Decongestants are a class of drugs that aim to ease breathing when the nose and upper airways
are congested. This is typically experienced as an uncomfortable full or stuffy sensation in your
nose, often accompanied by an upper respiratory infection, such as is the case with the flu. Nasal
congestion specifically arises from an increase in blood flow in the vasculature of the nose
and the associated mucosal membranes, and apart from upper respiratory infections this
can also arise from allergies, excessive dry air, stress, smoking, certain hormonal abnormalities,
foreign body exposure, and other causes. To reduce congestion, decongestive drugs aim to
restrict the blood flow to the mucosal membranes of the nose. This is achieved by activating the
α1 adrenergic receptor located on the smooth muscle of blood vessels in the nasal mucosa.
When the α1 adrenergic receptor is activated, the smooth muscle cell contractility increases. This
causes vasoconstriction and decreases the luminal space of the blood vessels, thereby reducing the
blood flow in these blood vessels and alleviating the symptoms of nasal congestion to some extent.
The α1 adrenergic receptor is a Gαq-coupled G-protein-coupled receptor. The mechanism
of drug-induced increase of smooth muscle cell contractility through agonism at the α1 adrenergic
receptor operates through the Gαq G-protein signalling cascade. This was described in detail
when discussing the muscarinic M3 receptor signalling cascade in one of the tutorials
on bronchodilators. But to review, this signalling cascade increases the activity of protein kinase C
and increases intracellular Ca2+ concentration . These effects are synergistic in bringing
about increased smooth muscle contractility. It should be appreciated that some G-protein-coupled
receptor signalling mechanisms are common to many GPCRs in different families.
For example, many GPCRs signal through Gαq, so it’s worth being familiar with.
Now that we understand how decongestive drugs work at the level of the receptor,
what types of drugs are used to activate the α1 adrenergic receptor? The commonly used
drugs that directly activate the α1 adrenergic receptor are called adrenergic receptor agonists,
but there are also drugs that achieve this effect indirectly by increasing the release of
noradrenaline and adrenaline. All of these drugs are sometimes referred to as sympathomimetic drugs
because they mimic the sympathetic nervous system. First let’s look at α1 adrenergic receptor
agonists. Common drugs of this class include phenylephrine, tramazoline,
and oxymetazoline. These drugs are typically taken either orally or in the form of a nasal spray.
In general, it could be argued that nasal sprays are superior in this pharmacological context
because they increase the local delivery of the drug, thereby reducing any systemic
effects that would occur with oral admission and subsequent distribution throughout the body.
And second, as we mentioned, decongestant drugs of the other class act by increasing the release of
adrenaline and noradrenaline from the sympathetic nervous system toward smooth muscle cells, which
then in turn activate the α1 adrenergic receptors. Some may have noticed that when you exercise while
experiencing a cold, the increase in circulating adrenaline will often have a decongestive effect,
which is one of the benefits of exercising while sick if one is capable. Of course adrenaline
and noradrenaline are relatively unselective and will activate all adrenoceptors, so this is less
preferable than selective α1 agonists, since drugs without this selectivity will produce side effects
associated with the sympathetic nervous system. An interesting example of a sympathomimetic drug
is ephedrine. This drug is available over the counter, but it has been heavily restricted in
many countries due to its chemical similarity and ease of synthesis toward the heavily abused drug
methamphetamine. In fact, the US, the largest market for pharmaceuticals, passed
the “Combat Methamphetamine Epidemic Act of 2005” limiting the over the counter sale of Ephedrine.
And with that we conclude an introduction to decongestants, and to pulmonary drugs
in general. Let’s move forward and investigate some other classes of drugs.