Dipivefrine Explained

Dipivefrine, or dipivefrin, also known as epinephrine pivalate and sold under the brand name Propine among others, is a sympathomimetic medication which is used in the treatment of open-angle glaucoma.[1] [2] It is available as a 0.1% ophthalmic solution (eye drop).[3] [4]

Side effects of dipivefrine include local eye reactions among others. Dipivefrine is a prodrug of epinephrine (adrenaline) and hence acts as a non-selective adrenergic receptor agonist.[5] It is a substituted phenethylamine and catecholamine and is an ester of epinephrine with much greater fat solubility.

Dipivefrine was first described by 1975.[6] It is widely marketed throughout the world. However, it is no longer available in the United States.[7]

Medical uses

Dipivefrine is used in the treatment of open-angle glaucoma.

Contraindications

Use in narrow-angle glaucoma may be dangerous because it could make the eye susceptible to an attack of angle closure,[2] causing an increase in pressure and pain and possibly loss of vision.

Side effects

The most common side effects of dipivefrine are burning, stinging, and other irritations of the eye. Possible but uncommon side effects are the same as those of epinephrine and include tachycardia (fast heartbeat), hypertension (high blood pressure) and arrhythmias (irregular heartbeat).[2]

Pharmacology

Dipivefrine penetrates the cornea and is then hydrolysed to epinephrine by esterase enzymes. It increases outflow of the aqueous humour and also reduces its formation (mediated by its action on α1- and α2-adrenergic receptors), thus reducing pressure inside the eye. It also increases the conductivity of trabecular filtering cells (a β2-adrenergic-receptor-mediated action). It is preferred to epinephrine because it is longer-acting, more consistent in its action, and better-tolerated.

Chemistry

Dipivefrine, also known as epinephrine dipivalate or as 3,4-dipivalyloxy-β-hydroxy-N-methylphenethylamine, is a substituted phenethylamine and catecholamine.[8] It is the 3,4-dipivalate ester of epinephrine (adrenaline).

The experimental log P of dipivefrine is 1.7 and its predicted log P ranges from 1.49 to 3.71.[9] [10] It is dramatically more lipophilic (600-fold) than epinephrine,[11] [12] which is highly hydrophilic and has a log P of -1.37.[13] The lipophilicity of dipivefrine allows it to penetrate the cornea much more readily (17-fold) than epinephrine. Eye drops containing 0.1% dipivefrine have similar effectiveness to conventional eye drops containing 2% epinephrine in lowering intraocular pressure.

Dipivefrine is used pharmaceutically mainly as the hydrochloride salt.

A similar compound that was never marketed is pivenfrine, which is the 3-pivalate ester of phenylephrine.

History

Dipivefrine was first described in the scientific literature by 1975.

Society and culture

Names

Dipivefrine is the generic name of the drug and its,, and, while dipivefrin is its and dipivefrina is its .[14] [15] [16] In the case of the hydrochloride salt, dipivefrine hydrochloride is its while dipivefrin hydrochloride is its and .

Synonyms of dipivefrine include epinephrine pivalate, adrenaline pivalate, and dipivalyl epinephrine, among others.

Dipivefrine has been sold under brand names including Diopine, Glaucothil, Pro-Epinephrine, Propine, Thilodrin, and Vistapine, among many others.

See also

Notes and References

  1. Book: Essentials of Medical Pharmacology. Jaypee Brothers Medical Publishers(P) Ltd.. 81-8061-187-6. 88. KD Tripari. 2004 . 5.
  2. Dipivefrin .
  3. Web site: Dipivefrin: Uses, Interactions, Mechanism of Action . DrugBank Online . 31 December 1995 . 31 August 2024.
  4. Baranowski P, Karolewicz B, Gajda M, Pluta J . Ophthalmic drug dosage forms: characterisation and research methods . ScientificWorldJournal . 2014 . 861904 . 2014 . 24772038 . 3977496 . 10.1155/2014/861904 . free .
  5. Arthur S, Cantor LB . Update on the role of alpha-agonists in glaucoma management . Exp Eye Res . 93 . 3 . 271–283 . September 2011 . 21524649 . 10.1016/j.exer.2011.04.002 .
  6. Book: McClure DA . The Effect of a Pro-drug of Epinephrine (Dipivalyl Epinephrine) in Glaucoma—General Pharmacology, Toxicology, and Clinical Experience . 225–235. Pro-drugs as Novel Drug Delivery Systems . American Chemical Society . Washington, D. C. . 14 . 1 June 1975 . 978-0-8412-0291-7 . 10.1021/bk-1975-0014.ch006 .
  7. Zhang L, Weizer JS, Musch DC. Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty . Cochrane Database Syst Rev . 2017 . CD010746 . 2017 . 2 . 28231380 . 10.1002/14651858.CD010746.pub2 . 5477062.
  8. Web site: Dipivefrin . PubChem . 31 August 2024.
  9. Web site: Dipivefrin: Uses, Interactions, Mechanism of Action . DrugBank Online . 31 December 1995 . 31 August 2024.
  10. Web site: C19H29NO5 . Dipivefrin . 31 August 2024 . la . 31 August 2024.
  11. Goldberg I, Kolker AE, Kass MA, Becker B . Dipivefrin: current concepts . Aust J Ophthalmol . 8 . 2 . 147–150 . May 1980 . 7004425 . 10.1111/j.1442-9071.1980.tb01673.x .
  12. Book: Stella V, Borchardt R, Hageman M, Oliyai R, Maag H, Tilley J . Prodrugs: Challenges and Rewards . Springer New York . Biotechnology: Pharmaceutical Aspects . 2007 . 978-0-387-49782-2 . 2024-08-31 . 130.
  13. Web site: Epinephrine . PubChem . 31 August 2024.
  14. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer US . 2014 . 978-1-4757-2085-3 . 2024-08-31 . 455,1001.
  15. Book: Schweizerischer Apotheker-Verein . Index Nominum: International Drug Directory . Medpharm Scientific Publishers . 2004 . 978-3-88763-101-7 . 2024-08-31 . 411.
  16. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Springer Netherlands . 2012 . 978-94-011-4439-1 . 31 August 2024 . 101.