Phentolamine

May 19, 2021 Rima Pharmacology 0

  • Phentolamine is imidazoline derivative which causes competitive non-selective blockade of α- adrenergic receptors.

Indications of phentolamine

  • Used in short -term control of hypertension or hypertensive emergencies in patients with pheochromocytoma. Also used in diagnosis of pheochromocytoma.
  • In dental field to reverse effects of local anesthetic.
  • To treat vasospasm of Raynaud’s disease and frost bite.
  • Used in treatment of hypertensive crisis which may be cause due to abrupt withdrawal of clonidine or by ingestion of tyramine containing food during use of non- selective MAO inhibitors.  
  • In prevention and treatment of dermal necrosis.
  • In treatment of erectile dysfunction.

Mechanism of action of phentolamine

Figure- Mechanism of action of phentolamine

Source- https://tmedweb.tulane.edu/pharmwiki/doku.php/phentolamine

  • It competitively blocks α-1 and α-2 adrenergic receptors mainly excitatory response of smooth muscle and exocrine glands. This leads to muscle relaxation and dilatation of blood vessels resulting in lowering of blood pressure.
  • It produces transient action and the blocking action produced by it is incomplete. It effectively antagonizes responses of circulating epinephrine and nor-epinephrine.

Pharmacological action of phentolamine

  • Phentolamine causes dilation of peripheral blood vessels, primarily arterioles and capillaries of skin. It increases gut motility and gastric secretion and also increases respiratory, lacrimal, pancreatic and salivary secretion.
  • It also causes blockade of β- adrenergic receptors which causes positive ionotropic and chronotropic effect on heart and increases cardiac output.
  • Causes blockade of 5-HT receptors and stimulate histamine release from mast cells.

Pharmacokinetics

  • It is administered through buccal, oral, IV or intracavernosal route. Absorption is poor when administered through oral route. About 1/10th of administered parenteral dose is excreted via urine. The remaining is metabolized.
  • Half-life is very short, around 19 minutes. It has rapid onset of action (usually 2 minutes).

Adverse effects

  • Hypotension is major side effect caused by phentolamine. It may also cause palpitation, flushing, headache, nausea, vomiting, diarrhea and epigastric distress.
  • Excessive dose may cause tachycardia. Anginal chest pain and cardiac arrhythmia may occur.

Drug Interaction

  • When used in combination with other alpha-adrenergic blocker like prazosin, it can produce synergistic effect. Hence such combination should be avoided. It may enhance hypotensive effect of CCB (calcium channel blocker).
  • Its effect may decrease when used in combination with drugs like amphetamine and dapoxetine.  

Contraindications

  • Contraindicated in myocardial infarction or history of myocardial infarction.
  • Contraindicated in patients allergic to phentolamine.
  • Also contraindicated in coronary insufficiency, angina and other coronary artery disease.
  • It should be used with caution in patients with history of peptic ulcer.

References

  1. https://accessmedicine.mhmedical.com/content.aspx?bookid=391&sectionid=42070035
  2. https://pubchem.ncbi.nlm.nih.gov/compound/Phentolamine
  3.  https://www.drugs.com/ppa/phentolamine.html#uses
  4. https://go.drugbank.com/drugs/DB00692
  5. Yan et al. Therapeutic efficacy of phentolamine in the management of severe hand, foot and mouth disease combined with pulmonary edema. Exp Ther Med. 2017; 13(4): 1403–1407.
  6. Goldstein I. Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction. International Journal of Impotence Research. 2000; 12: S75–S80.
  7. Pharmacology and Pharmacotherapeutics. 24th edition.
  8. Goodman and Gillman Manual of Pharmacology and Therapeutics.
  9. Essentials of Medical Pharmacology. 7th edition.