Pharmacology

Question 1

The normal state of the airway is one of broncho— mediated by the —system via (c–). However, this is offset by — (via c—) broncho–.

Answer 1

bronchoconstriction, parasympathetic, cGMP.

Sympathetic, cAMP, bronchodilation

Question 2

What is the general mechanism of action of bronchodilators?

Answer 2

• Reversal of airway smooth muscle contraction by increasing cAMP, decreasing cGMP or decreasing calcium ion concentration.
• Also decrease mucosal edema and are anti-inflammatory because they tend to prevent mediator release from inflammatory cells.

Question 3

Which three classes of drugs can serve as rapidly acting bronchodilators?

Answer 3

• B-receptor agonists
• Methylxanthines
• Cholinergic antagonists

Question 4

How do beta-receptor agonists function in promotion of bronchodilation?

What are the two main groups of beta-receptor agonists used in the management of respiratory disease?

Answer 4

• G-protein coupled interaction leading to production of cAMP, leading to dilation
• Also cause increased mucociliary clearance and an increase in ciliary beat frequency
• Non-selective
  
  • Ephedrine, epinephrine, isoproterenol
  • Alpha activity and B1 activity may lead to undesirable cardiovascular signs
• B2-selective agonists
  
  • Long acting: salmeterol, formoterol
  • Short acting: albuterol, terbutaline

Question 5

How to the methylxanthine derivatives (caffeine, theophylline…) cause bronchodilation?

Answer 5

• Non-specific inhibition of phosphodiesterases (PDE4 and 5) and increased concentrations of cAMP and cGMP
• Theophylline is non-selective; can result in bronchodilation and inhibition of inflammation
  
  • Inhibits mast cell degranulation and mediator release, enhances mucuciliary clearance and prevents microvascular leakage
• Theophylline has been shown to increase strength of respiratory muscles nad thus decrease the work of breathing
• Tachycardia, nervous system stimulation possible adverse effect

Question 6

How do anticholinergic drugs function in facilitation of bronchodilation?

Answer 6

• Reduce the sensitivity of irritant receptors and antagonize vagally mediated bronchoconstriction
• Have NOT proven clinically effective in the treatment of bronchial diseases in animals; use limited to treatment of bronchoconstriction associated with OP toxicity

Question 7

How do opioids function as anti-tussives?

Answer 7

Depression of the cough center sensitivity to afferent stimuli

Question 8

What 3 factors determine the amount of drug reaching the airways?

Answer 8

1. Anatomy
2. Ventilation
3. Aerosol characteristics

Question 9

What is the optimal size for aerosolized particle deposition in the trachea? The peripheral airways?

Answer 9

• Trachea: 2-10um
• Peripheral airways: 0.5-5um