Pharm - Asthma and COPD

Question 1

Structure vs. function of sweat glands

Answer 1

Anatomically SNS (long postganglionic fiber)
Functionally PNS (releases ACh)

Question 2

Non-specific beta agonists

Answer 2

Epi, ephedrine, isoproterenol

Question 3

Fast acting, short lived beta 2 agonists

Answer 3

Albuterol, levalbuterol, terbutaline

Question 4

LABAs

Answer 4

Salmeterol, formoterol

used with steroid

Question 5

Antiinflammatory meds

Answer 5

Steroids
Cromolyn
Leukotriene inhibitors

Question 6

Leukotriene receptor blockers

Answer 6

Montelukast, zafirlukast

Question 7

Leukotriene synthesis blocker

Answer 7

Zileuton

Question 8

IgE mab

Answer 8

Omalizumab

Question 9

What has highest density of B2R?

Answer 9

Bronchial smooth muscle cells

Question 10

Bronchial SMCs don’t have ___ innv, while blood vessels don’t have ___ innv

Answer 10

Symp

Parasymp

Question 11

What is unique about the adrenergic receptors in bronchial SMCs?

Answer 11

Epinephrine is their endogenous ligand rather than NE like other adrenergic receptors

Question 12

What type of cholinergic receptors are present on bronchial SMCs?

Answer 12

M2 and M3

Question 13

M2R responsible for ___ using what G protein?

Answer 13

Decreased ACh release (M2R is autoreceptor)

Gi

Question 14

M3R responsible for ___ using what G protein?

Answer 14

Bronchoconstriction

Gq –> increased Ca2+

Question 15

Relationship between eosinophils and asthma/COPD

Answer 15

Major basic protein of eo’s causes bronchoconstriction by inhibiting M2R (so increasing ACh)

Question 16

When would an M2R AGONIST cause bronchoconstriction?

Answer 16

In presence of a B2R agonist which would increase levels of cAMP and cause relaxation; by working through Gi, an M2R agonist would inhibit this effect and cause constriction.

Question 17

How do B2 agonists cause bronchial SMC relaxation?

Answer 17

Increase cAMP –> PKA –> phosphorylation of MLCK –> relaxation

Question 18

Which nerve is stimulated in asthma pts? Effect?

Answer 18

Vagal afferents –> sends messages to vagal afferents –> release ACh (parasymp) –> constriction of bronchial SMC

Question 19

Affinity of epi vs. ephedrine vs. isproterenol

Answer 19

Epi - B1, B2, alpha
Ephedrine - B1, B2, some alpha
Isoproterenol - B1, B2

Question 20

4 MOA beta agonists

Answer 20

1. Increase cAMP –> relaxation
2. Increase mucociliary transport
3. Decrease mast cell release of mediators
4. Decrease microvascular permeability

Question 21

How do LABAs cause increased mortality?

Answer 21

Through Gq –> PLC –> inflammation

(beta2 agonists do NOT treat inflammation of asthma/COPD; they might exacerbate it

Question 22

AE of sympathomimetics

Answer 22

N/V, HA, hypotension, arrhythmias, agitation, coma, convulsions, respiratory and vasomotor collapse

Question 23

Density of B2R vs. muscarinic receptors

Answer 23

B2R - bronchioles

MR - lower airways

Question 24

2 antimuscarinics

Answer 24

Atropine

Ipratropium

Question 25

2 MOA antimuscarinics

Answer 25

1. COMPETITIVE muscarinic block --> SMC relaxation | 2. Decrease mucus secretion

Question 26

AE atropine

Answer 26

Pupil dilation | Cycloplegia (paralysis of ciliary muscle causing loss of accommodation = blurry near vision)

Question 27

Combo beta2 agonist and antimuscarinic indicated for:

Answer 27

COPD

Question 28

List the methylxanthines

Answer 28

Theophylline Aminophylline Dyphylline Oxtriphylline

Question 29

Actions of methylxanthines

Answer 29

1. Increase cAMP --> SMC relaxation 2. Inhibit adenosine --> antiinflammatory 3. Weak diuretic 4. Increase skeletal muscle (diaphragm) strength 5. Positive inotropic and chronotropic effects 6. Increase gastric acid secretions 7. Decrease release of mediators

Question 30

Unique AE of methylxanthines

Answer 30

Hypokalemia Hyperglycemia Neuromuscular irritability

Question 31

Indications for cromolyn

Answer 31

Exercise or allergen induced asthma

Question 32

Actions of cromolyn

Answer 32

1. Inhibit mast cell degranulation********* 2. Inhibit Cl- channels 3. Inhibit eosinophilic inflammatory pathway 4. Reduce cough by action on airway nerves 5. Reduce bronchial hyperactivity

Question 33

AE cromolyn

Answer 33

1. Bad tase 2. Cough and bronchospasms after inhalations 3. CNS depression 4. Anorexia

Question 34

MOA of glucocorticoids

Answer 34

Cause dissociation of HSO90 --> recruitment of HDAC: 1. Decreased synthesis of pro-inflammatory cytokines 2. TRANSACTIVATION of anti-inflammatory cytokines 3. Recruitment of TTP, which decreases stability of mRNA of pro-inflammatory cytokines

Question 35

Overall effects of glucocorticoids

Answer 35

1. Reduce bronchial hyperactivity 2. Reduce mucus secretion 3. Reduce pro-inflammatory cytokines 4. Synergism with beta 2 agonists

Question 36

Which GC's are oral? IV?

Answer 36

PO - dexamethasone, prednisone IV - dexamethasone (rest are inhaled)

Question 37

AE of GC's

Answer 37

``` Cushingoid syndrome Bone demineralization Retarded growth in children Oral candidiasis/immunosuppression Weight gain Glucose intolerance HTN Cataracts ```

Question 38

Indication for leukotriene antagonists

Answer 38

Aspirin-induced asthma

Question 39

What does LTB4 do? LTC4 and D4?

Answer 39

``` LTB4 = neutrophil chemoattractant LTC4/D4 = mimic asthma; mucus secretion, bronchoconstriction, bronchial hyper-reactivity, edema ```

Question 40

MOA zileuton vs. montelukast/zafirlukast

Answer 40

``` ZiLeuton = Lipoxygenase inhibitor ZafiRlukast/montelukast = LTD4 receptor antagonist ```

Question 41

Which leukotriene inhibitor prevents neutrophil recruitment?

Answer 41

Zileuton = inhibits LTB4

Question 42

AE zafirlukast

Answer 42

Hepatic enzyme elevation | Bladder, liver, histocytic cancer

Question 43

AE montelukast

Answer 43

Infections | Suicidal ideations

Question 44

AE zileuton

Answer 44

Increase liver enzymes | Inhibit CYP1A2

Question 45

Which other asthma drug may interact with zileuton?

Answer 45

Theophylline (levels would increase if also taking zileuton)

Question 46

Name the IgE mab

Answer 46

Omalizumab

Question 47

Indication for omalizumab

Answer 47

ABPA (IgE > 700)

Question 48

AE of omalizumab

Answer 48

Severe allergic reaction (SOB, closing of throat, swelling of face, lips, tongue, hives)

Question 49

6 steps of therapy for asthma

Answer 49

1. SABA PRN 2. Low-dose ICS 3. Low-dose ICS + LABA or medium-dose ICS 4. Medium-dose ICS + LABA 5. High-dose ICS +LABA 6. High-dose ICS + LABA + PO CS

Question 50

Are steroids helpful in COPD?

Answer 50

Not really; poor response

Question 51

CI in COPD

Answer 51

``` Sedatives Beta blockers ACE inhibitors ASA/cox inhibitors Local anesthetics with epi ```

Question 52

MOA doxapram

Answer 52

Stimulate peripheral carotid receptors --> respiratory stimulant

Question 53

Indications for doxapram

Answer 53

COPD exacerbation | Post-anesthesia or drug-induced respiratory depression