Pharm of agents in pulmonary med I

Question 1

How do beta receptor agonists work? what is their class?

Answer 1

class: bronchodilator
MOA: increase adenylyl cyclase, increase cAMP, PKA –> smooth muscle relaxation and bronchodilation
also increase ciliary beat frequence and some minimal anti-inflammatory effects

Question 2

When are beta receptor agonists useful

Answer 2

acute attacks (rescue inhaler). Do NOT help with late onset response and do NOT prevent airway inflammation

Question 3

what is dynamic dose response of beta agonists?

Answer 3

in acute exacerbations, the dose response curve for beta agonists shits to the right- you need more med to get the same response

Question 4

Why is beta agonist selectivity important and what should we select for?

Answer 4

select for beta 1 receptors

important to decrease side effects of beta blockers in the heart

Question 5

adverse effects of beta agonists

Answer 5

tachycardia, arrhythmias, tremor, hypokalemia, vasodilation, increased mortality with LABAs

Question 6

how do we use beta agonists for asthma

Answer 6

good for acute exacerbations.
allbuterol (SABA) is good for PRN needs
LABAs like salmeterol and fomaterol are second line drugs when used in combination with corticosteroids

Question 7

Corticosteroids: summary

Answer 7

most important drugs for asthma treatment
multiple and complex effects on airway inflammation
controls gene expression through interactions with regulatory proteins. help to reduce late onset asthma effect by decreasing inflammatory response

Question 8

MOA of corticosteroids

Answer 8

remember that acetylated histones yield more active transcription of DNA. dimerized steroids enter the nucleus and activate acetyltransferases that enable acetylation of histones and expression of anti-inflammatory proteins. lower dose corticosteroids enter as monomers and inhibit histone acetyl transferase to prevent the expression of inflammatory proteins.

Question 9

Corticosteroid effects on inflammatory cells

Answer 9

decrease eosinophil number
decrease cytokines from T lymphocytes, which decrease eosinophils and mast cells
decrease mast cells
decrease macrophage cytokines
decrease dendrite cells

Question 10

corticosteroid effects on structural cells

Answer 10

decrease cytokins and mediators in epithelial cells
decrease leak from endothelial cells
increase B2 receptors and decrease cytokines on airway smooth muscle
decrease mucus secretion from mucus glands

Question 11

onset of action for coritcosteroids

Answer 11

4-12 hrs after PO or IV injection. Bronchiol hyperreactivity reduced over 1-4 wks
for inhalation, see a respone in 1-2 wks, best improvement in 4-8 wks, and the reversed bronchiole hyperreactivity over 1-3 months

Question 12

major side effects of steroids. 3 most important ones

Answer 12

growth retardation, myopathy, osteoporosis, panreatitis, psyche symptoms, Na and H20 retention, decreased K, increased glucose, HTN, decreased wound healing/immune function, central redistribution of fat, cataracts, glaucoma
2 most importatn: decreased bone density, subcapsular cataracts, increased risk of orgal pharyngeal candidasis (fluticasone)

Question 13

How are steroids used in asthma?

Answer 13

severe acute asthma relief. to prevent impending episode of severe asthma. best for short term use- 7-10 days, and no need to taper if only used short term

Question 14

pharmacogenomics of corticosteroids

Answer 14

GLCC1 gene