PHARM: Basics of Pulmonary Pharmacology

Question 1

True or false: the lung is more permeable to macromolecules than any other portal.

Answer 1

TRUE! IT is even more permeable to small molecules than the GI tract

Question 2

What is one of the major issues with the delivery of inhaled corticosteroids?

Answer 2

Deposition of a significant portion of the drug dose in the oral cavity –> thrush

Question 3

How can you minimize thrush due to inhaled corticosteroids?

Answer 3

Use a spacer or rinse mouth after use

Question 4

Lipid soluble compounds are absorbed via what route?

Answer 4

transcellular route (dissolve in the lipid bilayer)

Question 5

Lipid insoluble compounds are absorbed via what route?

Answer 5

paracellular (pass through intercellular tight junctions)

Question 6

Do ionized molecules have faster or slower absorption?

Answer 6

slower (because they have more interactions with the proteins and lipids that line the pore.

Question 7

For molecules above 1000 D, what is the most important factor for absorption rate?

Answer 7

molecular weight (and ionization)

Question 8

For molecules 100-1000 D, what is the most important factor for absorption rate?

Answer 8

Degree of ionization (the less ionized, the faster absorption)

Question 9

What are the 3 major lung issues that require pharmacological treatment?

Answer 9

Inflammation
Infection
Transformation

Question 10

What is interesting about mucolytics?

Answer 10

they never enter the body, but rather they break up the physical structure of mucus making it easier to be expectorated

Question 11

How do vasoconstrictors help the upper respiratory tract? What receptors to they act upon?

Answer 11

alpha-1 agonists that relieve congestion by relieving nasal congestion

Question 12

Which will produce more rapid relief for asthma: a beta-agonist or a corticosteroid?

Answer 12

Beta-agonist (controls smooth muscle directly) will provide more immediate relief while anti-inflammatory drugs may have same effect eventually over time by controlling inflammation

Question 13

What are the 3 major issues we are concerned about with anticancer drugs?

Answer 13

1) Toxicity
2) Resistance
3) Duration of clinical effect

Question 14

What two drug classes are used to control bronchospasm?

Answer 14

Beta-2 agonists

Muscarinic antagonists

Question 15

True or false: the SNS directly innervates bronchial smooth muscle.

Answer 15

FALSE: the SNS does not directly innervate bronchial smooth muscle but can modulate the activity of the PNS via hetero-receptors

Question 16

What class of drugs is contraindicated in asthma due to effect on receptors in the airway?

Answer 16

Nonspecific beta blockers (P-T olols) are contraindicated!

Question 17

What is the major role of M1 receptors in the airway?

Answer 17

• Transduce vagal signals to sub-mucosal glands and airway smooth muscle
• Increase glandular secretions in nasal mucosa

Question 18

What is the role of M2 receptors in the airway?

Answer 18

they are pre-synaptic inhibitory autoreceptors!

Question 19

What happens if ACh binds to M-3 receptors in the airway?

Answer 19

bronchoconstriction and mucus secretion

Question 20

What happens if ACh binds to M-2 receptors in airway smooth muscle?

Answer 20

they oppose the increase in cAMP production produced by Beta-2 adrenergic stimulation

Question 21

What is the “Jekyll and Hyde” aspect of muscarinic antagonists?

Answer 21

M3 antagonism inhibits bronchial smooth muscle, but antagonism of M2 could actually lead to increased release of Ach from the pre-synaptic membrane (and cause contraction)

Question 22

What is the name of the selective M-1/M-3 antagonist?

Answer 22

tiotropium

Question 23

Anticholinergic drugs have what effect on glandular secretions?

Answer 23

dries and thickens them!

Question 24

What drug has a very similar anticholinergic activity with respect to secretions (dries them)?

Answer 24

1st generation antihistamines

Question 25

What drugs have cholinergic activity with respect to secretions (increases them)?

Answer 25

acetylcholinesterase inhibitors and marijuana (these prevent the almost-immediatedegradation of Ach)

Question 26

What is albuterol?

Answer 26

beta-2 selective agonist

Question 27

What is the major response to the administration of albuterol?

Answer 27

relaxation of bronchial smooth muscle and bronchodilation

Question 28

Albuterol is only effective against what phase of asthma?

Answer 28

the early (bronchospastic) phase… it does nothing for the late (inflammatory) phase

Question 29

Beta-2 agonists may cause bronchoconstriction via what mechanism?

Answer 29

increasing PNS (bronchoconstrictive) tone

Question 30

Activation of beta-2 receptors on mast cells lead to what?

Answer 30

reduction of histamine release

Question 31

Beta-agonists have what effect on cilia?

Answer 31

increase beat frequency of cilia and facilitate mucociliary clearance

Question 32

Beta-agonists have what effect on vascular endothelial permeability?

Answer 32

decrease microvascular leakage

Question 33

At high concentrations, beta2 agonists have what effect on the heart?

Answer 33

Stimulation, prolongation of QT interval (especially in presence of hypokalemia)

Question 34

How do beta2 agonists lead to QT prolongation and tremor?

Answer 34

stimulate skeletal muscle Na/K ATPase to increase intracellular K+ and decrease serum K+

Question 35

Beta-2 receptors use what type of GPCR?

Answer 35

Gs

Question 36

If you too frequently stimulate your beta-2 receptors, what might happen?

Answer 36

internalizaiton and loss of physiologic function (“tolerization”)

Question 37

How might corticosteroids help with beta-2 agonist “tolerization”?

Answer 37

they transcriptionally upregulate the expression of beta-adrenergic receptor to renew the response to beta2-agonist inhaler treatment