Atenolol

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

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| _other_data=(RS)-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide

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| _datapage = Atenolol (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=S4Rx-only | _ATC_prefix_supplemental=C07 | _has_EMA_link = | CAS_number=29122-68-7 | PubChem=2249 | ChemSpiderID=2162 | ChEBI=2904 | ChEMBL=24 | DrugBank=DB00335 | KEGG=D00235 | _hasInChI_or_Key={{#if:1S/C14H22N2O3/c1-10(2)16-8-12(17)9-19-13-5-3-11(4-6-13)7-14(15)18/h3-6,10,12,16-17H,7-9H2,1-2H3,(H2,15,18)METKIMKYRPQLGS-UHFFFAOYSA-N |yes}} | UNII=50VV3VW0TI | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields= |Watchedfields=changed |verifiedrevid=458476745}} Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain.<ref name=AHFS2018/> Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Other uses include the prevention of migraines and treatment of certain irregular heart beats.<ref name=AHFS2018/><ref name=BNF76>Template:Cite book</ref> It is taken orally (by mouth) or by intravenous injection (injection into a vein).<ref name=AHFS2018/><ref name=BNF76/> It can also be used with other blood pressure medications.<ref name=BNF76/>

Common side effects include feeling tired, heart failure, dizziness, depression, and shortness of breath.<ref name=AHFS2018/> Other serious side effects include bronchial spasm.<ref name=AHFS2018/> Use is not recommended during pregnancy<ref name=AHFS2018/> and alternative drugs are preferred when breastfeeding.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It works by blocking β₁-adrenergic receptors in the heart, thus decreasing heart rate, force of heart beats, and blood pressure.<ref name=AHFS2018/>

Atenolol was patented in 1969 and approved for medical use in 1975.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2018>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2022, it was the 63rd most commonly prescribed medication in the United States, with more than 10Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Atenolol is used for a number of conditions including hyperthyroidism,<ref name="Rehman Sanchez Shah 2021 p. ">Template:Cite book</ref> hypertension, angina, long QT syndrome, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, essential tremor (ET), and the symptoms of alcohol withdrawal.<ref name=AHFS>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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 as ACE inhibitors, calcium channel blockers, thiazide diuretics and angiotensin receptor blockers, particularly in the elderly.<ref name="Cochrane2017">Template:Cite journal</ref><ref name="NHSnews">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Cruickshank2007">Template:Cite journal</ref>

Available forms

Atenolol is available in the form of 25, 50, and 100Template:Nbspmg oral tablets.<ref name="Drugs@FDA">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="TenorminLabel" /> It is also available in the form of oral tablets containing a combination of 50 or 100Template:Nbspmg atenolol and 50Template:Nbspmg chlortalidone.<ref name="Drugs@FDA" /> Atenolol was previously available in a 0.5Template:Nbspmg/mL solution for injection as well, but this formulation was discontinued.<ref name="Drugs@FDA" />

Side effects

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

β-blockers, of which atenolol is mainly studied, provides weaker protection against stroke and mortality in patients over 60 years old compared to other antihypertensive medications.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="Cochrane2017" /> Diuretics may be associated with better cardiovascular and cerebrovascular outcomes than β-blockers in the elderly.<ref name="pmid15530629">Template:Cite journal</ref>

Rarely, atenolol has been associated with induction of acute delirium.<ref name="KellerFrishman2003">Template:Cite journal</ref><ref name="WadworthMurdochBrogden1991">Template:Cite journal</ref><ref name="Arber1988">Template:Cite journal</ref>

Overdose

Symptoms of overdose are due to excessive pharmacodynamic actions on β₁ and also β₂-receptors. These include bradycardia (slow heartbeat), severe hypotension with shock, acute heart 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 as hexoprenalin or salbutamol 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.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

Interactions

Interactions with atenolol include catecholamine-depleting drugs like reserpine, calcium channel blockers, disopyramide, amiodarone, clonidine, prostaglandin synthase inhibitors like indomethacin, and digitalis glycosides.<ref name="Atenolol-Label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Most of these interactions involve either additive cardiovascular effects or reduction of atenolol's effects.<ref name="Atenolol-Label" />

Atenolol is mainly eliminated renally without being metabolized by the liver or by cytochrome P450 enzymes.<ref name="Atenolol-Label" /><ref name="BroddeKroemer2003">Template:Cite journal</ref><ref name="Scheen2011">Template:Cite journal</ref> As a result, it has little or no potential for cytochrome P450-related drug interactions, for instance with inhibitors and inducers of these enzymes.<ref name="BroddeKroemer2003" /><ref name="Scheen2011" /> Accordingly, the broad/non-selective cytochrome P450 inhibitor cimetidine had no effect on atenolol levels, whereas cimetidine has been found to significantly increase metoprolol and propranolol levels.<ref name="BroddeKroemer2003" />

Beta blockers like atenolol can reduce or block the cardiovascular effects of sympathomimetics and amphetamines, such as hypertension and tachycardia.<ref name="RichardsAlbertsonDerlet2015">Template:Cite journal</ref><ref name="VetterEliaErickson2008">Template:Cite journal</ref><ref name="SchindlerZhengTella1992">Template:Cite journal</ref><ref name="MoresCampiaNavarra1999">Template:Cite journal</ref><ref name="HassanGunaidElKhally2005">Template:Cite journal</ref><ref name="OConnellGross1990">Template:Cite journal</ref><ref name="OConnellGross1991">Template:Cite journal</ref>

Atenolol has been found to be safe in combination with the non-selective monoamine oxidase inhibitor (MAOI) phenelzine and actually improved orthostatic hypotension and hypertensive reactions with phenelzine.<ref name="Balon1998">Template:Cite book</ref><ref name="OBrienOyebode2003">Template:Cite journal</ref><ref name="MerikangasMerikangas1995">Template:Cite journal</ref> 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.<ref name="Balon1998" /><ref name="MerikangasMerikangas1995" />

Pharmacology

Pharmacodynamics

Atenolol is a beta blocker; that is, an antagonist of the β-adrenergic receptors.<ref name="pmid33572109" /><ref name="TenorminLabel" /> It is specifically a selective antagonist of the β₁-adrenergic receptor with no intrinsic sympathomimetic activity (i.e., partial agonist activity) or membrane-stabilizing activity.<ref name="pmid33572109" /><ref name="TenorminLabel" /> However, the preferential action of atenolol is not absolute, and at high doses, it can also block β₂-adrenergic receptors.<ref name="TenorminLabel" />

Beta-blocking effects of atenolol include reduction in resting and exercise heart rate and cardiac output, reduction of systolic and diastolic blood pressure at rest and with exercise, inhibition of tachycardia induced by isoproterenol (a non-selective β-adrenergic receptor agonist), and reduction of reflex orthostatic tachycardia.<ref name="TenorminLabel" />

The beta-blocking effects of atenolol, as measured by reduction of exercise-related tachycardia, are apparent within 1Template:Nbsphour and are maximal within 2 to 4Template:Nbsphours following a single oral dose.<ref name="TenorminLabel" /> The general effects of atenolol, including beta-blocking and antihypertensive effects, last for at least 24Template:Nbsphours following oral doses of 50 or 100Template:Nbspmg.<ref name="TenorminLabel" /> With intravenous administration, maximal reduction in exercise-related tachycardia occurs within 5Template:Nbspminutes and following a single 10Template:Nbspmg dose has dissipated within 12Template:Nbsphours.<ref name="TenorminLabel" /> The duration of action of atenolol is dose-related and is correlated with circulating levels of atenolol.<ref name="TenorminLabel" />

Pharmacokinetics

Absorption

The oral bioavailability of atenolol is approximately 50 to 60%.<ref name="WadworthMurdochBrogden1991" /><ref name="HeelBrogdenSpeight1979" /> The absorption of atenolol with oral administration is rapid and consistent but is incomplete.<ref name="TenorminLabel" /> About 50% of an oral dose of atenolol is absorbed from the intestines, with the rest excreted in feces.<ref name="TenorminLabel" /> Maximal concentrations of atenolol occur 2 to 4Template:Nbsphours following an oral dose, whereas peak concentrations occur within 5Template:Nbspminutes with intravenous administration.<ref name="TenorminLabel" /> The pharmacokinetic profile of atenolol results in it having relatively consistent plasma drug levels with about 4-fold variation between individuals.<ref name="TenorminLabel" />

Distribution

The plasma protein binding of atenolol is 6 to 16%.<ref name="TenorminLabel" />

Atenolol is classified as a beta blocker with low lipophilicity and hence lower potential for crossing the blood–brain barrier and entering the brain.<ref name="pmid33572109">Template:Cite journal</ref> This in turn may result in fewer effects in the central nervous system as well as a lower risk of neuropsychiatric side effects.<ref name="pmid33572109" /> Only small amounts of atenolol are said to enter the brain.<ref name="WadworthMurdochBrogden1991" /><ref name="HeelBrogdenSpeight1979" /> The brain-to-blood ratio of atenolol was 0.2 : 1 in one study, whereas the ratio for propranolol was 33 : 1 in the same study.<ref name="HeelBrogdenSpeight1979" />

Metabolism

Atenolol undergoes minimal or negligible metabolism by the liver.<ref name="TenorminLabel" /><ref name="BroddeKroemer2003" /> It has been estimated that about 5% of atenolol is metabolized.<ref name="KirchGörg1982">Template:Cite journal</ref> This is in contrast to other beta blockers like propranolol and metoprolol, but is similar to nadolol.<ref name="TenorminLabel" /> In accordance with its lack of hepatic metabolism, the pharmacokinetics of atenolol are not altered in hepatic impairment, unlike the case of propranolol.<ref name="BroddeKroemer2003" /> Two metabolites of atenolol have been identified: hydroxyatenolol and atenolol glucuronide.<ref name="WadworthMurdochBrogden1991" /> It has been said that it is unknown if these metabolites are active.<ref name="WadworthMurdochBrogden1991" /> However, another source stated that hydroxyatenolol has one-tenth the beta-blocking activity of atenolol.<ref name="HeelBrogdenSpeight1979" />

Elimination

Instead of by hepatic metabolism, atenolol is eliminated from the blood mainly via renal excretion.<ref name="TenorminLabel" /> Atenolol is excreted about 40 to 50% in urine and 50% in feces with oral administration.<ref name="HeelBrogdenSpeight1979">Template:Cite journal</ref><ref name="TenorminLabel" /> Conversely, it is excreted 85 to 100% in urine unchanged and 10% in feces with intravenous administration.<ref name="HeelBrogdenSpeight1979" /><ref name="TenorminLabel" /> Only very small amounts of hydroxyatenolol and atenolol glucuronide are found in urine with atenolol.<ref name="HeelBrogdenSpeight1979" />

The elimination half-life of atenolol is about 6 to 7Template:Nbsphours.<ref name="TenorminLabel" /> The half-life of atenolol does not change with continuous administration.<ref name="TenorminLabel" /> With intravenous administration, atenolol levels rapidly decline (5- to 10-fold) during the first 7Template:Nbsphours and thereafter decline at a rate similar to that with oral administration.<ref name="TenorminLabel" />

The elimination of atenolol is slowed in renal impairment, with the elimination rate being closely related to the glomerular filtration rate (GFR) and with significant accumulation occurring when the creatinine clearance rate is under 35Template:NbspmL/min/1.73Template:Nbspm².<ref name="TenorminLabel" /> At a GFR of less than 10Template:NbspmL/min, the half-life of atenolol increases up to 36Template:Nbsphours.<ref name="KirchGörg1982" />

Chemistry

Atenolol is a substituted phenethylamine derivative.<ref name="PubChem" /> It is specifically β-phenylethylamine with an α-keto substitution and a 4- substitution on the phenyl ring.<ref name="PubChem" />

The experimental log P of atenolol is 0.16 and its predicted log P ranges from −0.03 to 0.57.<ref name="PubChem">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="DrugBank">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="ChemSpider">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Atenolol is closely structurally related to metoprolol and certain other beta blockers. It is also structurally related to the catecholamine neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline).

Society and culture

Changing medical practices

Atenolol has been given as an example of how slow healthcare providers are to change their prescribing practices in the face of medical evidence that indicates that a drug is not as effective as others in treating some conditions.<ref name=":0">Template:Cite news</ref> In 2012, 33.8 million prescriptions were written to American patients for this drug.<ref name=":0"/> In 2014, it was in the top (most common) 1% of drugs prescribed to Medicare patients.<ref name=":0"/> 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.<ref name=":0"/> Despite its diminished efficacy when compared to newer antihypertensive drugs, atenolol and other beta blockers are still a relevant clinical choice for treating some conditions, since beta blockers are a diverse group of medicines with different properties that still requires further research.<ref name="Cochrane2017" /> 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.<ref>Template:Cite journal</ref>