Respiratory Agents Flashcards
1
Q
How do the SNS and PNS affect the pulmonary system?
A
- SNS:
- B2 adrenoceptors cause relaxation/dilation of smooth muscles in blood vessels, bronchi, the uterus, bladder, and other organs
- done by increasing cAMP
- PNS
- stimulation of the vagus nerve leads to bronchoconstriction and increase in mucus secretion
- M3 receptors are most important pharmacologically
- found on bronchial smooth muscle
- mediate bronchoconstriction by activating IP3 which increases intracellular Ca
- mediates mucus secretion
2
Q
How do non adrenergic, non cholinergic nerves affect the pulmonary system?
A
- relax airway smooth muscle by releasing NO and vasoactive intestinal peptide (VIP)
3
Q
What different parts of the asthma disease process do the drugs effect? (flow chart)
B2 agonists
glucocorticoids
A
- B2- reverse the bronchospasm caused by the histamines and prostaglandins released
- glucocorticoids- inhibit the chronic airway inflammation and hyperactivity
- **It is important to address both the inflammation and bronchoconstrictive aspects of the disease
4
Q
What are the advantages of inhalation drug therapy?
What are the different delivery methods (3)?
A
- Advantages:
- high local concentration of the drug in the bronchial tree, where it is needed
- enhanced pulmonary effects
- minimized systemic effects
- drug onset is rapid, useful for acute attacks
- high local concentration of the drug in the bronchial tree, where it is needed
- delivery methods:
- MDI- only 10% makes it into lungs
- dry powder inhalers (DPIs)
- Nebulizers
5
Q
What are the anti-inflammatory drugs used to treat asthma?
how often are they taken?
which one is most effective?
A
- Taken daily for long-term control
- inhaled corticosteroids (glucocorticoids)
- most effective preventative treatment for asthma
- Cromolyns
- leukotriene inhibitors
- Anti- IgE antibodies
- inhaled corticosteroids (glucocorticoids)
6
Q
Glucocorticoids
MOA?
target?
what effect does it have?
A
- MOA- suppress inflammation by altering genetic transcription
- target: glucocorticoid receptor alpha in cytoplasm of airway epithelial cells
- increases transcriptions of genes for B2 receptors and responsiveness
- increases trans of genes for anti-inflammatory proteins
- decreases trans of genes for pro-inflammatory proteins
- induces apoptosis in inflammatory cells (eosinophils, TH2, lymphocytes)
- indirect inhibition of mast cells over time
- reverses bronchial hyperreactivity
- used as suppressive therapy, does not change the progression of the disease NOT A CURE
7
Q
What are the different corticosteroids that may be used to help with asthma?
inhaled
IV
PO
A
- Inhaled:
- Budesonide (MDI, neb, or DPI)
- Beclomethasone
- Triamcinolone
- Fluticasone
- IV (status asthmaticus)
- Hydrocortisone
- Methylprednisolone
- PO (acute exacerbation, but limit time course)
- Prednisone
- Prednisolone
- *These patients may need stress dose steroids, but NOT if the steroids they use are inhaled
8
Q
How much of any MDI reaches the airway?
A
10-20%
9
Q
What are some side effects of inhaled corticosteroids?
A
- Adrenal suppression (mild compared with IV/PO routes)
- oropharyngeal candidiasis
- Hoarseness
- Delayed growth in children
- Osteopenia/osteoporosis
- encourage vit D, Ca, and weight bearing exercise
10
Q
What are side effects of IV/PO systemic corticosteroids?
A
- Minor when taken acutely (<10 days), can be severe if used long-term
- myopathy/weakness
- adrenal suppression (taper, do not stop suddenly)
- increased infection risk
- suppression of growth and development
- PUD- increased risk with NSAIDS
- weight gain, edema, hypokalemia
- hyperglycemia- may need to increase insulin dose in DM
11
Q
Cromolyn
MOA?
Principle use?
administration?
A
- MOA: Stabilizes pulmonary mast cells
- inhibits antigen-induced release of histamine and the release of inflammatory mediators from eosinophils, neutrophils, monocytes, etc…
- inhibits immediate allergic response to an antigen but not the allergic response once it has been activated
- Principle use: Prophylactic therapy of bronchial asthma
- can help prevent exercise induced bronchospasm
- does not releive an allergic response after initiation- not a rescue inhaler
- Administration via inhalation- 8-10% enters systemic circulation, poor oral absorption
- taken 4 times daily
12
Q
What are the SE of Cromolyn?
Route?
A
- Side effects are rare and it is the safest of all anti-asthma medications
- cough and/or bronchospasm
- Laryngeal edema
- angioedema
- urticaria
- anaphylaxis
- route: Inhaled
- MDI or neb
13
Q
What are Leukotrienes?
A
- Leukotrienes are made from Arachidonic Acid (AA) when inflammatory cells are activated
- C4, D4, and E4 promote bronchoconstriction, eosinophil infiltration, mucus production, and airway edema
- Inhibitors reduce these effects
14
Q
What are the Leukotriene inhibitors?
How effective are they?
A
- Zileuton (Zyflo)
- Zafirlukast (Accolate)
- Montelukast (Singulair)
- efficacy:
- Less effective than inhaled glucocorticoids
- not effective in treatement of acute attacks
15
Q
Zileuton
MOA?
pharmacokinetics?
What do you have to monitor?
SE?
A
- MOA- lipoxygenase inhibitor which blocks the biosynthesis of leukotrienes from AA
- produces bronchodilation, improves asthma symptoms, shows long-term improvement in PFT
- Pharmacokinetics:
- low bioavailability, low potency
- Hepatotoxic- monitor LFTs once/month early in tx
- SE:
- neuropsychiatric issues- depression, anxiety, agitation, hallucinations, suicidal thinking and behavior
- CYP450 interactions
16
Q
Montelukast (Singulair)
MOA?
Uses?
effects?
PB?
Metab?
A
- MOA- Leukotriene receptor antagonist that blocks the mechanism of bronchoconstriction and smooth muscle effects
- prevents leukotrienes from binding to leukotriene-1 receptor
- Uses
- used to treat asthma in pts <1 year
- prevents exercise induced bronchospasm >15 years old
- treats allergic rhinitis
- Effects:
- improve bronchial tone, pulmonary function, and asthma symptoms
- SE similar to placebo
- 99% PB
- Undergoes extensive metabolism by CYP450
- minimal drug interactions
17
Q
Omalizumab
Class?
target/MOA?
When is it used?
A
- Anti-IgE antibody- Humanized mouse monoclonal antibody
- Target: Prominence of IgE mediated allergenic responses in asthma
- binds to IgE in the blood inactivating it (IgE levels decrease for a year)
- decreased amt of circulating IgE prevents binding of IgE to mast cells
- Down regulation of receptors d/t less circulating IgE
- Only administered to pts who fail all other treatments because there are SO many SEs
18
Q
Omalizumab
Cost?
SE?
A
- $10,000 per year
- SQ, pt must be monitored at hospital, can’t be given at home
- 1/2 life of 26 days
- SE:
- injection site reactions
- viral infection
- URI and sinusitis
- pharyngitis
- H/A
- CV complications- get an EKG
- possible increased risk of cancer
- May trigger anaphylaxis
- monitor for 2 hours after 1st 3 doses
- monitor for 30 minutes after all later doses
19
Q
How do bronchodilators treat asthma?
What are the bronchodilators used?
A
- Provide symptomatic relief but do not alter the underlying disease process (inflammation)
- usually a pt requiring a bronchodilator will also be on glucocorticoid treatment for inflammation
- Bronchodilators:
- beta- adrenergic agonists (most effective in asthma)
- anticholinergics
- methylxanthines
20
Q
Beta Adrenergic receptors:
MOA?
What is the primary effect?
A
- Beta adrenergic receptors are coupled to G-proteins
- they activate adenlyl cyclase which increases the production of cAMP, causing bronchodilation
- Decreases intracellular Calcium and increases membrane K conductance
- Primary effect: dilate the bronchi by a direct action on the B2 adrenoreceptors
- results in smooth muscle relaxation and bronchodilation
- inhibits mediator release from mast cells
- increases mucous action of cilia
21
Q
What are the Beta adrenergic agonists selective to?
What are the short acting agents?
What are the long acting agents?
A
- Selective to B2
- 200-400x more strongly than to B1
- Short acting
- albuterol
- levalbuterol- even less B1 binding, but more expensive
- Long acting
- Salmeterol
- terbutaline- IV/PO
22
Q
Beta adrenergic agonists
onset
use
administration route
A
- Onset 15-30 minutes
- Good for use as a rescue inhaler
- administered via:
- inhalation or aerosol
- powder or nebulized
- orally or injected (SC)
- Short or long acting
23
Q
What are the side effects of Beta adrenergic agonists?
A
- *SE are minimized by inhalation delivery
- tremor
- increased HR
- vasodilation
- metabolic changes
- hyperglycemia
- hypokalemia (increased K conductance into cell)
- hypomagnesemia
- With high doses of oral drugs:
- angina, tachydysrhythmias
24
Q
What is the preferred Beta adrenergic agonist?
How is it administered?
doses?
DOA?
A
- Albuterol
- administered via MDI
- 2 puffs, q 4-6 hrs
- 100 mcg/puff
- Nebulizer 2.5-5.0 mg in 5 ml of saline
- DOA_ 4-8 hours
25
Q
What are the other Beta adrenergic (Beta2 selective) agonists used to treat asthma?
A
- Metaproterenol-Alupent
- beta2 agonist
- MDI
- not to exceed 16 puffs/day
- longer lasting than albuterol
- Bitolterol
- longer asting
- CV side effects are rare
- Daily metered dose is 16-20 puffs/day
- each dose is 270 mcg
26
Q
Terbutaline
class
use
administration/dose
A
- Beta 2 selective adrenergic agonist
- Used to treat asthma
- administration:
- SC peds: 0.01 mg/kg; adult: 0.25 mg q 15 min
- MDI 16-20 puffs/day- 200 mcg/puff
27
Q
Salmeterol or Formoterol
Class?
what makes it last longer?
DOA?
What is it used for?
Warning?
A
- Long acting B-agonist
- Has a lipophillic side chain that resists degradation and binds to receptor tightly
- DOA is 12-24 hours
- Good for prevention NOT acute flare
- BLACK BOX WARNING: may increase risk of fatal asthma attack
- should always be given with a steroid as well
28
Q
What are the long acting beta agonist/steroid combo drugs?
Indications?
Warnings?
A
- Available combination drugs:
- Fluticasone/Salmeterol (advair)
- Budesonide/Formoterol (symbicort)
- Indicated for long-term maintenance in adults and children
- convenient, but limited flexibility with dose
- reduces symptoms, reduces the risk of exacerbation, and helps reduce steroid dose
- Not recommended for initial treatments- many pts only need a glucocorticoid
- BLACK BOX WARNING: increased risk of asthma related death
29
Q
Methylxanthines
class?
MOA?
Effect?
Clinical applications?
Examples?
A
- Class: phosphodiesterase inhibitors
- MOA: unclear; possible inhibition of phosphodiesterase isoenzymes (Type III and IV) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells
- possible adenosine receptor blockade at A1 and A2 receptors
- may also have anti-inflammatory effect
- Drug effect: airway relaxation and bronchodilation
- Clinical applications:
- COPD
- asthma
- Theophylline (prototype), Aminophylline
30
Q
What are the problems with Methylxanthines?
metabolization?
A
- Multiple side effects and a narrow therapeutic index
- TI plasma level of 10-20 mg/ml
- Toxic >20 mg/ml
- wide 1/2 life variation; smokers metabolize 50% faster
- Susceptible to drug-drug interactions (CYP450)
- Cimetidine, Cipro, and antifungals (CYP450 inhibitors) increase plasma levels
- phenobarb and phytoin can decrease levels
- Caffeine is also a methylxanthine and can increase levels and promote CNS and CV toxicity
- Metabolized in liver and excreted in kidney
- Sustained release only
31
Q
What are the SE of methylxanthines?
A
- Almost always at toxic levels
- Cardiac arrhythmias
- N/V
- irritability
- insomnia
- sz
- brain damage
- hyperglycemia
- hypokalemia
- hypotension
- death from CV collapse
32
Q
Anticholinergic bronchodilators
MOA?
Uses?
A
- MOA: competative antagonists at muscarinic acetylcholine receptors
- promote smooth muscle relaxation and decreased mucus gland secretion by antagonizing endogenous Ach
- M3 is most important
- Uses
- treatment of COPD
- second line treatment of asthma
33
Q
Atropine
Class?
dose?
A
- Naturally occurring alkaloid
- formally considered 1st line treatment for asthma
- 1-2 mg diluted in 3-5 ml of saline via nebulizer
- Highly absorbed across respiratory epithelium, causing systemic anticholinergic effects
- tachycardia, nausea, dry mouth, GI upset
- Highly absorbed across respiratory epithelium, causing systemic anticholinergic effects
34
Q
Ipratroprium bromide (atrovent)
structure?
MOA?
dose?
onset?
DOA?
A
- Quanternary ammonium salt derivative of atropine
- does not easily absorb across pulmonary epithelium compared to atropine
- MOA: antagonizes the effect of endogenous acetylcholine at M3 receptor subtypes
- MDI 40-80 mcg in 2-4 puffs
- Onset: 30-90 minutes
- DOA: 4-6 hours
35
Q
Tiotropium
structure?
class?
use?
A
- Quaternary ammonium salt
- Long acting anticholinergic
- Not significantly absorbed across the resp. epithelium
- FDA approved for COPD
36
Q
How is initial treatment of asthma determined?
Goals of asthma treatment?
How can this be achieved chronically?
A
- Stepwise therapy
- step chosen for initial therapy is based on pre-treatment classification of asthma severity
- moving up or down a step is based on ongoing assessment of asthma control
- Goals: to reduce impairment and risk
- reduce exposure to allergens and triggers (dust mites, pets, mold, cockroaches)
- other factors: tobacco smoke, wood smoke, household sprays
37
Q
What should you do for acute exacerbation in the OR?
A
- This requires immediate attention
- Goal is to relieve airway obstruction and hypoxemia and normalize lung function as quickly as possible
- initial therapy:
- oxygen
- systemic glucocorticoid to reduce inflammation
- nebulized high dose SABA
- nebulized ipratroprium
- Try ketamine before epi
38
Q
Are steroids very helpful in COPD?
A
- Not really, sometimes a trial will be done, but they arent usually very useful
- Bronchodilators might work better, but only show modest improvement
39
Q
What drugs are usually used to treat COPD?
A
- Usually started on one agent and then will add another if one is not enough
- Long acting inhaled beta 2 agonist (salmeterol)
- long acting anticholinergic (tiotropium)
- Inhaled glucocorticoid (budesonide) is last choice
- If using two agents, usually LABA and steroid
40
Q
What is the new drug used to treat COPD?
MOA?
SE?
A
- Roflumilast (Daliresp)- a selective phosphodiesterase type 4 inhibitor that appears to reduce exacerbations
- MOA: increases cAMP levels resulting in reduced cough, inflammation, and mucus
- SE: diarrhea, weight loss, loss of appetite, nausea, HA, back pain, depression
