Pindolol

Pindolol

Systematic (IUPAC) name
(RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a684032
Pregnancy cat.	C(AU) B(US)
Legal status	℞ Prescription only
Routes	oral, iv
Pharmacokinetic data
Bioavailability	50% to 95%
Metabolism	Hepatic
Half-life	3–4 hours
Excretion	Renal
Identifiers
CAS number	13523-86-9 Y
ATC code	C07AA03
PubChem	CID 4828
IUPHAR ligand	91
DrugBank	APRD00678
ChemSpider	4662 N
UNII	BJ4HF6IU1D N
KEGG	D00513 Y
ChEBI	CHEBI:8214 N
ChEMBL	CHEMBL500 N
Chemical data
Formula	C14H20N2O2
Mol. mass	248.321 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C14H20N2O2/c1-10(2)16-8-11(17)9-18-14-5-3-4-13-12(14)6-7-15-13/h3-7,10-11,15-17H,8-9H2,1-2H3 N Key:JZQKKSLKJUAGIC-UHFFFAOYSA-N N
N(what is this?)  (verify)

Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin) is a beta blocker.

Pharmacology

Pindolol is a nonselective beta blocker with partial beta-adrenergic receptor agonist activity. It possesses ISA (Intrinsic Sympathomimetic Activity). This means that pindolol, particularly in high doses, exerts effects like epinephrine or isoprenaline (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 also functions as a 5-HT_1A receptor weak partial agonist / antagonist.

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 20 mg 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.

Indications

• Angina pectoris and hypertension. The use of pindolol in the treatment of unstable 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 sometimes added to a standard antidepressant therapy,^[1] 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.

• Augmentation therapy of premature ejaculation: According to a recent study, pindolol can be effectively added to a standard anti-premature-ejaculation therapy, which usually consists of daily doses of an SSRI antidepressant such as fluoxetine or paroxetine. Augmentation of pindolol results in substantial increase of ejaculatory latency, even in those who previously did not experience in an improvement with the SSRI monotherapy.^[2]

Contraindications

See also: Propranolol

Similar to propranolol with an extra contraindication for hyperthyroidism. In patients with thyrotoxicosis, possible deleterious effects from long-term use of pindolol have not been adequately appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or complications, and give a false impression of improvement. Therefore, abrupt withdrawal of pindolol may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.^[3]

Dosage

Usual doses are 5 mg 3 or 4 times daily or 15 to 20 mg in one single dose daily. Slow Release forms (20 mg) may be available to increase patient compliance. The maximum daily dose is 60 mg for hypertension and 40 mg 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 1 mg is injected i.v. under strict ECG-monitoring. Further treatment, if necessary, should then be oral.

The recommendation for augmentation in depressive patients is 2.5 mg (or possibly 5 mg) three times daily.

References

1. ^ Isaac MT (November 2004). "Review: combining pindolol with an SSRI improves early outcomes in people with depression". Evid Based Ment Health 7 (4): 107. doi:10.1136/ebmh.7.4.107. PMID 15504795. http://ebmh.bmj.com/cgi/pmidlookup?view=long&pmid=15504795. 
2. ^ Safarinejad, MR (2008). "Once-daily high-dose pindolol for paroxetine-refractory premature ejaculation: a double-blind, placebo-controlled and randomized study.". Journal of clinical psychopharmacology 28 (1): 39–44. doi:10.1097/jcp.0b013e31816073a5. PMID 18204339. 
3. ^ http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20V%29/VISKEN.html