Pulmonary: Asthma Drugs

Question 1

Bronchoconstriction is mediated by
what two pathways?

Answer 1

Bronchoconstriction is mediated by
what two pathways?

1. Inflammatory proccesses
2. Parasympathetic tone

Question 2

β₂-agonists Drugs?

Answer 2

β2-agonists Drugs?

• Albuterol (Salbutamol)
• Salmeterol (partial agonist)
• Formoterol (full agonist)
• Isoproterenol
• Metaproterenol
• Terbutaline

Question 3

• β₂-adrenoceptor agonists
• Stimulates adenylate cyclase, ↑ cAMP, myosin light-chain kinase phosphorylation and inactivation
• Relaxes Bronchial smooth muscle and bronchodilation
• ↓ release of Leukotrienes and Histamine, ↓ airway inflammation
• Use during acute exacerbation, Bronchospasm, Bronchitis, and COPD
• SE: Tremor, Sinus tachycardia

Answer 3

Albuterol

Question 4

• β₂-agonists
• Long-acting agents for phrophylaxis due to high lipid solubility and hence easier entry and buildup in smooth muscle cells
• Adverse effects are Tremor and Arrhythmia

Answer 4

• Salmeterol
• Formoterol

Question 5

Methylxantine Drugs?

Answer 5

• Theophyline (found in Tea)
• Theobromine (found in Cocoa and Chocolate)
• Caffeine (found in Coffee and Tea)
• When taken in combination with Acetaminophen and Aspirn, can be used to treat migranes

Question 6

• Methylxanthine
• Bronchodilation by inhibiting Phosphodiesterase (PDE inhibitor) → ↑ cAMP levels cause airway smooth muscle relaxation and tachycardia,
  Due to ↓ cAMP hydrolysis (PDE₄)
• Also blocks adenosine receptors (A₁ subtype of P₁ Purinergic receptors) → ↑ cAMP levels
• Usage is limited, SE: Tremor and Agitation
• Narrow Therapeutic Index (cardiotoxicity, neurotoxicity); metabolized by cytochrome P-450

Answer 6

Theophyline (found in Tea)

Question 7

• Non-selective Muscarinic antagonists that acts on receptors found at parasympathetic effector sites
• Derivative of atropine
• Competitive block of muscarinic receptors
  (M₃acetylcholine receptors)
• ↓ Bronchoconstriction and ↓ Bronchial secretions
• β₂-agonists > Antimuscarinics
• 1^st **COPD **and 2^nd Asthma
• SE: Poor absorption, Dry mouth, Sedation
• A long-acting muscarinic antagonist

Answer 7

Ipratropium (Atrovent)

Question 8

Aerosolized corticosteroids?

Answer 8

Aerosolized corticosteroids?

• Beclomethasone (Vanceril, Beclovent)
• Budesonide (Pulmicort)
• Ciclesonide (Alvesco)
• Flunisolide (AeroBid)
• **Fluticasone **(Flovent)
• Mometasone (Asmanex)
• Triamcinolone (Azmacort)

Question 9

• Corticosteroids (glucocorticoid)
• Inhibit synthesis of virtually all Cytokines - binds to cytosolic glucocorticoid receptor (GR) and induces GR nuclear translocation
• Block the release of AA and syn. of Leukotrienes - blocks Phospholipase A₂
• Inhibit the infiltration of airway by Basophils, Eosinophils, and Mast cells
• Inactivate NF-kB, the transcription factor that induces the production of TNF-α; and other inflammatory agents
• 1^st line therapy for Chronic Asthma

Answer 9

• Beclomethasone (Vanceril, Beclovent)
• Fluticasone (Flovent)

Question 10

• Antileukotrienes
• LTD₄ receptor blocker on Eosinophils, Mast cells, and Basophils via 5-lipoxygenase on Arachidonic Acid (AA)
• LTB4 - neutrophil chemoattractant
• LTC4 and LTD4 - potent bronchoconstrictors - “slow-reacting anaphylaxis” in asthma
• Especially good for Asprin-induced Asthma (AIA) - thought to be a shift from Prostaglandins to Leukotrienes induced by Aspirin
• SE: Churg-strauss syndrome (rare)

Answer 10

• Montelukast
• Zafirlukast

Question 11

• Antileukotrienes
• 5-lipoxygenase pathway inhibitor that catalyzes the commited step in Leukotriene synthesis
• Blocks conversion of Arachidonic acid to Leukotrienes
• Metabolized by the CYP450 sys. and can ↑ serum concentrations of Theophylline and Warfarin
• SE: Hepatotoxicity

Answer 11

Zileutron (Zyflo)

Question 12

• Anti-IgE Monoclonal antibody
• Binds mostly to unbound serum IgE
• Blocks binding of IgE to FcεRI on Mast cells and Basophils -> moderate to severe Asthma
• Does not activate already bound IgE
• Used in allergic asthma resistant to inhaled steroids and long-lasting β₂-agonists
• 0.2% risk of Anaphylaxis

Answer 12

Omalizumab (Xolair)

Question 13

• Non-selective Muscarinic receptor agonist
• Inhalation agent - Challange -> excessive Bronchoconstriction via M₃ receptors in Bronchial smooth muscle.
• Used to help diagnose Asthma

Answer 13

Methacholine

Question 14

• Endothelin antagonist
• Most potent vasoconstrictor known
  (Smooth muscle - ET_A, Endothelial cells - ET_B)
• Cx: Pulmonary Arterial Hypertension (PAH)
• Can cause ↓ levels of Warfarin
• Competitively antagonizes endothelin-1 receptors
• Pulmonary Vasodilation
• Oral medication

Answer 14

Bosentan