Sweaty Pulm from a Pharm Perspective

Question 1

What are some advantages to inhalation therapy?

Answer 1

1. large surface area for absorption with very little metabolism and efflux
2. more permialble to small molecules than the GI tract
3. non-invasive
4. affects seen quickly

Question 2

What are some disadvantages to inhalation therapy?

Answer 2

1. contamination –> infections/must clean after every use
2. less efficient due to dead volume loss and size of inhalation
3. pt compliance/ability to use correctly
4. deposition of the drug in the alveoli vs. the conducting airways (think surface area)

Question 3

How are lipophillic and hydrophillic drugs absorbed differently in the lung?

Answer 3

lipophillic are more rapidly absorbed and done so transcellularly

hydrophillic drugs are more slowly absorbed and done so through intracellular tight junctions

Question 4

What determines the rate at which a drug is absorbed in the lungs?

Answer 4

MW and ionization: smaller, less ionized molecules are abs faster

Question 5

What 4 drug types are used to treat URT diseases?

*not neosplastic

Answer 5

mucolytics
vasoconstrictors
Drugs acting on CNS cough center
antihistamines

Question 6

What 3 types of drugs are used to treat lung diseases?

*not neoplastic

Answer 6

anti-inflammatory
bronchial tone modulators
vascular tone modulators
(anti-neoplastics)

Question 7

What autonomic receptors are used to control bronchospasm? agonist or antagonists?

Answer 7

B2 agonists

Muscarinic antagonsits

Question 8

T or F: B2 receptors innervate bronchial smooth muscle

Answer 8

F: they innervate the airway SM , epithelial cells, mast cells and type II alveolar cells

Question 9

Where are B2 receptors found in the lung?

Answer 9

airway SM , epithelial cells, mast cells and type II alveolar cells

Question 10

What receptors are found in airway/bronchial smooth muscle? What effect do they have when they are active?

Answer 10

Sympatheic: NE or Epi binds B2 –> bronchodilation and decrease airway secreations

Parasympatheic: Ach binds M2 and M3 –> bronchoconstrict and increase airway secreations

Question 11

What effect does adenosine have on bronchial smooth muscle?

Answer 11

bronchoconstricts

Question 12

What effect does Ach have on bronchial smooth muscle?

Answer 12

bronchoconstricts

Question 13

What effect does theophylline have on bronchial smooth muscle?

Answer 13

inhibits bronchoconstriction –> dilation

Question 14

What effect does M1 receptor activation have in the lungs?

Answer 14

increased glandular secretions

**no effect on airway/bronchial smooth muscle!!

Question 15

What effect does presynaptic M2 auto receptors have in the lung?

Answer 15

binds Ach and inhibits futher release of Ach –> decreases bronchoconstriction

Question 16

What effect does blockage of the M2 autoreceptor have in the lungs? Why is this significant?

Answer 16

increases the release of endogenous Ach –> more bronchoconstriction
**it offsets any bronchodilatory drug effects

Question 17

What is the selectivity of Tiotropium?

Answer 17

M1 and M3 receptors

Question 18

What effect does M3 receptor activation have in the lungs?

Answer 18

increase secretions and bronchoconstriction

Question 19

What drug class (and drugs) causes drying of secretions?

Answer 19

1st gen antihistamines + anticholinergic activity
**block M1 and M3 –> dec secretions

Chloropheniramine
Doxylamine
Diphenhydramine

Question 20

What drug class (and drugs) cause an increase in airway secretions?

Answer 20

ACh-esterase inhibitors
**inc ACh levels –> inc M1 and M3 activity –> inc secretions

Edrophonium
Neostigmine
Marijuana

Question 21

What receptors control airway secretions?

Answer 21

M1 and M3

activation/Ach increases secretions

Question 22

What is albuterol?
What is the major effect of it?
When is it used/what does it treat?

Answer 22

B2 agonist –> bronchodilation

EARLY/acute phase of asthma attack
**ineffective against the later phase bc it is an inflammation problem

Question 23

What are the problems assc with high B2 agonist concentrations?

Answer 23

• CV stimulation/tachycardia (B1 activation –> inc HR, contractility, and CO) =
• prolong QT interval –> pro-arrhythmogenic
• hypokalemia –> pro-arrhythmogenic too!
• desensitization/tachyphylaxis

also of note:

• widening of pulse pressure
• arterial dilation in coronary, pulmonary. and skeletal muscle
• muscle tremor (due Na/K ATPase inc activity)

Question 24

How can B2 agonist use lead to hypokalemia?

Answer 24

stimulation of skeletal muscle Na/K ATPase causes and increase in intracell K+ and a decrease in serum K+

Question 25

What are the benefits of B2 agonist therapy for the treatment of asthma?

Answer 25

1. bronchodilaiton opens airways
2. anti-inflam by inhibiting mast cell degranulation
3. inc mucocilliary clearance by activ goblet cells and submucosal glands and increasing beat frequency of cillia
4. dec extravasation/leakage of plasma protein –> dec edema/airway obstruction
5. dec chemotaxis, adhesion, and activation of leukocytes

Question 26

What drugs should not be used at the same time as B3 agonists? Why?

Answer 26

1. Saquinavir: promotes hypokalemia –> arrhythmias
2. Tricyclic antidepressants (amitriptyline, desipramine): blocks re uptake of NE –> excessive bronchodilation
3. MAOIs (selegilene and rasagilene): blocks metabolism of amine –> excessive bronchodilation
4. loop and thiazide diuretics: hypokalemia –> arrhythmias
5. non-selective beta blockers (propranolol) –> opposes effects of B2 agonist

Question 27

How is the issue of desensitization addressed with the use of B2 agonists?

Answer 27

pts receive a short course of corticosteroids that will increase the transcriptional activity and lead to an increase production of B2 receptors –> restores drug sensitivity

Question 28

Describe the process of desensitization.

Answer 28

repeated stimulation causes phosphorylation of the C term of the BAR. B-arreston binds to the phosphorylated domain and blocks Gs binding = uncouples pathway and cAMP decreases–> signaling stops. Arrestin binds and the BAR becomes localized in a lysosome –> degradation and down-regulation

Question 29

How can glucocorticosteroids treat asthma?

Answer 29

1. anti-inflammatory
   - inhibit production of inflam cytokines
   - promote production of anti-inflam cytokines
   - promote apoptosis of macrophages, DC, and T cells
2. prevent desensitization of B2 receptor

Question 30

What is a complication of inhaled glucocorticosteroids?

Answer 30

oral infections like thrush if the mouth is not rinsed after use

Question 31

What role do leukotines play in asthma?

Answer 31

binds CysLT1 on airway smooth muscle –> bronchoconstriction, eosinophil migration, airway edema

Question 32

What maintains the vascular tone in the pulmonary arteries?

Answer 32

balance between mediators of vasoconstriction (Ca++ and endothelin) and vasodilation mediators (PGI2 and NO –> inc cAMP or cGMP intracell)

Question 33

What is the target/aim for drugs that treat PAH?

Answer 33

they try to restore the balance between the effects of the vasoconstrictos and the vasodilators by inhibiting intralcell Ca++ signaling and increasing intralcell cAMP and/or cGMP
**PGI2 analogs, exogenous NO, CCBs, PDE5i

Question 34

What effect does adenosine have?

Answer 34

proinflamm

• induce mast cell degranulation
• inc production of cytokines
• -> smooth muscle/broncho- constriction