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Substitution of phenylephrine for pseudoephedrine as a

nasal decongeststant. An illogical way to control

methamphetamine abuse

PE

PE is a poor substitute for PDE as an orally administered decongestant as

it is extensively metabolized in the gut and its efficacy as a decongestant isunproven.

the efficacy of PE as a nasal decongestant has received little attention in theliterature.

PE differs chemically from adrenaline only in the absence of one hydroxyl group

from the benzene ring.

PE contains a single chiral carbon atom and thus exists as an enantiomeric pair of stereoismers.

It is used commercially as the (-)-enantiomer [10] as PE hydrochloride.PE is arelatively selective a1 agonist. It has weak a2 adrenoceptor agonist activity and lowb agonist activity.

after oral administration PE is subject to extensive presystemic metabolism bymonoamine oxidase in the gut wall [10, 13].

As a consequence of metabolism, systemic bioavailability of PE is only around 40%[13]. Only about 3% of an oral dose of PE is excreted unchanged in the urine [10].

When administered intravenously, PE causes an increase in arterial blood pressureand bradycardia

[16] and may also cause coronary vasospasm. The threshold dosage of PEadministered orally in man for


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any effects on the cardiovascular system is about 50 mg and at this dose PE causesa decline in heart rate and a slight increase in arterial blood pressure

PE is a potent vasoconstrictor agent because of its direct a agonist activity,

The tolerability of PE as an oral nasal decongestant is likely to be due to its pooraccess to the

systemic circulation rather than to its pharmacological profile.

The1976 FDA monograph on OTC cold and cough products reports that PE is aneffective nasal decongestant on the basis of reports on in-house studies on PEprovided by representatives of pharmaceutical companies [18]. On the basis of these in-house studies, the FDAapproved PE as an effective nasal decongestant.

This decision by the FDAon the efficacy of PE was questioned by a commentto the FDA in 1985, which stated that the unpublished studies split evenly betweenmild successes and total failures; in addition, the comment questioned the oralbioavailability of PE and recommended that the FDA should not accept PE as an oraldecongestant [19]

The standard pharmaceutical textbooks provide informationabout the efficacy of PEas a vasoconstrictor used during surgery to counteract hypotension, and as eyedrops to dilate the pupil, but provide no information about the efficacy of PE as anasal decongestant [11, 21].

However, the efficacy of phenylephrine formulated as a topical nasal decongestantnasal spray (0.250.5% w/v) is supported by several studies [2224]. The only studyinvolving an oral dose of PE reported that 10 mg PE was no more effective thanplacebo as a nasal decongestant [17] (the study also reported a similar lack of effect for PDE),

As with all sympathomimetics, PE and PDE should not be taken by patients sufferingfrom hypertension, hyperthyroidism or heart disease because of the vasoconstrictoreffects of the medicines. Similarly, patients suffering from Raynauds syndrome ortaking medicines that inhibit monoamine oxidase (MAO) should consult their doctorbefore taking PE. PE and PDE may cause retention of urine in patients with prostateproblems.

The Effects of Phenylpropanolamine on Zucker Rats Selected for Fat FoodPreference

PP

In low-fat preferring animals, phenylpropanolamine decreased carbohydrate,protein,


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and total caloric intake, had no significant effect of spontaneous activity, andincreased serotonin and

5-hydroxyindole acetic acid levels in the PVN. It was found that in high-fat preferringanimals, phenylpropanolamine significantly decreased spontaneous open-field

activity, decreased only carbohydrate caloric intake, and increased serotonin and 5-HIAA levels in the paraventricular nucleus (PVN).

Adrenergic agonist

The main effect of 1 stimulation ( with agonist such as phenylephrine) isvasoconstriction. Local application of a vasoconstrictor to the nasal passagesdecreases blood flow locally and decreases secretions, thus acting as a nasaldecongestant. Phenylpropanolamine has also been used as an appetitesuppressant.

Adrenoceptor Agonists

- Are a large group of drugs whose diverse pharmacologic effects make themvaluable in the treatment of a wide spectrum of clinical conditions.

Agonists exert their effects on multiple organ systems,

Phenylephrine

Pharmacologic effect: Vasoconstriction, increased blood pressure, mydriasis

Clinical Use: Nasal and ocular decongestion, mydriasis, maintenance of bloodpressure and treatment of shock.

Mechanisms and effects

Causes smooth muscle contraction, to contraction of the iris dilator muscleand dilation of the pupil(myriasis).

Indications:

-nasal decongestant in patients with viral rhinitis

-used with allergic rhinitis


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