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Pindolol


Pronunciation

 (PIN doe lole)


Generic Available

 Yes


Canadian Brand Names

 Apo-Pindol®; Gen-Pindolol; Novo-Pindol; Nu-Pindol; PMS-Pindolol; Visken®


Use

 Management of hypertension


Use - Unlabeled/Investigational

 Potential augmenting agent for antidepressants; ventricular arrhythmias/tachycardia, antipsychotic-induced akathisia, situational anxiety; aggressive behavior associated with dementia


Pregnancy Risk Factor

 B


Pregnancy Implications

 Pindolol crosses the placenta. Beta-blockers have been associated with bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.


Lactation

 Enters breast milk/use caution


Contraindications

 Hypersensitivity to pindolol, beta-blockers, or any component of the formulation; uncompensated congestive heart failure; cardiogenic shock; bradycardia, sinus node dysfunction, or heart block (2nd or 3rd degree) except in patients with a functioning artificial pacemaker; pulmonary edema; severe hyperactive airway disease (asthma or COPD); Raynaud's disease


Warnings/Precautions

 Administer very cautiously to patients with CHF, asthma, diabetes mellitus, hyperthyroidism. May mask signs and symptoms of thyrotoxicosis. Abrupt withdrawal of the drug should be avoided, drug should be discontinued over 1-2 weeks. Do not use in pregnant or nursing women. May potentiate hypoglycemia in a diabetic patient and mask signs and symptoms. Use with caution in patients with myasthenia gravis or peripheral vascular disease. May cause CNS depression; use caution in patients with a history of psychiatric illness. May potentiate anaphylactic reactions and/or blunt response to epinephrine treatment. Beta-blockers with intrinsic sympathomimetic activity (including pindolol) do not appear to be of benefit in CHF.


Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (3%), edema (6%)

Central nervous system: Nightmares/vivid dreams (5%), dizziness (9%), insomnia (10%), fatigue (8%), nervousness (7%), anxiety (<2%)

Dermatologic: Rash, itching (4%)

Gastrointestinal: Nausea (5%), abdominal discomfort (4%)

Neuromuscular & skeletal: Weakness (4%), paresthesia (3%), arthralgia (7%), muscle pain (10%)

Respiratory: Dyspnea (5%)

<1%: Bradycardia, CHF, claudication, confusion, dry eyes, hallucinations, hypotension, impotence, mental depression, palpitation, thrombocytopenia, wheezing


Overdosage/Toxicology

 Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia, and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia. Atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol). CNS effects include convulsions, and coma. Respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs. Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia, and hypoglycemia.


Drug Interactions

 Substrate of CYP2D6 (major); Inhibits CYP2D6 (weak)

Albuterol (and other beta2 agonists): Effects may be blunted by nonspecific beta-blockers

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis

AV conduction-slowing agents (digoxin): Effects may be additive with beta-blockers.

Calcium channel blockers (diltiazem, verapamil): May have synergistic or additive pharmacological effects when taken concurrently with beta-blockers

Clonidine: Hypertensive crisis after or during withdrawal of either agent

CYP2D6 inhibitors: May increase the levels/effects of pindolol. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Epinephrine (including local anesthetics with epinephrine): Pindolol may cause hypertension

Glucagon: Pindolol may blunt the hyperglycemic action

Insulin and oral hypoglycemics: May mask symptoms of hypoglycemia

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam): May reduce the antihypertensive effects of beta-blockers

Salicylates: May reduce the antihypertensive effects of beta-blockers

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents


Ethanol/Nutrition/Herb Interactions

 Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension).


Stability

 Protect from light


Mechanism of Action

 Blocks both beta1- and beta2-receptors and has mild intrinsic sympathomimetic activity; pindolol has negative inotropic and chronotropic effects and can significantly slow AV nodal conduction. Augmentive action of antidepressants thought to be mediated via a serotonin 1A autoreceptor antagonism.


Pharmacodynamics/Kinetics

Absorption: Rapid, 50% to 95%

Protein binding: 50%

Metabolism: Hepatic (60% to 65%) to conjugates

Half-life elimination: 2.5-4 hours; prolonged with renal impairment, age, and cirrhosis

Time to peak, serum: 1-2 hours

Excretion: Urine (35% to 50% as unchanged drug)


Dosage

 Oral:

Adults:

Hypertension: Initial: 5 mg twice daily, increase as necessary by 10 mg/day every 3-4 weeks (maximum daily dose: 60 mg); usual dose range (JNC 7): 10-40 mg twice daily

Antidepressant augmentation: 2.5 mg 3 times/day

Elderly: Initial: 5 mg once daily, increase as necessary by 5 mg/day every 3-4 weeks

Dosing adjustment in renal and hepatic impairment: Reduction is necessary in severely impaired


Monitoring Parameters

 Blood pressure, standing and sitting/supine, pulse, respiratory function


Dietary Considerations

 May be taken without regard to meals.


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed. Do not alter dose or discontinue without consulting prescriber. If you have diabetes, monitor serum glucose closely (drug may alter glucose tolerance or mask signs of hypoglycemia). May cause nervousness, fatigue, dizziness, insomnia, or postural hypotension (use caution when changing position from lying or sitting to standing, when driving, or climbing stairs until response to medication is known); or nausea or abdominal discomfort (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain or swelling of extremities or unusual weight gain (>5 lb/week), unusual muscle weakness or pain; or other persistent adverse effects. Breast-feeding precaution: Consult prescriber if breast-feeding.


Nursing Implications

 Evaluate blood pressure, apical and radial pulses; do not discontinue abruptly


Anesthesia and Critical Care Concerns/Other Considerations

 Pindolol possesses intrinsic sympathomimetic activity. While beta-blockers with intrinsic sympathomimetic activity induce fewer side effects, the cardiovascular benefits are less clear than for beta-blockers without intrinsic sympathomimetic activity.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.


Cardiovascular Considerations

 This drug possesses intrinsic sympathomimetic activity. While beta-blockers with intrinsic sympathomimetic activity induce fewer side effects, the cardiovascular benefits listed below are less clear than for beta-blockers without intrinsic sympathomimetic activity.

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Unstable angina/non-ST-segment elevation MI: In the treatment of unstable angina/non-ST-segment elevation MI, a beta-blocker, with the first dose administered intravenously if there is ongoing chest pain, followed by oral administration, is recommended (in the absence of contraindications).

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.


Dental Health: Effects on Dental Treatment

 Pindolol is a nonselective beta-blocker and may enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia


Mental Health: Effects on Mental Status

 Insomnia is common; may cause dizziness, fatigue, nervousness, or nightmares; may rarely cause depression or hallucinations


Mental Health: Effects on Psychiatric Treatment

 Has been used as an augmentive agent to the SSRIs for the treatment of depression; barbiturates may decrease the effects of beta-blockers


Dosage Forms

 Tablet: 5 mg, 10 mg


References

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)," J Am Coll Cardiol , 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Erstad BL and Barletta JF, "Treatment of Hypertension in the Perioperative Patient," Ann Pharmacother , 2000, 34(1):66-79.

"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," Am J Cardiol , 1999, 83(2A):1A-38A.

Gibbons RJ, Abrams J, Chatterjee K, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: 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 , 2003, 41(1):159-68.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings," Chest , 2003, 123(3):897-922.


International Brand Names

 Apo-Pindol® (CA, CZ, TR); Apo-Pindolol® (NZ); Barbloc® (AU); Decreten® (ID); durapindol® (DE); Gen-Pindolol (CA); Glauco-Stulln® (DE); Hexapindol® (DK); Huma-Pindol® (HU); Novo-Pindol (CA); Nu-Pindol (CA); Pectobloc® (CH); Pinden® (IL); Pindocor® (FI); Pindol® (NZ); Pindolol Helvepharm® (CH); Pindolol NM® (DK); Pindolol NM Pharma® (SE); Pinloc® (FI); PMS-Pindolol (CA); Viskaldix® (BG); Viskeen® (NL); Visken® (AT, AU, BE, BR, CA, CH, CZ, DE, DK, FI, FR, GB, HU, IE, IN, IT, LU, MT, NZ, PL, RO, RU); Viskén® (SE); Visken® (TR); Vypen® (NZ)


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