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Wise et al.

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congestion, which may also be associated with chronic rhinosinusitis (CRS) and asthma. 37 In brief, NSAIDs inhibit cyclooxygenase (COX)-1 and COX-2 enzymes, shifting arachidonic acid metabolism toward the lipoxygenase pathway, with decreased production of prostaglandins and thromboxane in exchange for inflammatory leukotrienes (LT). Reduction in nasal mucosal prostaglandin E2, as well as increased LTC4, LTD4, and LTE4 causes mucus production and nasal mucosal edema, hallmarks of rhinitis. 35,38 Neurogenic and neuromuscular type.: Neurogenic type non-allergic rhinitis (NAR) is caused by drug-induced modulation of the autonomic nervous system. Antihypertensives and vasodilators are among the many classes of drugs that cause drug-induced NAR. Other nonspecific drugs, such as psychotropics and immunosuppressants, have unknown mechanisms and are categorized as idiopathic, but can cause neuromodulatory effects as well. Modulation of the autonomic nervous system leads to downstream changes in nasal mucosa, blood vessels, and secretory glands. 39 For example, α - and β -adrenergic antagonists, and presynaptic α -agonists, cause decreased sympathetic tone and unopposed parasympathetic stimulation producing mucosal engorgement, nasal congestion, and rhinorrhea. 40-42 Phosphodiesterase (PDE)-5 specific inhibitors promote penile vasodilation and erection. PDE-3 and nonselective PDE inhibitors result in vasodilation and increased extremity blood flow, relieving symptoms of peripheral artery disease. Nitric oxide (NO)/cyclic nucleotide mediated vasodilation occurs in the nasal mucosa as well, causing nasal mucosal engorgement and edema. 43-46 Finally, angiotensin converting enzyme inhibitors (ACE-Is) inhibit the conversion of angiotensin I to angiotensin II in the lungs, resulting in a decrease in sympathetic activity. Bradykinin is also formed. Bradykinin B1 and B2 receptors have been demonstrated in nasal mucosa 47 ; bradykinin application to the nasal mucosa has been shown to increase sneezing, 44,48 suggesting a role of ACE-Is in NAR. Illicit drug use.: The nose provides a unique portal for illicit drug use, as nasal mucosa is well vascularized and easily accessible. The illicit drug user can avoid invasive intravascular or intramuscular administration of a desired product by applying a crushed solid, liquid, or aerosolized form of the product directly to the nasal cavity. For some drugs, nasal administration increases bioavailability and shortens time to onset when compared to oral ingestion. 49,50 Cocaine is most commonly associated with nasal illicit drug use and exerts its effect by modulating dopamine transporters to inhibit reuptake at the synapse, increasing dopamine available for postsynaptic stimulation. 51 Cocaine-induced rhinitis is a result of vasoconstrictive events, which can be followed by rebound nasal mucosal edema and mucous production, similar to those seen in RM. 52-55 In the repeat user, vasoconstriction, direct trauma compounded by anesthetic effects, and/or injury secondary to contaminants may result in nasal septal perforation. 56-59 Similarly, prescription narcotics, 59 antidepressants, 47 anti-cholinergics, and psychostimulants can be abused by intranasal administration. 47,60 Intranasal hydrocodone has been shown to induce nasal tissue necrosis and loss in a similar manner to cocaine. 59 Antidepressants such as bupropion have been used to achieve a euphoria similar to that of cocaine and may induce seizures. 47

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.