Editing Pseudoephedrine (section)

==Side effects==
Common side effects with pseudoephedrine therapy may include [[central nervous system]] (CNS) [[psychostimulant|stimulation]], [[insomnia]], [[psychomotor agitation|restlessness]], [[stimulation|excitability]], [[dizziness]], and [[anxiety]].<ref name="MunafòFraraPerico2021" /><ref name="VanBerkelFuller2015" /><ref name="HughesEmpeyLand1983" /> Infrequent side effects include [[tachycardia]] or [[palpitation]]s.<ref name="MunafòFraraPerico2021" /> Rarely, pseudoephedrine therapy may be associated with [[mydriasis]] (dilated pupils), [[hallucination]]s, [[Heart arrhythmia|arrhythmia]]s, [[hypertension]], [[seizure]]s, and [[ischemic colitis]]; as well as severe [[skin reaction]]s known as recurrent pseudo-scarlatina, [[systemic contact dermatitis]], and non-pigmenting [[fixed drug eruption]].<ref name="MunafòFraraPerico2021" /><ref>{{cite journal | vauthors = Vidal C, Prieto A, Pérez-Carral C, Armisén M | title = Nonpigmenting fixed drug eruption due to pseudoephedrine | journal = Annals of Allergy, Asthma & Immunology | volume = 80 | issue = 4 | pages = 309–310 | date = April 1998 | pmid = 9564979 | doi = 10.1016/S1081-1206(10)62974-2 }}</ref><ref name="Rossi">{{cite book | veditors = Rossi S | title = [[Australian Medicines Handbook]] | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook | isbn = 0-9757919-2-3 }}</ref> Pseudoephedrine, particularly when combined with other drugs including [[narcotic]]s, may also play a role in the precipitation of episodes of [[psychosis]].<ref name="MunafòFraraPerico2021" /><ref>{{cite web |url=http://home.intekom.com/pharm/adcock/a-tussnd.html |title=Adco-Tussend |publisher=Home.intekom.com |date=15 March 1993 |access-date=6 May 2012 |archive-date=30 April 2012 |archive-url=https://web.archive.org/web/20120430182731/http://home.intekom.com/pharm/adcock/a-tussnd.html |url-status=dead }}</ref> It has also been reported that pseudoephedrine, among other [[sympathomimetics|sympathomimetic]] agents, may be associated with the occurrence of [[hemorrhagic stroke]] and other [[cardiovascular complication]]s.<ref name="MunafòFraraPerico2021" /><ref name="CantuArauzMurillo-Bonilla2003">{{cite journal | vauthors = Cantu C, Arauz A, Murillo-Bonilla LM, López M, Barinagarrementeria F | title = Stroke associated with sympathomimetics contained in over-the-counter cough and cold drugs | journal = Stroke | volume = 34 | issue = 7 | pages = 1667–1672 | date = July 2003 | pmid = 12791938 | doi = 10.1161/01.STR.0000075293.45936.FA | doi-access = free | title-link = doi }}</ref><ref name="VanBerkelFuller2015" />

Due to its sympathomimetic effects, pseudoephedrine is a [[vasoconstrictor]] and [[antihypotensive agent|pressor agent]] (increases [[blood pressure]]), a [[Chronotropic#Positive chronotropes|positive chronotrope]] (increases [[heart rate]]), and a [[Inotrope#Positive inotropic agents|positive inotrope]] (increases [[myocardial contractility|force of heart contraction]]s).<ref name="MunafòFraraPerico2021" /><ref name="GłowackaWiela-Hojeńska2021" /><ref name="SalernoJackson2005" /><ref name="TrinhKimRitsma2015" /><ref name="GheorghievHosseiniMoran2018" /> The influence of pseudoephedrine on blood pressure at clinical doses is controversial.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="SalernoJackson2005" /> A closely related sympathomimetic and decongestant, [[phenylpropanolamine]], was [[List of withdrawn drugs|withdrawn]] due to associations with markedly increased blood pressure and incidence of hemorrhagic stroke.<ref name="SalernoJackson2005" /> There has been concern that pseudoephedrine may likewise dangerously increase blood pressure and thereby increase the risk of stroke, whereas others have contended that the risks are exaggerated.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="SalernoJackson2005" /> Besides hemorrhagic stroke, [[myocardial infarction]], [[coronary vasospasm]], and [[cardiac arrest|sudden death]] have also rarely been reported with sympathomimetic [[ephedra (plant)|ephedra]] compounds like pseudoephedrine and [[ephedrine]].<ref name="MunafòFraraPerico2021" /><ref name="VanBerkelFuller2015" />

A 2005 [[meta-analysis]] found that pseudoephedrine at recommended doses had no meaningful effect on [[systolic blood pressure|systolic]] or [[diastolic blood pressure]] in healthy individuals or people with controlled [[hypertension]].<ref name="GłowackaWiela-Hojeńska2021" /><ref name="SalernoJackson2005">{{cite journal | vauthors = Salerno SM, Jackson JL, Berbano EP | title = Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis | journal = Arch Intern Med | volume = 165 | issue = 15 | pages = 1686–1694 | date = 2005 | pmid = 16087815 | doi = 10.1001/archinte.165.15.1686 | url = }}</ref> Systolic blood pressure was found to slightly increase by 0.99{{nbsp}}mm{{nbsp}}Hg on average and heart rate was found to slightly increase by 2.83{{nbsp}}bpm on average.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="SalernoJackson2005" /> Conversely, there was no significant influence on diastolic blood pressure, which increased by 0.63{{nbsp}}mg{{nbsp}}Hg.<ref name="SalernoJackson2005" /> In people with controlled hypertension, systolic hypertension increased by a similar degree of 1.20{{nbsp}}mm{{nbsp}}Hg.<ref name="SalernoJackson2005" /> [[Immediate-release]] preparations, higher doses, being male, and shorter duration of use were all associated with greater cardiovascular effects.<ref name="SalernoJackson2005" /> A small subset of individuals with [[dysautonomia|autonomic instability]], perhaps in turn resulting in greater adrenergic receptor sensitivity, may be substantially more sensitive to the cardiovascular effects of sympathomimetics.<ref name="SalernoJackson2005" /> Subsequent to the 2005 meta-analysis, a 2015 [[systematic review]] and a 2018 meta-analysis found that pseudoephedrine at high doses (>170{{nbsp}}mg) could increase heart rate and physical performance with larger [[effect size]]s than lower doses.<ref name="TrinhKimRitsma2015" /><ref name="GheorghievHosseiniMoran2018" />

A 2007 [[Cochrane review]] assessed the side effects of short-term use of pseudoephedrine at recommended doses as a nasal decongestant.<ref name="TavernerLatte2007" /> It found that pseudoephedrine had a small risk of [[insomnia]] and this was the only side effect that occurred at rates significantly different from placebo.<ref name="TavernerLatte2007" /> Insomnia occurred at a rate of 5% and had an [[odds ratio]] (OR) of 6.18.<ref name="TavernerLatte2007" /> Other side effects, including [[headache]] and [[hypertension]], occurred at rates of less than 4% and were not different from placebo.<ref name="TavernerLatte2007" />

[[Tachyphylaxis]] is known to develop with prolonged use of pseudoephedrine, especially when it is re-administered at short intervals.<ref name="GłowackaWiela-Hojeńska2021" /><ref name="MunafòFraraPerico2021" />

There is a case report of temporary [[depression (mood)|depressive symptoms]] upon [[drug discontinuation|discontinuation]] and [[drug withdrawal|withdrawal]] from pseudoephedrine.<ref name="MunafòFraraPerico2021" /><ref name="WebbDubose2013">{{cite journal | vauthors = Webb J, Dubose J | title = Symptoms of major depression after pseudoephedrine withdrawal: a case report | journal = J Neuropsychiatry Clin Neurosci | volume = 25 | issue = 2 | pages = E54–E55 | date = 2013 | pmid = 23686066 | doi = 10.1176/appi.neuropsych.12060138 | url = }}</ref> The withdrawal symptoms included worsened [[mood (psychology)|mood]] and [[sadness]], profoundly decreased [[mental energy|energy]], a worsened view of oneself, decreased concentration, [[psychomotor retardation]], increased [[appetite]], and increased need for [[sleep]].<ref name="MunafòFraraPerico2021" /><ref name="WebbDubose2013" />

Pseudoephedrine has psychostimulant effects at high doses and is a [[positive reinforcement|positive reinforcer]] with [[amphetamine-type stimulant|amphetamine]]-like effects in animals including rats and monkeys.<ref name="FreemanWangWoolverton2010">{{cite journal | vauthors = Freeman KB, Wang Z, Woolverton WL | title = Self-administration of (+)-methamphetamine and (+)-pseudoephedrine, alone and combined, by rhesus monkeys | journal = Pharmacol Biochem Behav | volume = 95 | issue = 2 | pages = 198–202 | date = April 2010 | pmid = 20100506 | pmc = 2838499 | doi = 10.1016/j.pbb.2010.01.005 | url = }}</ref><ref name="WeeOrdwayWoolverton2004">{{cite journal | vauthors = Wee S, Ordway GA, Woolverton WL | title = Reinforcing effect of pseudoephedrine isomers and the mechanism of action | journal = Eur J Pharmacol | volume = 493 | issue = 1–3 | pages = 117–125 | date = June 2004 | pmid = 15189772 | doi = 10.1016/j.ejphar.2004.04.030 | url = }}</ref><ref name="TongjaroenbuangamMeksuriyenGovitrapong1998">{{cite journal | vauthors = Tongjaroenbuangam W, Meksuriyen D, Govitrapong P, Kotchabhakdi N, Baldwin BA | title = Drug discrimination analysis of pseudoephedrine in rats | journal = Pharmacol Biochem Behav | volume = 59 | issue = 2 | pages = 505–510 | date = February 1998 | pmid = 9477001 | doi = 10.1016/s0091-3057(97)00459-0 | url = }}</ref><ref name="AkibaSatohMastumura1982" /> However, it is substantially less [[potency (pharmacology)|potent]] than [[methamphetamine]] or [[cocaine]].<ref name="FreemanWangWoolverton2010" /><ref name="WeeOrdwayWoolverton2004" /><ref name="TongjaroenbuangamMeksuriyenGovitrapong1998" />