Respiratory Agents

Question 1

SNS lung innervation

Answer 1

from thoracic ganglia, innervates smooth muscles of bronchi and pulmonary blood vessels

Question 2

PSNS lung innervation

Answer 2

via vagus nerve, bronchoconstriction via mostly M3 and a little bit of M1

Question 3

B2 adrenoreceptors cause (intracellular response)

Answer 3

increased intracellular cAMP which changes membrane potential of cells and decreases calcium release intracellularly, greater sensitivity to EPI v NE

Question 4

Non adrenergic non cholinergic nerves (NANC)

Answer 4

excitatory: related to substance p and neurokinin
inhibitory: NO, peptide release

Question 5

How do M3 mediate bronchoconstriction

Answer 5

via activation of IP3 (inositol triphosphate) which increases intracellular Ca2+ concentrations. also mediates mucous secretion.

Question 6

asthma histologic mediators include

Answer 6

eosinophils, mast cells, neutrophils, macrophages, basophils, t lymphocytes, cytokines, interleukins, arachidonic acid metabolites, leukotrienes, prostaglandins, histamine, adenosine, platelet activating factor

Question 7

emphysema/bronchitis pathological result

Answer 7

enlargement of air spaces, fibrosis, increased mucous production

Question 8

treatment of airway outflow disorders (5 steps)

Answer 8

1. short acting bronchodilators
2. inhaled corticosteroids
3. long acting bronchodilators
4. PD3 inhibitors, methylxanthines, leukotriene inhibitor
5. oral corticosteroid

Question 9

bronchodilator med classes

Answer 9

beta agonists
anticholinergics
methylxanthines

Question 10

short acting beta agonists (SALT)

Answer 10

terbutaline, albuterol, levalbuterol, salbutamol

Question 11

long acting beta agonists

Answer 11

salmeterol, formoterol

Question 12

B2 agonist bronchodilator MOA (general)

Answer 12

(3,5 cAMP production)
activate adenyl cyclase which increases production of cAMP (adenosine monophosphate) which causes bronchodilation. reduced intracellular calcium release and alters membrane conductance

Question 13

B2 agonist bronchodilator effects (general desirable effects)

Answer 13

dilates bronchi, smooth muscle relaxation, inhibits mediator release from mast cells, increase mucus clearance by action in cells

Question 14

B2 agonist SE’s (general)

Answer 14

minimized by inhalation delivery
tremor
increased HR
vasodilation
metabolic changes including hyperglycemia, hypokalemia, hypomagnesemia

Question 15

Albuterol class, dose, route of administration (2), duration of action, SE’s

Answer 15

beta 2 agonist
administered via metered dose at 100mcg/puff
2 puffs q4-6h
neb 2.5-5mg in 5ml of saline
can give 4 puffs to blunt AW response to tracheal intubation for asthmatics
duration 4 hours with relief evident up to 8h (additive effect with volatile anesthetics)
SE: tachycardia, hypokalemia,

Question 16

isomers of albuterol

Answer 16

R albuterol levalbuterol- more affinity for B2

S albuterol more affinity for B1

Question 17

Metaproterenol-Alupent class, route of administration, dose max

Answer 17

beta 2 agonist used for tx of asthma, administered via metered dose, dont exceed 16 puffs per day

Question 18

Pirbuterol-Maxair class, dose, dose max

Answer 18

beta 2 agonist, administered via metered dose (400mcg), do not exceed 12 puffs/day

Question 19

Terbutaline class, use, route of admin, dosage, drug comparison

Answer 19

beta agonist
used to treat asthma
administered oral, SQ(SC), inhaled
SQ dose pedes .01mg/kg
SQ dose adults .25mg q15min
metered dose inhaler 16-20puffs/day
each dose 200mcg
SQ administration resembles response of epi

Question 20

Salmeterol and Formoterol class, duration, use, chemical consideration

Answer 20

beta agonist
long acting, 12-24h duration
asthma prevention of flare
lipophilic side chains that resist degradation
salmeterol has fluticasone (steroid)

Question 21

Muscarinic Receptor Antagonist MOA

Answer 21

M1 and M3 most important in mediating smooth muscle relaxation and decreased mucous gland secretion, which produces bronchorelaxation and decreased secretions.

Question 22

Muscarinic Receptor Antagonist uses

Answer 22

tx of COPD

secondary line of tx for asthma (in patients resistant to B agonist or significant cardiac disease

Question 23

Atropine class, use, dose, route of administration, distribution, SE

Answer 23

muscarinic antagonist (naturally occurring alkaloid)
formally considered 1st line for asthma tx
1-2mg diluted in 3-5ml of saline via nebulizer
highly absorbed across respiratory epithelium
SE: systemic anticholinergic effects including tachycardia, nausea, dry mouth, GI upset

Question 24

Iatropium Bromide class, chemical structure, MOA, route of administration, dose, onset, duration of action, absorption consideration, SE

Answer 24

muscarinic antagonist
quaternary ammonium salt derivative of atropine
antagonizes effect of endogenous Ach at M3 receptor subtypes
administered via metered dose inhaler
40-80mcg in 2-4 puffs via nebulizer
slow onset of 30 min
duration 4-6h
not significantly absorbed compared to atropine
SE: dry mouth, Gi upset if oral absorption

Question 25

Tiotropium class, chemical structure, duration of action, absorption considerations, use

Answer 25

``` muscarinic antagonist quarternary ammonium salt long acting not significantly absorbed across respiratory epithelium which results in few side effects COPD ```

Question 26

Methylxanthine class, MOA, uses

Answer 26

(Inhibit breakdown of 3,5 cAMP) PDE inhibitors nonspecific inhibition of PDE isoenzymes (types III and V) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells. causes airway relaxation and bronchodilation used for COPD or asthma

Question 27

theophylline TI, caution, metabolism, excretion

Answer 27

TI 10-20mcg/ml caution with halothane drug-drug interactions r/t CYP450 metabolism (cimetidine, antifungals) excreted in kidney

Question 28

methylxanthine (PDI) consideration r/t SE

Answer 28

because they have multiple MOA's and are nonselective, have many SE's and narrow TI

Question 29

methylxanthine PDI SE's (general)

Answer 29

``` headache n/v irritability, restlessness insomnia cardiac arrhythmias seizures SJS ```

Question 30

Inhaled corticosteroids MOA, use

Answer 30

alter genetic transcription by: - increasing transcription of genes for B2 receptor and anti inflammatory proteins - decreasing transcription of genes for pro inflammatory proteins - induce apoptosis in inflammatory cells (eosinophils, TH2, lymphocytes) - indirect inhibition of mast cells over time - reducing number of inflammatory cells in airways reduced damage to epithelium - vascular permeability is reduced which decreases airway edema - overall reduction in airway hyper-responsiveness - used as suppressive therapy, major preventive tx for patients with asthma (most important asthma mgmt)

Question 31

Inhaled Corticosteroid Examples (4)

Answer 31

beclomethasone traimcinolone fluticasone budesonide

Question 32

Inhaled corticosteroid anesthesia considerations (periop use)

Answer 32

may consider use of corticosteroid 1-2h postop prolong response of B agonists may consider 5 day course of combined corticosteroid and albuterol to minimize risk of intubation invoked bronchospasm

Question 33

Corticosteroid inhaled and PO route considerations

Answer 33

80-90% of inhaled dose reaches oropharynx and is swallowed higher airway concentration than same dose given PO systemic effects decreased through inhalation

Question 34

Inhaled Corticosteroid SE's

Answer 34

``` oropharyngeal candidiasis osteopenia/osteoporosis delayed growth in children hoarseness hyperglycemia ```

Question 35

Cromolyn MOA

Answer 35

stabilizes mast cells inhibits antigen induced release of histamine including release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, leukotrienes from pulmonary mast cells inhibits immediate allergic response to antigen but not allergic response once it has been activated

Question 36

Cromolyn use, administration, SE's

Answer 36

prophylactic therapy of bronchial asthma (does not relieve allergic response after initiation, and is therefore not to be used as a rescue inhaler) -administered via inhalation, take 4x daily SE are rare but include laryngeal edema, angioedema, urticaria, anaphylaxis

Question 37

Leukotriene Inhibitors use

Answer 37

useful for bronchial asthma

Question 38

synthesis of leukotriene

Answer 38

from arachidonic acid when inflammatory cells are activated

Question 39

Zileuton class MOA, use, bioavailability, potency, SE

Answer 39

leukotriene inhibitor lipoxygenase inhibitor which blocks biosynthesis of leukotrienes from arachidonic acid produces bronchodilation, improves asthma symptoms, has shown long term improvement in PFT low bioavailability and potency hepatotoxicity is SE, not widely used because of many adverse effects

Question 40

Monteuklast-Singulair class, MOA, co administration considerations

Answer 40

leukotriene inhibitor block mechanism of bronchoconstriciton and smooth muscle effects by blocking ability of leukotrienes to bind to cysteinyl leukotriene 1 receptor improves bronchial tone, pulmonary function, and asthma symptoms caution with co admin with warfarin which would prolong PT

Question 41

Anti IgE Antibodies and Asthma

Answer 41

since asthma is an IgE mediated allergic response, the idea is that the removal of the IgE antibodies from circulation would mitigate acute response of inhaled allergen

Question 42

Omalizumab class, use, route of administration, duration of administration, SE, drug considerations

Answer 42

monoclonal antibody derived from DNA, binds to IgE to decrease the quantity of IgE and prevent binding of IgE to mast cells. in response to lower levels of IgE, mask cells, basophils, and dendritic cells are down regulated - given in early and late phase of asthmatic response - given SQ for 2-4w/parenterally infused - SE: rare but triggering of immune response - high cost and inconvenience

Question 43

which drug class is most utilized for COPD

Answer 43

anticholinergics

Question 44

what are the two ways in which leukotriene inhibitors work

Answer 44

block synthesis of leukotriene via arachidonic acid or block receptors

Question 45

Methylxanthine examples

Answer 45

theophylline, aminophylline