Pharmacodynamics dihydropyridine derivative – blocker “slow” calcium channels II generation, has antianginal and hypotensive action. Communicating with the dihydropyridine receptor, blocks calcium channels reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes). Antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, decreases total peripheral vascular resistance, decreases the preload on the heart, reducing myocardial oxygen demand. Expanding the major coronary arteries and arterioles in the unaltered and ischemic myocardial areas, increases the supply of oxygen to the myocardium (especially in vasospastic angina); It prevents the development of constriction of the coronary arteries (including those caused by smoking). In patients with angina single daily dose increases the run-time physical activity slows the development of angina and ‘ischemic’ ST segment depression, reduces the frequency of angina attacks and nitroglycerin consumption. Has a long dose-dependent hypotensive effect. The antihypertensive effect is due to the direct vasodilating effect on vascular smooth muscle. When hypertension single dose provides a clinically significant reduction in blood pressure (BP) for 24 hours (in the position of the patient “lying” and “standing”). It does not cause a sharp decline in blood pressure, reduce exercise tolerance, left ventricular ejection fraction. It reduces the degree of left ventricular hypertrophy, has anti-atherosclerotic and cardioprotective effect in ischemic heart disease (IHD). No effect on myocardial contractility and conductivity, does not cause reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy does not increase the severity of microalbuminuria. It has no adverse effects on lipid metabolism and blood plasma. Time of onset of effect – 2-4 hour duration of effect of 24 hours. Pharmacokinetics Following oral administration of proviron side effects slowly absorbed from the gastrointestinal tract. The mean absolute bioavailability of 64%, the maximum concentration in serum is observed after 6-9 hours. The concentration of stable equilibrium is reached after 7 days of treatment. Food does not affect the absorption of proviron side effects. The mean volume of distribution of 21 l / kg body weight, indicating that most of the drug is in the tissues and relatively smaller – in the blood. Most of the drug present in the blood (95%), bind to plasma proteins.proviron side effects undergoes slow but extensive metabolism (90%) in the liver into inactive metabolites, has the effect of “first pass” through the liver. Metabolites not possess significant pharmacological activity. After a single oral half-life (T ½ ) varies from 31 to 48 hours when re-assigning T ½ was about 45 hours. About 60% of an oral dose is excreted in the urine primarily as metabolites, 10% unchanged, and 20-25% in the feces and in breast milk. proviron side effects Total clearance is 0.116 ml / sec / kg (7 ml / min / kg and 0.42 L / h / kg). In older patients (over 65 years) proviron side effects delayed excretion (T ½ 65ch) compared to younger patients, however, this difference has no clinical significance. patients with liver failure elongation assumed T ½ and accumulation of long-term administration of the drug in the body is higher than (T ½ to 60 hours). Renal failure does not significantly affect the kinetics of proviron side effects. The drug crosses the blood-brain barrier. When hemodialysis is not removed.
Indications Arterial hypertension (monotherapy or in combination with other antihypertensive agents). Angina, vasospastic angina (Prinzmetal angina) Contraindications
- Hypersensitivity to proviron side effects and other dihydropyridine derivatives;
- severe hypotension;
- collapse, cardiogenic shock;
- pregnancy and lactation;
- age of 18 years (effectiveness and safety have been established).
With caution : liver dysfunction, sick sinus syndrome (bradycardia and tachycardia.), Decompensated chronic heart failure, mild or moderate hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and for 1 month after) , diabetes, lipid profile, old age.
Dosing and Administration
Inside, the initial dose for the treatment of hypertension and angina is 5 mg 1 time per day. The dose may be increased to a maximum of 10 mg once a day. When hypertension maintenance dose may be 2.5 to 5 mg per day.
When angina and vasospastic angina – 5-10 mg per day, once. To prevent strokes -. 10 mg /
Thin patients, patients with a short, elderly patients, patients with impaired liver function as antihypertensive, proviron side effects is administered in an initial dose of 2.5 mg, as anti-anginal agents – 5 mg.
Not required change the dose while appointing stiazidnymi diuretics, beta-blockers and angiotensin-converting enzyme (ACE).
not required dose modification in patients with renal insufficiency.
Side effect On the part of the cardiovascular system : heart rate, shortness of breath, marked reduction in blood pressure, fainting, vasculitis, edema (swelling of the ankles and feet), “tides” of blood to the face, rarely – arrhythmias (bradycardia, ventricular tachycardia, atrial flutter) , chest pain, orthostatic hypotension, very rarely – the development or exacerbation of congestive heart failure, arrythmia, migraine.On the part of the central nervous system : headache, dizziness, fatigue, drowsiness, mood changes, seizures, rare – loss of consciousness, hypoesthesia, nervousness , paraesthesia, tremor, vertigo, fatigue, malaise, insomnia, depression, abnormal dreams, very rarely – ataxia, apathy, agitation, amnesia. From the digestive system : nausea, vomiting, epigastric pain, rarely – increased level of “liver” transaminases and jaundice (caused by cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea) rarely – gastritis, increased appetite. From the urogenital system : rare – pollakiuria, tenesmus, nocturia, sexual dysfunction ( including reduction of potency); very rarely – dysuria, polyuria. For the skin : very rarely – dermatoxerasia, alopecia, dermatitis, purpura, skin discoloration.Allergic reactions : itching, rash (including erythematous, maculopapular rash, urticaria), angioedema. With side of the musculoskeletal system : rarely – arthralgia, arthrosis, myalgia (with prolonged use); very rarely – myasthenia gravis. Other : rarely – gynecomastia, poliurikemiya, increase / decrease in body weight, thrombocytopenia, leukopenia, hyperglycemia, impaired vision, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnoea, epistaxis, increased sweating, thirst; very rarely – a cold clammy sweat, cough, rhinitis, parosmiya, taste disturbance, disturbance of accommodation, kserofgalmiya.
Symptoms: marked reduction of blood pressure, tachycardia, excessive peripheral vasodilation.
Treatment: gastric lavage, the appointment of activated carbon, the maintenance function of the cardiovascular system, the control performance of the heart and lungs, limbs elevated position, control of blood volume and diuresis. To restore vascular tone – use of vasopressors (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade – intravenous calcium gluconate. Hemodialysis is not effective.
Interactions with other drugs
inhibitors of microsomal oxidation increase the concentration of proviron side effects in plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes decrease.
Antihypertensive effect of weakening non-steroidal anti-inflammatory drugs, especially indomethacin (sodium retention and synthesis prosgoglandinov kidney blockade), Alpha adrenostimulyatorov , estrogens (sodium retention), sympathomimetic.
Thiazide and “loop” diuretics, beta-blockers, verapamil, inhibitors of AIF and nitrates increase antianginal and antihypertensive effects.
Amiodarone, quinidine, alpha 1-blockers, antipsychotic drugs (neuroleptics) and blockers “slow “calcium channel may enhance the hypotensive effect.
It has no effect on the pharmacokinetic parameters of digoxin and warfarin.
cimetidine has no effect on proviron side effects pharmacokinetics.
in a joint application with drugs lithium may increase manifestations of their neyrogoksichnosti (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus ). Calcium can reduce the effect blockers “slow” calcium channels.
Procainamide, quinidine, and other drugs that cause lengthening of the interval QT, reinforce the negative inotropic effect and may increase the risk of significant lengthening QT interval.
Grapefruit juice may reduce plasma proviron side effects concentration, but this decrease is so small that not significantly alter the effect of proviron side effects.
During treatment requires monitoring of body weight and sodium intake, the appointment of an appropriate diet.
It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).
The dosage regimen for the elderly is the same as for patients in other age groups.
An increase in dose should be closely monitored for elderly patients.
Despite the lack of blockers “slow” calcium channels “cancellation” syndrome, before stopping treatment recommended a gradual reduction in dose. proviron side effects has no effect on plasma concentrations of K +, glucose, triglycerides, total cholesterol, LDL cholesterol, uric acid, uric kreaginina and nitric acid.
Effects on ability to drive a car and mechanisms
There were no reports on the effect of proviron side effects on driving or using machinery. However, some patients in the early treatment preferably may occur drowsiness and dizziness. If this happens, the patient must take special precautions when driving and operating machinery. pro bodybuilding cycle