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Atenolol

PFK Obnovlenie
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2019-09-19
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Clinical Pharmacology

It has antianginal, antihypertensive and antiarrhythmic effects. Does not possess membrane stabilizing and internal sympathomimetic activity. Reduces catecholamine-stimulated cyclic adenosine monophosphate (cAMP) formation from adenosine triphosphate (ATP), reduces intracellular Ca2 + current. In the first 24 hours after oral administration, on the background of a decrease in cardiac output, there is a reactive increase in the total peripheral vascular resistance, which gradually returns to the baseline within 1-3 days and then gradually decreases. The hypotensive effect is associated with a decrease in the minute volume of blood, a decrease in the activity of the renin-angiotensin system, the sensitivity of the baroreceptors and the effect on the central nervous system. The hypotensive effect is manifested as a decrease in systolic and diastolic blood pressure (BP), a decrease in stroke and minute blood volumes.

In moderate therapeutic doses, it does not affect the tone of the peripheral arteries. The antihypertensive effect lasts 24 hours, with regular use it stabilizes by the end of the second week of treatment.

The antianginal effect is determined by a decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastole lengthening and improvement in myocardial perfusion) and contractility, as well as a decrease in myocardial sensitivity to the effects of sympathetic stimulation. It slows down the heart rate (HR) at rest and during exercise. By increasing the end-diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles can increase the need for oxygen, especially in patients with chronic heart failure.

The antiarrhythmic effect is manifested by the suppression of sinus tachycardia and is associated with the elimination of arrhythmogenic sympathetic effects on the cardiac conduction system, a decrease in the rate of propagation of excitation through the sinoatrial node and an extension of the refractory period. Inhibits the conduction of impulses in the antegrade and to a lesser extent in the retrograde directions through the AV (atrioventricular) node and along additional pathways.

The negative chronotropic effect appears after 1 h after administration, reaches a maximum after 2-4 hours, lasts up to 24 hours.

Reduces the automatism of the sinus node, reduces the heart rate, slows AV conduction, reduces myocardial contractility, reduces the need for oxygen in the myocardium. Reduces the excitability of the myocardium. When used in moderate therapeutic doses, it has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries than non-selective beta-blockers.

Increases the survival of patients with myocardial infarction (reduces the incidence of ventricular arrhythmias and strokes).

Practically does not weaken the bronchodilatory effect of isoproterenol.

In contrast to non-selective beta-adrenergic blockers, when administered at moderate therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of the peripheral arteries, bronchi and uterus), and on carbohydrate metabolism; the severity of atherogenic action does not differ from that of propranolol. To a lesser extent, has a negative batmo-, chrono-, ino-and dromotropic effect. When used in large doses (more than 100 mg / day), it has a blocking effect on both subtypes of beta-adrenoreceptors.

Pharmacokinetics

Absorption from the gastrointestinal tract - fast, incomplete (50-60%), bioavailability - 40-50%, TCmax blood - 2-4 hours. Poor penetrates the blood-brain barrier, passes in small quantities through the placental barrier and into breast milk. Communication with plasma proteins - 6-16%. Practically not metabolized in the liver. T1 / 2 - 6-9 hours (increased in elderly patients). Excreted by the kidneys by glomerular filtration (85-100% unchanged).Impaired renal function is accompanied by T1 / 2 elongation and cumulation: when QA is below 35 ml / min / 1.73 m2, T1 / 2 is 16-27 h, if QC is below 15 ml / min / 1.73 m2 - more than 27 h (dose reduction is necessary). Excreted during hemodialysis.

Indications

- arterial hypertension;

- prevention of strokes (with the exception of Prinzmetal stenocardia);

- Heart rhythm disorders: sinus tachycardia, prevention of supraventricular tachyarrhythmias, ventricular extrasystole.

Composition

1 tab.

atenolol 50 mg

Atenolol is marketed under different brands and generic names, and comes in different dosage forms:

Brand nameManufacturerCountryDosage form
Atenolol PFK Obnovlenie Russia pills
Atenolol Synthesis AKOMP Russia pills
Atenolol-Belupo Belupo Croatia pills
Atenolol Nycomed Takeda GmbH Japan pills

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Atenolol

Dosage and Administration

Assign inside before a meal, without chewing, with a small amount of liquid.

Arterial hypertension. Treatment begins with 50 mg of atenolol 1 time per day. To achieve a stable hypotensive effect requires 1-2 weeks of admission. With insufficient severity of the hypotensive effect, the dose is increased to 100 mg in a single dose. A further increase in the dose is not recommended, since it is not accompanied by an increase in the clinical effect.

In ischemic heart disease, tachysystolic heart rhythm disturbances - 50 mg 1 time per day.

Angina pectoris The initial dose is 50 mg per day. If during the week the optimal therapeutic effect is not achieved, increase the dose to 100 mg per day.

Correction of the dosage regimen is necessary for patients of advanced age and patients with impaired renal excretory function.

In the presence of renal failure, dose adjustment is recommended depending on creatinine clearance. In patients with renal insufficiency with creatinine clearance values ​​above 35 ml / min. / 1.73 m2 (normal values ​​are 100-150 ml / min. 1.73 m2), there is no significant accumulation of atenolol.

Adverse reactions

Cardiovascular system: development (aggravation) of symptoms of chronic heart failure (swelling of ankles, feet; shortness of breath), impaired atrioventricular conduction, arrhythmia, bradycardia, marked reduction of blood pressure, palpitations, weakening of myocardial contractility, orthostatic hypotension, manifestations of angiospmama Raynaud's syndrome), vasculitis, chest pain.

CNS: dizziness, decreased ability to concentrate, slower reaction, drowsiness or insomnia, depression, hallucinations, increased fatigue, headache, weakness, nightmarish dreams, anxiety, confusion or short-term memory loss, paresthesias in the extremities (in patients with intermittent claudication and Raynaud's syndrome), muscle weakness, convulsions.

GI: dry mouth, nausea, vomiting, diarrhea, abdominal pain, constipation or diarrhea, change in taste.

Respiratory system: dyspnea, bronchospasm, apnea, nasal congestion.

Hematological reactions: platelet purpura, anemia (aplastic), thrombosis.

Endocrine system: reduced potency, decreased libido, hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), a hypothyroid state.

Skin reactions: urticaria, dermatitis, pruritus, photosensitivity, increased sweating, skin flushing, exacerbation of the course of psoriasis, reversible alopecia.

Sense organs: blurred vision, decreased secretion of tear fluid, dryness and soreness of the eyes, conjunctivitis.

Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia. Laboratory indicators: agranulocytosis, leukopenia, increased activity of liver enzymes, hyperbilirubinemia, thrombocytopenia (unusual bleeding and hemorrhage).

Others: back pain, arthropathy, "withdrawal" syndrome (tachycardia, increased angina attacks, increased blood pressure, etc.).

The frequency of side effects increases with increasing dose of the drug.

Contraindications

- cardiogenic shock;

- atrioventricular (AV) blockade II-III ;

- severe bradycardia (heart rate less than 40 beats / min.);

- Sick sinus syndrome;

- Sinoauricular block;

- acute or chronic heart failure in the decompensation stage;

- Cardiomegaly without signs of heart failure;

- Prinzmetal angina pectoris;

- arterial hypotension (in the case of use in myocardial infarction;

- systolic blood pressure less than 100 mm Hg);

- lactation period;

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- age up to 18 years (efficacy and safety of the drug have not been established);

- Hypersensitivity to the drug.

Precautions: diabetes mellitus, metabolic acidosis, hypoglycemia, history of allergic reactions, chronic obstructive pulmonary disease (including pulmonary emphysema), grade I AV block, chronic heart failure (compensated), obliterating diseases of peripheral vessels ("intermittent" lameness, Raynaud's syndrome), pheochromocytoma, liver failure, chronic renal failure, myasthenia, thyrotoxicosis, depression (including history), psoriasis, old age, pregnancy.

Drug interactions

With simultaneous use of atenolol with insulin, hypoglycemic means for oral administration - their hypoglycemic effect is enhanced. When used together with antihypertensive drugs of different groups or nitrates, the anti-hypertensive effect is enhanced. The simultaneous use of atenolol and verapamil (or diltiazem) can cause mutual enhancement of the cardiodepressive action.

The hypotensive effect is weakened by estrogens (sodium retention) and nonsteroidal anti-inflammatory drugs, glucocorticosteroids. With simultaneous use of atenolol and cardiac glycosides increases the risk of developing bradycardia and impaired atrioventricular conductivity.

With the simultaneous appointment of atenolol with reserpine, methyldopa, clonidine, verapamil, the occurrence of severe bradycardia is possible.

Simultaneous i.v. administration of verapamil and diltiazem may cause cardiac arrest; Nifedipine can lead to a significant decrease in blood pressure. At the same time taking atenolol with ergotamine derivatives, xanthine, its effectiveness decreases.

When discontinuing the combined use of atenolol and clonidine, treatment with clonidine is continued for several days after the abolition of atenolol.

Simultaneous use with lidocaine can reduce its excretion and increase the risk of toxic action of lidocaine.

Use in conjunction with phenothiazine derivatives, helps to increase the concentration of each of the drugs in serum.

Phenytoin with a / in the introduction, drugs for general anesthesia (derivatives of hydrocarbons) increase the severity of the cardiodepressive action and the likelihood of a decrease in blood pressure.

When combined with aminophylline and theophylline, mutual suppression of therapeutic effects is possible.

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in the hypotensive effect, the break in treatment between taking MAO inhibitors and atenolol should be at least 14 days.

Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis.

Means for inhalation anesthesia (derivatives of hydrocarbons) increase the risk of inhibition of myocardial function and the development of hypertension. Amiodarone increases the risk of bradycardia and suppression of AV conduction. Cimetidine increases plasma concentration (inhibits metabolism). Iodine-containing radiopaque agents for IV administration increase the risk of anaphylactic reactions.

Lengthens the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Three - and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase the depression of the central nervous system.

Unhydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.

Pregnancy and Lactation

Atenolol penetrates the placental barrier and is found in umbilical cord blood. Research on the use of atenolol in the first trimester has not been conducted and, therefore, the possibility of a damaging effect on the fetus cannot be excluded.For the treatment of hypertension in the third trimester of pregnancy, the drug is used under close medical supervision. The use of atenolol during pregnancy may be a cause of impaired growth of the fetus.

Atenolol should be prescribed to pregnant women or women planning pregnancy, only in cases where the benefit to the mother outweighs the potential risk to the fetus, especially in the first and second trimester of pregnancy, since beta-adrenergic blockers reduce the level of placental perfusion, which can lead to fetal death or its immaturity and premature birth. In addition, side effects such as hypoglycemia and bradycardia can occur in both the fetus and the newborn.

Special instructions

Monitoring of patients taking atenolol should include monitoring of heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), blood glucose content in patients with diabetes mellitus (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months).

The patient should be trained in the method of counting heart rate and instructed on the need for medical consultation with a heart rate of less than 50 bpm. In thyrotoxicosis, atenolol may mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Sharp cancellation in patients with thyrotoxicosis is contraindicated, as it can strengthen the symptoms. In case of diabetes mellitus it may mask tachycardia caused by hypoglycemia. Unlike non-selective beta-adrenergic blockers, the insulin-induced hypoglycemia practically does not increase and does not delay the restoration of blood glucose to normal concentrations.

In patients with coronary heart disease (CHD), abrupt cancellation of beta-blockers may cause an increase in the frequency or severity of angina attacks, so stopping atenolol in patients with CHD should be carried out gradually.

Compared with non-selective beta-blockers, cardio-selective beta-blockers have less effect on lung function, however, with obstructive respiratory diseases, atenolol is prescribed only in case of absolute indications. If necessary, their purpose in some cases, we can recommend the use of beta2-adrenomimetics.

Cardioselective adrenergic blockers can be prescribed to patients with bronchospastic diseases in case of intolerance and / or ineffectiveness of other antihypertensive drugs, but the dosage should be strictly followed. Overdose is dangerous for the development of bronchospasm.

Special care is required in cases where surgery is required under anesthesia in patients taking atenolol. The drug should be stopped 48 hours before the intervention. As an anesthetic one should choose a drug with possibly minimally negative inotropic action.

With the simultaneous use of atenolol and clonidine, atenolol is stopped for a few days before clonidine in order to avoid the symptom of canceling the latter. Perhaps an increase in the severity of hypersensitivity reactions and the lack of effect from the usual doses of epinephrine on the background of aggravated allergic history.

Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect pronounced decrease in blood pressure or bradycardia.

In the case of elderly patients with increasing bradycardia (less than 50 units / min), arterial hypotension (systolic blood pressure below 100 mm Hg), atrioventricular blockade, bronchospasm, ventricular arrhythmias, severe impaired liver function and kidney, reduce the dose or stop treatment.

It is recommended to stop therapy in the development of depression caused by taking beta-blockers.

If intravenous verapamil is needed, this should be done at least 48 hours after taking atenolol.

With the use of atenolol, it is possible to reduce the production of tear fluid, which is important in patients using contact lenses.

You can not abruptly interrupt treatment because of the risk of severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose for 2 weeks. and more (reduce the dose by 25% in 3-4 days).

It should be discontinued before the examination of the content in the blood and urine of catecholamines, normetanephrine and vanillyl almond acid; antinuclear titers. In smokers, the effectiveness of beta-blockers is lower. Pregnancy and lactation period.

Pregnant women should be appointed atenolol only in cases where the benefits to the mother outweigh the potential risk to the fetus. Atenolol is excreted in breast milk, so if during the period of breastfeeding the drug is indicated, it is better to stop breastfeeding for a while.

Influence on ability to drive motor transport and control mechanisms

During the period of treatment, it is necessary to refrain from engaging in potentially hazardous activities that require an increased concentration of attention and quickness of psychomotor reactions.

Overdosage

Symptoms: severe bradycardia, AV block II-III degree, increased symptoms of heart failure, excessive decrease in blood pressure, difficulty breathing, bronchospasm, dizziness, fainting, arrhythmia, ventricular extrasystole, cyanosis of the fingernails or palms of the fingernails or palms, convulsions.

Treatment: gastric lavage and prescription of absorbent drugs; in the event of bronchospasm, inhaled or intravenous beta2-adrenomimetika salbutamol is indicated. In violation of AV conduction, bradycardia - in / in the introduction of 1-2 mg of atropine, epinephrine or staging a temporary pacemaker; for ventricular premature beats, lidocaine (class 1A preparations are not used); with a decrease in blood pressure - the patient should be in the Trendelenburg position. If there are no signs of pulmonary edema - in / in plasma-substituting solutions, with inefficiency - the introduction of epinephrine, dopamine, dobutamine; in chronic heart failure - cardiac glycosides, diuretics, glucagon; with convulsions - in / in diazepam. Dialysis is possible.

  • Brand name: Atenolol
  • Active ingredient: Atenolol
  • Dosage form: pills white or white with a grayish or creamy shade of color; light marbling is allowed.
  • Manufacturer: PFK Obnovlenie
  • Country of Origin: Russia

Studies and clinical trials of Atenolol (Click to expand)

  1. Influence of atenolol and/or metformin on glutathione and magnesium levels in diabetic rats
  2. Nortriptyline and atenolol for the treatment of bulimia in a diabetic woman
  3. Novel thermo-responsive semi-interpenetrating network microspheres of gellan gum-poly(N-isopropylacrylamide) for controlled release of atenolol
  4. The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats
  5. Pharmacokinetics of Atenolol and Metoprolol Administered together with Piroxicam
  6. Pharmacokinetic Profile of Atenolol Aspirinate
  7. Bioavailability of atenolol formulations
  8. The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol
  9. Bioavailability in man of atenolol and chlorthalidone from a combination formulation
  10. Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol
  11. Pharmacokinetic studies with atenolol in the dog
  12. Levels of the beta-blockers atenolol and propranolol in the breast milk of women treated for hypertension in pregnancy
  13. Bioavailability in man of atenolol and chlorthalidone from a combination formulation
  14. A study of the pharmacokinetics and pharmacodynamics of nifedipine in combination with atenolol
  15. Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects
  16. Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin and Tenormin) in healthy human volunteers
  17. Atenolol developmental toxicity: Animal-to-human comparisons
  18. Determination of enalapril maleate and atenolol in their pharmaceutical products and in biological fluids by flow-injection chemiluminescence
  19. Determination of atenolol by the micelle-stabilized room-temperature phosphorescence methodology
  20. Direct TLC resolution of atenolol and propranolol into their enantiomers using three different chiral selectors as impregnating reagents
  21. Enantioselective bioanalysis of beta-blocking agents: Focus on atenolol, betaxolol, carvedilol, metoprolol, pindolol, propranolol and sotalol
  22. Reversed-phase liquid chromatographic determination of enantiomers of atenolol in rat plasma using derivatization with Marfey's reagent
  23. Simultaneous determination of atenolol and amiloride in pharmaceutical preparations by capillary zone electrophoresis with capacitively coupled contactless conductivity detection
  24. Simultaneous determination of atenolol, chlorthalidone and amiloride in pharmaceutical preparations by capillary zone electrophoresis with ultraviolet detection

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