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Timolol (Monograph)

Drug class: alpha-Adrenergic Blocking Agents

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Nonselective β-adrenergic blocking agent (β-blocker).111

Uses for Timolol

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).111 1200

β-Blockers generally not preferred for first-line therapy of hypertension according to current evidence-based hypertension guidelines, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).194 501 502 503 504 515 523 524 527 800 1200 Timolol is one of several β-blockers (including bisoprolol, carvedilol, metoprolol succinate, metoprolol tartrate, nadolol, and propranolol) recommended by a 2017 ACC/AHA multidisciplinary hypertension guideline as first-line therapy for hypertension in patients with stable ischemic heart disease/angina.1200

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

The 2017 ACC/AHA hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.176 180 181 501 504 1200 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

MI

Secondary prevention following acute MI.111

Administration within 7–28 days following MI associated with reductions in cardiovascular mortality and nonfatal reinfarction.a

Experts recommend β-blocker therapy in all patients with left ventricular systolic dysfunction and prior MI; a β-blocker with proven mortality benefit (bisoprolol, carvedilol, or metoprolol succinate) is preferred.525 Although benefits of long-term β-blockade in patients with normal left ventricular function are less well established, experts recommend continuing β-blocker therapy for at least 3 years in such patients.525

Vascular Headache

Prophylaxis of common or classic migraine headache.106 107 108 110 111 127 128

Chronic Stable Angina

Has been used in the management of chronic stable angina pectoris† [off-label].a

β-Blockers are recommended as first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.1101

Timolol Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally, usually twice daily.111

For management of hypertension, once-daily dosing may be possible in some patients.a

In patients with chronic stable angina pectoris† [off-label], administer orally in 3 or 4 divided doses.a

During maintenance therapy in patients with vascular headaches (migraine), may administer daily dosage as a single rather than divided dose.111

Dosage

Available as timolol maleate; dosage expressed in terms of the salt.111

Adults

Hypertension
Oral

Initially, 10 mg twice daily, either alone or in combination with a diuretic.111 a

Increase dosage gradually at weekly (or longer) intervals until optimum effect is obtained.111

Usual maintenance dosage is 20–40 mg daily, given in 2 divided doses; once-daily dosing may be possible in some patients.111 Increases up to a maximum of 60 mg daily (given in 2 divided doses) may be necessary.111

MI
Oral

Secondary prevention after acute phase of MI: Usual dosage is 10 mg twice daily.111

Optimal duration of therapy for secondary prevention remains to be established.527 802 804 Experts generally recommend long-term therapy in post-MI patients with left ventricular dysfunction, and at least 3 years of therapy in those with normal left ventricular function.525 802 804 1101

Chronic Stable Angina† [off-label]
Oral

15–45 mg daily, given in 3 or 4 divided doses.a Adjust dosage according to clinical response and to maintain a resting heart rate of 55–60 bpm.a

Vascular Headaches (Migraine)
Oral

Initially, 10 mg twice daily.107 108 110 111 Adjust dosage according to clinical response and patient tolerance; do not exceed 30 mg daily, given in divided doses (e.g., 10 mg in the morning and 20 mg in the evening).108 111

During maintenance therapy, can administer 20-mg daily dosage as a single rather than divided dose; some patients may respond adequately to 10 mg once daily.111

If an adequate response is not achieved after 6–8 weeks at the maximum recommended dosage, discontinue therapy.111

Prescribing Limits

Adults

Hypertension
Oral

Maximum 60 mg daily.111

Vascular Headaches (Migraine)
Oral

Maximum 30 mg daily.108 111

Special Populations

Hepatic Impairment

Must modify doses and/or frequency of administration in response to degree of hepatic impairment.111

Renal Impairment

Must modify doses and/or frequency of administration in response to degree of renal impairment.111

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.b Initiate at low end of dosing range.b

Detailed Timolol dosage information

Cautions for Timolol

Contraindications

Warnings/Precautions

Warnings

Heart Failure

Possible precipitation of heart failure.111

Avoid use in patients with overt heart failure; may use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).111

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending heart failure occur; if heart failure continues, discontinue therapy, gradually if possible.111

Abrupt Withdrawal of Therapy

Abrupt withdrawal of therapy is not recommended as it may exacerbate angina symptoms or precipitate MI in patients with coronary artery disease.111

Gradually decrease dosage over a period of 1–2 weeks and monitor patients carefully; advise patients to temporarily limit their physical activity during withdrawal of therapy.111

If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for management of unstable angina pectoris.111

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous catecholamines.111

Generally should not be used in patients with bronchospastic disease, but may use with caution in patients who do not respond to or cannot tolerate alternative treatment.111 a Use with caution in patients with nonallergic bronchospasm (e.g., chronic bronchitis, emphysema) or a history of nonallergic bronchospasm.a (See Contraindications under Cautions.)

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty restarting or maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.111

Some clinicians recommend gradual withdrawal before elective surgery.111 b Manufacturers recommend administration of β-agonists (e.g., dopamine, dobutamine, isoproterenol) to reverse β-adrenergic blockade if necessary during surgery.111 a b

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, but not sweating or dizziness).111 Use with caution in patients with diabetes mellitus receiving hypoglycemic drugs.111

Thyrotoxicosis

May mask signs of hyperthyroidism (e.g., tachycardia).111 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.111

Sensitivity Reactions

Anaphylactic Reactions

Patients with a history of atopy or anaphylactic reactions to a variety of allergens may be more reactive to repeated, accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents; such patients may be unresponsive to usual doses of epinephrine.111

General Precautions

Muscle Weakness

β-Adrenergic blockade reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, generalized weakness).111 b Increased muscle weakness reported rarely in some patients with myasthenia gravis or myasthenic symptoms.111 b

Cerebrovascular Insufficiency

Possible cardiovascular effects (e.g., hypotension, bradycardia) that can adversely affect cerebral blood flow.111 Use with caution in patients with cerebrovascular insufficiency.111 If signs or symptoms suggestive of reduced cerebral blood flow occur, consider discontinuance.111

Other Precautions

Shares the toxic potentials of β-blockers; observe usual precautions of these agents.a

Specific Populations

Pregnancy

Category C.111

Lactation

Distributed into milk.111 Discontinue nursing or the drug.111

Pediatric Use

Safety and efficacy not established.111

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.111

Substantially eliminated by the kidneys; assess renal function periodically and adjust dosage since geriatric patients are more likely to have decreased renal function.111 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution; dosage adjustment may be necessary.111 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution; dosage adjustment may be necessary.111 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Fatigue, headache, bradycardia, arrhythmia, pruritus, dizziness, dyspnea, eye irritation.111

Drug Interactions

Appears to be metabolized partly by CYP2D6.540 b

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Potential pharmacodynamic (increased β-adrenergic blockade) and pharmacokinetic interaction (increased plasma timolol concentrations).540 b

Specific Drugs

Drug

Interaction

Comments

Calcium-channel blocking agents

Potential hypotension, AV conduction disturbances, and left ventricular failure111

Avoid concomitant use in patients with impaired cardiac function111

Clonidine

β-Adrenergic blockade may exacerbate rebound hypertension which may occur following clonidine discontinuance145 146

Discontinue β-blockers several days before gradual withdrawal of clonidine145 146

If clonidine therapy is to be replaced by a β-blocker, delay administration for several days after clonidine discontinuance145 146

Digoxin

Possible additive effect in prolonging AV conduction time when used concomitantly with diltiazem or verapamil111

Hypotensive agents (hydralazine, methyldopa)

Possible increased hypotensive effecta

Careful dosage adjustment is recommendeda

NSAIAs

Potential blunting of hypotensive effects111

Monitor patients carefully111

Quinidine

Possible potentiation of β-adrenergic blockade (e.g., decreased heart rate)111

Reserpine

Possible additive effects111

Observe closely for evidence of marked bradycardia or hypotension (may be manifested as vertigo, presyncope or syncope, or orthostatic changes in BP without compensatory tachycardia)111
Timolol drug interactions (more detail)

Timolol Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is rapid; approximately 90% absorbed following oral administration.111 Peak plasma concentration usually attained within 1–2 hours.111

Distribution

Extent

Distributed into milk.111

Plasma Protein Binding

10–60%, depending on assay method employed.111

Elimination

Metabolism

Approximately 80% metabolized in the liver to inactive metabolites.111 a

Elimination Route

Excreted in urine as unchanged drug and metabolites.111

Half-life

3–4 hours.111 a

Special Populations

Only small amounts removed by hemodialysis.111 a

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.111 Protect from light.111

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Timolol Maleate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg*

Timolol Maleate Tablets

10 mg*

Timolol Maleate Tablets

20 mg*

Timolol Maleate Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

101. Moser M. Initial treatment of adult patients with essential hypertension: I. Why conventional stepped-care therapy of hypertension is still indicated. Pharmacotherapy. 1985; 5:189-95. http://www.ncbi.nlm.nih.gov/pubmed/2863806?dopt=AbstractPlus

102. Kaplan NM. Initial treatment of adult patients with essential hypertension: II. Alternating monotherapy is the preferred treatment. Pharmacotherapy. 1985; 5:195-200. http://www.ncbi.nlm.nih.gov/pubmed/4034407?dopt=AbstractPlus

103. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. http://www.ncbi.nlm.nih.gov/pubmed/6150424?dopt=AbstractPlus

104. Hyman D, Kaplan NM. Treatment of patients with mild hypertension. Hypertension. 1985; 7:165-70. http://www.ncbi.nlm.nih.gov/pubmed/3884501?dopt=AbstractPlus

105. Weber MA. Beta blockers in the initial therapy of hypertension. Drug Ther. 1980; 10(11):77-80.

106. Briggs RS, Millac PA. Timolol in migraine prophylaxis. Headache. 1979; 19:379-81. http://www.ncbi.nlm.nih.gov/pubmed/511540?dopt=AbstractPlus

107. Tfelt-Hansen P, Standnes B. Timolol vs propranolol vs placebo in common migraine prophylaxis: a double-blind multicenter trial. Acta Neurol Scand. 1984; 69:1-8. http://www.ncbi.nlm.nih.gov/pubmed/6367336?dopt=AbstractPlus

108. Stellar S, Ahrens SP, Meibohm AR et al. Migraine prevention with timolol: a double-blind crossover study. JAMA. 1984; 252:2576-80. http://www.ncbi.nlm.nih.gov/pubmed/6387197?dopt=AbstractPlus

110. Andersson KE, Vinge E. β-Adrenergic blockers and calcium antagonists in the prophylaxis and treatment of migraine. Drugs. 1990; 39:355-73. http://www.ncbi.nlm.nih.gov/pubmed/1970289?dopt=AbstractPlus

111. Merck & Co. Blocadren (timolol maleate) tablets prescribing information. Whitehouse Station, NJ; 2001 Apr.

112. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the early management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction). Circulation. 1990; 82:664-707. http://www.ncbi.nlm.nih.gov/pubmed/2197021?dopt=AbstractPlus

113. Roque F, Amuchastegui LM, Lopez Morillos MA et al. The TIARA Study Group. Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction. Circulation. 1987; 76:610-7. http://www.ncbi.nlm.nih.gov/pubmed/3304706?dopt=AbstractPlus

114. Goldman L, Sia STB, Cook EF et al. Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction. N Engl J Med. 1988; 319:152-7. http://www.ncbi.nlm.nih.gov/pubmed/2898733?dopt=AbstractPlus

115. Yusuf S, Peto R, Lewis J et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985; 27:335-71. http://www.ncbi.nlm.nih.gov/pubmed/2858114?dopt=AbstractPlus

116. Yusuf S, Sleight P, Held P et al. Routine medical management of acute myocardial infarction: lessons from overviews of recent randomized controlled trials. Circulation. 1990; 82(Suppl 11):11-117-34.

117. Held P, Yusuf S. Early intravenous beta-blockade in acute myocardial infarction. Cardiology. 1989; 76:132-43. http://www.ncbi.nlm.nih.gov/pubmed/2568179?dopt=AbstractPlus

118. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after acute myocardial infarction. N Engl J Med. 1985; 313:1055-8. http://www.ncbi.nlm.nih.gov/pubmed/2864634?dopt=AbstractPlus

119. Pedersen TR. The Norwegian multicenter study of timolol after myocardial infarction. Circulation. 1983; 67(Suppl 1):49-53.

120. The Beta-Blocker Pooling Project Research Group. The Beta-Blocker Pooling Project (BBPP): subgroup findings from randomized trials in post infarction patients. Eur Heart J. 1988; 9(Suppl 1):8-16.

121. β-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction: I. Mortality results. JAMA. 1982; 247(Suppl 12):1707-14. http://www.ncbi.nlm.nih.gov/pubmed/7038157?dopt=AbstractPlus

122. The Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 1981; 304(Suppl 14):801-7. http://www.ncbi.nlm.nih.gov/pubmed/7010157?dopt=AbstractPlus

123. Gheorghiade M, Schultz L, Tilley B et al. Effects of propranolol in non-Q-wave acute myocardial infarction in the beta blocker heart attack trial. Am J Cardiol. 1990; 66:129-33. http://www.ncbi.nlm.nih.gov/pubmed/2196771?dopt=AbstractPlus

124. Yusuf S, Wittes J, Probstfield J. Evaluating effects of treatment in subgroups of patients with a clinical trial: the case of non-Q-wave myocardial infarction and beta blockers. Am J Cardiol. 1990; 66:220-2. http://www.ncbi.nlm.nih.gov/pubmed/1973589?dopt=AbstractPlus

125. Griggs TR, Wagner GS, Gettes LS. Beta-adrenergic blocking agents after myocardial infarction: an undocumented need in patients at lowest risk. J Am Coll Cardiol. 1983; 1(Suppl 6):1530-3. http://www.ncbi.nlm.nih.gov/pubmed/6133891?dopt=AbstractPlus

126. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after myocardial infarction. N Engl J Med. 1986; 314:1052.

127. Dalessio DJ. β-Blockers and migraine. JAMA. 1984; 252:2614. http://www.ncbi.nlm.nih.gov/pubmed/6149322?dopt=AbstractPlus

128. Hart LL. Beta-blocking agents for migraine. DICP. 1989; 23:248-9.

129. Frishman WH, Furberg CD, Friedewald WT. β-Adrenergic blockade for survivors of acute myocardial infarction. N Engl J Med. 1984; 310:830-7. http://www.ncbi.nlm.nih.gov/pubmed/6142420?dopt=AbstractPlus

130. Roberts R, Rogers WJ, Mueller H et al. Immediate versus deferred β-blockade following thrombolytic therapy in patients with acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II-B study. Circulation. 1991; 83:422-37. http://www.ncbi.nlm.nih.gov/pubmed/1671346?dopt=AbstractPlus

131. Reviewers’ comments (personal observations).

133. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. http://www.ncbi.nlm.nih.gov/pubmed/8422205?dopt=AbstractPlus

134. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: an overview of randomized drug trials in their epidemiological context. Lancet. 1990; 335:827-38. http://www.ncbi.nlm.nih.gov/pubmed/1969567?dopt=AbstractPlus

135. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

136. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335:765-74. http://www.ncbi.nlm.nih.gov/pubmed/1969518?dopt=AbstractPlus

137. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265:3255-64. http://www.ncbi.nlm.nih.gov/pubmed/2046107?dopt=AbstractPlus

138. Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-hypertension). Lancet. 1991; 338:1281-5. http://www.ncbi.nlm.nih.gov/pubmed/1682683?dopt=AbstractPlus

139. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304:405-12. http://www.ncbi.nlm.nih.gov/pubmed/1445513?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1995577&blobtype=pdf

141. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. http://www.ncbi.nlm.nih.gov/pubmed/8622249?dopt=AbstractPlus

142. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. http://www.ncbi.nlm.nih.gov/pubmed/9042847?dopt=AbstractPlus

144. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. http://www.ncbi.nlm.nih.gov/pubmed/9515998?dopt=AbstractPlus

145. Merck & Co. Blocadren (timolol maleate) tablets prescribing information (dated 1997 Nov). In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998(Suppl A):A204-5.

146. Clonidine/beta blockers. In: Tatro DS, Olin BR, Hebel SK, eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1992 (July):200.

148. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

150. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. http://www.ncbi.nlm.nih.gov/pubmed/9827842?dopt=AbstractPlus

151. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. http://www.ncbi.nlm.nih.gov/pubmed/9831300?dopt=AbstractPlus

152. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. http://www.ncbi.nlm.nih.gov/pubmed/9732337?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=28659&blobtype=pdf

153. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15. From American Diabetes Association web site. http://www.diabetes.org

154. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. http://www.ncbi.nlm.nih.gov/pubmed/9732338?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=28660&blobtype=pdf

155. Davis TME. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

157. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: apporaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

159. Lim PO, MacDonald TM. Antianginal and β-adrenergic blocking drugs. In: Dukes MNG, ed. Meyler’s side effects of drugs. 13th ed. New York: Elsevier/North Holland Inc; 1996:488-535.

160. Gress TW, Nieto FJ, Shahar E et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med. 2000; 342:905-12. http://www.ncbi.nlm.nih.gov/pubmed/10738048?dopt=AbstractPlus

161. Sowers JR, Bakris GL. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000; 342:969-70. http://www.ncbi.nlm.nih.gov/pubmed/10738057?dopt=AbstractPlus

162. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. http://www.ncbi.nlm.nih.gov/pubmed/10818056?dopt=AbstractPlus

163. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. http://www.ncbi.nlm.nih.gov/pubmed/10818055?dopt=AbstractPlus

164. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. http://www.ncbi.nlm.nih.gov/pubmed/10977801?dopt=AbstractPlus

165. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351:1755-62. http://www.ncbi.nlm.nih.gov/pubmed/9635947?dopt=AbstractPlus

168. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 1999; 33:2092-7.

170. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60. http://www.ncbi.nlm.nih.gov/pubmed/12093785?dopt=AbstractPlus

171. Ramadan NM, Silberstein SD, Freitag FG et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. St. Paul, MN; 2001. From the American Academy of Neurology web site. http://www.aan.com

173. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. http://www.ncbi.nlm.nih.gov/pubmed/12479770?dopt=AbstractPlus

174. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-riskhypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. http://www.ncbi.nlm.nih.gov/pubmed/12479763?dopt=AbstractPlus

176. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

178. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

180. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. http://www.ncbi.nlm.nih.gov/pubmed/15811979?dopt=AbstractPlus

181. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. http://www.ncbi.nlm.nih.gov/pubmed/15811986?dopt=AbstractPlus

182. Thadani U. Beta blockers in hypertension. Am J Cardiol. 1983; 52:10-5D.

183. Conolly ME, Kersting F, Dollery CT. The clinical pharmacology of beta-adrenoceptor-blocking drugs. Prog Cardiovasc Dis. 1976; 19:203-34. http://www.ncbi.nlm.nih.gov/pubmed/10600?dopt=AbstractPlus

184. Shand DG. State-of-the-art: comparative pharmacology of the β-adrenoceptor blocking drugs. Drugs. 1983; 25(Suppl 2):92-9.

185. Breckenridge A. Which beta blocker? Br Med J. 1983; 286:1085-8. (IDIS 169422)

186. Anon. Choice of a beta-blocker. Med Lett Drugs Ther. 1986; 28:20-2. http://www.ncbi.nlm.nih.gov/pubmed/2869400?dopt=AbstractPlus

187. Wallin JD, Shah SV. β-Adrenergic blocking agents in the treatment of hypertension: choices based on pharmacological properties and patient characteristics. Arch Intern Med. 1987; 147:654-9. http://www.ncbi.nlm.nih.gov/pubmed/2881524?dopt=AbstractPlus

188. McDevitt DG. β-Adrenoceptor blocking drugs and partial agonist activity: is it clinically relevant? Drugs. 1983; 25:331-8.

189. McDevitt DG. Clinical significance of cardioselectivity: state-of-the-art. Drugs. 1983; 25(Suppl 2):219-26.

190. Frishman WH. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med. 1981; 305:500-6. http://www.ncbi.nlm.nih.gov/pubmed/6114433?dopt=AbstractPlus

191. Thadani U, Davidson C, Chir B et al. Comparison of the immediate effects of five β-adrenoceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979; 300:750-5. http://www.ncbi.nlm.nih.gov/pubmed/581782?dopt=AbstractPlus

192. Lewis RV, McDevitt DG. Adverse reactions and interactions with β-adrenoceptor blocking drugs. Med Toxicol. 1986; 1:343-61. http://www.ncbi.nlm.nih.gov/pubmed/2878346?dopt=AbstractPlus

193. Frishman WH. Clinical differences between beta-adrenergic blocking agents: implications for therapeutic substitution. Am Heart J. 1987; 113:1190-8. http://www.ncbi.nlm.nih.gov/pubmed/2883867?dopt=AbstractPlus

194. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995-1003.

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. http://www.ncbi.nlm.nih.gov/pubmed/24352797?dopt=AbstractPlus

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. http://www.ncbi.nlm.nih.gov/pubmed/24352710?dopt=AbstractPlus

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. http://www.ncbi.nlm.nih.gov/pubmed/24352759?dopt=AbstractPlus

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. http://www.ncbi.nlm.nih.gov/pubmed/24591473?dopt=AbstractPlus

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. http://www.ncbi.nlm.nih.gov/pubmed/22052934?dopt=AbstractPlus

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3695607&blobtype=pdf

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus

540. Ishii Y, Nakamura K, Tsutsumi K et al. Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J Clin Pharmacol. 2000; 40:193-9. http://www.ncbi.nlm.nih.gov/pubmed/10664926?dopt=AbstractPlus

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

600. Mylan Pharmaceuticals. Timolol tablets prescribing information. Morgantown, WV; 2006 Aug.

800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :.

802. Bockstall K, Bangalore S. How long should we continue beta-blockers after MI? 2017 Jan 23. From ACC website. Accessed 2017 May 17. http://www.acc.org/latest-in-cardiology/articles/2017/01/20/09/36/how-long-should-we-continue-beta-blockers-after-mi

804. Kezerashvili A, Marzo K, De Leon J. Beta blocker use after acute myocardial infarction in the patient with normal systolic function: when is it “ok” to discontinue?. Curr Cardiol Rev. 2012; 8:77-84. http://www.ncbi.nlm.nih.gov/pubmed/22845818?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3394111&blobtype=pdf

806. Freemantle N, Cleland J, Young P et al. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999; 318:1730-7. http://www.ncbi.nlm.nih.gov/pubmed/10381708?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=31101&blobtype=pdf

1101. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018; 71:el13-e115. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus

1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. http://www.ncbi.nlm.nih.gov/pubmed/29341841?dopt=AbstractPlus

1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus

1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus

1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus

1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus

1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. http://www.ncbi.nlm.nih.gov/pubmed/29159416?dopt=AbstractPlus

1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus

1223. LeFevre M. ACC/AHA hypertension guideline: what is new? what do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534?dopt=AbstractPlus

1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017

1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

1235. Mann SJ. Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient. J Am Soc Hypertens. 2017; 11(1):54-65. http://www.ncbi.nlm.nih.gov/pubmed/28057444?dopt=AbstractPlus

a. AHFS Drug Information 2018. McEvoy GK, ed. Timolol Maleate. American Society of Health-System Pharmacists; 2018:.

b. Merck & Co. Blocadren (timolol maleate) tablets prescribing information. Whitehouse Station, NJ; 2002 Mar

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