Comparative Oral and Topical Decongestant Effects of Phenylpropanolamine and d-Pseudoephedrine

Abstract

Nonselective adrenergic alpha-agonists such as phenylpropanolamine and d-pseudoephedrine are widely used as decongestants to treat nasal congestion associated with a variety of nasal diseases. Although the activity of these drugs is well established in clinical studies, a direct comparison of their nasal decongestant effect as determined by changes in nasal cavity dimensions and nasal architecture has not been studied. Using acoustic rhinometry, we evaluated the effects of these drugs on nasal cavity volume, minimum cross-sectional area (Amin), and the distance from the nosepiece to the Amin (Dmin) in a feline, pharmacological model of nasal congestion. Administration of topical compound 48/80 (1%), a mast cell histamine liberator, into the left nasal passageway decreased nasal volume by 66%, reduced Amin by 51%, and increased Dmin by 116%. The congestive responses to compound 48/80 (1%) were reproducible through six weeks. In a subset of cats, the nasal cavity volume effect of repetitive exposure to compound 48/80, given once every two weeks for six weeks, was not different from the nasal responses after the initial exposure to compound 48/80. Pretreatment with oral phenylpropanolamine (10 mg/kg) or oral d-pseudoephedrine (10 mg/kg) attenuated the nasal effects of compound 48/80, but were associated with a pronounced increase in systolic blood pressure of +51 and +82 mmHg, respectively. A similar decongestant profile was observed with phenylpropanolamine (1%) and d-pseudoephedrine (1%) when given topically. Topical phenylpropanolamine (1%) and d-pseudoephedrine (1%) 45 minutes after dosing increased blood pressure +44 and +17 mmHg, respectively, over control animals. We conclude that oral and topical phenylpropanolamine and d-pseudoephedrine display equieffective nasal decongestant activity and produce similar cardiovascular profiles characterized by significant increases in blood pressure.

Acoustic rhinometry in dog and cat compared with a fluid-displacement method and magnetic resonance imaging

“…Recent studies (4,13,14,(16)(17)(18) have used dogs and cats for drug evaluation. Terheyden et al (26) summarize several attempts to validate how precisely AR measures the nasal cavity in humans, including validation of AR by magnetic resonance (MR) imaging (2,8) and by a fluid-displacement method (FDM) (7).…”

Pharmacological Evaluation of Selectiveα2c-Adrenergic Agonists in Experimental Animal Models of Nasal Congestion

“…Specifically, the nasal cavity volume ratio after treatment was not restored to a baseline value of 1. With that being said, the maximum efficacies of compound A and compound B are equivalent to the maximum efficacies of a variety of decongestants that have previously been studied in this feline model (McLeod et al, 1999a;Erickson et al, 2001). The decongestant action of a2c-agonists is realized across the cavity, presumably as a consequence of nasal blood vessel constriction that lessens mucosal engorgement.…”

“…Presently, we used acoustic rhinometry, which is a highly sensitive, noninvasive, and reliable technology increasingly used clinically to evaluate nasal patency (Hilberg et al, 1989;Grymer et al, 1991;Riechelmann et al, 1993;Austin and Foreman, 1994;Cingi et al, 2013). Our laboratory was the first to apply this technology to the assessment of preclinical drugs targets in large animals, such as cats and dogs (McLeod et al, 1999a,b;Erickson et al, 2001;Koss et al, 2002;Rudolph et al, 2003). The method allows evaluation of changes in the geometry (cross-sectional area) of nasal airways by means of sound reflection.…”

Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants

“…Their psychotropic effect, well-known since their widespread use by belligerents on all sides of the Second World War, is one of stimulation with increased aggression and higher fatigue threshold. They are amines categorized as class A narcotics, listed in Table I The vasoconstriction effect these molecules exert when administered orally or directly on the nasal mucosa considerably increases blood pressure and vasospasm [22][23][24][25]. This effect, which on average lasts 5 to 6 times as long as that of adrenaline, may induce hypertension episodes, myocardial infarction, stroke and various neurological symptoms (Table 3) [10,[25][26][27][28][29][30][31][32][33][34][35][36][37][38].…”