Respiratory

Question 1

Describe innervation of the lungs

Answer 1

SNS from thoracic ganglia innervate smooth muscles of bronchi an pulmonary blood vessels, bronchodilation via B2
PSNS innvervation via the VAGUS nerve and M3 (muscarinic receptor) both cause bronchoconstriction, M3 increases mucus secretion too

Question 2

Non-adrenergic non-cholinergic (NANC) nerves relax airway smooth muscle by releasing ___ and _____

Answer 2

Nitric oxide and vasoactive intestinal peptide

Question 3

List histologic mediators of bronchoconstriction (in asthma)

Answer 3

Eosinophils, mast cells, neutrophils, macrophages, basophils, T lymphocytes
Other probable mediators include cytokines, interleukin 3,4,5, arachidonic acid metabolites of leukotrienes and prostaglandins, histamine, adenosine, platelet activating factor

Question 4

Do steroids work better for asthmatics or COPD?

Answer 4

Asthmatics, it helps with inflamed, edematous, hypersensitive airways
Almost never used for COPD

Question 5

Which is reversible/irreversible between asthma and COPD?

Answer 5

Asthma airflow obstruction is reversible, using albuterol and steroids
COPD is irreversible
In asthma, inhaled corticosteroids help reduce frequency of exacerbation, bronchodilators help with breathlessness

Question 6

Step 1-5 treating airway outflow disorders?

Answer 6

1: short-acting bronchodilators
2: regular inhaled corticosteroid
3: long-acting bronchodilators
4: phosphodiesterase inhibitors, methylanthines, leukotriene inhibitor
5: oral corticosteroid
Other: cromolyns

Question 7

List short-acting and long-acting B-adrenergic agonists that are selective to B2

Answer 7

Short-acting: terbutaline, albuterol, levalbuterol, salbutamol, metaproterenol-alupent, bitolterol
Long-acting: salmeterol

Question 8

B-adrenergic agonist MOA?

Answer 8

G proteins activate adenyl cyclase which increases the production of cAMP leading to bronchodilation, dec Ca increases K conductance
Primarily bronchodilates, also inhibits mediator release from mast cells and increases mucus clearance using cilia

Question 9

B-adrenergic agonist onset, DOA?

Answer 9

Rapid onset of 15-30 min

Short DOA 30-60 min (albuterol up to 4 hours)

Question 10

B-adrenergic agonist side effects?

Answer 10

Tremor
Inc HR
Vasodilation
Hyperglycemia, hypokalemia, hypomagnesemia

Question 11

What are the isomers of albuterol selective to? R-albuterol and S-albuterol

Answer 11

S-albuterol: beta1

R-albuterol: beta2

Question 12

What is terbutaline used for? Dose for adults and children? Route?

Answer 12

Status asthmaticus, also for preterm labor
Child: subq 0.01mg/kg
Adult: subq 0.25 mg q 15 min
Subq dose resembles response of epi

Question 13

What are salmeterol and formoterol used for?

Answer 13

Long-acting B-agonist used for prevention, NOT for acute flare-up or surgery
They are long-acting due to lipophillic side chains that resist degradation
Duration 12-24 hours

Question 14

Muscarinic receptor antagonist (anticholinergics) MOA?

Answer 14

Competivive antagonists at the muscarinic acetylcholine receptors
Antagonizing Ach results in broncho-relaxation and decreased mucus secrtion

Question 15

Airway smooth muscle extends as far distal as ____

Answer 15

Terminal bronchioles

Question 15

Which muscarinic receptor is the most important subtype in lung because it mediates smooth muscle relaxation (bronchodilation) and decreases mucus gland secretion?

Answer 15

M3

Question 17

Muscarinic receptor antagonist (anticholinergics) uses?

Answer 17

Treats COPD (especially chronic bronchitis to help with secretions)
Secondary line of treatment for asthma in patients resistant to beta agonist or significant cardiac disease

Question 18

Atropine: what class of drug is it? Side effects?

Answer 18

A muscarinic receptor antagonist/ anticholinergic/ bronchodilator
Administered 1-2 mg diluted in 3-5 mL of saline via nebulizer
Highly absorbed across respiratory epithelium
Side effects: tachycardia, nausea, dry mouth, GI upset

Question 19

How does ipratropium bromide compare to atropine?

Answer 19

Derivative of atropine
Not significantly absorbed compared to atropine
More dry mouth and GI upset, less tachycardia

Question 20

How does tiotropium compare to atropine?

Answer 20

Long acting anticholinergic

Not significantly absorbed across respiratory epithelium which results in few side effects

Question 21

Methylxanthines/ Phosphodiesterase inhibitor MOA? Uses? Examples?

Answer 21

MOA: nonspecific inhibition of phosphodiesterase isoenzymes (3,4) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells resulting in airway relaxation and bronchodilation
Uses: COPD and asthma
Theophylline and aminophylline

Question 22

Theophylline therapeutic plasma level?

Answer 22

NARROW

10-20 mg/mL

Question 23

Methylxanthine/PDI metabolism excretion?

Answer 23

Metabolized in the liver
CP450 INDUCER so interacts with CP450 inhibitors (such as cimetidine and antifungals)
Excreted by the kidney

Question 24

Methylxanthine/PDI side effects?

Answer 24

Many side effects due to multiple MOAs
Arrythmias, hypotension
N/V
Irritability, insomnia, seizures, brain damaged
Hyperglycemia, hypokalemia

Question 25

Inhaled corticosteroids: MOA, use?

Answer 25

MOA: alter genetic transcription by increasing transcription of genes for B2 receptors and anti-inflammatory proteins, decrease transcription of genes for pro-inflammatory proteins. Indirect inhibition of mast cells, reverse asthma features. Dec vascular permeability, dec airway edema, dec airway hyper-responsiveness

Question 26

Uses of inhaled corticosteroids? Name some inhaled corticosteroids.

Answer 26

Uses: preventative treatment for asthma patients (supportive therapy, not a cure), MOST IMPORTANT in managing asthma, also it prolongs the response of beta-agonists Beclomethasone, triamcinolone, fluticasone, budesonide

Question 27

____% of inhaled corticosteroids reaches the airway

Answer 27

25% 80-90% of the inhaled dose reaches oropharynx and is swallowed (unless mouth is rinsed after using inhaler) Systemic effects are decreased through inhalation

Question 28

Inhaled corticosteroid side effects?

Answer 28

``` Osteopenia/osteoporosis Delayed growth in children Oropharyngeal candidiasis Hoarseness Hyperglycemia, then hypokalemia ```

Question 29

Cromolyn MOA?

Answer 29

Inhibits antigen-induced release of histamine and inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes from pulmonary mast cells Inhibits allergic response to an antigen except one that has been activated

Question 30

Cromolyn side effects?

Answer 30

``` Rare but bad Laryngeal edema Angioedema Urticaria Anaphlyaxis ```

Question 31

Cromolyn use?

Answer 31

Prophylactic therapy of bronchial asthma, does NOT relieve allergic response

Question 32

Leukotriene inhibitors: MOA, use, name a couple?

Answer 32

Inhibits leukotriene pathway (leukotrienes are synthesized from arachidonic acid when inflammatory cells are activated) Used for bronchial asthma but NOT effective in acute asthma attacks Zileuton, Montelukast (singulair)

Question 33

Name two types of asthma drugs that you would NOT use in an acute asthma attack?

Answer 33

Cromolyn | Leukotriene inhibitors

Question 34

Zileuton key points? MOA?

Answer 34

Lipoxygenase inhibitor that blocks biosynthesis of leukotrienes from arachidonic acid Long-term improvement of PFT and asthma symptoms Low bioavailability, low potency, hepatotoxic, not widely use

Question 35

Montelukast (singulair)

Answer 35

Leukotriene receptor antagonist that blocks bronchoconstriction and smooth muscle effects Improves bronchial tone, pulmonary function, asthma symptoms Cysteinyl-leuktriene 1 receptor is what it blocks Caution with warfarin, will prolong PT

Question 36

Name an Anti-IgE antibody, what is it used for?

Answer 36

Omalizumab Binds to IgE and decreases quantity of IgE and prevents IgE binding to mast cells to mitigate acute response of inhaled allergen Down-regulates IgE receptors to reduce stimulation of T2 lymphocytes