Nifedipine

Pharmacological properties

pharmacadipine has an antianginal and antihypertensive effect. blocks the entry of calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries through slow voltage-dependent calcium channels of cell membranes. relaxes the smooth muscles of blood vessels, eliminates spasms and expands the coronary and peripheral arteries, reducing opss, hell, afterload and myocardial oxygen demand; slightly reduces myocardial contractility, slightly reduces platelet aggregation.

Pharmacokinetics When taken orally, it is well absorbed in the digestive tract, bioavailability is 40-60%. Especially quickly (after 5–10 min) the effect develops with sublingual administration. Typically, maximum action is recorded after 30–40 minutes. Eating does not significantly affect the absorption rate of the drug. The hemodynamic effect persists for 4-6 hours. Up to 90% of nifedipine binds to plasma proteins. It is metabolized in the liver and excreted mainly in the form of inactive metabolites. The total clearance of nifedipine is 0.4-0.6 l / kg / h. T_½ is 2–4 hours. In elderly people and patients with cirrhosis of the liver, nifedipine metabolism slows down, so they have T_½ the drug can be extended by almost 2 times, which requires a dose reduction and an increase in the intervals between doses of the drug. In the body, nifedipine does not cumulate. In small quantities penetrates the BBB and the placental barrier, excreted in breast milk.

Indications

Ag (for the treatment of hypertensive crises).

Application

Pharmadipine is used to treat hypertensive crisis as an emergency drug. it is not recommended to use the drug in this dosage form for course administration.

If it is necessary to conduct a course of antihypertensive therapy, the drug and dosage form are selected by the doctor.

With a sudden and significant increase in blood pressure, the initial single dose for adults is 3-5 drops (2–3.35 mg), for the elderly - no more than 3 drops (2 mg) under the tongue or dripped on a piece of cracker or sugar, as possible holding the mouth longer. With insufficient effectiveness, the dose can gradually be increased to a clinically significant effect. In the future, in cases of increased blood pressure, it is necessary to focus on this particular dose. If necessary (increase in blood pressure to 190 / 100–220 / 110 mm Hg), a single dose can be gradually increased in some cases to 10–15 drops (6.7–10 mg), taking into account individual changes in blood pressure in the patient.

It is necessary to take into account the individual sensitivity of individual patients to Pharmadipine. In such cases, the dose is selected individually, starting with 3 drops, and gradually increase by 2-3 drops (1.34–2 mg) until the clinical effect is achieved.

Exceeding the initial dose of the drug can lead to a sharp decrease in blood pressure!

Contraindications

• Acute myocardial infarction (first 4 weeks); cardiogenic shock; severe aortic and mitral stenosis; unstable angina pectoris; do not use for the treatment of angina attacks, secondary prevention of myocardial infarction; decompensated heart failure; arterial hypotension (systolic hell 90 mm Hg. Art.); ventricular tachycardia with an expanded complex of qrs; weak sinus syndrome; Wolf-Parkinson-White syndrome (wpw), Laun-Genong-Levine syndrome (lgl); av blockade of the II and III degrees; porphyria; ileostomy established after proctocollectomy; pregnancy period; the period of breastfeeding; childhood; hypersensitivity to nifedipine and other components of the drug; hypersensitivity to other dihydropyridines; do not take concomitantly with rifampicin.

Side effects

Subject to recommendations for the use of the drug, side effects are minor and transient, as a rule, do not require discontinuation of therapy.

With frequent and uncontrolled use, adverse reactions characteristic of drugs of this pharmacological group are possible.

From the cardiovascular system: often - edema, vasodilation, infrequently - tachycardia, increased heart rate, arterial hypotension, syncope.

From the central and peripheral nervous system: often - headache; infrequently - vertigo, migraine, dizziness, tremor, sleep disturbance, anxiety; rarely - short-term visual impairment, agitation, paresthesia, dysesthesia.

From the endocrine system: hyperglycemia (should be considered in patients with diabetes mellitus).

From the digestive system: often - constipation; infrequently - when using high doses, abdominal pain, dyspeptic symptoms, flatulence, nausea, vomiting (very rare), gum hyperplasia (with prolonged use), dry mouth, transient increase in liver enzymes.

From the urinary system: infrequently - polyuria, dysuria.

From the hemopoietic system: rarely - anemia, leukopenia, thrombocytopenia.

Allergic reactions: infrequently - an allergic reaction, allergic edema / angioedema (including laryngeal edema); rarely - itching, hives, rash; very rarely - anaphylactic / anaphylactoid reactions.

Others: often - poor health; infrequently - nosebleeds, nasal congestion, erythema; rarely - swelling of the leg, muscle cramps, joint swelling, erectile dysfunction, nonspecific pain, fever, dyspnea.

special instructions

The drug should be used only in conditions of close clinical observation of the patient: with unstable angina, severe heart failure and severe aortic stenosis, severe pulmonary hypertension, hypertrophic cardiomyopathy, severe cerebrovascular accident, diabetes, impaired liver and kidney function, as well as elderly patients. in elderly patients, a decrease in cerebral blood flow is more likely due to sharp peripheral vasodilation. in patients with malignant antigens and hypovolemia undergoing hemodialysis, a significant decrease in hell can be observed with nifedipine. especially at the beginning of treatment and with the simultaneous use of β-receptor blockers, hypotension may develop, which some patients do not tolerate. the condition of such patients requires careful monitoring. in patients taking β-receptor blockers, signs of congestive heart failure may appear at the beginning of treatment. in patients with severe coronary insufficiency, due to reflex tachycardia, the course of coronary heart disease may worsen, and along with this, angina attacks will become more frequent. nifedipine should be used with caution in patients with angina pectoris or after a heart attack. if nifedipine should be withdrawn during treatment with pain behind the sternum. do not drink alcohol and smoke during treatment with nifedipine.

Doses of other drugs used with nifedipine should be established individually. Cardiac glycosides can also be used during treatment with nifedipine. When using nifedipine, a false increase in the results of spectrophotometric determination of the concentration of vanillyl mindic acid in urine is possible.

When using nifedipine with simultaneous iv administration of magnesium sulfate, pregnant women need careful monitoring of blood pressure because of the possibility of its reduction, which can damage the mother and fetus.

Patients with impaired liver function require careful monitoring, and in severe cases, dose reduction.

Nifedipine is metabolized through the cytochrome P450 3A4 system. In this regard, drugs that inhibit or induce this system of enzymes can alter the first-pass effect or clearance of nifedipine (see INTERACTIONS).

With the concomitant use of nifedipine with these drugs, it is necessary to control blood pressure and, if necessary, consider reducing the dose of nifedipine.

Separate in vitro experiments have revealed a relationship between the use of calcium antagonists, in particular, nifedipine, and reverse biochemical changes in spermatozoa, which impair the ability of the latter to fertilize. If the in vitro fertilization attempt was unsuccessful in the absence of other explanations, calcium antagonists, in particular, nifedipine, can be considered as a possible cause of this phenomenon.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. When using the drug, one should refrain from potentially hazardous activities that require increased attention (driving, working with other mechanisms, etc.).

Use during pregnancy and lactation. Nifedipine is contraindicated during pregnancy. Nifedipine passes into breast milk, so you should stop breastfeeding while using the drug.

Children. The drug is not used to treat children.

Interactions

Nifedipine can increase the severity of the antihypertensive effect of antihypertensive drugs that are used simultaneously, such as diuretics, β-receptor blockers, apf inhibitors, at1 receptor antagonists, other calcium antagonists, α-adrenergic receptor blockers, fde-5, α-methyldopa inhibitors.

When combined with β-receptor blockers, along with an increase in the hypotensive effect, in some cases the development of heart failure is possible.

Diltiazem slows the elimination of nifedipine from the body (if necessary, reduce the dose of nifedipine).

Amiodarone and quinidine can enhance the negative inotropic effect of nifedipine. In some cases, with a combination of nifedipine and quinidine when administered orally, there is a decrease in the concentration of quinidine in the blood plasma.

Combinations of nifedipine with cardiac glycosides, theophylline are usually well tolerated by patients, in very rare cases, an increase in the level of digoxin and theophylline in blood plasma is possible (the content of the latter in blood plasma should be monitored).

Nifedipine increases the concentration of carbamazepine, phenytoin in blood plasma. The combined use of nifedipine and cimetidine can lead to an increase in the level of nifedipine in blood plasma.

Rifampicin induces the activity of liver enzymes, accelerating the metabolism of nifedipine, which can lead to a decrease in the clinical effect of nifedipine (such a combination is contraindicated).

Treatment with nifedipine should be discontinued 36 hours before the planned anesthesia with fentanyl. Nifedipine is compatible with radiopaque agents.

Nifedipine in combination with iv administration of magnesium sulfate in pregnant women can cause neuromuscular blockade.

Nifedipine is metabolized through the cytochrome P450 3A4 system, located in the intestinal and liver mucosa. On this basis, drugs that inhibit or induce this enzyme system can alter the first-pass effect (after oral administration) or the clearance of nifedipine. The concomitant use of macrolide antibiotics (e.g. erythromycin), anti-HIV protease inhibitors (e.g. ritonavir), azole antimycotics (e.g. ketaconazole), nefazodone, fluoxetine, quinupristine / dalphopristine, cimetidine, cisapride and nifedipine may increase plasma concentrations of nifedipine.

Valproic acid is known to increase the plasma concentration of a structurally similar calcium channel blocker nimodipine due to inhibition of enzymes. Therefore, an increase in the concentration and effectiveness of nifedipine in blood plasma cannot be ruled out.

It is known that tacrolimus is metabolized through the cytochrome P450 3A4 system.

Published data indicate that in some cases, the dose of tacrolimus with simultaneous use with nifedipine can be reduced. With the simultaneous use of two drugs should monitor the concentration of tacrolimus in blood plasma and, if necessary, consider reducing the dose of tacrolimus.

Grapefruit juice inhibits the cytochrome P450 3A4 system. The use of grapefruit juice with the use of nifedipine leads to an increase in the concentration of the drug in blood plasma and an increase in the duration of action of nifedipine due to a decrease in metabolism during the first passage or decrease in clearance. Because of this, the antihypertensive effect of the drug may be enhanced. After regular use of grapefruit juice, this effect can last for 3 days after the last juice consumption.

Therefore, grapefruit / grapefruit juice should be avoided during nifedipine therapy.

The use of nifedipine can lead to false results in the spectrophotometric determination of the concentration of vanillyl mindic acid in the urine (when using the method of high performance liquid chromatography, this effect was not observed).

Overdose

Symptoms of acute intoxication with nifedipine: impaired consciousness up to coma, decreased hell, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock, which is accompanied by pulmonary edema.

Treatment. First aid measures should primarily be aimed at removing the drug from the body and restoring stable hemodynamics.

After oral administration, it is recommended to completely empty the stomach, if necessary, in combination with washing the small intestine.

Since nifedipine is characterized by a high degree of binding to blood plasma proteins and a relatively low volume of distribution, hemodialysis is ineffective, but plasmapheresis is recommended.

Bradycardia can be eliminated with β-sympathomimetics. When slowing down a life-threatening heart rate, the use of an artificial pacemaker is recommended.

Hypotension, which arose as a result of cardiogenic shock and vasodilation, can be eliminated with calcium preparations (10–20 ml of 10% calcium chloride or gluconate solution is administered iv slowly, then repeated if necessary). As a result, the level of calcium in the blood plasma can reach the upper limit of the norm or be slightly increased. If the introduction of calcium is not effective enough, it is advisable to use sympathomimetics such as dopamine or norepinephrine. Doses of these drugs are selected taking into account the achieved therapeutic effect.

The additional introduction of fluid should be approached very carefully, as this increases the risk of heart overload.

Storage conditions

In a dry, dark place at a temperature of no higher than 25 ° c. after opening the bottle, the drug is stored for 28 days.