Pharmacological properties 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 action is due to a direct vasodilatory effect on the smooth muscle of blood vessels .. 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 dosage 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 dosage. 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 dosage 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 1/2 ) ranges from 31 to 48 hours when re-assigning the T 1/2 of 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 dosage 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 dosage slowed elimination (T 1/2 65ch) as compared to young patients, but the difference has no clinical significance. Patients with liver failure elongation assumed T 1/2 and prolonged drug accumulation assignment will be higher in the body (T 1/2 to 60 hours).Renal failure has no significant effect on the kinetics of proviron dosage. 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 dosage and other derivatives of dihydropyridine; – severe hypotension; – collapse, cardiogenic shock, – unstable angina (except Prinzmetal’s angina) – pregnancy and lactation; – age of 18 years (effectiveness and safety have been established).
With caution: liver dysfunction, sick sinus syndrome (bradycardia, tachycardia), chronic heart failure decompensation, mild or moderate degree of hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and for 1 months after), diabetes mellitus, 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 can be 5 mg per day. In angina pectoris and vasospastic angina – 5 – 10 mg per day dose. Thin patients, patients with a short, elderly patients, patients with impaired liver function as a hypotensive agent administered in an initial dose of 2.5 mg; as anti-anginal agents -. 5 mg does not require changing the dose with concomitant administration with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. 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, rarely -ataksiya, 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, anorexia, hyperbilirubinemia. From the urogenital system: rare – pollakiuria, tenesmus, nocturia, sexual dysfunction (including reduced 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 the musculoskeletal system: rarely – arthralgia, arthrosis, myalgia (with prolonged use); very rarely – myasthenia gravis. The other: seldom – gynecomastia, poliurikemiya, increase / decrease in body weight, thrombocytopenia, leukopenia, hyperglycemia, impaired vision, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnoea, epistaxis, increased sweating, thirst; rarely coldly clammy sweat, cough, rhinitis, parosmiya, taste disturbance, disturbance of accommodation, xerophthalmia.
Overdose 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 dosage 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 of prostaglandins kidney blockade), Alpha adrenostimulyatorov , estrogens (sodium retention), sympathomimetic. Thiazide and “loop” diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase antianginal and antihypertensive effects. Amiodarone, quinidine, alpha 1-blockers, antipsychotic drugs (neuroleptics) and blockers ” slow “calcium channels may increase the hypotensive effect. It has no effect on the pharmacokinetic parameters of digoxin and warfarin. cimetidine did not affect the pharmacokinetics of proviron dosage. in a joint application with drugs lithium may increase manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, noise ears). calcium can reduce the effect of blockers “slow” calcium channels. procainamide, quinidine and other drugs causing prolongation of the interval QT, reinforce the negative inotropic effect and may increase the risk of significant lengthening of the QT interval. Grapefruit juice can reduce blood plasma proviron dosage concentrations however this decrease is so small that it does not significantly alter the effect of proviron dosage.
Cautions 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 the patients in other age groups. By increasing the dose should be carefully monitored for elderly patients. Despite the lack of blockers “slow” calcium syndrome channels “cancel” before the termination of treatment is recommended a gradual reduction in dose. proviron dosage has no effect on plasma concentrations of K + , glucose, triglycerides, total cholesterol, LDL , uric acid, creatinine, uric acid and nitrogen. Effects on ability to drive a car and mechanisms There were no reports on the effect of proviron dosage 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. how much to inject for weight loss
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