Atenolol
Atenolol is a beta blocker medication
Atenolol was patented in 1969 and approved for medical use in 1975. It
is available as a generic medication. In the United States, the wholesale
cost per month is less than 15 USD as of 2018. In the United Kingdom,
a month of treatment costs the NHS less than 5 pounds. In 2016, it was
the 20th most prescribed medication in the United States, with more
than 26 million prescriptions.
Medical uses
Atenolol is used for a number of conditions
including hypertension, angina, long QT syndrome, acute myocardial
infarction, supraventricular tachycardia, ventricular tachycardia, and
the symptoms of alcohol withdrawal.
Atenolol is one of the most widely used β-blockers in the United
Kingdom and was once the first-line treatment for hypertension.
Off-label uses of atenolol, as with other cardioselective β-blockers,
include symptomatic treatment of anxiety. β-blockers are effective for
some of the physical effects of anxiety. In these instances, dosing is
used as needed instead of regular daily dosing.
Side effect
Along with its needed effects, atenolol may cause some unwanted
effects. Although not all of these side effects may occur, if they do
occur they may need medical attention.
ore common
• Blurred vision
• cold hands or feet
• confusion
• difficult or labored breathing
• dizziness, faintness, or lightheadedness when getting up from a
lying or sitting position suddenly
• shortness of breath
• sweating
• tightness in chest
• unusual tiredness or weakness
• wheezing
Pharmacodynamics
• Atenolol is a cardio-selective beta-blocker and as such exerts
most of its effects on the heart. It acts as an antagonist to sympathetic
innervation and prevents increases in heart rate, electrical conductivity,
and contractility in the heart due to increased release of norepinephrine
from the peripheral nervous system. Together the decreases in
contractility and rate produce a reduction in cardiac output resulting in
a compensatory increase in peripheral vascular resistance in the short-
term. This response later declines to baseline with long-term use of
atenolol. More importantly, this reduction in the work demanded of the
myocardium also reduces oxygen demand which provides therapeutic
benefit by reducing the mismatch of oxygen supply and demand in
settings where coronary blood flow is limited, such as in coronary
atherosclerosis. Reducing oxygen demand, particularly due to exercise,
can reduce the frequency of angina pectoris symptoms and potentially
improve survival of the remaining myocardium after myocardial
infarction. The decrease in rate of sinoatrial node potentials, electrical
conduction, slowing of potentials traveling through the atrioventricular
node, and reduced frequency of ectopic potentials due to blockade of
adrenergic beta receptors has led to benefit in arrhythmic conditions
such as atrial fibrillation by controlling the rate of action potential
generation and allowing for more effective coordinated contractions.
Since a degree of sympathetic activity is necessary to maintain cardiac
function, the reduced contractility induced by atenolol may precipitate
or worsen heart failure, especially during volume overload.
Mechanism of action
Atenolol is a cardioselective beta-blocker, called such because it
selectively binds to the β1-adrenergic receptor as an antagonist up to a
reported 26 fold more than β2 receptors.15 Selective activity at the β1
receptor produces cardioselectivity due to the higher population of this
receptor in cardiac tissue. Some binding to β2 and possibly β3 receptors
can still occur at therapeutic dosages but the effects mediated by
antagonizing these are significantly reduced from those of non-
selective agents. β1 and β2 receptors are Gs coupled therefore
antagonism of their activation reduces activity of adenylyl cyclase and
its downstream signalling via cyclic adenosime monophosphate and
protein kinase A (PKA).
Pharmacokinetics
Competitively blocks response to beta-adrenergic stimulation,
selectively blocks beta1-receptors with little or no effect on beta2-
receptors except at high doses
Absorption
Oral: Rapid, incomplete (~50%)
Distribution
Low lipophilicity; does not cross blood-brain barrier
Metabolism
Limited hepatic
Excretion
Feces (50%); urine (40% as unchanged drug)
Onset of Action
Oral: ≤1 hour; Peak effect: Oral: 2 to 4 hours
Time to Peak
Plasma: Oral: 2 to 4 hours
Duration of Action
Normal renal function: Beta-blocking effect: 12 to 24 hours;
Antihypertensive effect: Oral: 24 hours
Half-Life Elimination
Beta:
Newborns (<24 hours of age) born to mothers receiving atenolol:
Mean: 16 hours; up to 35 hours (Rubin 1983)
Children and Adolescents 5 to 16 years of age: Mean: 4.6 hours; range:
3.5 to 7 hours; Patients >10 years of age may have longer half-life (>5
hours) compared to children 5 to 10 years of age (<5 hours) (Buck
1989)
Adults: Normal renal function: 6 to 7 hours, prolonged with renal
impairment; End-stage renal disease (ESRD): 15 to 35 hours
Protein Binding
6% to 16%
Special Populations: Renal Function Impairment
Elimination is closely related to GFR. Significant accumulation occurs
when CrCl falls below 35 mL/minute/1.73 m2.
Toxicity
Carcinogenicity & Mutagenicity
Studies in rats and mice at doses of 300 mg/kg/day, equivalent to 150
times maximum recommended human dose, for durations of 18 and 24
months showed no carcinogenicity. One study in rats at doses of 500-
1500 mg/kg/day, 250-750 times maximum human dose, resulted in
increases benign adrenal medullary tumors in both sexes and increase
mammary fibroadenomas in females.
Atenolol showed no mutagenicity in the Ames test using S.
typhinarium, dominant lethal test in mice, or in vivo cytogenetics test
in chinese hamster ovary cells.
Contraindications
Hypersensitivity to atenolol or any component of the formulation; sinus
bradycardia; heart block greater than first-degree (except in patients
with a functioning artificial pacemaker); cardiogenic shock;
uncompensated cardiac failure
Documentation of allergenic cross-reactivity for beta-blockers is
limited. However, because of similarities in chemical structure and/or
pharmacologic actions, the possibility of cross-sensitivity cannot be
ruled out with certainty.
Administration
Oral: May be administered without regard to meals.
Storage
Store at 20°C to 25°C (68°F to 77°F).
Drug Interactions
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of
Beta-Blockers. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure
Lowering Agents. Monitor therapy
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic
hypotensive effect of Alpha1-Blockers. The risk associated with
ophthalmic products is probably less than systemic products. Monitor
therapy
Dosage Forms
Excipient information presented when available (limited, particularly
for generics); consult specific product labeling.
Tablet, Oral:
Tenormin: 25 mg, 50 mg, 100 mg
Generic: 25 mg, 50 mg, 100 mg
