Atenolol

Structure of Atenolol

Pharmacology and Indications

Atenolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases (hypertension, coronary heart disease, arrhythmias), and treatment of myocardial infarction after the acute event. Atenolol may be used to trat patients with compensated CHF (= Chronic Heart Failure). It is also used to treat other conditions, including dysautonomia, anxiety and hyperthyroidism. Due to its hydrophilic properties the drug is less suitable in migraine prophylaxis compared to Propranolol.

Atenolol is a so called beta1-selective (or 'cardioselective') drug. That means that it exerts greater blocking activity on myocardial beta1-receptors than on pulmonal beta2 ones. Therefore the risk of bronchospastic reactions is reduced compared to nonselective drugs. Atenolol can with extreme caution be given to asthmatic patients. The dose should be as low as possible, because in higher doses Atenolol may loose its cardioselectivity. If an asthma attack occurs the inhalation of an beta2-mimetic antiasthmatic will usually suppress the symptoms.

N.B. Provisonal data suggests that antihypertensive therapy with Atenolol provides weaker protective action against cardiovascular complications (myocardial infarction and stroke) compared to other antihypertensive drugs. In particular diuretics are superior. Propranolol and Metoprolol might be better alternatives. However, controlled studies are lacking (CARLBERG, B. et al.: Lancet 2004; 364: 1684-9).

Chemistry

Its chemical structure is C₁₄H₂₂N₂O₃ while its chemical name is (RS)-4-(2-hydroxy-3-isopropylaminopropoxy)phenylacetamide.

Pharmacokinetic Data

oral bioavailability : approx. 40 to 50% only, but low interindividual variations
t_cmax = 2 to 4 hours after oral dosing
More than 90% of an absorbed dose is found in plasma as the unchanged drug, less than 10% is metabolized hepatically. Only 3% of the drug is bound to plasma proteins.
The mean elemination halflife is 6 hours. However, the action of an usual oral dose of 25 to 100mg lasts over a period of 24 hours.
Atenolol is a hydrophilic drug. The concentration found in brain tissue is approx. 15% of the plasma concentration only. The drug crosses the placenta barrier freely. In the milk of breast feeding mothers approximately 3 times the plasma concentrations are measured.
Atenolol is almost exclusively eliminated renally and is well removable by dialysis. A compromised liver function does not lead to higher peak-activity and/or a longer halflife with possible accumulation. However, preexisting renal damage of higher degree makes dose-reductions necessary (see below) in order to avoid overdose.

Contraindications

bradycardia (puls less than 50 bpm)
cardiogenic shock
symptomatic hypotension
angina of the Prinzmetal type
metabolic acidosis (a severe condition with a more acid blood than normal)
severe circulatory disorder
AV-Blockage of 2nd. and 3rd. degree
acutely decompensated congestive heart failure
sick sinus syndrome
hypersensitivity to Atenolol
Caution : patients with preexisting asthma bronchiale
Caution : pregnancy - only if clearly needed, Atenolol may retard fetal growth and possibly causes other abnormalities

Side Effects

See Propranolol. However, Atenolol causes definetely less central nervous system side effects (depressions, night mares) and less bronchospastic reactions, both due to its particular pharmacologic profile.

Interactions

See Propranolol.

Dosage

In patients with normal renal function, the daily dose is 25 to 100mg (in one dose or in two divided doses) depending on the indication. In most patients, the physician will start with a low initial dose and make increments in weekly intervalls as tolerated.

In patients with chronic heart failure the initial dose should be particular low and increments should be made slowly.

In patients with a creatinin-clearance less than 35 ml/Min./1,73 m² the daily dose should be reduced to 25 to 50mg daily according to the clinical response of the individual patient. If a patient with end-stage renal failure is scheduled on regular dialysis, usually 50mg are given after each dialysis procedure. In these patients a severe hypotension may occur afterwards.

Overdose

Symptoms of overdose are due to excessive pharmacodynamic actions on beta1 and also beta2-receptors. These include bradycardia, severe hypotension with shock, acute heart failure, hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic. Hospitalization and intensive monitoring is indicated. In early cases emesis can be induced. Activated charcoal is useful to absorb the drug. Atropine will counteract bradycardia, Glucagon helps with hypoglycemia, Dobutamine can be given against hypotension and the inhalation of a beta2-mimetic as hexoprenalin or salbutamol will terminate bronchospasms.

External link

Atenolol, Molecule of the Month (uses flash).
Atenolol drug information