Bronchodilators

Mechanism of Action

The mechanism of action of bronchodilators includes targeting the beta-2 receptor, which is a G-protein coupled receptor, in the lung airways. When the beta-2 receptor is activated, the smooth muscle of the airway relaxes. Subsequently, the patient experiences better airflow for a period. Consistent use of beta-2 agonists for an extended amount of time reduces their efficacy due to the down-regulation of the beta-2 receptor in the airways. As such, a higher dose of medicine is necessary to achieve the same result. Bronchodilator metabolism occurs in the gastrointestinal tract by cytochrome P-450 enzymes. About 80% to 100% is excreted in the urine, and less than 20% is excreted in feces. Short-acting bronchodilators have a half-life of 3 to 6 hours, while longer-acting bronchodilators have a half-life of 18 to 24 hours.[4][5]

Anticholinergics target parasympathetic nervous system receptors in the airways and inhibit their function. Since the parasympathetic nervous system is responsible for increased bronchial secretions and constriction, reversing those should provide bronchodilation and fewer secretions.[6]

Administration

The administration of bronchodilators is primarily through inhalation devices to deliver the drug to the lung's bronchioles. Inhalation devices come in all shapes and sizes, but the critical factor is to maximize the amount of drug reaching the bronchioles. Even when used with a perfect technique, the bioavailability of this class of medications remains very low. The best way to achieve maximum bioavailability is by fully exhaling, placing the inhaler in the mouth, and taking a full inhalation. After the patient has inhaled completely, it is followed by 10 seconds of no breathing to wait for the medicine to dissipate into the lung space. Then, a slow exhalation back to normal breathing is advised.[7]

Failure to follow the correct steps risks not maximizing the full potential of the inhaled medicines. Patients taking short-acting bronchodilators should benefit from the medication's effects quickly, within seconds to minutes, and should have the clinical benefit for around 4 hours. These are sometimes called emergency inhalers due to their immediate impact on bronchodilation. Long-acting bronchodilators do not typically work as quickly and are not helpful in an emergency setting.[8]

Adverse Effects

The adverse effects of bronchodilators are due to sympathetic system activation. The most frequent and common adverse effects include trembling, nervousness, sudden, noticeable heart palpitations, and muscle cramps. More severe effects include sudden constriction of the bronchial airways, paradoxical bronchospasm, hypokalemia, and in rare cases, myocardial infarction. A patient should talk to their primary care physician if they have any comorbidities.[9] For anticholinergics, side effects include symptoms caused by a decrease in vagal tone. These can include dry mouth, urinary retention, tachycardia, constipation, and an upset stomach. Caution is always necessary when administering an anticholinergic agent to older patients due to the possibility of acute delirium.[5]

Contraindications

If a patient has a known hypersensitivity to the drug, then physicians should not prescribe it. These hypersensitivities include severe allergic reactions that can cause hemodynamic instability or loss of a patent airway. Use caution when treating patients with ischemic heart disease, arrhythmias, or hypokalemia, as bronchodilators have demonstrated worsening of the effects of these conditions.[1] Exercising care with this class of medication is also essential during labor and delivery and when treating elderly patients. In very high doses, caution is also necessary for patients with renal impairment.[10]

Monitoring

Clinicians should advise the patient on how to take the drug with the correct dosage. There are no recommended routine monitoring tests with this class of medications. Serious adverse effects of bronchodilators include bronchospasm, hypersensitivity reactions, hypertension, hypotension, cardiac arrest, hypokalemia, and hyperglycemia. Anticholinergics have correlated with dry mouth, constipation, urinary retention, and delirium. If a patient believes they are experiencing any of these symptoms or general discomfort after taking this medicine, they should be seen by emergency personnel quickly. In particular, patient chronically on short-acting beta-2 agonists patient risks not achieving the same relief from their medicine as they once did. This phenomenon is called receptor downregulation. It happens because a portion of the receptors targeted end up being inactivated by the body due to overuse. Since fewer receptors are available to be targeted by this medication class, a less than adequate relief of symptoms occurs. Higher dosages are then required to achieve the same result.[9]

Toxicity

If a patient uses a bronchodilator and experiences any of the adverse effects described, they should promptly seek medical attention. These effects include difficulty breathing, fever/chills, decreased urinary output, nausea or vomiting, tremors, or convulsions, among others. A doctor can measure the patient's vitals in an emergency room and take a blood sample to detect any electrolyte abnormalities.[11] From there, the patient can have conservative management. If more invasive interventions are needed, patients may be started on a standard saline drip or given potassium to replenish reserves. In severe cases, they may require intubation to protect and control the airway. 

Enhancing Healthcare Team Outcomes

Bronchodilators are prescribed by nurse practitioners, physician assistants, primary care providers, internists, emergency department clinicians, and others. Anyone who prescribes these agents must educate the patient on the potential adverse effects, which can include anticholinergic symptoms as well as cardiac symptoms. Patients must be informed when to return to their provider when these symptoms appear. Overall, bronchodilators are safe when prescribed and administered correctly and can significantly improve asthma patients' quality of life.