Asthma pharmacology Flashcards
What are the pharmacological therapies for asthma?
Bronchodilators (4
Anti-inflammatory agents (4)
8 total)
Bronchodilators:
(1) β2-adrenergic agonists
(2) Epinephrine
(3) Anticholinergics
(4) Methylxanthines
Anti-inflammatory agents
(1) Corticosteroids
(2) Leukotriene inhibitors
(3) Cromolyn/Nedrocromil
(4) Anti-IgE
How does airway morphology change in asthma?
(1) Increased muscle mass
(2) Subepithelial fibrosis
(3) Edema
(4) Epithelial cell damage
How is asthma diagnosed?
hmm
What inflammatory mediators are released at different time intervals in asthma?
Immediate (4)
Minutes (2)
Hours (2)
(8 total)
Immediate (granule contents):
(1) Histamine
(2) TNF-α
(3) Proteases
(4) Heparin
Minutes (lipid mediators):
(5) Prostaglandins
(6) Leukotrienes
Hours (cytokine production):
(7) IL-4
(8) IL-13
What is the neurogenic cause of asthma?
hmm
What are the three main approaches to asthma therapy?
3
(1) Avoidance of causative factors
(2) Reverse bronchoconstriction
(3) Anti-inflammatory agents
What are characteristics of β-adrenergic agonists used to treat asthma?
(3)
(1) β2 most effective for bronchodilation without cardiovascular side effects
(2) Effective after oral or inhaled administration
(3) Stimulate adenylyl cyclase and increase cAMP, favoring bronchodilation
What are sites of drug action of β-adrenergic agonists?
hmm
What is a short-acting β2 adrenergic agonist and what are its features?
(1) Albuterol (Proventil)
(2) Maximal effect in 30 minutes but lasts several hours
What is a long-lasting β2 adrenergic agonist and what are its features?
(4)
(1) Salmeterol (Serevent)
(2) 12+ hour duration
(3) Not for acute attacks - 2 puffs daily for about 2 weeks for maximal effectiveness)
(4) Should not be used without corticosteroids
What are the adverse effects of β2 adrenergics?
2
Minimal due to low systemic absorption
(1) Tachycardia
(2) Muscle tremors
What are the non-selective β-adrenergic agonists used to treat asthma?
(1) Epinephrine - drug of choice for anaphylaxis, but with severe cardiovascular side effects
(2) Isoproterenol - very potent and fast acting, but can cause cardiac arrhythmias
What is the antimuscarinic/anticholinergic asthma drug and what are its features?
(1) Ipratropium bromide
(2) Not acute - peak effect in 1-2 hours
What are the adverse effects of ipratropium bromide?
Minimal side effects, alleviated by spacers
Drying of mouth and upper airways
What are the methylxanthines and their sources?
3
(1) Caffeine (coffee)
(2) Theobromine (cocoa)
(3) Theophylline (tea)
What is the mechanism of theophylline?
hmm
What are the features of theophylline?
(1) Methylxanthine
(2) Oral administration
(3) Therapeutic dose: 5-15 ug/ml
(4) Not for acute bronchospasm
What are the adverse effects of theophylline at therapeutic doses?
(5)
Therapeutic dose 5-15 ug/ml
(1) Headaches
(2) Nervousness
(3) Insomnia
(4) Nausea/vomiting
(5) Epigastric pain
What are the adverse effects of theophylline at greater than therapeutic doses?
(3)
> 30 ug/ml:
(1) Hypokalemia
(2) Cardiac dysfunction
> 40 ug/ml:
(3) Seizures
How is theophylline metabolized?
Theophylline is metabolized by cytochrome p450 in the liver
What are some theophylline drug interactions?
5
Increase serum theophylline:
(1) Erythromycin
(2) Oral contraceptives
(3) Anti-leukotrienes
Decrease serum theophylline:
(4) Barbiturates
(5) Chemicals in cigarette smoke, NOT nicotine
What disease states may affect theophylline serum concentrations?
Increase (4)
Decrease (1)
(5 total)
Increase:
(1) Liver diseases
(2) Febrile illness: (a) pneumonia and (b) influenza
Decrease:
(3) Cystic fibrosis
What corticosteroids are used to treat asthma?
Inhaled (2
Systemic (1)
3 total)
Inhaled:
(1) Flunisolide
(2) Fluticasone
Systemic:
(3) Prednisone
What are the mechanisms by which corticosteroids treat asthma?
(4)
(1) Control eosinophils
(2) Reduce mucosal edema
(3) Potentiate β-adrenergic agonists
(4) Inhibit transcription of inflammatory agents
What are the side effects of corticosteroids?
2
(1) Minimal if inhaled
(2) Oropharyngeal candidiasis
Systemic:
(3) Hypertension
(4) Diabetes
(5) Iatrogenic cushings
(6) Adrenal suppression
(7) Peptic ulcers
What is Advair?
Combined therapy drug containing fluticasone and salmeterol
What leukotrienes are involved in asthma?
(1) LTB4 - attracts neutrophils
(2) LTC4/D4 (SRS-A) - causes (a) bronchoconstriction, (b) hyperreactivity, (c) mucosal edema, and (d) mucus secretion
What antileukotrienes are used to treat asthma?
(1) Zileutin - inhibits 5-lipoxygenase (converts arachidonic acid to leukotrienes)
(2) Zafirlukast - leukotriene receptor antagonist
How are anti-leukotrienes metabolized?
In the liver by cytochrome p450
What are anti-leukotriene drug interactions?
5
(1) Increases theophylline levels
(2) Decreases warfarin clearance (increased prothrombin time)
(3) Increases carbamazepine effect
(4) Erythromycin decreases zafirlukast
(5) Can be used to reduce dose of glucocorticoids
What are the side effects of anti-leukotrienes?
(1) Abnormal liver function tests
(2) Tachycardia
(3) Alopecia
(4) Rash
(5) Fibromyalgia-like symptoms
(6) Churg-Strauss syndrome (eosinophilic)
What is notable about the efficacy of anti-leukotrienes?
(1) Anti-leukotrienes don’t work on everyone and efficacy is unpredictable
(2) Not as potent of a bronchodilator as β-adrenergics or theophylline
(3) Less potent anti-inflammatory than glucocorticoids
What is cromolyn/nedrocromil?
(1) Inhibitor of mediator release from mast cells, neutrophils, and eosinophils
(2) Causes interaction between secretory vesicles and cytoskeleton
(3) May suppress Ca2+ and Cl- channel activity
How is cromolyn/nedrocromil used?
(1) Used prophylactically
(2) Administered by inhaler
What are side effects of cromolyn/nedrocromil?
3
Minimal side effects and localized to site of action:
(1) Throat irritation
(2) Cough
(3) Mouth dryness
What is the anti-IgE drug and how does it work?
(1) Omalizumab
(2) Binds circulating IgE regardless of specificity
(3) Forms biologically inert Omalizumab:IgE complexes
(4) Decreases IgE levels and downregulates IgE receptors within 90 days
Overall, how are different severities of asthma treated?
(1) Mild (2 episodes per week) - long-acting β2 adrenergic agonist (salmeterol), inhaled glucocorticoids (fluticasone) or advair
(3) Severe (daily episodes) - oral glucocorticoids (not good chronically)
