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Pharm Unit 4 > Asthma/COPD > Flashcards

Asthma/COPD Flashcards

1
Q

Salmeterol (Serevent)

A

Class: Bronchodilator - long-acting β2 agonist
Mech: Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability (BMMM)
Thera: used for long-term control of asthma symptoms (always in comination with inhaled steroids)
Important SE’s: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia
Other SE’s: Tolerance with chronic use, Prolonged QTc, lactic acidosis, paradoxical bronchospasm
Misc: 10-15 minutes to take action, 6-12 hours (max) of duration; nebulizer delivers more, but greater side effects; oral is least effective (requires more dose –> side effects); can be used night symptoms, but not ideal

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2
Q

Asthma is

A
  1. chronic inflamm of airways
  2. recurrent episodes of wheezing, SOB, chest tightness (SEC)
  3. Variable airway obstruction, often completely reversible
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3
Q

COPD is a

A
  1. persistent airway limitation
  2. progressive (not fully reversible)
  3. enhanced chronic inflamm responses (cough, SOB, increased sputum)
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4
Q

Some key similarities and differences b/w COPD and asthma:

A 
Sim: both inflamm; 
Diff: 1. TH2 dom in astham, TH1 in COPD
2. IgE producing in asthma
3. reversible in asthma, fixed in COPD
4. Bronchial hyperreactivity in asthma
5. Smoking risk factor for COPD; genetics, environment in asthma
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5
Q

Some epidemiology:

A
  1. Females > males for percent asthma
  2. Females more likely to get asthma as we get older, and more AA pop mortality
  3. Men with greater death rate by COPD than females, but more females die of it
  4. Could be underdiagnosing COPD and hence undertreating
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6
Q

In asthma and the ____ model, what helps mediate early inflamm? Late inflamm?

A

allergen;
leads to IgE coating mast cells and degranulation, and also T lymphocyte activity (both with IL4, IL5; mast cells with leukotriens, prostaglandin D, platelet activating factor);
late: eosinophils and neutrophils with their mediators (e.g. MBP for eosinophils) and this leads to more bronchospasm

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7
Q

Rather than think of the allergen model of asthma, what is a viable model to think of?

A

Bronchial hyper-reactivity model (cold air or maybe exercise)

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8
Q

What three things does COPD help cause? Why?

A
  1. fibrosis (small airways)
  2. Alveolar wall destruction (emphysema)
  3. Mucus hypersecretion (hypertrophy of mucous glands0;
    Imbalance of proteases and antiproteases
    FAM
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9
Q

Important mech of action of bronchodilators (beta 2 agonist)?

A

increases cAMP through G-protein receptor interaction and activation of AC;

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10
Q

Albuterol, terbutaline, metoproterenol, pirbutol:

A

Class: Bronchodilator - short-acting β2 agonist)
Mech: Relax bronchial smooth muscle, inhibit mediator release (mast cells, basophils), increase mucociliary clearance, suppression of microvascular permeability
Thera: Prevent or reduce exercise-induced bronhospasms; mild asthma & acute exacerbations
Important SE’s: Musculoskeletal tremor, Tachycardia, hyperglycemia, hypokalemia, hypomagnesemia; Tolerance with chronic use (downregulate beta 2 receptors), Prolonged QTc, lactic acidosis, paradoxical bronchospasm
Misc: 5 minutes to take action, 4-6 hours duration; nebulizer delivers more, but greater side effects. Note: Levalbuterol is R-isomer of albuterol.

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11
Q

Levalbuterol:

A
  1. R isomer of albuterol
  2. Just beta agonist effects
  3. No inflamm or SE’s like tachy due to no S isomer
  4. No significant difference in clinical or pharmacological outcome
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12
Q

Salmeterol, formoterol, indacaterol:

A

S: partial agonist; F: full agonist; I: ultra long acting (only in COPD);
Onset: 10-30 min; duration: 12 hrs or more;
Highly lipid soluble and binds to secondary exosite;
USED IN COMBO WITH INHALED CS IN ASTHMA!!!!!

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13
Q

Comparison of tiotropium and ipratropium bromide:

A
  1. Half life of tio is longer at M3 receptor (can dose 1x/day);
  2. Tio will dissociate faster from M2 receptor and keep its M3 activity longer
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14
Q

Ipratropium (Atrovent); Tiotropium; Atropine

A

Class: Quarternary amine antimuscarinic
Mech: Blocks vagal pathways and decreases vagal tone to bronchial smooth muscle; also blocks the reflex bronchoconstriction caused by inhaled irritants
Thera: First-line agent for chronic COPD; status asthmaticus (w/ nebulized β2-agonists); no role in chronic stable asthma
SE’s: Typical antimuscarinic effects; acute angle glaucoma; paradoxical bronchospasm GAP (inhibition of vagal induced bronchoconstriction would require high dose than current therapeutic doses); consider receptor selectivity;
Misc: Note: tiotropium has anti-inflammatory properties and decreases mucus secretion.

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15
Q

Aclidinium bromide:

A

Class: Quarternary amine antimuscarinic
Mech: Blocks vagal pathways and decreases vagal tone to bronchial smooth muscle; also blocks the reflex bronchoconstriction caused by inhaled irritants
Thera: Functionally similar to tiotropium
1. structurally and functionally similar to tio
2. M3>M2 affinity
3. Half life at M3: 29 hours
4. Short circulation half life: 2.4 min (Less systemic & CNS side effects than other antimuscarinics due to extremely short circulation half-life)
5. Higher dose can be given safely;
same SE’s as antimuscarainics

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16
Q

Theophylline, theobromine, caffein:

A

Class: relatively weak bronchodilator
Mech: non-selective PDE inhibitors (PDE 3, 4, 5): Phosphodiesterase inhibition and enhanced signalling via increased cAMP and cGMP; relax bronchial smooth muscle to get bronchodilation; improve contractility and reverse fatigue of diaphragm in COPD patients; can restore CS sens at low dose!!! Get him a PR Contract
Thera: Reduce inflammation (suppress inflamm genes) and bronchospasm in moderate to severe asthma, night symptoms
SE’s: CNS stimulation or seizures, tachycardia/arrythmias, anorexia, nausea STAN; serum level doesn’t correlate with symptoms in chronic users of theophylline; drug interactions because it’s metabolized by ctyp450 system
Misc: Low therapeutic index! Metabolized by liver; cimetidine and quinoline increase blood levels

17
Q

Roflumilast:

A

Class: selective PDE4 inhibitor (methylxanthine)
Mech: anti-inflamm (prevents neutrophil migration by inhibiting PDE4 isoforms); improvement in lung function secondary to anti-inflamm more so than bronchodilation;
Thera: COPD
SE’s: same as other the methyxanthines

18
Q

Corticosteroids (Budesonide; Fluticasone propionate; beclomethasone):

A

Class: Corticosteroid - anti-inflammatory agent
Mech: Anti-inflammatory effects: inhibition of growth factor secretion, inhibition of arachidonic acid metabolites and platelet activation factor, inhibition of leukocyte accumulation, decreased vascular permeability, inhibition of neuropeptide-mediated responses, inhibition of mucous glycoprotein secretion Luis Vasquez can’t hit into the GAP No More
Thera: Cornerstone treatment of persistent asthma; beneficial combination with beta-2 agonist; limited role in COPD (restore steroid sens with low dose theophylline);
Important SE’s: Inhaled has thrush, hoarseness, dry cough, mild adrenal suppression (higher doses) CHAT; oral has mood-swings, increased appetite, and suppression of adrenocorticotropic hormone secretion (Cushing’s Syndrome) AMA
Misc: combine with beta 2 agonist (one helps with transcription of B2 receptor gene; other helps with translocation of glucocorticoid receptor from cytoplasm to nucleus)

19
Q

Ciclesonide (CS):

A

Class: Corticosteroid - anti-inflammatory agent
Mech: Same as other corticosteroids, but is a prodrug and only activated by airway esterase.
Thera: Cornerstone treatment of persistent asthma; beneficial comination with beta-2 agonist; limited role in COPD
Important SE’s: Less side effects than other corticosteroids (on site activation required);
3. less systemic absorption
4. less systemic side effects

20
Q

About how large should particles be for inhaled therapies?

A

1-5 micrometers;
solution or suspension: metered dose inhaler;
solid particles: dry powder inhaler;
latter, patient can control inhalation and it’s patient actuated, but requires faster inspiratory flow than MDI

21
Q

Leukotriene inhibitor: Montelukast (Singulair); Pranlukast (Azlaire); Zafirlukast (Accolate)

A 
Class: Leukotriene inhibitor
Mech: Leukotriene receptor antagonist
Thera: Add-on therapy in mild persistent asthma; aspirin-induced asthma; prophylaxis for exercise-induced bronchospasm
Important SE's: Well tolerated
Misc: Must monitor liver function test.
22
Q

Na cromoglycate and Nedocromil Na:

A

Class: Anti-inflammatory agent
Mech: Prevent mast cell degranulation and mediator release from mast cells
Thera: Prophylaxis for inhibiting both early and late phase reactions (maybe preventive treatment before exercise or exposure to known allergens); best results in mild and allergic asthma
Important SE’s: Minimal local side effect (cough & throat irritation)

23
Q

Omalizumab (Xolair)

A

Class: anti-IgE MAB
Mech: Blocks IgE function.
Thera: Poorly controlled severe asthma
Misc: Administered by subQ injection every 3 weeks

24
Q

To deal with intermittent asthma, what is step 1? What can you do for step 2?

A

1: short acting B2 agonist as needed

2. Can use low-dose ICS (by now persistent asthma)

25
Q

When do you use ICS for COPD?

A

Only as the risk increases to around C or D

26
Q

Treatment of exacerbation of asthma and COPD

A
  1. differences disappear b/w two with exacerbations
  2. systemic CS for short period (5-7 days)
  3. Short acting beta 2 agonist and short acting antiCh via nebulizer (albuterol or ipratropium)
  4. Antibiotics usually prescribed in COPD exacerbation
  5. No role of long acting beta agonist and long acting antiCh
27
Q

Zileuton (Zyflo)

A

Class: Leukotriene inhibitor
Mech: Inhibits 5-lipoxygenase and blocks leukotriene synthesis
Thera: Add-on therapy in mild persistent asthma; aspirin-induced asthma; prophylaxis for exercise-induced bronchospasm
Important SE’s: Liver toxicity

Pharm Unit 4 (13 decks)

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