Bronchodilator drugs

Bronchodilator drugs - as their name implies - are drugs that dilate bronchial smooth muscle, thus facilitating breathing in patients with asthma or chronic obstructive pulmonary disease (COPD).

There are basically three categories of bronchodilator drugs:

β2-adrenergic receptor agonists;
antimuscarinics (or anticholinergics);
the methylxanthines.

The characteristics of these drug categories will be briefly illustrated below.

Β2-adrenergic receptor agonists

These bronchodilator drugs act on β2-adrenergic receptors present on bronchial smooth muscle.
The β2 receptors present on the bronchi - when activated by their endogenous substrate (noradrenaline) - are able to induce bronchodilation.
More precisely, with the activation of these receptors there is a decrease in the levels of calcium ions (Ca ++) in the cells of the bronchial smooth muscles. Calcium ions are responsible for bronchoconstriction, therefore, it is clear how a reduction in their concentration can favor the reverse process, namely bronchodilation.
These drugs, therefore, as β2-adrenergic receptor agonists, stimulate them and induce bronchodilation.

Classification of β2-adrenergic receptor agonists

Bronchodilator drugs belonging to the β2-adrenergic receptor agonist class can be divided into three groups according to their duration of action:

Short-acting β2-agonists. They are drugs used in acute asthma attacks, the "bronchodilator action" sets in within 5 minutes and has a duration of action of 4-6 hours.
Salbutamol and terbutaline belong to this category.
Long-acting β2-agonists. These drugs are used primarily to control and prevent nocturnal asthma symptoms (bronchoconstriction). They have a slow onset of action (20-30 minutes), but the bronchodilation they induce lasts 8-12 hours.
Formoterol and salmeterol belong to this category.
Ultra long acting β2-agonists, also known as ultra-LABAs. These drugs have a duration of action of 24 hours and this allows for a single daily administration, unlike long-acting beta-agonists which require at least two administrations per day.
Indacaterol belongs to this category of bronchodilator drugs.

Routes of administration

Generally, β2-adrenergic receptor agonists are administered by inhalation so that they can easily and quickly reach the bronchi.
The pharmaceutical formulations in which they are available may vary but are usually found in the form of:

Capsules containing powder for inhalation that must be administered through a special dispenser;
Pressurized suspensions for inhalation.

However, there are also pharmaceutical formulations suitable for oral administration (generally, tablets or syrups) and pharmaceutical formulations suitable for parenteral administration (injectable solutions).

Side effects

Obviously, the side effects that can occur following the intake of the β2-adrenergic receptor agonists vary according to the type of active ingredient used.
However, some side effects are common to all compounds belonging to this category of bronchodilator drugs. These side effects are:

Tremors
Tachycardia;
Hypokalaemia (i.e. the decrease in blood potassium concentrations);
QT interval prolongation (the amount of time it takes for the ventricular myocardium to depolarize and repolarize).

Antimuscarinics (or anticholinergics)

These bronchodilator drugs are able to interact with the muscarinic receptors present on the smooth muscle of the bronchi.
In particular, M3-type muscarinic receptors are present on the bronchi. When these receptors are activated by their endogenous substrate (acetylcholine) they induce bronchoconstriction.
The task of antimuscarinics is precisely to antagonize the M3 receptors, in such a way as to promote bronchodilation.
Ipratropium bromide and tiotropium belong to this category of bronchodilator drugs.

Routes of administration

As with beta-agonists, antimuscarinics are routinely administered by the inhalation route and are available as a nebuliser solution or as an inhalation powder that must be administered via the dispenser.

Side effects

Typical side effects of this category of bronchodilator drugs are:

Dry mouth
Headache;
Tachycardia;
Indistinct vision;
Urinary difficulty;
Exacerbation of closed-angle glaucoma.

Due to the side effects that can occur in the eye, it is essential that these drugs never come into contact with the eyes. If this happens, you should contact your doctor immediately.

Methylxanthines

Methylxanthines are bronchodilator drugs of natural origin. The best known, probably, is the theophylline which is found in nature in the tea plant and - even if in smaller quantities - also in the coffee and cocoa plant. Aminophylline also belongs to this category of bronchodilator drugs.
In reality, the exact modality with which these drugs induce bronchodilation has not yet been fully understood and several possible mechanisms of action have been proposed.
However, from the studies conducted it seems that the mechanism responsible for the bronchodilator action of methylxanthines is the inhibition of phosphodiesterase (PDE) enzymes at the level of bronchial smooth muscle cells.

With the inhibition of these enzymes there is an increase in the levels of cyclic AMP inside the aforementioned cells with consequent bronchodilation.

Routes of administration

Methylxanthines are available in different pharmaceutical formulations suitable for administration by different routes. In fact, these bronchodilator drugs can come in the form of:

Oral solutions, capsules or tablets for oral administration;
Suppositories;
Injectable solutions for parenteral administration.

Side effects

The main side effects that can occur during treatment with methylxanthines are:

Cardiac arrhythmias;
Gastrointestinal disorders;
Convulsions.

Furthermore, since methylxanthines have a very narrow therapeutic index, it is necessary to perform regular blood tests and carefully monitor patients on this type of bronchodilator drugs.