Komiskey: Anti-asthmatics, Antihistamine, and COPD

Question 1

Synthesis of histamine occurs primarily in which two cell types?

Answer 1

mast cells and basophils

Question 2

Histamine receptor H1 is found on smooth muscle, endothelium, and CNS tissue. Its activation results in?

Answer 2

vasodilatation, bronchoconstriction, smooth muscle activation, and separation of endothelial cells

Question 3

Which histamine receptor regulates the release of other neurotransmitters?

Answer 3

H3

Question 4

Stimulation of which cranial nerve causes bronchoconstriction and leads to cough?

Answer 4

Vagus

Question 5

What type of receptor is H1?

Answer 5

G-protein coupled, linked to intercellular Gq, which activates phospholipase C

Question 6

6 common first generation anti-histamines?

Answer 6

Diphenhydramine (Benadryl®)
Chlorpheniramine (Chlor-Trimeton®)
Brompheniramine (Dimetane®)
Hydroxyzine (Atarax®)
Cyproheptadine (Periactin®)
Promethazine (Phenergan®)

Question 7

Second generation anti-histamines? (unlikely to cause drowsiness)

Answer 7

Fexofenadine (Allegra®) (14h)
 Cetirizine (Zyrtec®) (8h) (kids metabolize faster)
 Levocetirizine (Xyzal®)
 Loratadine (Claritin®) (up to 28h)
 Desloratadine (Clarinex®)

LEVOcetirizine:
This drug is the active enantiomer of cetirizine and is believed to be more effective and have fewer adverse side effects.
Also it is not metabolized and is likely to be safer than other drugs due to a lack of possible drug interactions (Tillement).
It does not cross the BBB and does not cause significant drowsiness

Question 8

Intranasal anti-histamines?

Answer 8

Azelastine, Olopatadine (better SE)

Question 9

Antagonists of H1 receptor?

Answer 9

Mepyramine, triprolidine, cetirizine

Question 10

Agonist of H1?

Answer 10

Histaprodifen

Question 11

Antihistamines are_______ ________ _________, meaning that they shift the equilibrium of the receptor configuration to the inactive state and thus block histamine effects.

Answer 11

competitive inverse agonists

Question 12

What could be a later development of asthma? What cell type will show up?

Answer 12

COPD, neutrophils

Question 13

What is the early phase reaction of asthma?

Answer 13

bronchoconstriction

Question 14

What is the late phase reaction of asthma?

Answer 14

inflammation, mucus hypersecretion, hyperresponsiveness

Question 15

List “relievers” of asthma

Answer 15

SABAs:
Salbutamol
Fenoterol

Anti-Cholinergics:
Ipratropium Bromide
Tiotropium

Question 16

List “controllers” of asthma

Answer 16

LABAs (bronchodilation lasts >12h; good for EIB prevention):
Formoterol (***onset in 5-10m)
Salmeterol (onset in 30-40m)

ICSs (used more as prophylaxis):
Ciclesonide (**a PROdrug)
Flunisolide (MDI, BID)
Beclomethasone (MDI, BID)
Triamcinolone (MDI, BID)
Memotasone (MDI, BID)
Budesonide (breath-activated powder delivery)
Fluticasone (breath-activated powder delivery)

Oral CS (when ICS no longer work):
Prednisone
Prednilosone

(IV CS: Methylpredisolone, for untreatable asthma)

Leukotriene receptor agonist:
Monteluksat

Question 17

What are combos of asthma drugs?

Answer 17

Budesonide + Formeterol

Fluticasone + Salmeterol

Question 18

Which B2 adrenergic agent (specific SABA) is safe in pregnancy?

Answer 18

albuterol

Question 19

What is the mechanism of albuterol?

Answer 19

stimulate AdCyl, increase cAMP, decrease Ca

Question 20

How does Methylxanthine work? (& theophylline)

Answer 20

Blocks PDE (phosphodiesterase)

Question 21

LABAs will dilate for at least how long?

Answer 21

6h

Question 22

How do corticosteroids work in the prevention or fix of asthma attacks?

Answer 22

1. block phospholipase A and thus decrease PGs
2. decrease cytokine/chemokine produciton
3. inhibit the accumulation of basophils, eosinophils
4. decrease vascular permeability
5. enhance responsiveness of B2 receptors (thus decrease tolerance risk of SABAs, LABAs)

Overall, you see less leakage out of endothelial cells, improved airway smooth muscle, and decrease in mucus secretion.

Question 23

For MDI that is delivering and ICS, the patient should always use a _______.

Answer 23

Spacer

Question 24

List three common second=line therapy for asthma

Answer 24

Mast cell inhibitors: cromolyn/nedocromil (EIB)
Theophylline (if SABA/LABA fail)
Albuterol-Ipratropium combo (Combivent, DuoNeb)

Question 25

How do mast cell inhibitors work?

Answer 25

(think crumbs - degranulation. sounds like crom) (cromolyn, nedocromil) Mech is unknown but it inhibits release of cell mediators from eosinophils and lung mast cells, inhibits IgE synthesis and activation of inflammatory cells and promotes relaxation by interfering with Ca influx; given by inhalation. must be taken several times a day or BEFORE AN ATTACK NEDOcromil is approved for patients 12 and older; Cromolyn for ALL AGES

Question 26

What drug blocks arachidonic acid from becoming 5-HPETE and thus blocks leukotriene synthesis?

Answer 26

Zileuton (lipo-oxygenase inhibitor). Can be used to treat aspirin allergy. Other leukotriene pathway inhibitors (leukotriene receptor antagonists): - Montelukast (good for EIB. mountain) (ok for 6yo and older) - Zafirlukast (Liver test needed) (ok for 12yo and older)

Question 27

List three muscarinic antagonists used to calm the vagus nerve.

Answer 27

- ipratropium bromide (short-acting) - tiotropium (24 hr duration of action; Slow dissociation from receptor) (long-acting) - aclidinium (long-acting)

Question 28

If your patient reports that s/he is using their SABA more than twice a week, what is your new plan of tx?

Answer 28

``` Start: 1. ICS If needed add 2. LABA Other options: 3. Cromolyn sodium or Nedocromil 4. Leukotriene inhibitors ```

Question 29

Drug that binds IgE?

Answer 29

Omazilumab

Question 30

What drug is a PDE4 inhibitor and is used to reduce COPD exacerbations?

Answer 30

Roflumilast

Question 31

After how many months of controlled asthma can you consider stepping down treatment?

Answer 31

3 months

Question 32

What cells are active in asthma versus COPD?

Answer 32

Asthma: mast cells, eosinophils, CD4 T cells, MPs COPD: Neutrophils, CD8 T cells, MPs

Question 33

Does COPD show a response to steroids like asthma does?

Answer 33

No

Question 34

In COPD, what is the preferred tx if your patient has few sx and a low risk of exacerbation?

Answer 34

Short-acting anticholingergic or SABA as needed

Question 35

In COPD, what is the preferred tx if your patient has more sx and a low risk of exacerbation?

Answer 35

Long-acting anticholingergic or LABA

Question 36

In COPD, what is the preferred tx if your patient has few sx and a high risk of exacerbation?

Answer 36

ICS + Long-acting anti-choligergic OR LABA

Question 37

In COPD, what is the preferred tx if your patient has many sx and a high risk of exacerbation?

Answer 37

ICS + Long-acting anti-choligergic **&/OR** LABA

Question 38

What is a new LABA on the market for tx in COPD but has insane SE?

Answer 38

Striverdi Respimat

Question 39

What can help reverse corticosteroid in COPD patients?

Answer 39

Theophylline

Question 40

What drugs may work in ACOS (asthma-COPD overlap syndrome)?

Answer 40

anticholinergics