Name the 4 short-acting B2 agonists and the 3 long-acting B2 agonists.
(Hint: most of them end in -rol)
Beta2 agonism --> G protein --> AC --> increase cAMP --> bronchodilation.
Short-Acting Inhaled B2 Agonists
Long-Acting Inhaled B2 Agonists
1. Salmeterol (partial agonist)
2. Formoterol (full agonist)
What are the two therapeutic uses of the short-acting B2 agonists?
What is the therapeutic use of the long-acting B2 agonists?
Short-Acting B2 Agonists
1. asthma: as needed for acute exacerabations
2. prevent exercise-induced bronchospasm
Long-Acting B2 Agonists
1. long-term control of asthma
**always in combination with inhaled steroid**
Tolerance with chronic use is a problem for all B2 agonists. Side effects include hypokalemia, hypomagnesemia, hyperglycemia, and what others?
B2 Agonists Side Effects
--MSK tremor, tachycardia
(+ hypokalemia, hypomagnesemia, hyperglycemia)
Compare the onset and duration of action for short-acting versus long-acting B2 agonists.
Short-Acting B2 Agonists Onset: 5m; Duration: 4-6h
Long-Acting B2 Agonists Onset: 10-30m; Duration: 12h
What is the "ultra" long-acting B2 agonist that can be used in treating COPD?
The most important Inhaled Antimuscarinics are Ipratropium bromide and Tiotropium bromide.
Which one is first-line for treating COPD? What other condition can this be used to treat?
Which one is second-line? What other condition is it involved in treating?
Tiotropium Bromide 1st line for COPD; also treats chronic asthma
Ipratropium Bromide 2nd line for COPD; also used as additive to albuterol in severe acute asthma
Which M-receptor is the desired target to block for the Inhaled Antimuscarinics?
At which receptor is their crossover activity?
Describe the functions of these two receptors.
Target: block the M3 receptors, which mediate bronchoconstriction
Crossover at M2 receptors, which provide negative feedback inhibtion on the bronchoconstriction
Besides blocking M3 receptors, how does Tiotropium act with regards to inflammation and mucus management?
1) block M3 receptors
2) anti-inflammatory via reducing neutrophil migration and airway remodeling
3) decrease mucus production via blocking M3 receptors on mucus glands
Which inhaled antimuscarinic has the greatest functional selectivity and longest half-life at the M3 receptor?
Which inhaled antimuscarinic needs more frequent dosing and is less effective?
Tiotropium --greatest functional selectivity for M3
Ipratropium --less effective
Side effects of Tiotropium/Ipratropium include dry mouth, bladder obstruction, acute angle glaucoma, and paradoxical bronchospasm.
What additional risks are associated with Tiotropium?
What newer antimuscarinic agent is similar in structure to Tiotropium, but with less systemic & CNS side effects?
Tiotropium carries risk of cardiovascular mortality and cerebrovascular accidents.
Aclidinium is the newer agent.
Slow-release theophylline has weak bronchodilator activity through what mechanism?
What mechanism explains it's anti-inflammatory activity?
Bronchodilator activity --nonselective PDE inhibitor
Anti-inflammatory --enhance histone deacetylation --> suppress inflammatory genes
Besides being a weak bronchodilator and anti-inflammatory agent, what is the other therapeutic use of theophylline?
Improve contractility and reverse diaphragm fatigue in COPD
At low doses, theophylline can cause anorexia, nausea, headache, insomnia, and GERD.
What side effects does it have at high doses?
How is theophylline metabolized?
High dose side effects --cardiac arrhythmia, seizures
Metabolism via cytochrome P450
Inhaled Corticosteroids are used in combo with B2 agonists for treatment of persistent asthma.
Which of the following is a prodrug with less systemic absorption and fewer side effects?
What is the mechanism of inhaled corticosteroids?
Describe the two main clinical uses of inhaled corticosteroids.
Also, just know that these drugs have a ton of side effects.
--suppress pro-inflammatory genes
--activate anti-inflammatory genes
1) cornerstone treatment of persistent asthma --often in combo with B2 agonist
2) limited role in severe COPD
Which Leukotriene inhibitors prevent bronchoconstriction via LT-receptor antagonism?
Which LT inhibitor prevents bronchoconstriction through inhibition of 5-Lipoxygenase? This one also has liver toxicity.
LT receptor antagonism --Montelukast --Zafirlukast
5-Lipoxygenase inhibition --Zileuton *liver toxicity
Besides being used with limited effectiveness as an add on therapy in the treatment of mild asthma, what are the 2 clinical uses of LT inhibitors?
1) drug of choice for aspirin-induced asthma
2) prophylaxis for exercise-induced bronchospasm
The Cromones have anti-inflammatory action via inhibiting function of Cl channels --> prevent mast cell degranulation & mediator release from macrophages/eosinophils.
Name the 2 Cromones. What are their two therapeutic uses?
Their side effects include cough and throat irritation.
1. Sodium cromoglycate
2. Nedocromil sodium
1. alternative treatment for asthma
2. preventive treatment before exercise or allergen exposure
Side Effects: cough, throat irritation
What anti-inflammatory is an anti-IgE monoclonal antibody?
What are its clinical uses?
1) patients with severe asthma that is poorly controlled by oral corticosteroids
--> it reduces asthma exacerbations, and reduces required corticosteroid dosage