Pseudoephedrine
 Pseudoephedrine | |
|
(1R,2R)-2-methylamino-1-phenylpropan-1-ol | |
| Empirical formula | C10H15NO |
| Molecular weight | 165.2 |
| Bioavailability (Oral) | unknown |
| Metabolism | hepatic |
| Half life | unknown |
| Excretion | renal |
| Pregnancy category | B2 (Australia) |
Pseudoephedrine is a sympathomimetic amine commonly used as a decongestant. The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations either as single-ingredient preparations, or more commonly in combination with antihistamines and/or paracetamol/ibuprofen.
Unlike antihistamines, which modify the systemic histamine-mediated allergic response, pseudoephedrine only serves to relieve nasal congestion commonly associated with colds or allergies. The advantage of oral pseudoephedrine, over topical nasal preparations such as oxymetazoline, is that it does not cause rebound congestion (rhinitis medicamentosa).
Pseudoephedrine does not cause sedation. In fact, one of pseudoepedrine's side effects is "excitability", as it acts as a very weak stimulant. (see below)
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Sympathomimetic amines
Pseudoephedrine is an isomer of ephedrine. They differ in that ephedrine has opposite stereochemistry around each of its chiral centres, while pseudoephedrine has the same. That is, (1R,2R)- and (1S,2S)-enantiomers are designated pseudoephedrine; while (1R,2S)- and (1S,2R)-enantiomers are designated ephedrine.
As with other phenylethylamines, it is also somewhat chemically similar to methamphetamine, although the methamphetamines are more potent and have additional biological effects which are absent from pseudoephedrine.
This chemical similarity has made pseudoephedrine a sought-after reagent in the illicit manufacture of methamphetamine. U.S. federal law prohibits buying cold preparations containing pseudoephedrine in quantities greater than 3 packages in any 24-hour period. Individual states also have varying laws on the matter. Various other legislatures around the world similarly restrict the sale of pseudoephedrine-containing products.
Mode of Action
Pseudoephedrine is a sympathomimetic amine - that is, its principal mechanism of action relies on its indirect action on the adrenergic receptor system. Whilst it may have weak agonist activity at α- and β-adrenergic receptors, the principal mechanism is to displace noradrenaline from storage vesicles in presynaptic neurons. The displaced noradrenaline is released into the neuronal synapse where it is free to activate postsynaptic adrenergic receptors.
The vasoconstriction that pseudoephedrine produces is believed to be principally an &alpha-adrenergic receptor response. Whilst all sympathomimetic amines, to some extent, have decongestant action; pseudoephedrine shows greater selectivity for the nasal mucosa and a lower affinity for central nervous system (CNS) adrenergic-receptors than other sympathomimetic amines. (1R,2R)-pseudoephedrine, the enantiomer used, shows far lesser affinity for CNS adrenergic-receptors than other Ephedra alkaloids, ephedrine and (1S,2S)-pseudoephedrine.
Clinical use
By acting on α-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine produces vasoconstriction, which shrinks swollen nasal mucous membranes; reduces tissue hyperaemia, oedema, and nasal congestion. Other beneficial effects may include increasing the drainage of sinus secretions, and opening of obstructed Eustachian tubes.
Pseudoephedrine is thus indicated for:
- Nasal congestion
- Sinus congestion
- Eustachian tube congestion
Pseudoephedrine is also indicated for vasomotor rhinitis, and as an adjunct to other agents in the optimum treatment of allergic rhinitis, croup, sinusitis, otitis media, and tracheobronchitis.
There have also been reports of off-label uses of pseudoephedrine for its stimulant properties. Some patients, long-haul truck drivers have been implicated in particular, have reportedly used pseudoephedrine as a stimulant to increase their state of alertness/awakedness. It is doubtful that pseudoephedrine would be of significant benefit, except in sensitive-individuals, due to its minimal effect in the CNS (see Mode of Action above).
Adverse effects/Precautions
Pseudoephedrine has been associated with the following adverse drug reactions (ADRs).
Common ADRs include: nervousness, restlessness, insomnia.
Infrequent ADRs include: difficult/painful urination, dizziness/lightheadedness, heart palpitations, headache, increased sweating, nausea/vomiting, trembling, troubled breathing, unusual paleness, weakness.
Categories: Sympathomimetic amines