Atenolol
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Atenolol
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| Systematic (IUPAC) name | |
| 2-[4-[2-hydroxy-3-(1-methylethylamino )propoxy]phenyl]ethanamide OR 2-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide |
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| Identifiers | |
| CAS number | |
| ATC code | C07 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C14H22N2O3 |
| Mol. mass | 266.336 g/mol |
| SMILES | & |
| 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. | |
| Legal status |
℞ Prescription only |
| Routes | Oral or IV |
Atenolol is a β1 receptor specific antagonist, a drug belonging to the group of β-blockers, a class of drugs used primarily in cardiovascular diseases. Introduced in 1976, atenolol was developed as a replacement for propranolol in the treatment of hypertension. The chemical works by slowing down the heart and reducing its workload. There is no evidence to suggest that it is addictive.[1] Unlike Propranolol, atenolol does not pass through the blood-brain barrier thus avoiding various CNS side effects.[2]
Whilst atenolol, the most widely used β-blocker in the United Kingdom, was once first-line treatment for hypertension, the role for β-blockers in hypertension was downgraded in June 2006 in the United Kingdom to fourth-line as they perform less well than other drugs, particularly in the elderly, and there is increasing evidence that the most frequently used β-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes.[3]
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[edit] Indications
Atenolol (trade name Tenormin) can be used to treat cardiovascular diseases and conditions such as hypertension, coronary heart disease, arrhythmias, angina (chest pain) and to treat and reduce the risk of heart complications following myocardial infarction (heart attack)
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 β1-selective (or 'cardioselective') drug. That means that it exerts greater blocking activity on myocardial β1-receptors than on β2 ones in the lung. The β2 receptors are responsible to keep the bronchial 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 β2-mimetic antiasthmatic, such as hexoprenalin or salbutamol, will usually suppress the symptoms.
Provisional 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. However, controlled studies are lacking.[4]
Unlike most other commonly-used β-blockers, atenolol is excreted almost exclusively by the kidneys. This makes it attractive for use in individuals with end-stage liver disease.
[edit] Pharmacokinetic data
- tcmax = 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 the usual oral dose of 25 to 100 mg 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)
[edit] Contraindications
- bradycardia (pulse less than 50 bpm)
- cardiogenic shock
- asthma (may cause broncho-constriction), although unlikely as atenolol is cardioselective
- symptomatic hypotension (blood pressure of less than 100/60 mm Hg 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 peripheral 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
- phaeochromocytoma (a rare type of tumor above the kidneys)
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.)
[edit] Side effects
- See also: Propranolol
Atenolol causes significantly fewer central nervous system side effects (depressions, nightmares) and fewer bronchospastic reactions, both due to its particular pharmacologic profile.
It was the main β-blocker identified as carrying a higher risk of provoking type 2 diabetes, leading to its downgrading in the United Kingdom in June 2006 to fourth-line agent in the management of hypertension.[3]
In addition, β-blockers blunt the usual sympathetic nervous system response to hypoglycemia (i.e. sweating, agitation, tachycardia). These drugs therefore have an ability to mask a dangerously low blood sugar, which further decreases their safety and utility in diabetic patients.
Side effects include:
- indigestion, constipation
- dry mouth
- fatigue or dizziness (especially cases of orthostatic hypotension)
- hair loss
- problems with sexual function
- runny/blocked nose
- depression and confusion
- difficulty sleeping, nightmares
- weakness or lack of energy
These side effects may or may not be experienced, but if they are, you should notify your doctor.
More serious side effects can include:
- hallucinations
- low blood pressure (hypotension)
- skin reactions, eg. rash, hives, flaking of skin, worsening of psoriasis
- sensation of 'pins and needles' hands or feet
- irritated eyes, visual disturbances
- difficulty hearing
- difficulty speaking
- unsteadiness when walking
These side effects can be serious and may indicate urgent medical attention is necessary. All of these side effects are very rare, and others not mentioned in the above list can occur in some people.
[edit] Interactions
- See also: Propranolol
[edit] Dosage
In patients with normal renal function, the daily dose is 25 to 50 mg for the management of hypertension 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. Dosage can vary from as little as 25 mg to 200mg a day. In cases of doses over 100mg, the dosage is usually divided and taken twice daily.
For the management of angina, 100mg daily may be given.
In patients with impaired renal function the daily dose should be reduced 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.
[edit] Combination treatment of hypertension
If atenolol alone fails to control arterial hypertension, the drug can be combined with a diuretic (e.g. with chlortalidone in co-tenidone) and/or a vasodilator (hydralazine, or in severe cases minoxidil). Central alpha-agonists (e.g. clonidine), ACE Inhibitors or Angiotensin II receptor antagonists such as losartan can also be given additionally. Exert caution with calcium-antagonists of the verapamil-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.
[edit] Overdose
Symptoms of overdose are due to excessive pharmacodynamic actions on β1 and also β2-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 β2-mimetic as hexoprenalin or salbutamol will terminate bronchospasms.
[edit] References
- ^ Wu A (November 2007). "Should beta-blockers still be used as initial antihypertensive agents in uncomplicated hypertension?". Ann. Acad. Med. Singap. 36 (11): 962–4. PMID 18071610.
- ^ Agon P, Goethals P, Van Haver D, Kaufman JM (August 1991). "Permeability of the blood-brain barrier for atenolol studied by positron emission tomography". J. Pharm. Pharmacol. 43 (8): 597–600. PMID 1681079.
- ^ a b Sheetal Ladva (28/06/2006). NICE and BHS launch updated hypertension guideline. National Institute for Health and Clinical Excellence.
- ^ Carlberg B, Samuelsson O, Lindholm LH (2004). "Atenolol in hypertension: is it a wise choice?". Lancet 364 (9446): 1684–9. doi:. PMID 15530629.
- (2003) Patient Information Leaflet — Atenolol tablets BP. CP Pharmaceuticals Limited.
[edit] External links
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