Term
| What are the Tx strategies for asthma & COPD? |
|
Definition
| control the underlying condition & provide symptomatic relief |
|
|
Term
| Why are aerosol agents used whenever possible in the Tx of COPD & asthma? |
|
Definition
1) high concentration of drug in lungs with low systemic effects
2) PK parameters are based on lung function response
3) minimal drug interactions if delivered by inhalation vs systemic |
|
|
Term
| What are the main types of medical therapies used in the Tx of asthma & COPD? |
|
Definition
1) bronchodilators & anti-inflam. agents
2) quick relief & long acting |
|
|
Term
| What 7 drug classes are used in the Tx of asthma? |
|
Definition
2) corticosteroids
3) mast cell stabilizers
4) anticholinergics
5) methylxanthines
6) immunomodulators
7) leukotriene modifiers |
|
|
Term
| What 7 drug classes are used in the Tx of COPD? |
|
Definition
| 1) β agonists
2) corticosteroids
3) anticholinergics
4) methylxanthines
5) oxygen
6) α1antitrypsin
7) phosphodiesterase 4 inhibitors |
|
|
Term
| What are the 3 types of non-selective bronchodilators? |
|
Definition
| 1) α receptor stimulation
2) β1 receptor stimulation
3) β2 receptor stimulation |
|
|
Term
|
Definition
1) vasoconstriction
2) vasopressor
=> decongestion in the upper airways (nasal) |
|
|
Term
|
Definition
1) increased myocardial conductivity
2) increased HR
3) increased contractile force |
|
|
Term
|
Definition
1) relaxation of bronchial smooth muscle
2) inhibition of inflam. mediator release
3) stimulation of mucociliary clearance |
|
|
Term
| What receptors do epinephrine non-selectively stimulate? |
|
Definition
|
|
Term
| What receptors do ephedrine non-selectively stimulate? |
|
Definition
|
|
Term
| What receptors do isoproterenol non-selectively stimulate? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| CAD or HTN => can induce myocardial stress & MI |
|
|
Term
| When might a non-selective α, β agonist be used in the Tx of asthma or COPD? |
|
Definition
not in COPD
occassionally in severe asthma exacerbation |
|
|
Term
|
Definition
| bind β2 receptor => increased AC => increased CAMP => decreased bronchocontriction (smooth muscle relaxation) |
|
|
Term
| What are the 3 short acting (quick relief) β2 agonists used in Tx of asthma & COPD? |
|
Definition
1) albuterol
2) levalbuterol
3) pirbuterol
(βe Prepared for Al to Leave) |
|
|
Term
| Onset/duration
quick relief β2 agonists |
|
Definition
onset: 3-5 min
duration: 4-6 hr |
|
|
Term
|
Definition
tachycardia
tremor
hypokalemia |
|
|
Term
| How does albuterol exist? |
|
Definition
| as a racemic mixture b/w R & S enantiomers |
|
|
Term
| For albuterol, are both the R & the S enantiomers of the reacemic mixture equally as effective? |
|
Definition
no, the therapeutic activity lies primarily with the R enantiomer
(S enantiomer may have deleterious effects) |
|
|
Term
| How does levalbterol compare to albuterol? |
|
Definition
| levalbuterol is the isometric formulation & is as effective as the racemic formulation of albuterol, but only needs 1/2 dose to get comparable bronchodilation & sustemic SE |
|
|
Term
| What are the 5 ling-acting β2 agonists used in COPD & asthma? |
|
Definition
1) Salmeterol
2) Formoterol
3) Aformotrol
4) albuterol SR
5) Indacaterol
(βe somewhat ready [SR] For Al to Stay After Indicated) |
|
|
Term
|
Definition
onset: 30-45 min
duration: 12 hr |
|
|
Term
Onset/duration
formeterol & arformotrol |
|
Definition
onset: 5-15 min
duration: 12 hr |
|
|
Term
onset/duration
albuterol SR |
|
Definition
onset: 15 min
duration 8-12 hr |
|
|
Term
onset/duration
indacaterol |
|
Definition
onset: 15 min
duration: 24 hr |
|
|
Term
| What 2 long acting β2 agonists are also used in combination products? |
|
Definition
1) salmeterol
2) formoterol |
|
|
Term
| In 2011 indacaterol was approved for use in what disease? |
|
Definition
|
|
Term
| SE
long acting β2 agonists |
|
Definition
tachycardia
tremor
hypokalemia
prolinged QT (in OD) |
|
|
Term
| What makes the long-acting β2 agonists last longer than the short acting ones? |
|
Definition
|
|
Term
| Why does salmeterol have a longer time before onset than the other long-acting β2 agonists? |
|
Definition
|
|
Term
| Why does formoterol have a shorter onset than salmeterol? |
|
Definition
|
|
Term
| Is there a difference in efficacy of salmeterol & formoterol? |
|
Definition
|
|
Term
| Is there tachyphylaxis (tolerance) associated with chronic β2 agonist use? |
|
Definition
| conflicting data: probably, but only with certain polymorphisms of the receptor |
|
|
Term
| What is the black box warning on β2 agonists in asthmatic patients? |
|
Definition
1) don't use as a monotherapy
2) only use with patients who are not controlled on a low or medium dose corticosteroid
3) increased risk of asthma-related deaths |
|
|
Term
|
Definition
inhibit muscarinic cholinergic receptors & reduce vagal tone of the airway
may cause drying of pulmonary secretions
(on smooth muscle muscarinic receptors are responsible for sm. muscle contraction & inhibition of relaxation) |
|
|
Term
| What is the short acting anticholinergic used in COPD & asthma? |
|
Definition
ipratropium
(I PRAY i can breathe shortly) |
|
|
Term
onset/duration
ipratropium |
|
Definition
onset: 10-15 min
duration: 4-8 hr |
|
|
Term
|
Definition
dry mouth
blurred vision (if sprayed in eyes) |
|
|
Term
| Does ipratropium come in a combo product? |
|
Definition
|
|
Term
|
Definition
| allergy to soy lecithin or peanuts (contains ouls of lecitin) |
|
|
Term
| What is the long acting anticholinergic used in COPD & asthma? |
|
Definition
|
|
Term
|
Definition
onset: 30 min
duration: 24+ hrs |
|
|
Term
|
Definition
|
|
Term
| Is tiotropium part od a combo product? |
|
Definition
|
|
Term
| What receptors does tiotropium block? |
|
Definition
|
|
Term
| For which muscarinic receptors does tiotropium exert it's long lasting effects? |
|
Definition
| M1 & M3 (rapidly dissocaites from M2) |
|
|
Term
| What are the 3 antileukotriene agents used in asthma? |
|
Definition
1) Monteleukast
2) Zafirlukast
3) Zileuton |
|
|
Term
| What are the 2 leukotriene receptor antagonists used in asthma? |
|
Definition
1) Montelukast
2) Zafirlukast |
|
|
Term
|
Definition
| selectively & competetively inhibit Cys LT1 receptor |
|
|
Term
Onset/duration
montelukast |
|
Definition
onset: 3-4 hrs
duration: 24 hrs |
|
|
Term
Onset/duration
zafirlukast |
|
Definition
onset: 30 min
duration: 12 hrs |
|
|
Term
|
Definition
montelukast: none
zafirlukast: reversible hepatitis & rare irreversible hepatitis |
|
|
Term
| What is the 5-lipooxygenase inhibitor used in asthma? |
|
Definition
Zileuton
(when you have COPD, you have have Zilch LOX) |
|
|
Term
MOA
5-lipoxygenase inhibitor |
|
Definition
| inhibts production of LTs from arachidonic acid, LTB4 & cysteinyl LTs |
|
|
Term
|
Definition
onset: 30 min
duration: 12 hr |
|
|
Term
|
Definition
| elevated LFTs & reversible hepatitis |
|
|
Term
| What is the effect of antileukotriene agents? |
|
Definition
decreased allergy
decreased bronchocontriction
decreased mucus production |
|
|
Term
| When are antileukotriene agents used in the asthma regimen? |
|
Definition
| chronic ONLY since maximal efficacy develops progressively & may take several days |
|
|
Term
| How often in monteleukast dosed? |
|
Definition
|
|
Term
| Is monteleukast indicated in children? |
|
Definition
|
|
Term
| How often is zafirlukast dosed? |
|
Definition
|
|
Term
| When during the day should zafirlukast be taken in order to obtain maximum benefit? |
|
Definition
| 1 hr before or 2 hours after meal |
|
|
Term
| Is zafirlukast indicated in children? |
|
Definition
|
|
Term
| When is dose reduction of zafirlukast needed? |
|
Definition
| with hepatic insufficency since metabolized extensively in the liver |
|
|
Term
| Which liver enzymes metabolize zafirlukast? |
|
Definition
|
|
Term
| How often is zileuton dosed? |
|
Definition
| 2 times daily (a lot higher dose than zafirlukast) & w/o regard to meals |
|
|
Term
| Is zileuton indicated in children? |
|
Definition
|
|
Term
| What tests must be done prior to zileuton administration? |
|
Definition
|
|
Term
| Is zileuton bound to proteins? |
|
Definition
|
|
Term
| How is zileuton metabolized? |
|
Definition
hepatic metabolism
phase I: CYP1A2, CYP2C9, CYP3A4
phase II: glucuronidation |
|
|
Term
|
Definition
mutliple sites of action:
1) inhibits leukocyte recruitment to airways
2) induce anti-inflam. protein lipocortin
3) decrease inflam. by stabilization of lysosomes & PMNs
4) upregulation of anti-inflam. genes
5) decrease stability of selected mRNAs => altered gene transcription after interaction with glucocorticoid receptor |
|
|
Term
|
Definition
1) inhibits phospholipase A2
2) decreased production of PGs & LTs |
|
|
Term
Effect
stabilization of lysosomes & neutrophils |
|
Definition
| prevents degranulation & resulting inflam. response |
|
|
Term
| What are the 6 inhaled corticosteroids used in COPD & asthma? |
|
Definition
1) Beclomethasone
2) Triamcinolone
3) Budnesonide
4) Mometasone
5) Flunisolide
6) Fluticasone |
|
|
Term
SE
inhaled corticosteroids |
|
Definition
1) cough
2) dyspnea
3) oral thrush
4) high doses: postential for adrenal suppression, osteoporosis, skin thinning
5) low/med dose: decrease growth velosity in children (may be transient) |
|
|
Term
| Which 3 inhaled corticosteroids come in a combo product? |
|
Definition
1) budesonide
2) fluticasone
3) mometasone |
|
|
Term
Onset/duration
inhaled corticosteroids |
|
Definition
onset: variable, but can day from days to 2 weeks
duration: asthma stability usually persists for several days after discontinuation |
|
|
Term
| Is there any difference b/w efficacy & SE profile of inhaled corticosteroids? |
|
Definition
|
|
Term
| What is the difference b/w the different inhaled corticosteroids? |
|
Definition
| amount of drug aerosolized per inhaler activation ∴ the # of puffs per day per dose is different per drug |
|
|
Term
| How many puffs would a patient need for high dose trimcinolone? |
|
Definition
|
|
Term
| How many puffs would a patient need for high dose fluticasone? |
|
Definition
|
|
Term
| What are the 3 oral corticosteroids used in asthma & COPD? |
|
Definition
1) methylprednisolone
2) prednisolone
3) prednisone |
|
|
Term
| What is prednisone activated to in vivo? |
|
Definition
|
|
Term
SE
short term PO corticosteroids |
|
Definition
1) reversible abnormality in glucose metabolism
2) increaed appetite
3) fluid retention
4) wt. gain
5) mood alteration
6) HTN
7) peptic ulcer
8) rare: aseptic necrosis |
|
|
Term
SE
long term PO corticosteroids |
|
Definition
1) immune suppression
2) osteoporosis
3) HTN
4) Cushing's disease
5) growth suppression
6) cataracts
7) adrenal suppression |
|
|
Term
| What are the 3 methylxanthines used in COPD & asthma? |
|
Definition
1) theobromine
2) theophylline
3) caffiene
4) aminophylline
(Theo & Amy eXit the Cafe) |
|
|
Term
|
Definition
1) non-selective inhibtion of phosphodiesterase => increase in cAMP => smooth muscle relaxtion
2) direct & indirect effect on intracellular calcium
3) mild anti-inflam. activity |
|
|
Term
Onset/duration
theophylline & aminophylline |
|
Definition
onset: 1 hr
duration: variable |
|
|
Term
SE
theophylline & aminophylline
usual dose |
|
Definition
1) insomnia
2) GERD
3) GI upset
4) hyperactivity in children
5) difficulty urinating if BPH |
|
|
Term
SE
throphylline & aminophylline
dose related toxicity |
|
Definition
1) tachycardia
2) N/V
3) SVT
4) CNS stimulation
5) seizures
6) hyperglycemia
7) hypokalemia |
|
|
Term
| How is 90% of methylxanthines metabolized? |
|
Definition
liver
CYPA2, CYP2E1, CYP3A3 |
|
|
Term
| Why must theophylline be monitored closely? |
|
Definition
|
|
Term
What is the goal level of theophylline?
What is the toxic level of theophylline? |
|
Definition
goal: 5-15 mcg/mL
toxic: >20 mcg/mL |
|
|
Term
| How equivalent is aminophylline to theophylline? |
|
Definition
| 0.8 of eqipotent throphylline dose |
|
|
Term
| What should be taken into consideration of each patient prior to a theophylline regimen? |
|
Definition
| caffeine ingestion & smoking status |
|
|
Term
|
Definition
anti-inflam agent & mast cell stablizer:
blocks release of mediators of hypersensitivity rxns from mast cells, eosinophils, neutrophils, macs, monocytes, histamine, & platelets |
|
|
Term
| Do mast cell stablizers exert any bronchodilating, antihistaminic or corticosteroid effects? |
|
Definition
|
|
Term
| What drug is a mast cell stabilizer used in asthma? |
|
Definition
|
|
Term
|
Definition
onset: 1+ weeks for max benefit (∴ not for an acute attack)
duration: 3-4 weeks after multiple doses |
|
|
Term
|
Definition
1) cough
2) irritation
3) bad taste |
|
|
Term
|
Definition
1) inhibt binding of IgE to high-affinity IgE receptor on surface of mast cells & basophils
2) reduction of surface-bound IgE => limits degree of release of mediators of allergic response |
|
|
Term
| What immunomodulator is used in asthma? |
|
Definition
| omalizumab (monoclonal Ab) |
|
|
Term
| What additional MOA does omalizumab have? |
|
Definition
| reduce number of high-affinity IgE receptors on basophils in atopic patients |
|
|
Term
|
Definition
onset: 1-2 hr (steady state in 2 weeks)
duration: 2-4 weeks |
|
|
Term
|
Definition
1) pain/brusing @ injection site
2) anaphylaxis in 0.2% of patients
3) malignant neoplasms in .5% of patients (vs. 0.2% on placebo) |
|
|
Term
|
Definition
| replacement therapy with α1Pl plasma protein & the principal inhibitor of neutrophil elastase => adequate antineutrophil elastase activity & protection in the lungs of individuals with α1antitrypsin deficiency |
|
|
Term
| What α1antitrypsin drug is used in patients with COPD? |
|
Definition
|
|
Term
| Onset/duration
α1 proteinase inhibitor |
|
Definition
onset: 1-2 hr
duration 2-4 weeks |
|
|
Term
| SE
α1 proteinase inhibitor |
|
Definition
1) increased LFTs
2) headache
3) somnolence |
|
|
Term
MOA
phosphodiesterase 4 inhibitor |
|
Definition
| selective inhibitor of phosphodiesterase 4 (PDE4) => accumulation of cAMP within inflam. & structural cells in the pathogenesis of COPD |
|
|
Term
| What anti-inflam. effects are seen with a PDE1 inhibitor? |
|
Definition
1) suppression of cytokine release
2) inhibitor of lung infiltration by neutrophils & other leukocytes
(also pulmonary remodeling & mucociliary malfunction becomes better) |
|
|
Term
| What PDE4 inhibitor is used in COPD? |
|
Definition
roflumilast
(Peepee makes you ROFL) |
|
|
Term
Onset/duration
roflumilast |
|
Definition
onset: 1 hr
duration: 17-30 hrs |
|
|
Term
|
Definition
1) diarrhea
2) wt. loss
3) insomnia
4) anxiety
5) depression |
|
|
Term
| What are the 4 drug names of the combinations used for Tx in asthma/COPD? |
|
Definition
1) combivent
2) advair
3) symbicort
4) dulera
(Combos Are Super Duper) |
|
|
Term
| What combo drugs are used in both COPD & asthma? |
|
Definition
|
|
Term
What combo drug is ONLY used in COPD?
asthma? |
|
Definition
COPD: combivent
asthma: dulera |
|
|
Term
| What is the only combo drug used for quick relief (∴ the rest are used for control)? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Which of the following is the MOA for cromolyn?
A) blocks the release of mediators of hypersensitivity rxns from mast cells, eosinophils, neutrophils, macs, monocytes, histamine, & platelets
B) non-selective inhibition of PDE4 => increase cAMP => smooth muscle relaxtion
C) agonism of the beta receptors => increased AC => increased cAMP => smooth muscle relaxtion
D) inhibits binding of IgE to high affinity IgE receptor on the surface of mast cells & basophils, limiting the degree of release of mediators of allergic response |
|
Definition
|
|
Term
Which of the following dsease state interactions would NOT be responsible for increasing theophylline levels, potentially causing toxicity?
A) decompensated CHF
B) ciprofloxacin
C) rifampin
D) cimetidine |
|
Definition
|
|
