pharm agents in pulmonary med II

Question 1

anticholinergics summary. MOA, use, and comparison with beta agonists

Answer 1

competitive antagonist at muscarinic ACh receptors.
quaternary nitrogen compounds are better tolerated b/c they have less access to the CNS
slower onset than SABAs
helps with COPD chronically and with acute exacerbations of asthma and COPD
esp. important in COPD populations who can’t tolerate the heart side effects of beta agonists

Question 2

evidence for use of anti-cholinergics in asthma maintenance

Answer 2

LABAs and anti-cholinergics help more in pts with uncontrolled asthma than doubling the corticosteroid dose. MAy also lead to a better change in FEV1 and fewer severe exacerbations than standard combo therapy.

Question 3

Name of anticholinergic I should know

Answer 3

tiotropium

Question 4

evidence for anti-cholinergic use in COPD

Answer 4

compared with salmeterol (LABA), see fewer COPD exacerbations

Question 5

methylxanthines. primary agent

Answer 5

theophylline

Question 6

MOA of theophylline

Answer 6

inhibits phosphodiesterase in a non-selective manner to increase cAMP (PDE breaks down cAMP). this leads to bronchodilation

Question 7

effects of theophylline

Answer 7

bronchodilation. Also it is an adenosine antagonist (adenosine is a bronchoconstrictior0, has anti-inflammatory effects, and increases mucociliary clearance.

Question 8

theophilline limitations

Answer 8

very narrow therapeutic rance with non-linear phmacokinetics and variable clearance
may lead to nausea, vomiting, tachycardia, arrhythmias, anxiety, CNS excitation, seizures and death. therefore 4th line treatment

Question 9

effects of mast cell stabilizers

Answer 9

inhibit release of mediators from mast cells after activation (primary mechanism)
also decrease chemotaxis of PMNs, lymphocytes, eosinophils to inhibito bronchospasm and airway inflammation

Question 10

mast cell stabilizers names

Answer 10

cromolyn and nedocromil

Question 11

advantages and disadvantages of mast cell stabilizers

Answer 11

advantages: few side effects, could help with both acute and late onset response
but doesn’t work as well as corticosteroids, so they are second line controller agents and second line for exercised induced bronchospasm (first line is beta agonists)

Question 12

leukotriene modifiers: 2 approaches and names

Answer 12

CysLT1 receptor antagonists: montelukast and zafirlukast

lipo-oxyegenase inhbitor: zileuton

Question 13

what does the cyst LT receptor do

Answer 13

when activated, it promotes mucus production, broncho constriction, edema and eosinophilia. Not responsible for granulocyte chemotaxis

Question 14

advantages and disadvantages of leukotriene modifiers. include side effects

Answer 14

advantages: few side effects, rapid onset, can be taken orally
disadvantages: inconsistent response, rare churg struass. both zafirlukast and zileuton interact with many other drugs. zileuton also can cause hepatic problems.

Question 15

Role for leukotriene modifiers

Answer 15

2nd line for asthma. no role in COPD

Question 16

Omalizumab

Answer 16

anti-IgE Ab that prevents its binding to mast cell membrane to decrease release of mediators when exposed to antigen.

Question 17

Omalizumab disadvantages and use

Answer 17

problems: must be administered every 2-4 weeks and is expensive. also may cause anaphylaxis, malignancy, injection site irritation. used for 5-6 level asthma. No use in COPD

Question 18

Roflumilast

Answer 18

PDE4 (phosphodiesterase) inhibito. increase cAMP and decrese PMNs. better FEV1. reduces COPD exacerbations in COPD patients with a history of chronic bronchits and exacerbations

Question 19

problems with foflumilast

Answer 19

weight loss, GI intolerabuility, increased suicidality, drug interaction potential. not a big impact on quality of life or symptoms

Question 20

role of antibiotics in COPD

Answer 20

macrolids like azithromycin may decrease COPD exacerbations