Atenolol is abeta blocker medication primarily used to treathigh blood pressure andheart-associated chest pain.[6] Although used to treat high blood pressure, it does not seem to improvemortality in those with the condition.[7][8] Other uses include the prevention ofmigraines and treatment of certainirregular heart beats.[6][9] It is takenorally (by mouth) or byintravenous injection (injection into a vein).[6][9] It can also be used with otherblood pressure medications.[9]
Commonside effects includefeeling tired,heart failure,dizziness,depression, andshortness of breath.[6] Other serious side effects includebronchial spasm.[6] Use is not recommended duringpregnancy[6] and alternative drugs are preferred whenbreastfeeding.[10] It works by blockingβ1-adrenergic receptors in theheart, thus decreasingheart rate,force of heart beats, andblood pressure.[6]
Atenolol was patented in 1969 and approved for medical use in 1975.[11] It is on theWorld Health Organization's List of Essential Medicines.[12] It is available as ageneric medication.[6] In 2023, it was the 75th most commonly prescribed medication in the United States, with more than 9 million prescriptions.[13][14]
Atenolol is used for a number of conditions includinghyperthyroidism,[15]hypertension,angina,long QT syndrome,acute myocardial infarction,supraventricular tachycardia,ventricular tachycardia,essential tremor (ET), and the symptoms ofalcohol withdrawal.[16]
The role for β-blockers in general in hypertension was downgraded in June 2006 in the United Kingdom, and later in the United States, as they are less appropriate than other agents such asACE inhibitors,calcium channel blockers,thiazide diuretics andangiotensin receptor blockers, particularly in the elderly.[17][18][19]
Atenolol has been used to treatanxiety disorders, such asgeneralized anxiety disorder andsocial anxiety disorder.[20][21][22] It is thought that beta blockers do not directly treat psychological symptoms ofanxiety, but can help control physical symptoms such aspalpitations, and this may interfere with a positive feedback loop to indirectly reduce psychological anxiety.[20] A 2025systematic review andmeta-analysis that included atenolol found widespread prescription of beta blockers for treatment anxiety disorders, but found no evidence of a beneficial effect relative to placebo orbenzodiazepines in people with social phobia orpanic disorder.[20] However, thequality of evidence, including both numbers of studies and patients as well as quality and risk ofbias of those studies, was limited.[20]
Contraindications of atenolol includesinus bradycardia,heart block greater than first degree,cardiogenic shock, and overtheart failure.[23] There is no basis for use of atenolol in people withheart rate of lower than 50 bpm orsystolic blood pressure of less than 100 mm Hg and hence these can be considered contraindications.[23] It is also contraindicated in people with a history ofhypersensitivity to atenolol or any of the drug product's other components.[23]
Hypertension treated with a β-blocker such as atenolol, alone or in conjunction with a thiazide diuretic, is associated with a higher incidence of new onset type 2 diabetes mellitus compared to those treated with an ACE inhibitor or angiotensin receptor blocker.[24][25]
β-blockers, of which atenolol is mainly studied, provides weaker protection againststroke and mortality in patients over 60 years old compared to other antihypertensive medications.[26][27][28][17]Diuretics may be associated with better cardiovascular and cerebrovascular outcomes than β-blockers in the elderly.[29]
Rarely, atenolol has been associated with induction of acutedelirium.[30][1][31]
Symptoms ofoverdose are due to excessive pharmacodynamic actions on β1 and also β2-receptors. These includebradycardia (slow heartbeat), severehypotension withshock, acuteheart failure,hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic. Hospitalization and intensive monitoring is indicated.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 such ashexoprenalin orsalbutamol will terminate bronchospasms. Blood or plasma atenolol concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 3 mg/L during therapeutic administration, but can range from 3–30 mg/L in overdose victims.[32][33]
Interactions with atenolol includecatecholamine-depleting drugs likereserpine,calcium channel blockers,disopyramide,amiodarone,clonidine,prostaglandin synthase inhibitors likeindomethacin, anddigitalis glycosides.[23] Most of these interactions involve either additive cardiovascular effects or reduction of atenolol's effects.[23]
Atenolol is mainlyeliminatedrenally without beingmetabolized by theliver or bycytochrome P450enzymes.[23][4][34] As a result, it has little or no potential for cytochrome P450-related drug interactions, for instance withinhibitors andinducers of these enzymes.[4][34] Accordingly, the broad/non-selective cytochrome P450 inhibitorcimetidine had no effect on atenolol levels, whereas cimetidine has been found to significantly increasemetoprolol andpropranolol levels.[4]
Beta blockers like atenolol can reduce or block thecardiovascular effects ofsympathomimetics andamphetamines, such ashypertension andtachycardia.[35][36][37][38][39][40][41]
Atenolol has been found to be safe in combination with thenon-selectivemonoamine oxidase inhibitor (MAOI)phenelzine and actually improvedorthostatic hypotension andhypertensive reactions with phenelzine.[42][43][44] However, more research is still needed to assess whether addition of a beta blocker like atenolol to MAOI therapy is safe and effective for improving orthostatic hypotension with MAOIs.[42][44]
| Site | Ki (nM) | Species | |
|---|---|---|---|
| 5-HT1A | 10,000 | Rat | |
| 5-HT1B | >10,000 | Rat | |
| 5-HT2A | >10,000 | Human | |
| 5-HT2C | >10,000 | Pig | |
| α1 | ND | ND | |
| α2 | ND | ND | |
| β1 | 170–1,500 | Human | |
| β2 | 8,140–9,550 | Human | |
| β3 | >10,000 | Human | |
| D1 | ND | ND | |
| D2 | >10,000 | Rat | |
| Notes: Values are Ki (nM), unless otherwise noted. The smaller the value, the more avidly the drug binds to the site.Refs:[45][46] | |||
Atenolol is abeta blocker; that is, anantagonist of theβ-adrenergic receptors.[47][3] It is specifically aselective antagonist of theβ1-adrenergic receptor with nointrinsic sympathomimetic activity (i.e.,partial agonist activity) ormembrane-stabilizing activity.[47][3] However, the preferential action of atenolol is not absolute, and at high doses, it can also blockβ2-adrenergic receptors.[3]
Beta-blocking effects of atenolol include reduction inresting andexerciseheart rate andcardiac output, reduction ofsystolic anddiastolic blood pressure at rest and with exercise, inhibition oftachycardia induced byisoproterenol (a non-selective β-adrenergic receptoragonist), and reduction ofreflex orthostatic tachycardia.[3]
The beta-blocking effects of atenolol, as measured by reduction of exercise-related tachycardia, are apparent within 1 hour and are maximal within 2 to 4 hours following a single oral dose.[3] The general effects of atenolol, including beta-blocking andantihypertensive effects, last for at least 24 hours followingoral doses of 50 or 100 mg.[3] With intravenous administration, maximal reduction in exercise-related tachycardia occurs within 5 minutes and following a single 10 mg dose has dissipated within 12 hours.[3] Theduration of action of atenolol is dose-related and is correlated with circulating levels of atenolol.[3]
Theoralbioavailability of atenolol is approximately 50 to 60%.[1][2] Theabsorption of atenolol with oral administration is rapid and consistent but is incomplete.[3] About 50% of an oral dose of atenolol is absorbed from theintestines, with the restexcreted infeces.[3]Maximal concentrations of atenolol occur 2 to 4 hours following an oral dose, whereas peak concentrations occur within 5 minutes withintravenous administration.[3] Thepharmacokinetic profile of atenolol results in it having relatively consistent plasma drug levels with about 4-fold variation between individuals.[3]
Theplasma protein binding of atenolol is 6 to 16%.[3]
Atenolol is classified as ahydrophilic beta blocker with lowlipophilicity and hence lower potential for crossing theblood–brain barrier and entering the brain.[47] This in turn may result in fewer effects in thecentral nervous system as well as a lower risk ofneuropsychiatric side effects.[47] Only small amounts of atenolol are said to enter the brain.[1][2] Thebrain-to-blood ratio of atenolol in humans has been found to be 0.2:1, whereas the ratio for the highly lipophilicpropranolol has been found to range from 15:1 to 33:1.[48][2]
Atenolol undergoes minimal or negligiblemetabolism by theliver.[3][4] It has been estimated that about 5% of atenolol is metabolized.[5] This is in contrast to other beta blockers likepropranolol andmetoprolol, but is similar tonadolol.[3] In accordance with its lack of hepatic metabolism, the pharmacokinetics of atenolol are not altered inhepatic impairment, unlike the case of propranolol.[4] Twometabolites of atenolol have been identified: hydroxyatenolol and atenolol glucuronide.[1] It has been said that it is unknown if these metabolites are active.[1] However, another source stated that hydroxyatenolol has one-tenth the beta-blocking activity of atenolol.[2]
Instead of by hepatic metabolism, atenolol iseliminated from the blood mainly viarenalexcretion.[3] Atenolol is excreted about 40 to 50% inurine and 50% infeces with oral administration.[2][3] Conversely, it is excreted 85 to 100% in urine unchanged and 10% in feces with intravenous administration.[2][3] Only very small amounts of hydroxyatenolol and atenolol glucuronide are found in urine with atenolol.[2]
Theelimination half-life of atenolol is about 6 to 7 hours.[3] The half-life of atenolol does not change with continuous administration.[3] With intravenous administration, atenolol levels rapidly decline (5- to 10-fold) during the first 7 hours and thereafter decline at a rate similar to that with oral administration.[3]
The elimination of atenolol is slowed inrenal impairment, with the elimination rate being closely related to theglomerular filtration rate (GFR) and with significant accumulation occurring when thecreatinineclearance rate is under 35 mL/min/1.73 m2.[3] At a GFR of less than 10 mL/min, the half-life of atenolol increases up to 36 hours.[5]
Atenolol is asubstituted phenethylaminederivative.[49] It is specificallyβ-phenylethylamine with an α-ketosubstitution and a 4- substitution on thephenyl ring.[49]
The experimentallog P of atenolol is 0.16 and its predicted log P ranges from −0.03 to 0.57.[49][50][51] Atenolol showed the lowest predicted lipophilicity of 30 clinically relevant beta blockers.[52]
Atenolol waspatented in 1969 and was approved for medical use in 1975.[11]
Atenolol has been given as an example of how slow healthcare providers are to change their prescribing practices in the face ofmedical evidence that indicates that a drug is not as effective as others in treating some conditions.[53] In 2012, 33.8 million prescriptions were written to American patients for this drug.[53] In 2014, it was in the top (most common) 1% of drugs prescribed to Medicare patients.[53] Although the number of prescriptions has been declining steadily since limited evidence articles contesting its efficacy was published, it has been estimated that it would take 20 years for doctors to stop prescribing it for hypertension.[53] Despite its diminished efficacy when compared to newerantihypertensive drugs, atenolol and otherbeta blockers are still a relevant clinical choice for treating some conditions, sincebeta blockers are a diverse group of medicines with different properties that still requires further research.[17] As consequence, reasons for the popularity of beta blockers cannot be fully attributed to a slow healthcare system –patient compliance factor, such as treatment cost and duration, also affect adherence and popularity of therapy.[54]
Atenolol is only minimally, if at all, metabolized and renally excreted in mostly unchanged form; thus an interaction with drugs that interfere with the hepatic metabolism is not to be expected. It is also very unlikely that the genetic polymorphisms of the CYP-family might affect the pharmacokinetics of atenolol. In fact it has been shown that plasma concentrations of nonmetabolized atenolol was not significantly different between "extensive" and "poor debrisoquine metabolizers" – in contrast to the plasma concentrations of metoprolol that were significantly increased in "poor metabolizers" (Dayer et al. 1985, Lewis et al. 1985). Furthermore, in healthy volunteers cimetidine (CAS 70059- 30-2) did not affect plasma concentrations of atenolol but significantly increased plasma concentrations of metoprolol or propranolol (Kirch et al. 1981).
Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people [...] Beta-blockers were not as good at preventing the number of deaths, strokes, and heart attacks as other classes of medicines such as diuretics, calcium-channel blockers, and renin-angiotensin system inhibitors. Most of these findings come from one type of beta-blocker called atenolol. However, beta-blockers are a diverse group of medicines with different properties, and we need more well-conducted research in this area." (p. 2-3)
β-Blockers still represent widely prescribed drugs as they cover a wide spectrum of CV indications. Obviously, it is not trivial which β-blocker to choose as they differ both with regard to their PD and PK profiles [82]. It is well known when comparing the characteristics of atenolol, bisoprolol, metoprolol (each β-1 selective) and carvedilol (β-1 and β-2 nonselective). Among these β-blockers, atenolol is mainly eliminated by renal excretion; bisoprolol is in part excreted as parent compound via the renal route (50%); the other 50% are hepatically metabolized; whereas metoprolol and carvedilol are metabolized by CYP2D6. DDIs are mainly observed with those β-blockers that are metabolized via CYP enzymes. However, it should be emphasized that, in general, β-blockers are well-tolerated safe drugs with a large therapeutic index [83].
Amphetamines (Adderall, Dexedrine): Electrophysiological Effects of Amphetamines: Amphetamines have been associated with tachyarrhythmias and sudden death.113–115 Many of the electrophysiological effects of amphetamines may be initiated by the release of norepinephrine stores from presynaptic vesicles and blocking of norepinephrine reuptake.116,117 In addition, amphetamines are potent blockers of dopamine uptake and strong central nervous system stimulants. Dopaminergic Effects of Amphetamines: In addition to the β-agonist effects of amphetamines, the dopamine receptors D1 and D2 contribute to the cardiovascular effects of methamphetamine by producing a pressor response accounting for the increase in blood pressure. The D1 receptor also is involved in mediating the positive tachycardic effects of methamphetamine.117
Interestingly, in one study, orthostatic hypotension was eliminated in a group of 61 patients treated for migraine headaches with phenelzine, when a beta-blocker, atenolol, was added (15). The authors have reported that hypertensive reactions were also less frequent when the two drugs were combined. We need further experience with this combination to determine whether addition of a beta-blocker is a safe and an effective strategy for alleviation of postural hypotension in depressed patients receiving an MAOI.
Postural hypotension is also a risk when antipsychotics are taken with β-blockers (probably because of pharmacokinetic interaction) or with diuretics (because of Na+ or volume depletion). The same hypotensive effects might be anticipated when tricyclic antidepressants or MAOIs are co-prescribed with peripheral antihypertensive agonists. One possible exception concerns phenelzine, whose hypotensive action was reversed on co-therapy with atenolol (Merikangas & Merikangas, 1995).
