Article: Atenolol

Atenolol
Systematic (IUPAC) name
2-[4-[2-hydroxy-3-(1-methylethylamino )propoxy]phenyl]ethanamide
Identifiers
CAS number	29122-68-7
ATC code	C07AB03
PubChem	2249
DrugBank	APRD00172
Chemical data
Formula	C14H22N2O3
Mol. weight	266.336 g/mol
Pharmacokinetic data
Bioavailability	40-50%
Protein binding	6-16%
Metabolism	Hepatic <10%
Half life	6-7hours
Excretion	Renal Lactic (In lactiferous females)
Therapeutic considerations
Pregnancy cat.	C(AU) D(US)
Legal status	℞ Prescription only
Routes	oral iv

Atenolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. Introduced in 1976, Atenolol was developed as a replacement for propanolol in the treatment of hypertension. Hypertension is a clinical condition in which the arterial blood pressure in rest exceeds constantly 140/90 mm Hg (as defined by the World Health Organization). Hypertension is a risk factor for stroke, myocardial infarction (heart attack), and serious renal damage.

Propranolol is known to readily cross the blood-brain barrier (BBB) and can pass into the brain, causing side-effects such as depression and nightmares; atenolol was specifically developed to be unable to pass through the blood-brain barrier in order to prevent this effect.

Indications

Atenolol (trade name Tenormin) can be used to treat cardiovascular diseases such as hypertension, coronary heart disease, arrhythmias, and treatment of myocardial infarction after the acute event. Patients with compensated congestive heart failure may be treated with Atenolol as a comedication (usually together with an ACE inhibitor, a diuretic and a digitalis-glycoside, if indicated). In patients with congestive heart failure, it reduces the need for and the consumption of oxygen of the heart muscle. It is very important to start with low doses, as atenolol reduces also the muscular power of the heart, which is an undesired effect in congestive heart failure.

The drug is also used to treat other conditions, including dysautonomia, anxiety and hyperthyroidism (overfunction of the thyroid gland).

Due to its hydrophilic properties, the drug is less suitable in migraine prophylaxis compared to Propranolol, because for this indication, atenolol would have to reach the brain in high concentrations, which is not the case (see below).

Atenolol is a so-called beta1-selective (or 'cardioselective') drug. That means that it exerts greater blocking activity on myocardial beta1-receptors than on beta2 ones in the lung. The beta2 receptors are responsible to keep the bronichal system open. If these receptors are blocked, bronchospasm with serious lack of oxygen in the body can result. However, due to its cardioselective properties, the risk of bronchospastic reactions if using atenolol is reduced compared to nonselective drugs as propranolol. Nonetheless, this reaction may also be encountered with atenolol, particularly with high doses. Extreme caution should be exerted if Atenolol is given to asthma patients, who are particularly at risk; the dose should be as low as possible. If an asthma attack occurs, the inhalation of a beta2-mimetic antiasthmatic, such as hexoprenalin or salbutamol, will usually suppress the symptoms.

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

Unlike most other commonly-used beta blockers, atenolol is excreted almost exclusively by the kidneys. This makes it attractive for use in individuals with end-stage liver disease.

Pharmacokinetic Data

• t_cmax = 2 to 4 hours after oral dosing (time elapsed before maximal concentration in the blood plasma is reached)
• The mean elimination 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 approximately 15% of the plasma concentration only. The drug crosses the placenta barrier freely. In the milk of breastfeeding 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 insufficience of higher degree makes dose-reductions necessary (see below) in order to avoid overdose.

Contraindications

• bradycardia (pulse less than 50 bpm)
• cardiogenic shock
• symptomatic hypotension (blood pressure of less than 100/60 mmHg with dizziness, vertigo etc.)
• angina of the Prinzmetal type (vasospastic angina)
• metabolic acidosis (a severe condition with a more acid blood than normal)
• severe disorders in perpheral arterial circulation
• AV-Blockage of second and third degree (a particular form of arrhythmia)
• acutely decompensated congestive heart failure (symptoms may be fluid retention with peripheral edema and/or abdominal fluid retention (ascites), and/or lung edema)
• sick sinus syndrome (a particular form of arrhythmia, very rarely encountered)
• hypersensitivity and/or allergy to Atenolol
• Caution: patients with preexisting asthma bronchiale
• Caution: only if clearly needed during pregnancy, as atenolol may retard fetal growth and possibly causes other abnormalities. (If you are pregnant or plan to become pregnant, ask your doctor.)

Side effects

See Propranolol. However, Atenolol causes significantly fewer central nervous system side effects (depressions, nightmares) and fewer 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 100 mg (in one dose or in two divided doses) depending on the indication and severity of the disease. In most patients, the physician will start with a low initial dose and make increments in weekly intervals as tolerated.

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

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

Combination treatment of hypertension

If atenolol alone fails to control arterial hypertension, the drug can be combined with a diuretic and/or a vasodilator (hydralazine, or in severe cases minoxidil). Central alpha-agonists (e.g. clonidine), ACE-Inhibitors or AT-Antagonists such as losartan can also be given additionally. Exert caution with calcium-antagonists of the verapamile-type as adjunct therapy because of additional negative impact on the muscular strength of the heart. Use of calcium-antagonists of the nifedipine-type is controversial.

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 (= low blood sugar) 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.