Asthma Treatment: Beta Adrenoceptors Effects

Pharmacology (2)

• This document covers Pharmacology (2), including book notes, records, translations, important notes, and mind maps/illustrations.
• A specific section on asthma part 2 is included.

Sympathomimetic Agents

• Adrenoceptor agonists bind to β-ARs, stimulating AC and increasing intracellular cAMP.
• This relaxation of airway smooth muscle inhibits the release of bronchoconstrictors from mast cells.
• Microvascular leakage is also inhibited, and mucociliary transport is enhanced.
• Side effects include tachycardia, skeletal muscle tremors, and decreased serum potassium levels.
• Inhalation delivery is preferred for greatest local effect and reduced systemic toxicity.
• Albuterol and other β2-selective agents are widely used in asthma treatment.
• Epinephrine and isoproterenol have reduced use due to their effects on cardiac contraction (mediated by β1 receptors).
• Aerosol deposition depends on particle size, breathing pattern, and airway geometry.

Epinephrine

• An effective and fast-acting bronchodilator.
• Maximal bronchodilation is achieved 15 minutes post-inhalation, lasting 60-90 minutes.
• Stimulates β1, β2, and α receptors, leading to potential side effects like tachycardia, arrhythmias, and angina worsening.
• Primarily used for acute anaphylaxis-related vasodilation and bronchospasm.
• It's largely replaced by other β2-selective agents in asthma treatment.
• Ephedrine is a less potent alternative with longer duration and oral activity, though now less frequently used.

Isoproterenol

• A potent β1 and β2 bronchodilator.
• Rapid maximal bronchodilation (within 5 minutes) and extended duration (60-90 minutes) post-inhalation.
• Increased asthma mortality rate in the UK in the mid-1960s linked to cardiac arrhythmias.
• Now rarely used for asthma due to this risk.

Beta 2-Selective Drugs

• Albuterol, terbutaline, metaproterenol, and pirbuterol are metered-dose inhalers.
• Produce bronchodilation comparable to Isoproterenol (maximal within 15-30 minutes, lasting 3-4 hours).
• Primarily R isomer; R isomer activates the β2-agonist receptor.
• Available in oral form in addition.

Side Effects

• Skeletal muscle tremor, nervousness, occasional weakness are possible side effects.
• Oral administration is less desirable than inhalation due to more pronounced side effects.
• Parenteral terbutaline may be used in premature labor cases to inhibit uterine contractions.

Methylxanthine Drugs

• Theophylline, theobromine, and caffeine are the key methylxanthines sourced from beverages.
• In high concentrations, they inhibit multiple phosphodiesterase (PDE) enzymes.
• This increases intracellular cAMP and cGMP levels, affecting smooth muscle relaxation, cardiac function, and immune responses.
• PDE3 inhibition is critical for smooth muscle relaxation, and PDE4 inhibition decreases immune cell activation.
• Roflumilast, a selective PDE4 inhibitor, is FDA-approved for COPD but not asthma.

Other Notes

• Theophylline, once a key asthma treatment, is now less commonly used because of its narrow therapeutic index, frequent drug interactions, and associated toxicities (nausea, vomiting, tremors, arrhythmias).
• It is still used in some countries due to its lower cost.
• Adenosine receptors inhibition helps in treating asthma symptoms.
• Corticosteroids, along with low-dose theophylline, can act through histone deacetylase recruitment for increased inflammatory response reduction.