anadrol cycle

The complementary mechanism of action of selective beta 1 -adrenoblocker metoprolol (reduced cardiac output) and vazoselektivnogo blocker “slow” calcium channels (BCCI), felodipine (reduced total peripheral vascular resistance) leads . to a antihypertensive effect and a better tolerability in comparison with the performance which can be obtained felodipine and metoprolol monotherapy hypotensive effect of the drug persists for days. metoprolol metoprolol – antagonist cardioselective beta 1 adrenoceptor not affected at therapeutic doses on beta 2 adrenergic receptors are localized mainly in peripheral vessels and bronchi. It has a small membrane-stabilizing effect and has no intrinsic sympathomimetic activity. Beta-blockers have negative inotropic and chronotropic effect. Metoprolol reduces the stimulatory effect of catecholamines on the myocardium and contributes to slowing of heart rate (HR), a decrease in cardiac output and blood pressure (BP). In the state of stress in increased secretion of adrenaline does not interfere with normal physiological vasodilation. At therapeutic doses metoprolol less affects the bronchial musculature than nonselective beta-blockers. To a lesser degree than the non-selective beta-blockers affect insulin secretion and metabolism of carbohydrates, and therefore, can be administered to patients with diabetes. Metoprolol has less effect on such cardiovascular responses during hypoglycemia such as tachycardia. When therapy with metoprolol in plasma glucose concentration is reduced to normal values faster than the non-selective beta-blocker therapy. Metoprolol reduces high blood pressure in the position of “standing” and “lying down”, as well as during exercise. At the beginning of therapy causes an increase in total peripheral vascular resistance (SVR). However, long-term treatment there is a decrease in blood pressure due to decreased peripheral vascular resistance with an unchanged cardiac output. In patients with hypertension, metoprolol reduced mortality from cardiovascular causes. In patients receiving no marked changes in the values of water-electrolyte balance of blood. Felodipine Felodipine -. Dihydropyridine derivative is selective BCCI and is intended for the treatment of hypertension, stable angina Felodipine is a racemic mixture. The conductivity and contractility of vascular smooth muscle is inhibited by exposure to calcium channels of cell membranes. Due to the high selectivity to the smooth muscle of the arterioles, felodipine in therapeutic doses has no negative inotropic effect on myocardial contractility or conductivity. Felodipine relaxes smooth muscles of the airways and has little effect on the motility of the gastrointestinal tract. With anadrol cycle prolonged use has no clinically significant effect on the concentration of lipids in the blood. In patients with type 2 diabetes when using felodipine within 6 months no clinically significant effect on the concentration of glycated hemoglobin (HbAlc). Felodipine can also be used in patients with left ventricular dysfunction receiving standard therapy, and patients with asthma, diabetes, . gout or dyslipidemia antihypertensive effect:. decrease in blood pressure while taking felodipine due to a decrease in peripheral vascular resistance felodipine is effective in reducing blood pressure in patients with hypertension in the position of “lying” and “sitting”, “standing”, at rest and during exercise. Since felodipine no effect on smooth muscle veins or adrenergic action, the development of orthostatic hypotension occurs. At the beginning of treatment, due to a decrease in blood pressure in the patients receiving felodipine, may be a temporary reflex increase in heart rate and cardiac output, which is leveled when combined with beta-blockers. Action felodipine on blood pressure and peripheral vascular resistance correlates with the plasma concentration of felodipine. Once stable equilibrium concentration in plasma felodipine antihypertensive effect is maintained throughout the dosing interval of at least 24 hours. Treatment of felodipine leads to regression of left ventricular hypertrophy. Felodipine reduces vascular resistance in the kidney possesses natriuretic and diuretic effect and has no kaliyureticheskim effect (for by reducing the rate of tubular reabsorption of sodium and water). Felodipine has no effect on glomerular filtration rate and urinary albumin.

The pharmacokinetics of metoprolol After oral metoprolol completely absorbed in the intestine. Systemic bioavailability of metoprolol tablets with sustained release Betalok ® KRC is 30-40%. Metabolized in the liver to form the 3 major metabolites, do not possess pharmacological activity and have no clinical significance. Metoprolol eliminated via the kidneys. Half-life is an average of 3.5 hours. About 5% of the dose is excreted unchanged, the remainder of the dose – in the form of metabolites. Communication with low plasma proteins, approximately 5-10%. Felodipine display felodipine systemic bioavailability is about 15% and is independent of food intake. Meal influences the absorption rate of felodipine resulting in increased speed to maximum concentration (C max ) in plasma by about 65%. The C max in plasma achieved in 3-5 hours after ingestion of the drug. Communication to plasma proteins is approximately 99%. The volume of distribution at steady state of approximately 10 l / kg. The half-life (T 1/2 ) in the final phase of felodipine about 25 hours, the equilibrium concentration reached after 5 days. Not accumulates. Total plasma clearance averaged 1200 ml / min. In patients with impaired liver function and elderly patients felodipine plasma concentration increases. However, only partially explains the age of the individual plasma concentrations of felodipine changes. It is metabolized in the liver, all pharmacologically inactive metabolites. About 70% of the dose is excreted as metabolites by the kidneys, the rest – through the intestines. Less than 0.5% is excreted by the kidneys unchanged. In violation of the plasma concentration of felodipine does not change in renal function, but there is accumulation of inactive metabolites. Felodipine does not appear in hemodialysis. Metoprolol + Felodipine Admission Logimaks drug® does not alter the bioavailability of active ingredients, compared to separate simultaneous reception of metoprolol and felodipine. Absorption figures are independent of food intake.

Indications
Hypertension (can be used in cases where the treatment of beta-blockers or dihydropyridine derivatives BCCI, used in monotherapy, did not have a clinically meaningful effect).

Contraindications
: Hypersensitivity to metoprolol, felodipine, or other components of the drug, as well as other derivatives of dihydropyridine
Unstable angina
atrioventricular block II and III degree of
chronic heart failure decompensation (pulmonary edema, hypoperfusion or hypotension, heart failure III-IV functional class NYHA classification) and continuous or intermittent inotropic therapy agonists beta adenoretseptorov.
bradycardia or severe hypotension with the presence of clinical symptoms of
sick sinus syndrome
Cardiogenic shock
severe peripheral circulatory disorders (with the threat of gangrene)
suspected acute myocardial infarction stage (heart rate less than 45 bpm. / min ., the PQ interval is more than 0.24 seconds or systolic blood pressure less than 100 mm Hg. Art.)
Age 18 years (effectiveness and safety have not been established)
Pheochromocytoma (without the simultaneous use of alpha-blockers).
lactose intolerance, lactase deficiency and glucose-syndrome galactose malabsorption (product contains lactose). Precautions (comparing the benefit / risk): severe renal insufficiency (. creatinine clearance (CC) of less than 30 ml / min), aortic stenosis, abnormal liver function, myocardial infarction, hypotension, acute metabolic acidosis , chronic heart failure (I-II functional class NYHA classification), bronchial asthma, chronic obstructive pulmonary disease (COPD), Prinzmetal angina.

Pregnancy and lactation Pregnancy  should not be administered during pregnancy. Metoprolol can be used during pregnancy and lactation only if absolutely necessary, when benefit to the mother outweighs the potential risk to the fetus and / or the child. Beta-blockers are cause bradycardia in the fetus, infants and children who are breastfed. This should be considered when deciding on the appointment of the drug during the last trimester of pregnancy and just before delivery. Currently, there is insufficient data on the use of felodipine in pregnant women. Based on the data obtained in animal abuse fetal development, felodipine should not be administered during pregnancy. BCCI may reduce uterine contractions in preterm labor, however, is not enough evidence to support an increase in the duration of physiological childbirth. Possible risk of fetal hypoxia in the presence of maternal arterial hypotension and a decrease in perfusion in the uterus due to redistribution of the blood flow and peripheral vasodilation. Breastfeeding metoprolol and felodipine are allocated into breast milk. If necessary, use of the drug Logimaks ® during lactation, breast-feeding should be discontinued.

 

Dosing and Administration
Inside, taken in the morning with water. The tablet does not share, do not crush or chew. The tablets can be used on an empty stomach or with a small amount of food is low in fat and carbohydrates.
The dose of the drug Logimaks ® selected individually. When selecting the starting dose is recommended to take into account the effect of the previously received doses of beta-blockers or the BCCI.Typically, the initial dose: 1 tablet Logimaks ® 1 times daily. If necessary, the dose may be increased up to 2 tablets 1 in one step once a day. Impaired renal function Renal impairment does not affect the concentration of drug in blood plasma. No need to adjust the dose for patients with renal impairment, however caution should be exercised when administering the drug to patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) (see. Sections “Contraindications” and “Special Instructions”). Abnormal liver function usually no need to adjust the dose for patients with liver cirrhosis, as metoprolol blood protein binds only to a small extent (5- 10%). In the presence of symptoms liver function abnormalities (eg, patients who have undergone bypass surgery portocaval) should not take more than 1 tablet of the drug Logimaks ® per day. Elderly patients usually enough 1 tablet of the drug Logimaks ® 1 times daily. If necessary, the dose can be increased up to 2 tablets 1 time per day.Children experience of the drug in children under 18 years is missing.

Overdose Toxicity metoprolol: metoprolol dose of 7.5 g in an adult caused lethal intoxication with. At the 5-year-old child, who took 100 mg of metoprolol, after gastric lavage were observed signs of intoxication. Receiving 450 mg metoprolol teenager 12 years has led to a moderate intoxication. Admission 1.4 g and 2.5 g of metoprolol adult caused moderate and severe intoxication, respectively.Admission for adults 7.5 g resulted in extremely severe intoxication. Felodipine: when using 10 mg felodipine in a 2-year-old minor child toxicity was noted. 150-200 mg felodipine in a 17-year-old patient and 250 mg in adult intoxication caused by mild to moderate. Probably, felodipine has a more significant effect on the peripheral circulation than the heart compared to other drugs of this pharmacotherapeutic group. Symptoms of overdose In case of overdose, prolonged dosage forms of intoxication symptoms appear 12-16 hours after ingestion, severe symptoms can occur within a few days after reception.metoprolol: an overdose of metoprolol most serious are the symptoms of the cardiovascular system, but sometimes, especially in children and adolescents, may predominate symptoms of the central nervous system (CNS) and impaired function of the lungs, bradycardia, atrioventricular (AV) blockade I- III degree, asystole, marked reduction in blood pressure, poor peripheral perfusion, cardiac failure, cardiogenic shock; sleep apnea, as well as fatigue, impaired consciousness, tremors, convulsions, sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycaemia (especially in children), or hyperglycemia, hyperkalemia; impairment of renal function; transient myasthenic syndrome; concomitant use of alcohol, antihypertensives, quinidine or barbiturates may aggravate the patient’s condition. The first signs of overdose can be observed 20 minutes – 2 hours after taking the medication. Felodipine: an overdose of felodipine there is the greatest influence on the cardiovascular system: bradycardia (sometimes tachycardia), marked reduction in blood pressure, AV block, ventricular premature beats, atrioventricular dissociation, asystole, ventricular fibrillation; headache, dizziness, impairment of consciousness (coma), convulsions; shortness of breath, pulmonary edema and apnea; may develop respiratory distress syndrome in adults; acidosis, hypokalemia, hyperglycemia, hypocalcemia possible; “Tides” of blood to the upper half of the body, hypothermia; nausea and vomiting.

Treatment of overdose. Metoprolol: administration of activated charcoal, if necessary gastric lavage. IMPORTANT! Atropine (0.25-0.5 mg / in adults, 10-20 mg / kg for children) must be assigned to gastric lavage (the risk of stimulation of the vagus nerve). If necessary, maintain the airway (intubation), and adequate ventilation of the lungs. Restores the volume of circulating blood and infusion of dextrose (glucose). ECG monitoring. Atropine 1.0-2.0 mg / in repeated administration (particularly in the case of vagal symptoms) as needed. In the case of reducing myocardial shown infusion dobutamine or dopamine. It is also possible to use glucagon. In some cases, it may be effective to add to the treatment of epinephrine (adrenaline). When arrhythmias and the expansion of the QRS complex of infusion solutions administered sodium (chloride or bicarbonate). Installation of an artificial pacemaker. When cardiac arrest due to an overdose may require resuscitation for several hours. Symptomatic treatment.Felodipine: administration of activated charcoal, if necessary gastric lavage, in some cases is effective even at a late stage of intoxication. Symptomatic therapy. IMPORTANT! Atropine (0.25-0.5 mg / in adults, 10-20 mg / kg for children) must be assigned to gastric lavage (the risk of stimulation of the vagus nerve). ECG monitoring. If necessary, maintain the airway and adequate ventilation of the lungs. It is shown that correction of acid-base balance and water-electrolyte balance of the blood serum. In the case of bradycardia and AV blockade atropine administered at 0.5-1 mg / per adult (20 to 50 mg / kg for children), if necessary, repeat administration, or administered first isoprenaline 0.05-0.1 ug / kg / min. In acute toxicity at an early stage may require installation of an artificial pacemaker. Marked anadrol cycle reduction in blood pressure is adjusted in / increase in the circulating liquid. If desired infusion administered epinephrine (adrenaline) or dopamine. In acute toxicity can be administered glucagon. If cardiac arrest due to an overdose may require resuscitation for several hours. In convulsions diazepam prescribed. Pursue other symptomatic treatment.

The interaction with other drugs, and other kinds of interaction
partner with the reception means, interacting with the cytochrome P450 enzyme system, may affect the concentration of felodipine and metoprolol in plasma. There was no interaction between metoprolol and felodipine, as they are metabolized through various cytochrome P450 isoenzyme system. Interactions with metoprolol Metoprolol is a substrate for the isoenzyme CYP2D6. Drugs that inhibit isozyme CYP2D6, such as quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine may alter the concentration of metoprolol in the blood plasma. You may need to decrease the dose of the drug Logimaks ® during concomitant use with these drugs. Interactions with felodipine Felodipine is a substrate of CYP3A4 isoenzyme for. Drugs that induce or inhibit isoenzyme of CYP3A4, have a significant impact on the concentration of felodipine in plasma. Drugs that induce cytochrome P450 system: phenytoin, carbamazepine, phenobarbital and rifampicin, and St. John’s wort preparations increase the metabolism of felodipine due to induction of cytochrome P450 system. The combined use of phenytoin, carbamazepine, phenobarbital and rifampin reduces the area under the curve values “concentration – time» (AUC) and 93% C max felodipine 82%. Avoid joint use with inducers of CYP3A4 isoenzyme. Drugs that inhibit the cytochrome P450 system: antifungal azole agents (itraconazole, ketoconazole), macrolide antibiotics (eg, erythromycin) and HIV protease inhibitors are inhibitors of CYP3A4 isoenzyme. In a joint application itraconazole Cmax of felodipine increased by 8 times, AUC – 6 times. In a joint application Erythromycin Cmax and AUC values of felodipine increased about 2.5 times. Avoid joint use of felodipine and inhibitors of CYP3A4. Grapefruit juice inhibits the enzyme CYP3A4 isoenzyme system. Application of felodipine with grapefruit juice increased C max and AUC felodipine about 2 times. Avoid sharing application. Tacrolimus: Felodipine may cause an increase tacrolimus concentration in blood plasma. In a joint application is recommended to monitor the concentration of tacrolimus in the blood serum may require adjustment of the dose of tacrolimus.Tacrolimus: in the combined use of cyclosporine and felodipine the C max of felodipine increased by 150%, the AUC increased by 60%. However, the effects of felodipine on the pharmacokinetic parameters of cyclosporine minimum. Cimetidine: concomitant use of cimetidine and felodipine leads to an increase in the C max and AUC of felodipine at 55%. Avoid joint use of the drug Logimaks ® with the following means: barbituric acid derivatives: Barbiturates (the study was conducted with fenofarbitalom ) slightly increase the metabolism of metoprolol, resulting induction of microsomal liver enzymes. propafenone:when using propafenone 4th patients treated with metoprolol, showed an increase in plasma concentrations of metoprolol by 2-5 times, while at 2 patients had side effects that are typical of metoprolol. This interaction was confirmed in a study in 8 volunteers. Probably due to inhibition of the interaction of propafenone, like quinidine, metoprolol metabolism by cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of beta-blocker, the joint use of the drug Logimaks ® and propafenone does not seem appropriate. Verapamil: a combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil may cause bradycardia and lead to a reduction in blood pressure. Verapamil and beta-blockers are mutually inhibitory effect on AV conduction and function of the sinus node.Correction dose Logimaks drug ® may be required for simultaneous use with the following drugs: antiarrhythmic agents of Class I: antiarrhythmics class I and beta-blockers, while the application may result in to the summation of the negative inotropic effect, which leads to serious adverse hemodynamic effects in patients with left ventricular dysfunction. Also avoid the use of such a combination in patients with sick sinus syndrome and AV conduction disorder. The interaction is described by the example of disopyramide. Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to alpha-gidroksimetoprolola 2.5 times. At the same time strengthening the metoprolol action observed. Clonidine: increased blood pressure during sharp lifting of clonidine may be more pronounced when a joint reception with beta-blockers. In a joint application, in the case of clonidine, the termination of receiving beta-blockers should start several days before clonidine. Diltiazem: Diltiazem and beta-blockers reinforce inhibitory effect on AV conduction and sinus node function. When combined with metoprolol diltiazem were cases of severe bradycardia. Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs weaken the antihypertensive effect of beta-blockers. This reaction is the most studied of indomethacin. There was no specified interactions for sulindac. In studies with diclofenac this reaction was observed.Phenylpropanolamine: phenylpropanolamine (norephedrine) in single doses of 50 mg may cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol generally prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers can cause paradoxical reaction of hypertension in patients receiving high doses of phenylpropanolamine. A few cases of hypertensive crisis in patients receiving phenylpropanolamine. Epinephrine: reports of 10 cases of severe hypertension and bradycardia in patients treated with non-selective beta-blockers (including pindolol and propranolol) and treated with epinephrine. Interaction observed in the group of healthy volunteers. It is assumed that these reactions can also occur when using epinephrine in conjunction with local anesthetics Accidental contact with the bloodstream. It is assumed that this risk is much lower with cardioselective beta blockers. Quinidine: quinidine inhibits metoprolol metabolism in a particular group of patients with the “fast” hydroxylation (in Sweden about 90% of the population), causing mostly a significant increase in plasma concentrations of metoprolol and gain beta adrenoblockade. It is believed that such interaction is typical for other beta-blockers, metabolism involving cytochrome P4502D6. Amiodarone: concomitant use of amiodarone and metoprolol may lead to severe sinus bradycardia. Taking into account the extremely long half-life of amiodarone (50 days), to consider the possible interaction after a long time after the abolition of amiodarone. Rifampicin: rifampicin may enhance the metabolism of metoprolol by reducing the plasma concentration of metoprolol. Cardiac glycosides: in combination with beta-blockers may violate AV conduction and cause bradycardia. The concentration in the blood plasma of metoprolol may increase with concomitant administration with cimetidine, hydralazine, selective serotonin reuptake inhibitors such as paroxetine, fluoxetine and sertraline.Patients simultaneously receiving metoprolol and other beta-blockers (in the form of eye drops), or monoamine oxidase inhibitors (MAOIs) should be monitored carefully. While taking beta-blockers inhalation anesthetics enhance cardiodepressive action. In patients receiving beta-blockers to patients receiving hypoglycemic agents for oral administration may require dose correction last.

Cautions
Use caution when combined with cardiac glycosides. Logimaks ® may exacerbate symptoms of peripheral circulatory disorders, such as “intermittent” claudication. Extreme care is required in the following conditions: severe renal insufficiency (creatinine clearance less than 30 ml / min), aortic stenosis, abnormal liver function, myocardial infarction, complicated with acute heart failure, hypotension, which in predisposed patients may cause myocardial ischemia, acute metabolic acidosis.
It is not recommended to start treatment with Logimaks ® in patients not previously treated with antihypertensive therapy.
Do not be prescribed to patients with latent or diagnosed heart failure with clinical manifestations without appropriate therapy.
The use of Logimaks drug ® may affect carbohydrate metabolism or mask hypoglycaemia, together with so when using the drug Logimaks ® risk of effects on carbohydrate metabolism less than with non-selective beta-blockers.
In some cases, existing AV conductivity of disorders may increase, leading to an AV blockade.
Patients taking Logimaks ® should not be administered intravenously such as BCCI verapamil.
In patients with Prinzmetal angina frequency and severity of angina attacks may increase due to spasm of the coronary vessels, caused by stimulation of alpha-adrenergic receptors. In this connection, not recommended for non-selective beta-blockers anadrol cycle of this group of patients. It should be used with caution selective beta1-blockers.
In patients with asthma or chronic obstructive pulmonary disease should be implemented concomitant therapy with beta 2 -adrenomimetikami. In the case when the patient begins taking Logimaks ® , you may need to increase the dose betag-agonists.
While taking beta-blockers anaphylactic shock may take a more severe form. Application of epinephrine (adrenaline), in the commonly used dosage does not always lead to the expected therapeutic effect.
Patients with pheochromocytoma recommended in parallel with the preparation Logimaks ® assign alpha blockers.
The combined use of drugs that induce isoenzyme CYP3A4, leads to a significant decrease in plasma felodipine concentration and insufficient The therapeutic effect of the drug is (see. section “interaction with other medicinal products and other forms of interaction”). Avoid combined use of these drugs.
The combined use of drugs that inhibit the isoenzyme of CYP3A4, resulting in a significant increase in plasma felodipine concentrations.
Avoid reception Logimaks drug ® with grapefruit juice due to the significant increase in felodipine plasma concentrations.
It is necessary to avoid abrupt withdrawal of reception beta-blockers, especially in patients with high risk of cardiovascular complications due to the possible increase in symptoms of chronic heart failure and increased risk of myocardial infarction and sudden death. If necessary, the abolition of the drug Logimaks ® should be done gradually by reducing the dose over 1-2 weeks. In the case of surgical intervention should be warned anesthetist that the patient is taking Logimaks ® . Running low dose t3 clen cycle trying to lose bodyfat isn’t a real hot idea imo.