Updates on Pseudoephedrine concern its use, contraindications and chemical compounds usually associated with medicinal formulations.

 Laccourreye O, Werner A, Giroud JP, Couloigner V, Bonfils P, Bondon-Guitton E. Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants. Eur Ann Otorhinolaryngol Head Neck Dis. 2015;132(1):31–34. doi:10.1016/j.anorl.2014.11.001

Abstract. Due to their vasoconstrictive action on the nasal mucosa, ephedrine and pseudoephedrine are highly efficient amines for relief of nasal congestion. As with any vasoconstrictor and as underscored by the French Society of Otorhinolaryngology in its 2011 guideline, these molecules should not be used in patients under the age of 15. Furthermore, due to unpredictable severe cardiovascular and neurological adverse events that may occur even at low dose and in the absence of any pre-existing pathology, they should not be prescribed for the common cold, and ENT physicians must carefully weigh the risk/benefit ratio in patients with allergic rhinitis. Distribution should be regulated and over-the-counter sales banned. Copyright © 2014 Elsevier Masson SAS.

Głowacka K, Wiela-Hojeńska A. Pseudoephedrine-Benefits and Risks. Int J Mol Sci. 2021 May 13;22(10):5146. doi: 10.3390/ijms22105146. 

Abstract. Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.

Munafò A, Frara S, Perico N, Di Mauro R, Cortinovis M, Burgaletto C, Cantarella G, Remuzzi G, Giustina A, Bernardini R. In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine. Rev Endocr Metab Disord. 2021 Dec;22(4):1013-1025. doi: 10.1007/s11154-021-09658-w. 

Abstract. Obesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree. © 2021. The Author(s).

Nakamori S, Takahashi J, Hyuga S, Yang J, Takemoto H, Maruyama T, Oshima N, Uchiyama N, Amakura Y, Hyuga M, Hakamatsuka T, Goda Y, Odaguchi H, Hanawa T, Kobayashi Y. Analgesic Effects of Ephedra Herb Extract, Ephedrine Alkaloids-Free Ephedra Herb Extract, Ephedrine, and Pseudoephedrine on Formalin-Induced Pain. Biol Pharm Bull. 2019;42(9):1538-1544. doi: 10.1248/bpb.b19-00260.

Abstract.  The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids-free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0-5 min; second phase, 10-45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, "authentic" EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse-and at 4 to 6 h after administration of EHE-Ts-only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4-6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.

Tuncer I, Unsal U. Acute effect of pseudoephedrine on macular microcirculation in healthy subjects: an optical coherence tomography angiography study. Jpn J Ophthalmol. 2022 Jan;66(1):94-100. doi: 10.1007/s10384-021-00859-z.

Abstract. Purpose: To quantitatively evaluate the acute effects of pseudoephedrine on the macular microvasculature using optical coherence tomography angiography (OCTA)....Conclusion: Oral pseudoephedrine intake causes a significant decrease in superficial macular blood flow and SFCT. Impairmant of macular microcirculation can be detected noninvasively and quantitavitely by OCTA. © 2021. Japanese Ophthalmological Society.

Spencer BG, Baskin J, Giarola BF, Craig JE. Single Dose of Pseudoephedrine Induces Simultaneous Bilateral Acute Angle Closure Crisis. Case Rep Ophthalmol. 2019;10(3):365–368. Published 2019 Oct 24. doi:10.1159/000503854

Abstract. Simultaneous bilateral acute angle closure crisis (AACC) is a sight-threatening ocular emergency. Many "cold and flu" preparations contain compounds with sympathomimetic or anticholinergic qualities that confer a risk of inducing AACC. We present a review of cold and flu preparation-induced AACC, and present a case of simultaneous bilateral AACC triggered by a single oral dose of pseudoephedrine. The challenges facing the clinician in recognizing simultaneous bilateral AACC in the context of an upper respiratory tract infection are addressed. An awareness of this uncommon clinical entity, its pertinent clinical features, risk factors, and the drug classes that may precipitate an attack is critical for the timely diagnosis and management of this ocular emergency. Notably, clinicians must be aware that even a single dose of an implicated medication may trigger an attack of AACC. Copyright © 2019 by S. Karger AG, Basel