Block 1 - Asthma + COPD Pharmacology Flashcards
What are examples of the relievers?
- SABA
- Systemic steroids
What are SABAs used for?
Relieves acute symptoms associated with asthma or COPD (rescue)
What are systemic steroids used for?
for moderate to severe acute exacerbations, but can be used for severe asthma as controller
Why are nonselective sympathomimetic bronchodilators not used has often for exacerbations?
Contains a, b1, and b2 activity leading to numerous ADRs (injection or nebulizer)
Undergoes COMT metabolism
What are examples of b nonselective?
isoproterenol (isuprel)
List some isoproterenol (isuprel) characteristics?
- IV prep only
- Good for bronchial relaxation but cardiac effects due to b1 activity
- Positive chronotropic and inotropic actions on heart
- Primarily for cardio stimulatory effects
What do B2-agonists achieve?
- Relaxes bronchial airways smooth muscle directly and by raising cAMP that inhibits contraction
- Stabilizes mast cells by inhibiting mediators suppressing parasympathetic ganglionic activity
What is the difference between nonselective b and selective b2 agonists?
Non: cardiac stimulation, causing palpitations, tachycardia, headache, flushed skin
Sel: limits cardiac stimulation but not absolute selectivity, increases HR with increasing dose
What are examples of SABAs?
- Albuterol (Proventil, Ventolin)
- Levalbuterol (Xopenex)
- Terbuline Sulfate
What are the ADRs of b2 agonists (SABA)?
Albuterol (Ventolin, Proventil)
Levalbuterol (Xopenex)
What is the relations between albuterol and levalbuterol?
Albuterol: GOLD standard, racemic mixture, oral and inhalation
Levalbuterol: R enantiomer, inhaler and nebulizer
What is the GOLD standard b agonist?
Albuterol (Ventolin, Proventil)
What are the benefits of using SABA (albuterol and levalbuterol)?
- Relaxes bronchial airways
- 2 min onset
- Inhaled med -> enhanced therapy -> rapid onset with fewer ADRs
What are the disadvantages of using SABA (albuterol and levalbuterol)?
- > 1 canister/month means inadequate control of disease
- PRN not for chronic use
- Can have CV effect, fine muscle tremors, anxiety, restlessness, tachyphylaxis
In what occasions would you use terbutaline sulfate instead of albuterol/levalbuterol?
- status asthaticus
- tocolysis (uterine contraction)
What are the categories of controller therapies?
- Anti inflammatory medications
- Long acting bronchodilators
What are categories of anti inflammatory meds?
- inhaled glucocorticosteroids
- oral glucocorticoids
- leukotriene receptor antagonists
- Cromolyn
What are categories of long acting bronchodilators?
- LABAs
- Ipratropium
- Tiotropium
- Theophylline
What are the benefits of using ICS?
- preferred treatment alone or in combo for all persistent asthma
- potent and safe
- reduces asthma symptoms
- reduces dependence on SABAs
What is the MOA for ICS?
- Suppresses IL and CK
- Reduces eosinophil infiltration and function
- Inhibits macrophages and release of the chemical mediators of inflammation
- Increases B2 receptors
- Binds to intracellular GCR to regulate gene transcription within target cells
What are the main ICS?
- Budesonide (Pulmicort)
- Ciclesonide (Alvesco)
- Mometasone (Asmanex Twisthaler)
- Beclomethasone diproprionate (Beclovent, Vanceril)
- Fluticasone propionate (Flonase)
Why is fluticasone propionate a good ICS?
Drug undergoes rapid metabolism where derivative has 1/2000 affinity for GR than FP overcoming potential ADRS
What are the physiological effects of GC?
- Regulates carb, protein, and lipid metabolism
- Maintenance of fluid and electrolyte balance
- Preservation of normal function of systems
- Preservation of homeostasis
What are examples of systemic steroids?
Prednisone or Prednisolone
When would you prescribe someone a systemic steroid?
- Rescuer for acute asthma
- Severe persistant asthma that is uncontrolled (chronic use)
What are the side effects of ICS?
- Deposition in mouth and throat may promote oral candidiasis (rinse mouth after use)
- Mild reversible increases in glucose, decreased potassium, fluid retention, and HTN
What are the side effect of short term systemic steroid use?
Reversible increases in glucose, decreased potassium, fluid retention, and HTN
What are the side effect of long term systemic steroid use?
- growth and immune suppression
- iatrogenic Addision’s syndrome (must taper)
- Iatrogenic cushing syndrome
What are the symptoms of iatrogenic cushing syndrome?
- lipid tissue redistribution
- fragile skin and easy bruising
- Mask of infection
- Mental
- metabolic disturbances (hyperglycemia, steroid diabetes, osteoporosis, water and salt retention, potassium wasting)
What is the cause and effects of secondary adrenal insufficiency?
- Rapid withdrawn from exogenous steroids due to chronic inhibitor of AcTH release in pituitary
Results:
1. Decrease in ACTH
2. Weakness and fatigue
3. Addisonian crisis
4. Hypoglycemia
5. Hypotension
What are examples of LABAs for Asthma and COPD?
Salmeterol (Serevent)
Formoterol (Foradil)
Arformoterol (Brovana)
What is the onset of salmeterol?
15-30 minutes
What should be prescribed in concurrence with LABA?
ICS
Why should are shouldn’t Salmeterol be used as a resume inhaler?
- Not PRN
- Slow onset of action 15-30 min
What are the combo products with salmeterol?
With fluticasone as Advair diskus or HFA
What are the benefits of using formoterol and arformoterol?
- Onset is minutes
- Effective over nocturnal asthma
What are the combos with formoterol or arformoterol?
- Budesonide (symbicort)
- Mometasone (Dulera)
What are the ultra labas and what are they primarily used for?
Treatment for COPD but some are approved for asthma
What ultra labas are approved for asthma?
Vilanterol + Fluticasone (Breo Ellipta)
Vilanterol + umeclidinium + fluticasone (Trilogy)
What do antimuscarinics mainly treat?
COPD or serve persistant asthma
Describe the MOA of antimuscarinics?
- ACh causes bronchoconstriction (M3 receptors) and an increase in secretion predominately in large and medium sized airways
2.
Why are antimuscarinics used for COPD?
- Airways are narrow in COPD therefore the vagal cholinergic tone has a greater effect on airway resistance
2, Muscarinic receptor antagonists block the parasympathetic cholinergic induced bronchoconstriction and reduces mucus hyper secretion
What are examples of antimuscarinics for COPD?
- Ipratropium
- Tiotropium
- Aclidinium
- Umeclidinium
- Glycopyrrolate
Which antimuscarinics are for bronchospasm?
- Ipratropium (Atrovent)
- Tiotropium (Spiriva)
Why would we use ipratropium for COPD?
- quat amine ensures poor absorption and fewer ADRs
- Doesn’t impede mucociliary clearance of mucous, avoiding accumulation
3.
Why is tiotropium a little better than ipatropium
- Longer duration, QD
- Selectivity for M1 and M3 receptors
What are dosages of spiriva?
Handihaler COPD: 18mcg QD
Respimat COPD: 2.5 mcg QD
Respimat Asthma: 1.25 mcg QD
How does Aclidinium BR (tudorza Pressair) differ from ipatropium or tiotropium?
- Muscarininc antagonist for COPD management
- Antagonizes M2 and 3 receptors
- rapidly hydrolyzed in plasma leading to lower systemic exposure and reduced ADRs
- Used twice daily
What are common ADRS with antimuscarinics?
- Dry mouth (inhaled)
- Pharyngitis (inhaled)
- Gastroenteritis (systemic or swallowing)
- Headache (systemic or swallowing)
Who are contraindicated when using antimuscarinics?
BPH, urinary retention, closed angle glaucoma
What are the delivery options of asthma meds?
- Dry powder inhaler
- Metered dose inhalers
- Nebulizers
What is the most effective particle size for asthma inhalers?
1-5 µm
What are spacers?
help patients who have difficulty with technique, thus increasing response and reducing potential side effects
What are nebulizers?
uses compressed air machine to deliver medicine as an inhaled mist
good for younger children, older adults, are severe asthma episodes
What is the MAO of leukotrienes?
- Increase vascular permeabiliuty
- Increase bronchiolar smooth muscle contraction
- Increase mucus secretions
- Augment neutrophils and eosinophils migration
How are leukotrienes synthesized?
- Lipoxygenase Pathway produces the leukotrienes
- Leukotriene inflame airways in asthma causing anaphylactic shock
3, Cysteinyl leukotriene receptors CysLT1 and CysLT2 are present on mast cells, eosinophil, and endothelial cells.
What is the MAO of zileuton (zyflo)?
5-lipoxygenase (enzyme) inhibitor
What are warning that is associated with zyflo?
Inhibits metabolism of theophylline and warfarin, requires montioring