Respiratory Flashcards
Where a.w smooth muscle extends to
Terminal bronchioles
SNS action and activation of which receptor
B2 adrenoreceptors mediate relaxation of smooth muscles in vessels, bronchi, uterus, bladder, and other organs. Activation= bronchodilation, increased cAMP
Non adrenergic, non cholinergic nerves
Do what to a/w
Relax smooth muscle by releasing NO and VIP
PSNS
Action
Receptors
Pathway
Stim vagus leads to bronchoconstriction. M3 receptors are pharmacologically most imp. In bronchial muscle, mediate constriction by activ of IP3 which increases intracellular Ca. Mediates mucus secretion
ANS impact on resp system through 2 things
Adrenergic B2: bronchial smooth muscle relaxation, bronchodilation
Cholinergic: smooth muscl contraction, increased gland secretion- constriction and inc mucus
Asthma results in what
S/s
Variable airflow obstruction that’s reversible.
Breathlessness, tight chest, wheeze, dyspnea, cough
What you’re addressing w drugs in asthma
2 main classes
Inflammation and bronchoconstriction
- Anti-inflammatories- steroids, prednisone
- Bronchodilators- B2 agonists, albuterol
Which drugs taken for asthma daily for long term control
Anti inflammatories Inhaled corticosteroids Cromolyns Leukotriene inhibitors Anti IgE antibodies
Most important preventative tx for asthma
Glucocorticoids
Glucocorticoids
MOA
Suppress inflammation by altering genetic transcription
Glucocorticoids
Target
Glucocorticoids receptor alpha in cytoplasm of a/w epithelial cells.
Glucocorticoid transcription effects: 3
Inc transcription of genes for: B2 receptors/responsiveness, anti-inflammatory proteins
Decreases transcription of genes for pro inflammatory proteins: decreases mucus production and edema
Glucocorticoids
3 other effects than transcription
Induces apoptosis in inflammatory cells (eosinophils, th2, lymphocytes)
Indirect inhibition of mast cells over time
Reverses bronchial hyperreactivity
Glucocorticoids
Use, what it doesnt do
Usual route
Suppressive therapy, not a cure
Inhalation. (IV and oral also available)
Inhaled corticosteroids
Use
Long term prophylaxis in mod to severe asthma
Inhaled steroids
Which nebulized for who
Budesonide, kids too young to use MDI or DPI
Inhaled steroids
4
Budesonide
Beclomethasone
Triamcinolone
Fluticasone
IV steroids, use in asthma, 2
Hydrocortisone and methylprednisone, status asthmaticus
Corticosteroids
PO- for what, 2 ex
Acute exac, chronic severe asthma.
Prednisone and prednisolone
Inhaled corticosteroid
How much reaches airway, what increases concentration in lung
Conc in lung compared to PO
Adrenal suppression compared to PO/iv
10-20%, beta 2 agonist before inhalation
Higher
Mild
Inhaled corticosteroid
Side effects
Candidiasis
Hoarseness
Delayed growth kids
Osteopenia/porosis
Systemic corticosteroids AE
When minor
Long term effects
<10 days
Weakness, adrenal suppression, infection risk, growth suppression, PUD, wt gain, edema, hypokalemia, hyperglycemia
Systemic corticosteroids
Give extra when or what
IV or PO during physiologic stress (surgery, trauma, infection) or pt could die
Cromolyn
MOA
Stabilizes pulmonary mast cells. Inhibits antigen induced release of histamine, inflammatory mediators from: eos, neutro, mono, mac, lymph, Leuko. Inhib allergic response to antigen but not once its activated
Cromolyn
Principle use
Bronchial asthma prophylaxis, prevents exercise induced bronchospasm. Not a rescue inhaler.
Cromolyn
Route
How much goes systemic
Take how often
Inhalation
8-10%
4 times daily
Cromolyn
SE
Comparison to other asthma meds
Route
Cough, bronchospasm, laryngeal edema, angioedema, urticaria, anaphylaxis
Safest of them all, SE rare
Neb or MDI
Leukotriene modifiers
How leukotrienes are synthesized, which we’re concerned about and why
From Arachidonic acid when inflammatory cells are activated. C4, D4, E4. Promote bronchoconstriction, eosinophils, mucus, and airway edema
Leukotriene modifiers
Comparison to glucocorticoids
Not effective for
Few what
Less effective
Acute attacks
Extrapulmonary effects
Leukotriene modifiers
3 ex
Zyflo (zileuton)
Accolate (zafirlukast)
Montelukast/singular
Zileuton
Class
Action
Uses
Leukotriene inhib.
Lipoxygenase inhib, blocks leukotriene synth from arachidonic acid
Bronchodilation, for asthma, long term improvement PFT
Zileuton
Metab
AE
Low bioavailability and low potency Hepatotoxic- monitor LFT early Neuro: depression, anxiety, halluc, suicidal thinking Interacts w CYP450 Not widely used
Montelukast
Action
Blocks bronchoconstriction and smooth muscle effects. Blocks binding to leukotriene 1 receptor. Improves bronchial tone, pulm function, and asthma symptoms
Montelukast
Use in who
Asthma in <1 y/o, exercised induced bronchospasm >15 y/o, allergic rhinitis
Montelukast Adverse effects Max effect when Metab What inc drug level
Placebo, rare psych effects
24 hrs after 1st dose
99% protein bound, by cyp 450, minimal interactions
Phenytoin
Omalizumab
Class
Target
Anti IgE antibodies. Mouse monoclonal antibody.
IgE mediated allergic responses in asthma
Omalizumab
Action
Binds to IgE and inactivates it. Decreases overall amt, prevents IgE binding to mast cells. Down regulates receptors on mast/baso/dendritic cells. Reduces stim T2 lymph.
Omalizumab Downside Route Taken when 1/2 life
10k per year
Sq
Allergy induced asthma not tx by glucocorticoids
26 days
Omalizumab
SE
Injection site rxn, viral infec, URI, sinusitis, HA, pharyngitis, CV (inc MI and CVA, HF, dysrhythmias, thromboembolism risk), possible inc risk cancer
Omalizumab
Rare AE
Triggers anaphylaxis. Monitor 2 hrs after first three doses, then 30 min after all subsequent doses
Bronchodilators
How they work
Symptomatic relief, dont tx underlying cause of inflammation.
Should also take glucocorticoids
Bronchodilators
3 types
Beta adrenergic agonists
Anticholinergics
Methylxanthines
B adrenergic agonists
MOA
B adrenergic receptors coupled to stim G proteins. Activate adenylyl cyclase which inc cAMP, then bronchodil. Dec Ca inc K. Dilates bronchi, smooth muscle relax, inhib mast cell and inc mucus clearance
B adrenergic agonists
Most effective drugs for
Acute bronchospasm and prevention of exercise induced bronchospasm. Quick relief and long term control
B adrenergic agonists
Receptor selectivity
Short v long acting types
B2 200-400x more than b1
Short: albuterol, levalbuterol
Long: salmetrol, terbutaline (po or iv)
B adrenergic agonists
Onset
Routes
15-30 min. Short or long acting
Inhalation, aerosol
Powder, neb
Orally or sc
B adrenergic agonists
SE
Minimized by inhalation route. Tremor, inc HR, vasodilation, hyperglycemia, hypokalemia, hypomagnesemia
B adrenergic agonists
Oral preps excessive dose leads to
Angina and tacky dysrhythmias
Albuterol
Doses
MDI: 100 mcg/puff. 2 puffs q4-6 h
Neb: 2.5-5 mg in 5 ml saline
Albuterol
Duration
Isomers
4 hrs, up to 8 hrs.
R albuterol levalbuterol, more affinity B2.
S albuterol, more affinity b1.
Metaproterenol
Indic
Route
Max dose
Beta 2 agonist for asthma. MDI
16 puffs a day
Bitolterol Class Duration AE Dose
Selective B2 lasts longer than albuterol
Rare cv effects
Metered dose 16-20 puffs a day. Each dose 270 mcgs
Terbutaline
Class
Routes
Indic
B adrenergic agonist
Oral, sc, inhalation
Treats asthma
Terbutaline Sc admin resembles Sc dose peds Sc dose adults Medi dose and amt
Epi response 0.1 mg/kg 0.25 mg q15 min 16-20 puffs/day Each dose 200 mcgs
Salmetrol Class Other drug like it Duration For what Warning
Formoterol. Long acting b agonist
12-24 h, lipophilic side chains
Prevention not flare up
May inc risk of fatal asthma attack
Methylxanthines
Class
MOA
Bronchodilators, phosphodiesterase inhib
Unclear. May inhib pdi isoenxymes and prevent camp degred in airway. Anti inflammatory. Possible adenosine receptor block
Methylxanthines
Drug effect
Clinical applic
Types
Airway relaxation and bronchodilation
COPD and asthma
Theophylline and aminophylline
Methylxanthines Theophylline Downside Therap plasma level When toxic 1/2 life
Mult SE and narrow therapeutic index
10-20 mg/ml
>20 mg/ml
Wide variation, esp smokers who metab faster
Methylxanthines
Drug interactions
Cimetidine, cipro, and antifungals inc levels (cp450 inhib)
Phenobarbital and phenytoin decrease levels
Caffeine can inc levels and be toxic to cns and cv
Methylxanthines
Metab and excretion
Only in what form
Liver, kidney
Sustained release only
Methylxanthines
SE
Cv arrhythmias
NV
Irritable, insomnia, seizures, brain damage, hyperglycemia, hypokalemia, hypotension,death from cv collapse
Muscarinic receptor antagonists
MOA
Competitive antagonists at muscarinic acetylcholine receptors.
Promotes smooth musc relax and decreased mucus secretion
Muscarinic receptor antag
Which subtype most imp
Uses
Muscarinic 3
Tx COPD, secondary line of tx for asthma in pts resistant to beta agonist or significant cv disease
What m3 receptors do when stimulated
Drop inflammatory mediators
Atropine
What it is
Indic
Dose
Naturally occurring alkaloid
Used to be 1st line for asthma
1-2 mg diluted in 3-5 ml saline via neb
Atropine
Absorption
SE
Highly abs across respiratory epithelium
Systemic anticholinergic fx: tachycardia, nausea, dry mouth, gi upset
Ipratropium bromide
What it is
What it does
Quaternary ammonium salt, deriv of atropine. Anticholinergic
Antagonists effect of ach at M3
Ipratropium Dose Onset Duration Absorption
40-80mcg MDI or in 2-4 puffs via neb
30-90 min
4-6 hours
Not absorbed as well as atropine. Inadvertent oral abs can lead to gi upset and dry mouth
Tiotropium What it is Class Absorption Approved for
Quaternary ammonium salt
Long acting anticholinergic
Not abs sig in resp epithelium, less SE
FDA approved for COPD
Glucocorticoid/LAB2A combos
2 types
Indic for
Fluticason and salmetrol (advair)
Budesonide and formoterol (symbicort)
Long term maintenance in adults and kids. Reduces symptoms
Glucocorticoid and LAB2A combos
Not for
Black box warning
Initial therapy. Many pts controlled on inhaled glucocorticoid
Asthma related death inc risk
Lab2a stands for what
Long acting beta 2 agonist
Asthma
Source of allergens
What can exac it
Dust mites, pets, cockroaches, mold
Tobacco Smoke, wood smoke, household sprays
Drugs for severe asthma exac
Give o2 (hypoxia), Systemic glucocorticoid (inflam), neb high dose Saba (obstruc), neb ipratropium (obs)
COPD
What drugs have ltd effect
What reduces exac freq
What modestly improves air outflow
Steroids
Inhaled corticosteroids
Bronchodilators- for pts w breathlessness worsened by exertion
COPD
Monotherapy started which of 3
Long acting beta 2 (salmetrol)
Long acting anticholinergic (tiotropium)
Inhaled glucocorticoid (budesonide)
One of the 3. Bud- last choice
COPD
If monotherapy doesnt work then what
Add a second class of drug. Usually laba and a steroid
Roflumilast (daliresp)
For what
What it does
New COPD drug. Selective phosphodiesterase type 4 inhib, reduces exac
Daliresp
Moa
Inc cAMP levels resulting in reduced cough, inflammation, and mucus
Daliresp
SE
Diarrhea, wt loss, loss of appetite, nausea, HA, back pain, depression
