testosterone propionate side effects – selective beta 1 adrenoblokator without intrinsic sympathomimetic activity. It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses of beta-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), decreases intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effect (slows the heart rate (HR ), inhibits cardiac conduction, reduces the excitability and contractility of the myocardium). With increasing doses blocks the beta 2 -adrenergic receptors.
Total peripheral vascular resistance at the beginning of the use of beta-blockers in the first 24 hours is increased (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of the beta 2 -adrenoceptor), it returns to the original, but with long-term appointment is reduced by 1-3 days. |
The antihypertensive effect is associated with a decrease in cardiac output, the suppression of the sympathetic stimulation of peripheral blood vessels, reduction in activity of the renin-angiotensin-aldosterone system by inhibiting beta-adrenergic juxtaglomerular kidney machine (which leads to a decrease in renin secretion), restoration of the sensitivity of the baroreceptors of the aortic arch (not going to increase their activity in response to a decrease in blood pressure) and the effect on the central nervous system. When hypertension effect develops after 2-5 days, stable operation – through 1-2 months.therapy.
Hydrochlorothiazide is a thiazide diuretic, violates the reabsorption of sodium, chlorine, potassium, magnesium in the distal nephron, delaying the excretion of calcium, uric acid. Increased renal excretion of these ions is accompanied by increased urine output (due to osmotic binding of water). Hydrochlorothiazide reduces the volume of blood plasma renin activity increases in plasma and aldosterone secretion.When taken in high doses of hydrochlorothiazide increases the excretion of bicarbonate, with a long reception reduces calcium excretion.
The antihypertensive effect develops due to a decrease in circulating blood volume (CBV), reactivity changes of the vascular wall, reducing the effect of pressor amines vasoconstrictor (epinephrine, norepinephrine) and strengthening the depressive effect on ganglia. No effect on normal blood pressure (BP).
The diuretic effect is observed within 1-2 hours, reaches a peak after 4 hours and lasts for 6-12 hours. The antihypertensive effect occurs within 3-4 days, but in order to achieve optimal therapeutic effect requires 3-4 weeks.
testosterone propionate side effects
, testosterone propionate side effects almost completely absorbed in the gastrointestinal tract, food intake does not affect absorption. The effect of “first pass” through the liver is insignificant, resulting in a high bioavailability (about 90%).
testosterone propionate side effects is metabolized by oxidative way without subsequent conjugation. All metabolites have a strong polarity and the kidneys. Major metabolites detected in plasma and urine did not exhibit pharmacological activity. Data obtained from experiments with microsomes in vitro human liver demonstrate that testosterone propionate side effects is metabolized mainly via isoenzyme CYP3A4 (about 95%) and CYP2D6 isozyme plays only a minor role.
Communication with the plasma proteins around 30%. Distribution Volume – 3.5 l / kg. The total clearance – about 15 l / h. The maximum plasma concentration is determined after 2-3 hours. Permeability through the blood brain barrier and the placental barrier – is low.
The half-life of plasma (10-12 hours) have provided efficiency within 24 hours after receiving a single daily dose.
testosterone propionate side effects excreted two paths, 50% of the dose is metabolized in the liver to inactive metabolites. About 98% is excreted by the kidneys, of which 50% is excreted as unchanged; less than 2% – through the intestines (in the bile). Because removal takes place in the kidneys and liver alike, patients with impaired liver function or renal insufficiency correction dose is not required.
After oral administration, absorption and bioavailability of hydrochlorothiazide is approximately 70%. Contact with blood plasma proteins – 60-80%.
The ingestion of 12.5 mg of hydrochlorothiazide the maximum plasma concentration is reached after 1.5-4 hours and 70 ng / ml, while ingestion of 25 mg of hydrochlorothiazide the maximum plasma concentration is reached in 2 to 5 hours and is 142 ng / mL.
In the therapeutic dose range of the average value of the area under the curve “concentration – time» (AUC) increases in direct proportion to the dose, the appointment of 1 time per day accumulation is negligible. It penetrates through the blood-barrier and into breast milk. The half-life (T 1/2 ) – 5-6 hours.
Hydrochlorothiazide slightly metabolized in the liver. Hydrochlorothiazide is derived almost entirely (95%) by the kidneys in an unmodified form. 50-70% of an oral dose is excreted within 24 hours.
Hypertension mild to moderate severity.
- Hypersensitivity to testosterone propionate side effects and other ingredients;
- hypersensitivity to hydrochlorothiazide or other sulfonamide derivatives;
- severe bronchial asthma and chronic obstructive pulmonary disease;
- congestive heart failure or chronic heart failure decompensation requiring of inotropic therapy;
- cardiogenic shock;
- sick sinus syndrome (including sinoatrial block);
- atrioventricular block II and III degree, without a pacemaker;
- severe bradycardia (heart rate less than 50 beats / min..);
- pheochromocytoma (without the simultaneous use of alpha-blockers);
- unmanageable diabetes;
- late stages of peripheral circulation (including Raynaud’s syndrome);
- severe hypotension (systolic blood pressure less than 100 mm Hg);
- Refractory hypokalaemia, hyponatraemia, hypercalcaemia;
- metabolic acidosis;
- acute renal failure;
- chronic renal insufficiency (creatinine clearance (CC) of less than 30 ml / min.), anuria;
- severe liver dysfunction, including coma and precoma;
- simultaneous use with floctafenine, sultopride.
- simultaneous reception of monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors);
- age of 18 years (effectiveness and safety have been established);
- lactose intolerance, lactase deficiency or glkzhozo-galactose malabsorption;
The caution should be used in heart failure, atrioventricular block I degree, Prinzmetal angina, peripheral circulatory disorders, coronary heart disease, liver failure, renal failure (creatinine clearance 30 mL / min.); hyperthyroidism, pheochromocytoma (during treatment with alpha-blockers), fluid and electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia); depression (including history), myasthenia gravis, gout, psoriasis, as well as in elderly patients, hyperuricemia, diabetes mellitus with significant fluctuations in blood glucose levels, a strict diet, hypovolemia, asthma, bronchospasm (in history), conducting desensitizing therapy.
Pregnancy and lactation
Use of the drug Bisangil contraindicated during pregnancy.
It is currently unknown is displayed whether testosterone propionate side effects in breast milk.
Diuretics from the group thiazides are excreted in breast milk and, therefore, during the treatment breastfeeding preparation Bisangil not recommended.
If the use of the drug is necessary during lactation, breast-feeding should be abolished .
Dosing and Administration
Bisangil recommended to take the morning (during the meal).
The tablets should be swallowed whole, without chewing, with a small amount of liquid, 1 time per day.
The dose should be selected individually.
The initial dose of the drug Bisangil – 1 tablet of 2.5 mg / 6.5 mg (testosterone propionate side effects 2.5 mg / hydrochlorothiazide 6.25 mg), 1 per day. If the antihypertensive effect is insufficient dose increase (2 weeks) – 1 tablet of 5 mg / 6.25 mg (5 mg testosterone propionate side effects / hydrochlorothiazide 6.25 mg), 1 time per day.
Patients with impaired hepatic function, as well as elderly patients correction mode is not required.
In patients with impaired renal function (creatinine clearance 30 mL / min.), The maximum daily dose of testosterone propionate side effects should not exceed 10 mg.
testosterone propionate side effects
The frequency of adverse reactions listed below was determined according to the following (World Health Organization): very often – at least 10%; often – at least 1% but less than 10%; infrequently – at least 0.1% but less than 1%; rare – less than 0.01% but less than 0.1%; very rarely – less than 0.01%, including isolated reports.
On the part of the heart and blood vessels:
very often – slowing of heart rate (bradycardia, particularly in patients with chronic heart failure (CHF)); palpitations, often – marked reduction of blood pressure (especially in patients with CHF), a manifestation of vasoconstriction (increased peripheral circulatory disorders, feeling of cold in the extremities (paraesthesia); rarely – a violation of atrioventricular (AV) conduction (until the development of a complete transverse blockade and heart failure ), arrhythmia, orthostatic hypotension, worsening of heart failure with the current development of peripheral edema (swelling of the ankles, feet, shortness of breath), chest pain.
From the nervous system:
often – dizziness, headache, asthenia, fatigue, sleep disturbances, depression, anxiety;
rare – confusion, or short-term memory loss, “nightmarish” dream, hallucination, myasthenia gravis, tremor, muscle cramps.
Typically, these events are mild and are usually within 1 to 2 weeks after initiation of treatment.
From the sensory organs:
rarely – visual disturbances, reduced lacrimation (to consider when wearing contact lenses), tinnitus, hearing loss, ear pain;
very rare – dryness and soreness of the eyes, conjunctivitis, taste disturbances.
The respiratory system: rarely – bronchospasm in patients with asthma or obstructive airways disease; rarely – allergic rhinitis; nasal congestion.
From the digestive system:
often – nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, stomach pain,
rarely – hepatitis, increased activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase), increasing the concentration of bilirubin, a change of taste.
From the musculoskeletal system:
rarely – arthralgia, back pain.
From the urogenital system:
very rarely – a violation of potency, libido weakening.
rarely – increased concentration of triglycerides in the blood; in some cases – thrombocytopenia, agranulocytosis, leukopenia.
rarely, pruritus, rash, urticaria
For the skin:
rarely – increased sweating, flushing of the skin, rash, psoriasiform skin reactions;
very rare – alopecia, beta-blockers may exacerbate psoriasis.
Other: a syndrome of “cancellation” (increased frequency of angina attacks, increased blood pressure).
Violation of water and electrolyte balance: hypokalemia, hypomagnesemia, hypercalcemia and alkalosis gipohloremichesky: dryness of the oral mucosa, thirst, irregular heart rhythm, changes in mood or psyche, cramps and muscle pain, nausea, vomiting, unusual tiredness or weakness. Gipohloremichesky alkalosis may cause hepatic encephalopathy or hepatic coma.
Hyponatremia: confusion, convulsions, lethargy, slowing of thought processes, increased fatigue, irritability, muscle cramps.
hyperglycemia, glycosuria, hyperuricemia with the development of a gout attack. Thiazide treatment can disrupt glucose tolerance, and diabetes can latentnoprotekayushy manifest. At high doses may be increased lipid concentration in the blood serum.
From the digestive system:
cholecystitis, or pancreatitis, cholestatic jaundice, I, diarrhea, sialadenitis, constipation, anorexia.
On the part of the heart and blood vessels:
arrhythmia, orthostatic hypotension, vasculitis.
From the nervous system:
dizziness, temporary blurred vision, headache, paresthesia.
From the side of hematopoiesis:
rarely – leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.
urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and non-cardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.
decreased potency, renal dysfunction, interstitial nephritis.
testosterone propionate side effects
The most common symptoms of an overdose of beta-blockers: marked reduction of blood pressure, bradycardia, atrioventricular block, bronchospasm, acute cardiac insufficiency and hypoglycaemia.
Clinical manifestations of acute or chronic overdose of hydrochlorothiazide due to a large loss of fluid and electrolytes.
The most common symptoms of hydrochlorothiazide overdose: dizziness, nausea, somnolence, hypovolaemia, marked reduction in blood pressure, hypokalemia.
In case of overdose, it is first necessary to stop taking the drug, gastric lavage, appoint absorbent means and begin to carry out supportive symptomatic therapy.
In severe bradycardia: atropine intravenous administration. Sometimes it may require temporary staging an artificial pacemaker.
In marked decrease in blood pressure: intravenous plasma-solutions.
In atrioventricular block (II and III): patients should be under constant supervision, possibly appointment of epinephrine, in case of need – setting an artificial pacemaker.
During exacerbation of chronic heart failure: intravenous diuretics, drugs with positive inotropic effect and vasodilators.
When bronchospasm: the appointment of bronchodilators, beta 2 -simpatomimetikov and / or aminophylline.
When hypoglycemia: intravenous administration dextrose (glucose).
Interaction with other drugs
testosterone propionate side effects
Combinations whose use is contraindicated
In the event of shock or hypotension caused by taking floctafenine, beta-blockers cause a reduction in compensatory cardiovascular reactions.
testosterone propionate side effects should not be used concurrently with sultopride, since in this case there is a high risk of ventricular arrhythmias, including “pirouette” type.
MAO Inhibitors type a should not be taken concurrently with testosterone propionate side effects, as there is a risk of hypertensive crisis.
Not recommended combinations
Class I antiarrhythmic agents (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), while the use of testosterone propionate side effects may reduce AV conduction and contractile ability of the heart. Blockers “slow” calcium channels (BCCI) verapamil type and to a lesser extent, diltiazem, while the use of testosterone propionate side effects may lead to a decrease in myocardial contractility and AV conduction disorders. In particular, intravenous administration of verapamil in patients receiving beta-blockers may lead to severe hypotension and AV blockade.
Antihypertensive drugs central action (such as clonidine, methyldopa, moxonidine, rilmenidine) may cause heart rate slowing and reduction in cardiac output, as well as vasodilation due to the reduction of the central sympathetic tone. Abrupt withdrawal of antihypertensive drugs central action, especially to the abolition of beta-blockers may increase the risk of “rebound” hypertension.
Combinations requiring caution
Class III antiarrhythmics (eg, amiodarone) may increase the violation of AV conduction. The action of beta-blockers for topical application (eg eye drops for glaucoma treatment) may enhance the systemic effects of testosterone propionate side effects (lowering blood pressure, slowing of the heart rate).
Parasympathomimetics while the use of testosterone propionate side effects may increase the violation of AV conduction and increase the risk of bradycardia. Simultaneous use of the drug Bisangil beta-agonists (e.g., isoprenaline, dobutamine) may reduce the effects of both drugs. testosterone propionate side effects combination with agonists affecting the beta- and alpha-adrenergic receptors (such as norepinephrine, epinephrine), may enhance the effects of vasoconstrictor agents occurring with alpha adrenergic receptors, resulting in an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.
Mefloquine while the use of testosterone propionate side effects may increase the risk of developing bradikardyi. The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving testosterone propionate side effects.
Iodosoderzhaschie radiopaque diagnostic agents for intravenous administration increases the risk of anaphylactic reactions.
Phenytoin intravenous administration, the means for inhalation anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive action and the likelihood of blood pressure lowering.
The effectiveness of insulin and hypoglycemic agents for the reception can vary inside the treatment with testosterone propionate side effects (masking the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).
The clearance of lidocaine and xanthine (except theophylline) may be reduced due to the possible increase of their plasma concentrations, especially in patients with initially increased clearance of theophylline under the influence of smoking.
The antihypertensive effect of weakening the nonsteroidal anti-inflammatory drugs (NSAIDs) (delay sodium and kidney of prostaglandin synthesis blockade), corticosteroids, and estrogens (delay of sodium ions).
Cardiac glycosides, methyldopa, reserpine and guanfacine blockers “slow” calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradikardyi, AV block, cardiac arrest and heart failure.
Antiarrhythmic agents that can cause tachycardia type “pirouette” (the IA class, such as quinidine, gidrohidin, disopyramide and Class III, eg amiodarone, dofetilide, Ibutilide) and sotalol: hypokalemia can trigger the occurrence of tachycardia type “pirouette”.
Other arrhythmic agents that can cause tachycardia of the type “pirouette” (eg, astemizole, erythromycin, intravenous, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamine): hypokalemia can induce tachycardia type “pirouette”.
Nifedipine can lead to a significant reduction in blood pressure.
Diuretics, clonidine, sympatholytic, hydralazine and other antihypertensive drugs may lead to an excessive reduction in blood pressure.
The action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin during treatment with testosterone propionate side effects may lengthen.
Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase central nervous system depression.
Not recommended simultaneous application with MAO inhibitors due to a significant increase in anti-hypertensive action. Break in treatment between receiving MAO inhibitors and testosterone propionate side effects must not be less than 14 days.
Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.
Ergotamine increases the risk of peripheral circulatory disorders.
Sulfasalazine increases the concentration of testosterone propionate side effects in blood plasma.
Rifampicin shortens the half-life of testosterone propionate side effects.
With thiazide diuretics drugs such as ethanol, barbiturates and narcotics, may potentiate the risk of orthostatic; hypotension.
Hypoglycemic agents (for oral and insulin) – I may require dosage adjustment hypoglycemic agents,
Other antihypertensives – additive effect.
Cholestyramine and colestipol – in the presence of anion exchange resin absorption of hydrochlorothiazide is violated. Cholestyramine and colestipol bind a single dose hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85% and 43%, respectively.
Corticosteroids, ACTH (adrenocorticotropic hormone) or glycyrrhizin acid | (Found in liquorice) – marked reduction of electrolytes, in I particular, the risk of hypokalemia.
Pressor amines (e.g., epinephrine, norepinephrine) – reduction of expression of pressor response to receiving amines.
Muscle relaxants nondepolarizing type of action (eg, tubocurarine) – strengthening the muscle relaxant effect.
Lithium – diuretics reduce the renal clearance of lithium and increase the risk of toxic action of lithium; concurrent use is not recommended.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors (COX-2)) – may reduce the diuretic, natriuretic and antihypertensive effects of diuretics.
In some patients with impaired renal function (eg, elderly patients or patients with dehydration, including taking diuretics), receiving NSAID therapy, including COX-2 inhibitors, treatment with angiotensin II receptor antagonists or ACE inhibitors may cause further deterioration in renal function, including the development of acute renal failure.
These effects are reversible.
The simultaneous use of these drugs should be used with caution in patients with impaired renal function.
In connection with the effect on calcium metabolism taking them may distort the results of the research function of the parathyroid glands.
During therapy with Bisangil necessary to monitor heart rate and blood pressure (at the beginning of treatment – daily, then – 1 every 3-4 months), the concentration of blood glucose in patients with diabetes (1 every 4-5 months).
In elderly patients, it is recommended to monitor renal function (1 every 4-5 months). It is necessary to train the patient’s heart rate calculation method.
During therapy with Bisangil must also monitor the performance of acid-base status and electrolytes (potassium, sodium, calcium).
A more frequent monitoring of potassium in patients at high risk.
Patients with impaired peripheral circulation need to be careful in appointing Bisangil drug.
When thyrotoxicosis Bisangil drug (due to content in the testosterone propionate side effects) may mask clinical signs (eg, tachycardia).
Patients with pheochromocytoma should not be prescribed the drug Bisangil as long as prescribed treatment of alpha-blockers. It is necessary to control blood pressure.
In patients with mild asthma or chronic obstructive pulmonary disease, treatment is initiated with the lowest dose.
It is recommended to discontinue therapy with Bisangil in the development of depression caused by the intake of beta-blockers (due to content in the testosterone propionate side effects). In elderly patients treatment with Bisangil should begin with the formulation of the preparation containing a low dose of testosterone propionate side effects (2.5 mg). This requires regular monitoring of patients.
Do not abruptly discontinue therapy, especially in patients with coronary heart disease. The dose should be reduced gradually over a period of two weeks. If necessary, at the same time initiate appropriate antianginal therapy.
Particular attention is required in cases of surgery under general anesthesia in patients taking beta-blockers. Such patients should stop the drug Bisangil 48 hours before surgery, to warn the surgeon-anesthetist that the patient is taking the drug Bisangil. As a means for general anesthesia should choose the drug with minimal negative inotropic effect.
The therapy of beta-blockers may increase the flow of psoriasis. Patients with this disease Bisangil drug should be used with caution. When specifying a history of anaphylactic reactions, regardless of their causes, especially during desensitizing therapy, treatment with Bisangil (due to content in the testosterone propionate side effects) may increase the risk of allergic reactions and contribute to the development of resistance to treatment with epinephrine (adrenaline) in normal doses .
Patients who use contact lenses, you should be careful when using the drug Bisangil as beta-blockers may reduce the production of tear fluid.
In patients with hyperuricemia increased risk of acute gout. In this case, the dose of the drug should be Bisangil selected individually controlled by the concentration of uric acid in the blood serum. Before examining the function of the parathyroid glands Bisangil drug treatment should be discontinued, as the background of his admission may occur transient hypercalcemia.
Athletes should be informed that the drug Bisangil contains testosterone propionate side effects, which may give false-positive results during a doping control.
Effects on ability to drive vehicles and management mechanisms Bisangil should be used with caution in the management of vehicles and mechanisms in relation to the possibility of dizziness. mgf pegylated