Article: Pindolol

Pindolol
Systematic (IUPAC) name
1-(1H-indol-4-yloxy)-3-(1- methylethylamino)propan-2-ol
Identifiers
CAS number	13523-86-9
ATC code	C07AA03
PubChem	4828
DrugBank	APRD00678
Chemical data
Formula	C14H20N2O2
Mol. weight	248.321 g/mol
Pharmacokinetic data
Bioavailability	50% to 95%
Metabolism	Hepatic
Half life	3–4 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C(AU) B(US)
Legal status	℞ Prescription only
Routes	oral, iv

Pindolol is a beta blocker drug.

Pharmacology

Pindolol is a nonselective beta blocker in terms of cardioselectivity, but possesses ISA (Intrinsic Sympathomimetic Activity). This means that pindolol particularly in high doses exerts effects like epinephrine or isoproterenole (increased pulse rate, increased blood pressure, bronchodilation), but these effects are limited. Pindolol also shows membrane stabilizing effects like quinidine, possibly accounting for its antiarrhythmic effects. It acts on serotonin (5-HT1A) receptors in the brain resulting in increased postsynaptic serotonin concentrations.

Pharmacokinetics

Pindolol is rapidly and well absorbed from the GI tract. It undergoes some first-pass-metabolization leading to an oral bioavailability of 50 to 95%. Patients with uremia may have a reduced bioavailability. Food does not alter the bioavailability, but may increase the resorption. Following an oral single dose of 20mg peak plasma concentrations are reached within 1 to 2 hours. The effect of Pindolol on pulse rate (lowering) is evident after 3 hours. Despite the rather short halflife of 3 to 4 hours, hemodynamic effects persist for 24 hours after administration. Plasma halflives are increased to 3 - 11.5 hours in patients with renal impairment, to 7 - 15 hours in elderly patients, and from 2.5 to 30 hours in patients with liver cirrhosis. Approximately 2/3 of pindolol are metabolized in the liver giving hydroxylates, which are found in the urine as gluconurides and ethereal sulfates. The remaining 1/3 of pindolol is excreted in urine in unchanged form.

Uses

• Angina pectoris and hypertension. The use of pindolol in the treatment of instable angina may be less effective compared to beta blockers without ISA.
• In some other countries also arrhythmias and prophylaxis of acute stress reactions.

Investigational use

• Augmentation therapy of clinical depression : Pindolol is added to a standard antidepressant therapy, if the patient fails to respond to the standard therapy alone. Fluoxetine is the most commonly used standard antidepressant. The results of augmentation therapy are encouraging. It is not known, whether pindolol has antidepressive activities as monotherapeutic agent.

Contraindications and precautions

See the article on Propranolol.

Side effects

See the article on Propranolol.

Dosage

Usual doses are 5mg 3 or 4 times daily or 15 to 20mg in one single dose daily. Slow Release forms (20mg) may be available to increase patient compliance. The maximum daily dose is 60mg for hypertension and 40mg for angina. Treatment should be started with low doses and slowly increased according to the clinical response. The initial and maintenance doses should be reduced in patients with severe liver disease. In some countries pindolol exists as injection concentrate for the emergency treatment of serious arrhythmias. In these cases 0.4 to 1mg is injected i.v. under strict ECG-monitoring. Further treatment, if necessary, should then be oral. The recommendation for augmentation in depressive patients is 2,5mg daily as single dose.

Brand names

• Visken
• Betapindol
• Calvisken
• Decreten
• Durapindol