Asthma Drugs

Question 1

Inhaled Corticosteroids (ICS)

Answer 1

Ex: Mometasone, Budesonide, Fluticasone

MOA: Activates GRs (steroid receptors) on many different immune cells (including mast cells)
- also upregulates beta-2 receptors on bronchiole smooth muscle
- Days to weeks for maximal effect (genomic effects?)
- not effective for asthma attacks

AEs: Dysphonia (thins vocal cords) Oral thrush (fungal infections)

Higher dose –> increased systemic effects
Osteoporosis
Skin thinning
increased blood glucose
increased blood pressure
decreased growth velocity in kids

Question 2

Beta-2 Agonists

Answer 2

Ex: Albuterol: short-acting (SABA); Salmeterol: long acting (LABA)

(Inhaled)
MOA: agonist to beta-2 adrenergic receptor on bronchiole smooth muscle –> bronchodilation

AEs: Skeletal muscle tremor (stimulation of noninnervated beta-2 on SKM)
Hypokalemia (stimulation of noninnervated beta-2 on SKM)
CNS: Anxiety
Cardiac stimulation of beta-1 –> tachycardia, palpitations (not 100% selective for beta-2)
Prolonged QTc (Kr blockade)
Overuse –> diminished effect (minimized if combined with ICS)

Clinical Trials:
LABA monotherapy –> increased asthma-related death
*Cannot use LABA as monotherapy for asthma
(must combine with ICS)

Question 3

Leukotriene Modifiers 1

Answer 3

Ex: Montelukast, Zafirlukast

(Oral)
MOA: block CysLT1 receptors –> bronchodilation
–> decreases inflammation

AEs: Neuropsychiatric

Question 4

Leukotriene Modifiers 2

Answer 4

Ex: Zileuton

(Oral)
MOA: block LOX –> synthesis of LTs
–> bronchodilation –> inflammation

AEs: Neuropychiatric
Hepatotoxicity (need to monitor LFTs)

Question 5

Methylxanthines

Answer 5

Ex: Theophylline

(Oral)
MOA: block PDE –> increases cAMP/PKA effects block adenosine receptors other effects (immunological and other)

Bronchodilation, decreases inflammation

AEs:
Tachycardia
Nausea/vomiting
Headache
Seizures
Hypokalemia

Question 6

Cromolyns

Answer 6

Ex: Cromolyn

(inhaled)
MOA: inhibits mast cells (takes weeks for max effect)
*prevention prior to exposure or exercise
Bronchodilation, decreased inflammation

AEs: minimal

Question 7

Muscarinic Antagonists

Answer 7

Ex:
Ipratropium (short-acting- “SAMA”)
Tiotropium (long-acting- “LAMA”)

(Inhaled)
MOA: nonselective muscarinic antagonist
block M3 on bronchiole smooth muscle g bronchodilation

AEs: confusion
drowsiness
attacks of narrow angle (“angle-closure”)
glaucoma
decreased accommodation for near vision
(cycloplegia)
xerostomia
tachycardia
constipation
urinary retention
anhidrosis -> increased body temp -> reflex
vasodilation

Question 8

Anti-IgE Antibodies

Answer 8

Ex: Omalizumab

(SQ injections)
MOA: Antibody to IgE –> prevents binding of IgE to receptors on mast cells –> decreases activation of mast cells –> bronchodilation
–> decreases inflammation

AEs: Pain/burning at injection site
allergic reaction

Question 9

Drug-Induced Asthma

Answer 9

1. NSAIDs –> increases LT synthesis
2. Beta blockers (nonselective > beta-1 selective) –> block beta-2 mediated
   bronchodilation
3. Muscarinic agonists, AChEIs
   –> Stimulation of M3 on bronchiole smooth muscle