Respiratory drugs — how they work
The following article was originally published as part the following CD ROM—National Respiratory Training Centre. Respiratory Therapeutics. Warwick: Education for Health, 2006. ISBN 1-904039-21-9.
Autonomic nervous system
The bronchial smooth muscle’s action is entirely involuntary and is controlled by the autonomic nervous system.
The autonomic nervous system consists of two complementary systems, the sympathetic and the parasympathetic nervous systems.
The sympathetic nervous system stems from the spinal cord. The neurotransmitter is noradrenaline. The target receptors for noradrenaline are known as ‘adrenergic’ receptors. Stimulating these receptors causes smooth muscle to relax. During periods of activity, adrenaline levels rise which relaxes bronchial smooth muscle. This enables the airways to widen and allows maximum airflow to the lungs.
The parasympathetic nervous system stems from the vagus nerve. The neurotransmitter is acetylcholine and the target receptors are known as ‘cholinergic’ receptors.
Under normal conditions, the two systems are balanced. During periods of rest or sleep, when breathing becomes much shallower, acetylcholine stimulates bronchial smooth muscle to contract. As a result airways become narrower and reduce available airflow to the lungs.
In asthma, the balance is upset when the vagus nerve triggers excessive acetylcholine to be released from the parasympathetic nervous system. This causes the bronchoconstriction characteristic of an asthma attack.
Bronchodilators
Bronchodilator drugs reverse bronchoconstriction. They are therefore often referred to as ‘reliever’ medication.
The simple answer to bronchoconstriction is to overcome the effects of acetylcholine, by flooding the sympathetic nervous system with a drug like epinephrine (adrenaline) which mimics the natural neurotransmitter. This stimulates the adrenergic receptors and forces the bronchial smooth muscle to relax. However, there are many different adrenergic receptors throughout the body and epinephrine (adrenaline) binds to all of them, producing numerous side-effects.
Specific receptors that control bronchial smooth muscle tone are known as Β2 adrenergic receptors.
Selective drugs, β2 agonists, have been developed to target only β2 receptors and counteract bronchospasm with minimal side-effects.
The alternative to counteracting the effect of acetylcholine is to inhibit its ability to cause bronchoconstriction.
Antagonist drugs bind ‘competitively’ to the cholinergic receptors, i.e. they take the place of acetylcholine molecules already engaged with a receptor. This removes the sources of stimulation and blocks the receptor from any further intrusion. These drugs are known as ‘anticholinergic’ medications.
Anti-inflammatory medications
Anti-inflammatory medications are used for their prophylactic effect and are often referred to as ‘preventers’ when used for asthma treatment.
They are quite different from bronchodilators and have no direct effect on bronchial smooth muscle. They work on cells within the epithelium and submucosa.
The most widely used drugs in this group are the corticosteroids. They stimulate steroid receptors within the nuclei of cells and control the inflammatory process by regulating genetic activity within the cell’s DNA.
The leukotriene receptor antagonists inhibit the ability of leukotrienes. Leukotrienes are powerful mediators released by eosinophils and other inflammatory cells. They act on epithelial cells by blocking their leukotriene receptors.
Cromones act on and stabilise mast cells which contribute to the control of bronchoconstriction and inflammation in the airway. They control degranulation and the release of early and late-phase mediators.
Routes of administration
Inhalation is the ideal way to deliver respiratory drugs, particularly when a rapid response is needed, e.g. with β2 agonists. A large proportion of the drug goes straight to its target without any need to pass into the body’s system. This avoids the risk of metabolism before the drug reaches its target and allows it to be excreted directly from the lungs.
Oral administration is the other common route. In respiratory disease this allows for high dose corticosteroids to be given, e.g. prednisolone. Leukotriene receptor antagonists are also oral drugs.
Oral drugs are absorbed into the system through the intestines and reach their target via the bloodstream. They are designed to withstand first pass metabolism.
Intravenous respiratory drugs are most commonly used in secondary care. They are given either by injection or continuous infusion.
