VA Class:CV100
Pindolol is a nonselective β-adrenergic blocking agent (β-blocker) possessing intrinsic sympathomimetic activity.1, 2, 3, 4
Pindolol is used in the management of hypertension.1, 2, 1200 The drug also has been used in the management of angina†.2, 5, 15, 22
The choice of a β-adrenergic blocking agent (β-blocker) depends on numerous factors, including pharmacologic properties (e.g., relative β-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity, lipophilicity), pharmacokinetics, intended use, and adverse effect profile, as well as the patient's coexisting disease states or conditions, response, and tolerance.4, 12, 85, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 While specific pharmacologic properties and other factors may appropriately influence the choice of a β-blocker in individual patients,1235 evidence of clinically important differences among the agents in terms of overall efficacy and/or safety is limited.4, 12, 91, 93, 94, 95, 96, 97, 98, 99, 100 Patients who do not respond to or cannot tolerate one β-blocker may be successfully treated with a different agent.4, 93, 94, 95, 96, 97, 99, 100
In the management of hypertension or chronic stable angina pectoris†, many clinicians prefer to use low dosages of a β1-selective adrenergic blocking agent (e.g., atenolol, metoprolol), rather than a nonselective agent like pindolol, in patients with chronic obstructive pulmonary disease (COPD) or insulin-dependent diabetes mellitus.4 However, selectivity of these agents is relative and dose dependent.4, 29, 30 Although a β-blocker with intrinsic sympathomimetic activity (ISA) (e.g., pindolol) does not eliminate sympathetic activity entirely, there is no evidence from well-controlled studies that pindolol is safer in these patients than other nonselective β-blockers that do not possess ISA.15 Some clinicians also will recommend using a β1-selective agent or pindolol (because of its ISA), rather than a nonselective agent, for the management of hypertension or angina pectoris in patients with peripheral vascular disease, but there is no evidence that the choice of β-blocker substantially affects efficacy.4, 5, 15
Pindolol is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1, 1200
Current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of drugs from 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics).501, 502, 503, 504, 1200 Most guidelines no longer recommend β-blockers as first-line therapy for hypertension because of the lack of established superiority over other recommended drug classes and evidence from at least one study demonstrating that β-blockers may be less effective than angiotensin II receptor antagonists in preventing cardiovascular death, myocardial infarction (MI), or stroke.101, 501, 503, 504, 515, 1200 However, therapy with a β-blocker may still be considered in hypertensive 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.501, 502, 523, 524, 527, 800, 1200 (See Considerations for Drug Therapy in Patients with Underlying Cardiovascular and Other Risk Factors under Uses: Hypertension, in Atenolol 24:24 and in Metoprolol 24:24.) Ultimately, choice of antihypertensive therapy should be individualized, considering the clinical characteristics of the patient (e.g., age, ethnicity/race, comorbid conditions, cardiovascular risk factors) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, costs).501, 502, 503, 504, 515, 1200, 1201
A 2017 multidisciplinary hypertension guideline of the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations generally recommends a target blood pressure goal (i.e., blood pressure to achieve with drug therapy and/or nonpharmacologic intervention) of less than 130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, a systolic blood pressure goal of less than 130 mm Hg generally is recommended for noninstitutionalized ambulatory patients 65 years of age or older with an average systolic blood pressure of at least 130 mm Hg.1200 These blood pressure goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of systolic blood pressure.1200, 1202, 1210 Previous hypertension guidelines, such as those from an expert panel of the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), generally have recommended initiation of antihypertensive treatment in patients with a systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg, targeted a blood pressure goal of less than 140/90 mm Hg regardless of cardiovascular risk, and used higher systolic blood pressure thresholds and targets in geriatric patients501, 504, 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200 The blood pressure thresholds used to define hypertension, the optimum blood pressure threshold at which to initiate antihypertensive drug therapy, and the ideal target blood pressure values remain controversial.501, 503, 504, 505, 506, 507, 508, 515, 523, 526, 530, 1200, 1201, 1207, 1209, 1222, 1223, 1229
Most patients with hypertension, especially black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blocking agents than to monotherapy with β-blockers.85, 89, 90, 501, 504, 1200 Although β-blockers have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients; however, this population difference in response does not appear to occur during combined therapy with a β-blocker and a thiazide diuretic.500 (See Race under Hypertension: Other Special Considerations for Antihypertensive Drug Therapy, in Uses in Atenolol 24:24 and in Metoprolol 24:24.)
For additional information on the role of β-blockers in the management of hypertension, see Uses: Hypertension, in Atenolol 24:24 and in Metoprolol 24:24. For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults and also see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Pindolol has been used in the long-term management of chronic stable angina pectoris†.2, 5, 15, 22β-Blockers are recommended as the anti-ischemic drugs of choice 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 indication.1101
Combination therapy with a β-blocker and a nitrate appears to be more effective than either drug alone because β-blockers attenuate the increased sympathetic tone and reflex tachycardia associated with nitrate therapy while nitrate therapy (e.g., nitroglycerin) counteracts the potential increase in left-ventricular wall tension associated with a decrease in heart rate.1101 Combined therapy with a β-blocker and a dihydropyridine calcium-channel blocker also may be useful because the tendency to develop tachycardia with the calcium-channel blocker is counteracted by the β-blocker.1101 However, caution should be exercised in the concomitant use of β-blockers and the nondihydropyridine calcium-channel blockers verapamil or diltiazem because of the potential for excessive fatigue, bradycardia, or atrioventricular (AV) block.1101 (See Drug Interactions: Cardiovascular Drugs.)
Long-term use of β-blockers in patients with chronic stable angina has been shown to reduce the frequency of anginal attacks, allow a reduction in nitroglycerin dosage, and increase exercise tolerance.2, 5, 15, 22, 1101 It has been suggested that pindolol may be a particularly useful β-blocker in patients with exercise-induced angina and substantial resting bradycardia and heart failure, since the drug has little effect on heart rate or cardiac output at rest;22 however, additional study is needed to determine the specific role of pindolol in the management of angina. In patients who do not respond to maximal dosages of a β-blocker or nitroglycerin, concurrent use of the 2 drugs may be beneficial.5
Pindolol is administered orally.1
Dosage of pindolol must be individualized and adjusted according to the patient's response and tolerance.1 If long-term pindolol therapy is to be discontinued, dosage of the drug should be gradually reduced over a period of 1-2 weeks.1 (See Cautions: Precautions and Contraindications.)
For the management of hypertension, the usual initial adult dosage of pindolol is 5 mg twice daily, administered alone or in combination with other antihypertensive agents.1, 52, 600 Although a hypotensive effect usually is seen within 1 week, maximum therapeutic response may not be seen until 2 weeks or longer.1 If an adequate reduction in blood pressure with the initial dosage does not occur within 3-4 weeks, dosage of pindolol may be gradually increased by 10 mg daily at 3- to 4-week intervals as necessary up to a maximum dosage of 60 mg daily.1 Some experts state that the usual adult dosage range is 10-60 mg daily, given in 2 divided doses.1200
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic) may be added; if target blood pressure is still not achieved with the use of 2 antihypertensive agents, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with pindolol, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1200, 1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 While previous hypertension guidelines have based target blood pressure goals on age and comorbidities,501, 504, 536 the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline incorporates underlying cardiovascular risk into decision making regarding treatment and generally recommends the same target blood pressure (i.e., less than 130/80 mm Hg) for all adults.1200 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
For additional information on target levels of blood pressure and on monitoring therapy in the management of hypertension, see Blood Pressure Monitoring and Treatment Goals under Dosage: Hypertension, in Dosage and Administration in the Thiazides General Statement 40:28.20.
For the management of chronic stable angina pectoris†, pindolol dosages of 15-40 mg daily, given in 3 or 4 divided doses, have been used.2, 5, 22
In patients with hepatic impairment, doses and/or frequency of administration of pindolol must be modified in response to the degree of hepatic impairment.1
Pindolol shares the toxic potentials of β-adrenergic blocking agents (β-blockers).4, 5, 25 In therapeutic dosage, pindolol usually is well tolerated and has a low incidence of adverse effects.2, 4, 5, 25, 26 The incidence and severity of adverse reactions may occasionally be obviated by a reduction in dosage.4, 5 Although there is some evidence that abrupt withdrawal of pindolol may be better tolerated than that of β-blockers that do not possess ISA,23, 24 abrupt withdrawal of pindolol should be avoided, especially in patients with coronary artery disease, since it may exacerbate angina or precipitate myocardial infarction.1, 15
Potentially serious adverse effects attributed to pindolol's action on the heart occur in less than 2% of patients and include bradycardia, heart block, hypotension, and precipitation of heart failure.1, 2 Bradycardia and hypotension usually can be reversed with an antimuscarinic agent like IV atropine or with isoproterenol.1 Congestive heart failure usually responds to digitalization and diuresis.1 Other cardiovascular effects include peripheral edema, occurring in 6-16% of patients;1 dyspnea, occurring in about 10% of patients;1 weight gain, occurring in 3% of patients;1 and palpitation, claudication, coldness of the extremities, syncope, and tachycardia, usually occurring in less than 2% of patients.1, 2
Common adverse CNS effects, occurring in 15-19% of patients receiving pindolol, include dizziness, fatigue, and insomnia.1, 2 Bizarre dreams or an increased number of dreams, visual disturbances, paresthesia, weakness, and nervousness or anxiety reportedly occur in about 4-10% of patients.1, 2 Hallucinations and lethargy reportedly occur in 1 and 3% of patients, respectively.1 Development or exacerbation of tremor (e.g., essential tremor) also has been reported in patients receiving the drug.34, 35, 36 Adverse CNS effects seen with other β-blockers that may occur with pindolol include disorientation, short-term memory impairment, emotional lability, catatonia, and impaired performance on neuropsychometric tests.1
Adverse GI reactions, reportedly occurring in about 2-7% of patients receiving pindolol, include nausea and abdominal discomfort.1, 2 Diarrhea and vomiting occur in less than 2% of patients.1, 2 A few cases of mesenteric arterial thrombosis and ischemic colitis have been reported in patients receiving other β-blockers.1
Results of a large prospective cohort study of nondiabetic adults 45-64 years of age indicate that use of β-blockers in hypertensive patients is associated with increased risk (about 28%) of developing type 2 diabetes mellitus compared with hypertensive patients who were not receiving hypotensive therapy.69, 70 In this study, the number of new cases of diabetes per 1000 person-years was 33.6 or 26.3 in patients receiving a β-blocker or no drug therapy, respectively.69 The association between the risk of developing type 2 diabetes mellitus and use of β-blockers reportedly was not confounded by weight gain, hyperinsulinemia, or differences in heart rate.69, 70 It is not known if the risk of developing diabetes is affected by β-receptor selectivity.69 Further studies are needed to determine whether concomitant use of ACE inhibitors (which may improve insulin sensitivity) would abrogate β-blocker-induced adverse effects related to glucose intolerance.70 Therefore, until results of such studies are available, the proven benefits of β-blockers in reducing cardiovascular events in hypertensive patients must be weighed carefully against the possible risks of developing type 2 diabetes mellitus.69
Hypoglycemia,68 which may result in loss of consciousness, also may occur in nondiabetic patients receiving β-blockers. Patients most at risk for the development of β-blocker-induced hypoglycemia are those undergoing dialysis, prolonged fasting, or severe exercise regimens.68
β-Blockers may mask signs and symptoms of hypoglycemia (e.g., palpitation, tachycardia, tremor) and potentiate insulin-induced hypoglycemia.1, 68 Although it has been suggested that nonselective β-blockers are more likely to induce hypoglycemia than selective β-blockers, such an adverse effect also has been reported with selective β-blockers (e.g., atenolol).68 In addition, selective β-blockers are less likely to mask symptoms of hypoglycemia or delay recovery from insulin-induced hypoglycemia than nonselective β-blockers because of their vascular sparing effects; however, selective β-blockers can decrease insulin sensitivity by approximately 15-30%, which may result in increased insulin requirements.68
Slight but persistent increases in serum AST (SGOT) and ALT (SGPT) concentrations, without findings of liver injury, occur in about 7% of patients receiving pindolol.1 Rarely, increases in serum alkaline phosphatase, LDH, and uric acid concentrations may occur.1
Other adverse effects noted during pindolol use include muscle, leg, or joint pain or cramps, occurring in 2-10% of patients;1, 2, 34 chest pain, occurring in 5% of patients;1 and wheezing, pruritus, rash, burning eyes, hyperhidrosis, pollakiuria (urinary frequency), and impotence, occurring in less than 2% of patients.1
The possibility that other adverse effects associated with other β-blockers may occur during pindolol therapy should be considered.1 These include hematologic reactions (e.g., agranulocytosis, nonthrombocytopenic or thrombocytopenic purpura); allergic reactions characterized by fever, sore throat, laryngospasm, and respiratory distress; reversible alopecia; and Peyronie's disease.1
Precautions and Contraindications
Pindolol shares the toxic potentials of β-blockers, and the usual precautions of these agents should be observed.1, 4, 5, 25
In patients with heart failure, sympathetic stimulation is vital for the support of circulatory function.1 Pindolol should be used with caution in patients with inadequate cardiac function, since heart failure may be precipitated by blockade of β-adrenergic stimulation when pindolol therapy is administered.1 In addition, in patients with latent cardiac insufficiency, prolonged β-adrenergic blockade may lead to cardiac failure.1 Although β-blockers should be avoided in patients with overt heart failure, pindolol may be administered cautiously, if necessary, to patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1 Patients receiving pindolol therapy should be instructed to consult their physician at the first sign or symptom of impending cardiac failure and should be adequately treated (e.g., with a cardiac glycoside and/or diuretic) and observed closely; if cardiac failure continues, pindolol should be discontinued, gradually if possible.1
Abrupt withdrawal of pindolol may exacerbate angina symptoms or precipitate myocardial infarction in patients with coronary artery disease, or precipitate thyroid crisis in patients with thyrotoxicosis.1 Therefore, patients receiving pindolol (especially those with ischemic heart disease) should be warned not to interrupt or discontinue therapy without consulting their clinician.1 When discontinuance of long-term pindolol therapy is planned, particularly in patients with ischemic heart disease, dosage of the drug should be gradually reduced over a period of 1-2 weeks.1 When pindolol therapy is discontinued, patients should be carefully monitored.1 If exacerbation of angina occurs or acute coronary insufficiency develops after pindolol therapy is interrupted or discontinued, treatment with the drug should be reinstituted promptly, at least temporarily, and appropriate measures for the management of unstable angina pectoris should be initiated.1 Because coronary artery disease is common and may be unrecognized, the manufacturers caution that it may be prudent not to discontinue pindolol therapy abruptly, even in patients being treated only for hypertension.1
Since β-blockers may inhibit bronchodilation produced by endogenous catecholamines, the drugs generally should not be used in patients with bronchospastic disease.1 Pindolol should be used with caution in patients with nonallergic bronchospasm (e.g., chronic bronchitis, emphysema).1
Pindolol should be used with caution in hyperthyroidism,1 since β-blockers may mask the tachycardia associated with hyperthyroidism.1 In addition, it is recommended that pindolol be used with caution in patients with diabetes mellitus since β-blockers may mask the tachycardia associated with hypoglycemia (a few cases have been reported in patients with type 2 diabetes mellitus), and β-blockers, especially nonselective ones, may potentially precipitate severe, acute hyperglycemia.8, 27, 28 (see Cautions: Endocrine Effects.) However, many clinicians state that patients with diabetes mellitus may be particularly likely to experience a reduction in morbidity and mortality with the use of β-blockers.66 (See Uses: Heart Failure, in Metoprolol 24:24.)β-Blockers usually will not completely mask dizziness and sweating seen with hypoglycemia.8, 28 If pindolol is administered concurrently with an antidiabetic agent, dosage of the latter agent may need to be adjusted.1
Pindolol should be used with caution in patients undergoing major surgery involving general anesthesia.1 The necessity of withdrawing β-blocker therapy prior to major surgery is controversial, but the manufacturers state that, if possible, pindolol should be withdrawn well before surgery.1 Severe, protracted hypotension and difficulty in restarting or maintaining a heart beat have occurred during surgery in some patients who have received β-blockers.1 If patients continue to receive pindolol prior to surgery, the anesthesiologist should be advised that the patient is receiving the drug.1 The manufacturers recommend administration of β-agonists (e.g., dopamine, dobutamine, isoproterenol, norepinephrine) to reverse pindolol's β-adrenergic blockade if necessary during surgery.1
Patients with a history of atopy or severe anaphylactic reactions to a variety of allergens may be more reactive to repeated, accidental, diagnostic, or therapeutic challenge with such allergens while receiving a β-blocker.1 These patients may be less responsive than other patients to usual dosages of epinephrine used to treat anaphylactic reactions.1
Pindolol should be used with caution and in reduced dosage in patients with impaired hepatic function.1
Pindolol is contraindicated in patients with bronchial asthma, second- or third-degree AV block, severe bradycardia, cardiogenic shock, or overt cardiac failure.1
Pindolol also is contraindicated in patients receiving thioridazine.73 (See Drug Interactions: Thioridazine.)
Safety and efficacy of pindolol in children have not been established.1 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Studies in rats and mice using oral pindolol dosages up to 5 and 100 times the recommended maximum human doses, respectively, have not revealed evidence of carcinogenicity.1
Reproduction studies in rats and rabbits using doses exceeding 100 times the recommended maximum human doses have not revealed any evidence of embryotoxicity or teratogenicity.1 There are no adequate and controlled studies to date using pindolol in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.1
Nursing should not be undertaken in women receiving pindolol, since the drug is distributed into milk.1
Concomitant administration of pindolol with reserpine may increase the incidence of hypotension and bradycardia as compared with pindolol alone, because of reserpine's catecholamine-depleting activity.1 Pindolol also is additive with and may potentiate the hypotensive actions of other hypotensive agents (e.g., hydralazine, hydrochlorothiazide).1 This effect usually is used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concurrently.1
Slowing or complete suppression of SA node activity with development of slow ventricular rates (e.g., 30-40 bpm), often misdiagnosed as complete AV block, has been reported in patients receiving the nondihydropyridine calcium-channel blocking agent mibefradil (no longer commercially available in the US), principally in geriatric patients and in association with concomitant β-blocker therapy.49, 50
Slight transient decreases in serum digoxin concentrations have occurred when pindolol and digoxin were used concurrently;1 however, this effect is not considered clinically important.1, 18
Concomitant use of pindolol and thioridazine is contraindicated because such use may be associated with prolongation of the QTc interval and a possible increase in the risk of serious, potentially fatal cardiac arrhythmia (e.g., torsades de pointes) as a result of moderate, dose-related increases in serum concentrations of thioridazine and 2 of its metabolites.73 Higher than expected serum concentrations of pindolol also have occurred following combined use of these drugs. 73
Limited information is available on acute pindolol toxicity.1 In general, overdosage of pindolol may be expected to produce effects that are mainly extensions of pharmacologic effects, including symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure.1, 11 In one hypertensive patient who ingested 500 mg of pindolol, blood pressure increased and heart rate was at least 80 beats/minute; recovery was uneventful.1 In another individual, 250 mg of pindolol was ingested with 150 mg of diazepam and 50 mg of nitrazepam, resulting in coma and hypotension; the patient recovered in 24 hours.1
In acute pindolol overdosage, the stomach should be emptied immediately by gastric lavage.1, 11 Supportive and symptomatic treatment should be initiated.1, 11, 33 For symptomatic bradycardia, IV atropine sulfate may be given;1, 11 if bradycardia persists, IV isoproterenol hydrochloride may be administered cautiously.1, 11 A vasopressor (e.g., epinephrine, norepinephrine) may be given for severe hypotension.1, 11, 33 For heart failure, a cardiac glycoside and diuretic may be used.1 Glucagon may also be useful for the management of myocardial depression and hypotension.1, 11, 33 A β-adrenergic agonist (e.g., isoproterenol) and/or a theophylline derivative may be used for bronchospasm.1, 11, 33
Pindolol has pharmacologic actions similar to those of other β-adrenergic blocking agents (β-blockers).1, 4, 5 The principal physiologic action of pindolol is to competitively block β-adrenergic receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors).2, 4, 5 In addition to inhibiting access of physiologic or synthetic catecholamines to the β-adrenergic receptors, pindolol causes slight activation of the β-receptors, making the drug a partial β-agonist.2, 4, 5 This intrinsic sympathomimetic activity (ISA) of pindolol differs from the β-agonist activity of epinephrine and isoproterenol in that the maximum β-adrenergic stimulation that can be obtained with pindolol is less.4 Other β-blockers can block pindolol's ISA.1, 2, 4 Pindolol also has been shown to possess membrane-stabilizing activity or a quinidine-like effect, but this occurs only at plasma concentrations well above those obtained therapeutically.4 Unlike atenolol and metoprolol, pindolol is not a β1-selective adrenergic blocking agent; pindolol is a nonselective β-blocker, inhibiting both β1- and β2-adrenergic receptors.2, 4, 5
By inhibiting myocardial β1-adrenergic receptors, pindolol produces negative chronotropic and inotropic activity.2, 4, 5 Both of these actions are reversed somewhat, but not entirely, by the drug's partial agonist activity.2, 4, 5 The negative chronotropic action of pindolol on the sinoatrial (SA) node results in a decrease in SA node discharge and recovery time, thereby decreasing stress- and exercise-stimulated heart rate.1, 2, 4, 5 Pindolol has a lesser effect on resting heart rate than do β-blockers that do not possess ISA, usually decreasing resting heart rate only by about 4-8 beats/minute or not at all.1, 2, 4, 5, 15, 22 The blunting of stress- and exercise-stimulated tachycardia by pindolol, however, is similar to that of the other β-blockers.4, 15, 22 Pindolol also slows conduction in the atrioventricular (AV) node but usually to a lesser extent than do the other β-blockers.4 Pindolol reduces exercise-stimulated cardiac output, but pindolol probably has a slightly lesser effect on cardiac output than do β-blockers without ISA.2, 4, 13, 22 Pindolol has a lesser effect on resting cardiac output than on that stimulated by exercise.1, 15, 22 The decrease in myocardial contractility, blood pressure, and heart rate produced by pindolol during stress and exercise leads to a reduction in myocardial oxygen consumption which accounts for the effectiveness of the drug in chronic stable angina pectoris.4, 5, 13, 15, 22 Pindolol is probably not effective in patients who develop angina at rest or at low exercise levels.15, 22
Unlike other β-blockers, pindolol does not consistently suppress plasma renin activity.1, 15 In some studies, the drug has increased plasma renin concentrations and reversed the suppression of plasma renin induced by other β-blockers.7 Pindolol has not been shown to cause sodium retention.2
The precise mechanism of pindolol's hypotensive effect has not been determined.1β-Blockers without ISA acutely increase peripheral vascular resistance (PVR) at rest and with exercise; pindolol does this to a lesser extent than do other β-blockers or the drug produces no acute change in PVR.13, 16
In a limited number of studies, chronic administration of pindolol has reduced PVR.2, 15, 16 It has been suggested that pindolol-induced reduction in PVR is mediated via peripheral β2-adrenergic stimulation.15 Although it has been postulated that β-blockers reduce blood pressure by blocking peripheral (especially cardiac) adrenergic receptors (decreasing cardiac output), by decreasing CNS sympathetic outflow, and/or by suppressing renal renin release,1 pindolol does not consistently affect cardiac output or renin release, and other mechanisms (e.g., decreased peripheral resistance) probably contribute to its hypotensive effect.1, 15, 16
Pindolol inhibits β2-adrenergic receptors in the lungs, resulting in an increase in airway resistance, as measured by a decreased forced expiratory volume in 1 second (FEV1).1, 2, 4 Pindolol's effect on FEV1 appears to depend in part on the patient's pretreatment sympathetic tone; patients with high pretreatment tone show a decrease in FEV1, whereas those with low pretreatment tone may show little, if any, change in FEV1.17 Thus, pindolol's ISA may be physiologically evident in some patients, depending on the pretreatment level of sympathetic tone.17
Pindolol is rapidly absorbed from the GI tract.1 Reported bioavailability ranges from 502 -951, 2 %; bioavailability in uremic patients may be at the lower end of this range. Food does not reduce bioavailability1 but may increase the rate of GI absorption.2 Pindolol reportedly does not undergo substantial metabolism on first pass through the liver;1 the manufacturers state that only about 20% of an oral dose is metabolized on first pass.18 Peak plasma concentrations of 45-167 ng/mL are reached within 1-2 hours after administration of a single 20-mg dose. The extent of absorption may be decreased in patients with impaired renal function.19 The effect of pindolol on heart rate usually is seen within 3 hours and acute hemodynamic effects persist for 24 hours after administration of the drug.2
Approximately 40-60% of pindolol is bound to plasma proteins.1, 2 In healthy adults, the drug has an apparent volume of distribution (Vd) of 1.2-2 L/kg;1, 2 Vd may be decreased by 50% in uremic patients.1 Pindolol is distributed into milk.1
Elimination of pindolol appears to be a first-order process over a dose range of 5-20 mg.1 The drug has a plasma half-life (t½) of 3-4 hours in healthy adults.1, 2 Plasma t½ increases to 3-11.5 hours in patients with renal failure,2, 20 to 7-15 hours in geriatric patients,1 and varies from 2.5-30 hours in patients with hepatic cirrhosis.1 Approximately 60-65% of pindolol is metabolized in the liver to hydroxylated metabolites which are then excreted in urine as glucuronides and ethereal sulfates.1, 2 In healthy adults, about 35-50% of the drug is excreted in urine unchanged;1, 2, 18 in patients with creatinine clearances less than 20 mL/minute, less than 15% is excreted in urine unchanged.1, 18, 20
Pindolol is a nonselective β-adrenergic blocking agent (β-blocker) possessing intrinsic sympathomimetic activity.1, 2, 3, 4 The drug occurs as a white to off-white, crystalline powder with a faint odor and is practically insoluble in water and slightly soluble in alcohol.14
Pindolol tablets should be protected from light and stored in well-closed containers at controlled room temperature between 15-30°C.1, 31
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 5 mg* | Pindolol Tablets | |
10 mg* | Pindolol Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Zenith Goldline. Pindolol tablets prescribing information Miami, FL; 1999 Jan .
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3. Weber MA. Beta blockers in the initial therapy of hypertension. Drug Ther . 1980; 10(11):77-80.
4. Frishman WH. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med . 1981; 305:500-5. [PubMed 6114433]
5. Opie LH. Drugs and the heart. Lancet . 1980; 1:693-8. [PubMed 6103100]
6. Talbert RL. Use of β-adrenergic blocking agents after myocardial infarction. Clin Pharm . 1983; 2:68-74. [PubMed 6136362]
7. Weber MA, Drayer JIM. Renal effects of beta-adrenoceptor blockade. Kidney Int . 1980; 13:686-99.
8. Waal-Manning HJ. Hypertension: which beta-blocker? Drugs. 1976; 12:412-41.
9. Leonard RG, Talbert RL. Calcium-channel blocking agents. Clin Pharm . 1982; 1:17-33. [PubMed 6764159]
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