency should use lower doses with a gradual increase until the desired therapeutic effect is obtained. In general, dose modification of molsidomine is not recommended when treating patients with renal impairment. But, taking into account that 90–95% of molsidomine metabolites are excreted by the kidneys, it is possible to reduce the dose or increase the intervals between doses of the drug, taking into account the individual response of patients.
Due to the fact that the drug contains lactose, it cannot be used in the treatment of patients with a rare form of congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
Use during pregnancy and lactation. In animal studies, no teratogenic effect of the drug was revealed. However, due to the lack of convincing data on the safety of the drug, the use of Molsikor in the treatment of pregnant women is contraindicated.
During breastfeeding, the use of the drug is contraindicated.
Children. Do not use the drug in children.
The ability to influence reaction speed when driving vehicles and working with other mechanisms. Considering the adverse reactions of the drug (dizziness) and the possible negative effect on concentration in people who drive a car or operate other machinery, the drug can be prescribed with caution only after a thorough assessment of the possible risk.
