Etilefrine Explained

Etilefrine, sold under the brand name Effortil among others, is a sympathomimetic medication used as an antihypotensive agent to treat orthostatic hypotension. It is usually used by mouth, but is also available as an injectable.[1] [2]

Side effects of etilefrine include nausea, tremors, and palpitations, among others. Etilefrine is an agonist of the α- and β-adrenergic receptors.[3] It is a substituted phenethylamine and is related to epinephrine, phenylephrine, and norfenefrine.

Etilefrine was first described and introduced for medical use by 1949.

Medical uses

Etilefrine is used to treat orthostatic hypotension and as a nasal decongestant. It has also been used off-label to treat priapism.

Side effects

Side effects of etilefrine include nausea, tremors, and palpitations, among others.

Pharmacology

Pharmacodynamics

Etilefrine is an agonist of the α1-adrenergic receptor.[4] It is a vasoconstrictor and antihypotensive agent. It has also been described as a β1-adrenergic receptor agonist with some agonistic actions at the α- and β2-adrenergic receptors.

Intravenous infusion of this compound increases cardiac output, stroke volume, venous return, and blood pressure in humans and animals, suggesting stimulation of both α- and β-adrenergic receptors.[5] [6] [7] [8] [9] However, in vitro studies indicate that etilefrine has a much higher affinity for β1 (cardiac) than for β2 adrenoreceptors.[10]

Intravenous etilefrine increases the pulse rate, cardiac output, stroke volume, central venous pressure, and mean arterial pressure of healthy individuals. Peripheral vascular resistance falls during the infusion of 1 to 8mg etilefrine but begins to rise at higher dosage. Marked falls in pulse rate, cardiac output, stroke volume, and peripheral blood flow, accompanied by rises in mean arterial pressure, occur when etilefrine is infused after administration of intravenous propranolol 2.5mg. These findings indicate that etilefrine has both β1- and α1-adrenergic receptor actions in humans.

Pharmacokinetics

Absorption

Etilefrine is rapidly absorbed with oral administration. The oral bioavailability of etilefrine is approximately 50%. Peak concentrations of etilefrine occur after 30minutes.

Distribution

The plasma protein binding of etilefrine is 23%. About 8.5% is bound to albumin.

Etilefrine is a peripherally selective drug.[11]

Metabolism

Etilefrine is metabolized by conjugation, for instance glucuronidation, in the liver and gastrointestinal tract. There appears to be significant first-pass metabolism. About 3% is metabolized into hydroxymandelic acid.

Elimination

The elimination of etilefrine is dependent on route of administration. Regardless of route, about 80% is excreted in urine within 24hours. With oral administration, 7% is eliminated unchanged in urine and 73% as conjugates. Conversely, with intravenous administration, 28% is eliminated unchanged in urine and 44% as conjugates.

Chemistry

Etilefrine, also known as 3,β-dihydroxy-N-ethylphenethylamine, is a substituted phenethylamine derivative. It is an analogue of epinephrine (3,4,β-trihydroxy-N-methylphenethylamine), of phenylephrine ((R)-β,3-dihydroxy-N-methylphenethylamine), of metaterol (3,β-dihydroxy-N-isopropylphenethylamine), and of norfenefrine (3,β-dihydroxyphenethylamine), as well as of metaraminol ((1R,2S)-3,β-dihydroxy-α-methylphenethylamine).

Etilefrine pivalate (K-30052) is the 3-pivalyl ester of etilefrine. In contrast to etilefrine, etilefrine pivalate was never marketed.

History

Etilefrine was first described and introduced for medical use by 1949.[12] [13]

Society and culture

Names

Etilefrine is the generic name of the drug and its and, while étiléfrine is its and etilefrina is its .[14] [15] In the case of the hydrochloride salt, its generic name is etilefrine hydrochloride and this is its and . Synonyms of etilefrine include ethylnorphenylephrine, ethylphenephrine, etiladrianol, aethyladrianol, and M-I-36.[16] Brand names of the drug include Effortil, Circupon, Apocretin, Palsamin, Kertasin, Pressoton, Effoless, and Sanlephrin.

Notes and References

  1. Book: Aviado D, Bowman W, Burnstock G, Greven J, Hannappel J, Juul P, Kahan A, Kovacs L, Micozzi M, Osswald H . Adrenergic Activators and Inhibitors: Part II . Springer Berlin Heidelberg . Handbook of Experimental Pharmacology . 2012 . 978-3-642-67584-3 . 31 August 2024 . 364–366.
  2. Book: Wein A, Kavoussi L, Novick A, Partin A, Peters C . Campbell-Walsh Urology . Elsevier Health Sciences . 2011 . 978-1-4557-2298-3 . 2024-08-31 . 758–761.
  3. Graham BA, Wael A, Jack C, Rohan MA, Wayne HJ . An overview of emergency pharmacotherapy for priapism . Expert Opin Pharmacother . 23 . 12 . 1371–1380 . August 2022 . 35815373 . 10.1080/14656566.2022.2099271 .
  4. Skylynn T, Abel T, Christopher L, Suliman G, Dominic R, Joel V, Yu Z, Pemminati S . Benefits and Risks of Medications Used in the Management of Hypotension: A Review . Cureus . 16 . 1 . e51608 . January 2024 . 38313995 . 10.7759/cureus.51608 . free . 10837047 .
  5. Nusser E, Donath H, Russ W . [On the circulatory action of depot-Effortil in patients with hypotonic regulation circulator disorders] . German . Die Medizinische Welt . 32 . 1824–7 . August 1965 . 5320529 .
  6. Mellander S . Comparative effects of acetylcholine, butyl-nor-synephrine (Vasculat), noradrenaline, and ethyl-adrainol (Effonti) on resistance, capacitance, and precapillary sphincter vessels and capillary filtration in cat skeletal muscle . Angiologica . 3 . 2 . 77–99 . 1966 . 4380206 . 10.1159/000157650 .
  7. von Limbourg P, Just H, Lang KF . Positive inotrope Wirkung von Etilefrinhydrochlorid (EffortilR) . Kardiol . 586 . 1 . 1973 .
  8. Tarnow J, Brückner JB, Eberlein HG, Patschke D, Reinecke A, Schmicke P . Experimentelle Untersuchungen zur Beeinflussung der Hämodynamik in tiefer Halothannarkose durch Dopamin, Glucagon, Effortil, Noradrenalin und Dextran . Der Anaesthesist . 22 . 8–15 . 1973 .
  9. Carrera AL, Aguilera AM . Algunos effectos circulatorios de la m− oxifenil etanol etilmaina y sus modificaciones por el bloqueo α y β adrenergico. . Arch. Inst. Cardiol. . Mexico . 43 . 279–287 . 1973 .
  10. Offermeier J, Dreyer AC . A comparison of the effects of noradrenaline, adrenaline and some phenylephrine derivatives on alpha-, beta1- and beta2- adrenergic receptors . South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde . 45 . 10 . 265–267 . March 1971 . 4396765 .
  11. Calkins H . Pharmacologic approaches to therapy for vasovagal syncope . Am J Cardiol . 84 . 8A . 20Q–25Q . October 1999 . 10568557 . 10.1016/s0002-9149(99)00626-8 . free .
  12. Neue Spezialitäten . Klinische Wochenschrift . 28 . 19–20 . 1950 . 0023-2173 . 10.1007/BF01485958 . 350 . de.
  13. Spitzbarth H . [Results with effortil in arterial hypotension] . de . Medizinische Klinik . 45 . 50 . 1593–1596 . December 1950 . 14815173 .
  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 . 61.
  15. Book: Schweizerischer Apotheker-Verein . Index Nominum: International Drug Directory . Medpharm Scientific Publishers . 2004 . 978-3-88763-101-7 . 2024-08-31 . 480.
  16. Docherty JR . Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA) . Br J Pharmacol . 154 . 3 . 606–622 . June 2008 . 18500382 . 2439527 . 10.1038/bjp.2008.124 .