PHARM-pulm-overview

Question 1

what are some of the disadvantages to inhalation or aerosol therapy?

Answer 1

expense
contamination possible
device preparation
cleaning required after dose
not all meds available
less efficient than other devices (dead volume loss)

Question 2

why is the lung a good target for pharmacotherapy?

Answer 2

permeable to macromolecules
very low capacity for metabolic and efflux activity
delivers drug clean without metabolites produced
very fast delivery system

Question 3

what’s a problem with some inhalers depositing drugs onto epithelial surfaces

Answer 3

adverse effects, as with inhaled steroids

Question 4

for small hydrophillic compounds, ____________dominates; above this MW is also a factor

Answer 4

ionization (things that are less ionized are absorbed at a faster rate because it forms fewer interaction with proteins and lipids that line the pore)

Question 5

is the parasympathetic or sympathetic nervous system dominant on bronchial smooth muscle tone

Answer 5

parasympathetic nervous system

Question 6

___________________nerves do NOT supply airway smooth muscle in humans.

Answer 6

sympathetic (but probably supplied by parasympathetics, also beta-2 adrenergic receptors are found throughout lung in small bronchioles airway SM, epithelial cells, mast cells and type II alveolar cells)

Question 7

When are beta-2 adrenergic agonists most effective in response to inhaled antigen?

Answer 7

effective against early bronchospastic response (ineffective against late inflammatory phase)

Question 8

what is an important CV adverse effect when using beta-2 agonists?

Answer 8

can have non-specific stimulatory effects
can have prolonged QT interval, especially in presence of hypokalemia
Tremors
Tolerance

Question 9

how do beta 2 stimulation cause/worsen hypokalemia?

Answer 9

beta-2 stimulation of skeletal muscle Na/K-ATPase leads to increase in the intracellular K+ and decrease serum K+ making QT prolongation worse

Question 10

what effect do beta-2 agonists have on mast cells?

Answer 10

prevent degranulation and release of tryptase, cytokines and histamine

Question 11

how do beta-2 agonists effect mucociliary clearance?

Answer 11

1. change composition (increase glycoproteins)

2. increase beat freq. of cilia (facilitates clearance)

Question 12

what effect do beta-2 agonists have on vascular endothelial permeability?

Answer 12

decrease microvascular leakage–>decrease airway obstruction in asthma

Question 13

what can you do to fix the problem of loss of beta-adrenergic activity?

Answer 13

give short course of corticosteroids that increase transcriptional activity in favor of producing newly functional receptors restoring drug sensitivity

Question 14

where are the cholinergic receptors located in the lungs?

Answer 14

in large bronchioles and have vagal innervation

Question 15

where are the beta2 receptors located in the lung?

Answer 15

small bronchioles, no direct innervation

Question 16

beta2 agonists at high concentrations can have what adverse CV efffects?

Answer 16

tachycardia, prolongation of the QT interval especially in the presence of hypokalemia (acts to stimulate Na/K ATPase and increases intracellular K+ and decreases extracellular K+ making hypokalemia worse)

Question 17

glucocorticoids inhibit production of what cytokines?

Answer 17

IL-1, TNF

Question 18

glucocorticoids promote production of what cytokines?

Answer 18

antiinflammatory cytokines like IL-10

Question 19

what are all the benefits f using a beta2 adrenergic agonist?

Answer 19

1. bronchodilator
2. antiinflammatory (inhibits mast cell degranulation)
3. decreased chemotaxis, adhesion and activation of wbcs
4. increased mucociliary clearance
5. dereased extravasation of plasma protein and edema