Issar-Asthma Drugs

Front 1

Describe the MOA of Beta 2 agonists for inhibiting constriction of smooth muscle

Back 1

a) Activates adenylyl cyclase-cAMP-->activates PKA
PKA does the following:
1) inactivates MLCK
2) activates Ca2+ pumps
b) Activates Ca2+ sensitive K+ channels-->K+ efflux-->hyperpolarization and relaxation

Front 2

What are the minor MOA of Beta 2 agonists?

Back 2

1. Inhibits degranulation of mast cells that leads to reduction in histamine
2. Stimulates β2 receptors on cholinergic terminals-->↓ Ach release (at rest, PNS causes bronchoconstriction; ↓Ach release mediates DILATION)

Front 3

What are the short acting Beta 2 agonists

Back 3

mnemonic-LEave ME ALone
Levalbuterol-most selective
Metaproterenol-least selective (can cause cardiac stimulation)
Albuterol

Front 4

What are the long acting Beta 2 agonists

Back 4

mnemonic-FArSI
Formoterol-rapid onset
Arformoterol
Salmeterol-slow onset
Indacaterol

Front 5

What are the major side effects of Beta 2 agonists?

Back 5

A. BBW: increased risk of asthma deaths with long-acting β2-adrenergic agonists; use w/ long-term asthma control medication (corticosteroid)
B. paradoxical bronchospasm
C. potential cardiac effects (increased w/ MAOIs)
D. tachyphylaxis (decreased response to drug); add glucocorticoid to counter this

Front 6

What are the MOAs of corticosteroids?

Back 6

bind to glucocorticoid response elements on DNA:
a) Down regulates genes for pro-inflammatory cytokines (PAF, IL-2-3-4-5-11-13-15, TNF)
b) Up regulates genes for annexin-1-->inhibition of PLA2--> decreases arachidonic acid
c) Induces apoptosis in TH2 lymphocytes
d) Drug-receptor complex (DRC) binds & inactivates pro-inflammatory transcription factors AP-1 and NF-kB that are upregulated in inflammation

Front 7

What are the names of the corticosteroids?

Back 7

contain 'son' or 'lone' in their name
A. inhalational steroids
TRIAMCINOLONE CICLESONIDE-extensively bound to plasma proteins (safer drug)
BECLOMETHASONE
MOMETASONE
BUDESONIDE
FLUTICASONE
B. oral steroids (cheapest)
Prednisone-inactive pro-drug; safe to give in pregnancy
Prednisolone-active form

Front 8

Describe the side effects of inhalational steroid therapy

Back 8

1. suppression of hypothalamic-pituitary-adrenal (HPA) function
2. Oral Candidiasis-rinse mouth and throat w/ water or use a spacer or reservoir
3. Decreased bone mineral density (especially females)
4. growth suppression

Front 9

Describe the side effects of oral steroid therapy

Back 9

BBW-DEATHS have occurred when switching from chronic systemic steroids to inhalationals (If tx>7 days, wean systemic drug gradually)
1. HPA axis suppression
2. Candidiasis
3. increased bone resorption
4. Osteonecrosis (femoral head)
5. ↑’d opportunistic infections
6. Mental disturbances, weight gain, Cushing’s like features (moon facies and buffalo hump)

Front 10

What are the MOAs of methylxanthines?

Back 10

a) 1. Inhibition of phosphodiesterase (PDE) isoenzymes III and IV--> prevents cAMP degradation in bronchial airways-->bronchodilation
2. Inhibit PDE IV in T lymphocytes & eosinophils--> anti-inflammatory effect
b) Adenosine receptor antagonist-->prevents bronchoconstriction and inflammation
c) Activates histone deacetylases-->↓ transcription of pro-inflammatory genes and potentiates effects of corticosteroids

Front 11

What are the names of the methylxanthines?

Back 11

name contains 'phylline'
a. theophylline-elimination follows 0 order kinetics
b. aminophylline

Front 12

What are the side effects of methylxanthines (theophylline)?

Back 12

1. susceptible for drug-drug interaction w/ P450 inhibitors
2. Febrile viral illness, CHF & liver dysfunction
3. narrow therapeutic index
4. Arrhythmias, convulsions, or sudden death
5. Drug interactions-anything that inhibits or induces P450 can alter drug levels

Front 13

Describe roflulimast

Back 13

MECHANISM-selectively inhibits phosphodiesterase-4 enzyme that inactivates cAMP to AMP in lung tissue
USE: tx of COPD

Front 14

Describe anticholinergic drugs

Back 14

name contains 'tropium'
MOA-blocks M3 muscarinic receptors
1. Ipratropium-doesn't discriminate b/t muscarinic receptor subtypes (reduces effectiveness); minimal protein binding
Side effects
a. caution if narrow-angle glaucoma-relaxes ciliary muscle-->raises intra-ocular pressure in the eye
b. worsens urinary retention
2. tiotropium-long acting; renally excreted
side effects-long term use by COPD patients increases risk of CV events

Front 15

Describe leukotriene receptor antagonists

Back 15

name contains 'lukast'
MOA-blocks cyteinyl LT-1 receptors
1. zafirlukast-rapidly absorbed; inhibits CYP2C9 and CYP3A4; highly bound to plasma proteins (albumin)
Side effects
a. liver dysfunction increases drug levels
b. theophylline and erythromycin decrease drug levels
2. montelukast-similar to 'zafir'; drugs that induce hepatic metabolism decrease drug levels

Front 16

Describe zileuton

Back 16

MOA-Inhibitor of 5-lipoxygenase-->inhibits leukotriene (LTB4, LTC4, LTD4 and LTE4)
Side effects
1. CNS effects
2. drug-drug interactions
a. alters (double) theophylline drug concentration
b. significantly ↑warfarin prothrombin times
c. doubles systemic exposure of propranolol-->↑ β-blocker activity

Front 17

Describe mast cell stabilizers

Back 17

name contains 'crom'
MOA-inhibits Cl- transport required for Ca2+ induced histamine release
1. CROMOLYN SODIUM-not for immediate relief
2. NEDOCROMIL-ophthalmic only

Front 18

Describe omalizumab

Back 18

MOA-binds to Fc region of IgE Ab; formed complex has no affinity to FcєRI-->inhibits mast cell degranulation-->↓’d stimulation TH2
Description-monoclonal Ab; long half life
Side effects
BBW-Risk of acute delayed onset anaphylaxis (bronchospasm, hypotension, syncope, urticaria, and angioedema of throat or tongue)

Front 19

Describe adult asthmatics sensitivity to aspirin

Back 19

1/5 asthmatic adults is sensitive to aspirin
MECHANISM: Inhibiting COX might shift arachidonic acid metabolism from PGs to LTs-->exacerbation of asthma symptoms
Inhibitors of LTs ↓’s this response to ASA