Respiratory Agents Flashcards
SNS lung innervation
from thoracic ganglia, innervates smooth muscles of bronchi and pulmonary blood vessels
PSNS lung innervation
via vagus nerve, bronchoconstriction via mostly M3 and a little bit of M1
B2 adrenoreceptors cause (intracellular response)
increased intracellular cAMP which changes membrane potential of cells and decreases calcium release intracellularly, greater sensitivity to EPI v NE
Non adrenergic non cholinergic nerves (NANC)
excitatory: related to substance p and neurokinin
inhibitory: NO, peptide release
How do M3 mediate bronchoconstriction
via activation of IP3 (inositol triphosphate) which increases intracellular Ca2+ concentrations. also mediates mucous secretion.
asthma histologic mediators include
eosinophils, mast cells, neutrophils, macrophages, basophils, t lymphocytes, cytokines, interleukins, arachidonic acid metabolites, leukotrienes, prostaglandins, histamine, adenosine, platelet activating factor
emphysema/bronchitis pathological result
enlargement of air spaces, fibrosis, increased mucous production
treatment of airway outflow disorders (5 steps)
- short acting bronchodilators
- inhaled corticosteroids
- long acting bronchodilators
- PD3 inhibitors, methylxanthines, leukotriene inhibitor
- oral corticosteroid
bronchodilator med classes
beta agonists
anticholinergics
methylxanthines
short acting beta agonists (SALT)
terbutaline, albuterol, levalbuterol, salbutamol
long acting beta agonists
salmeterol, formoterol
B2 agonist bronchodilator MOA (general)
(3,5 cAMP production)
activate adenyl cyclase which increases production of cAMP (adenosine monophosphate) which causes bronchodilation. reduced intracellular calcium release and alters membrane conductance
B2 agonist bronchodilator effects (general desirable effects)
dilates bronchi, smooth muscle relaxation, inhibits mediator release from mast cells, increase mucus clearance by action in cells
B2 agonist SE’s (general)
minimized by inhalation delivery tremor increased HR vasodilation metabolic changes including hyperglycemia, hypokalemia, hypomagnesemia
Albuterol class, dose, route of administration (2), duration of action, SE’s
beta 2 agonist
administered via metered dose at 100mcg/puff
2 puffs q4-6h
neb 2.5-5mg in 5ml of saline
can give 4 puffs to blunt AW response to tracheal intubation for asthmatics
duration 4 hours with relief evident up to 8h (additive effect with volatile anesthetics)
SE: tachycardia, hypokalemia,
isomers of albuterol
R albuterol levalbuterol- more affinity for B2
S albuterol more affinity for B1
Metaproterenol-Alupent class, route of administration, dose max
beta 2 agonist used for tx of asthma, administered via metered dose, dont exceed 16 puffs per day
Pirbuterol-Maxair class, dose, dose max
beta 2 agonist, administered via metered dose (400mcg), do not exceed 12 puffs/day
Terbutaline class, use, route of admin, dosage, drug comparison
beta agonist used to treat asthma administered oral, SQ(SC), inhaled SQ dose pedes .01mg/kg SQ dose adults .25mg q15min metered dose inhaler 16-20puffs/day each dose 200mcg SQ administration resembles response of epi
Salmeterol and Formoterol class, duration, use, chemical consideration
beta agonist long acting, 12-24h duration asthma prevention of flare lipophilic side chains that resist degradation salmeterol has fluticasone (steroid)
Muscarinic Receptor Antagonist MOA
M1 and M3 most important in mediating smooth muscle relaxation and decreased mucous gland secretion, which produces bronchorelaxation and decreased secretions.
Muscarinic Receptor Antagonist uses
tx of COPD
secondary line of tx for asthma (in patients resistant to B agonist or significant cardiac disease
Atropine class, use, dose, route of administration, distribution, SE
muscarinic antagonist (naturally occurring alkaloid)
formally considered 1st line for asthma tx
1-2mg diluted in 3-5ml of saline via nebulizer
highly absorbed across respiratory epithelium
SE: systemic anticholinergic effects including tachycardia, nausea, dry mouth, GI upset
Iatropium Bromide class, chemical structure, MOA, route of administration, dose, onset, duration of action, absorption consideration, SE
muscarinic antagonist
quaternary ammonium salt derivative of atropine
antagonizes effect of endogenous Ach at M3 receptor subtypes
administered via metered dose inhaler
40-80mcg in 2-4 puffs via nebulizer
slow onset of 30 min
duration 4-6h
not significantly absorbed compared to atropine
SE: dry mouth, Gi upset if oral absorption
Tiotropium class, chemical structure, duration of action, absorption considerations, use
muscarinic antagonist quarternary ammonium salt long acting not significantly absorbed across respiratory epithelium which results in few side effects COPD
Methylxanthine class, MOA, uses
(Inhibit breakdown of 3,5 cAMP)
PDE inhibitors
nonspecific inhibition of PDE isoenzymes (types III and V) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells. causes airway relaxation and bronchodilation
used for COPD or asthma
theophylline TI, caution, metabolism, excretion
TI 10-20mcg/ml
caution with halothane
drug-drug interactions r/t CYP450 metabolism (cimetidine, antifungals)
excreted in kidney
methylxanthine (PDI) consideration r/t SE
because they have multiple MOA’s and are nonselective, have many SE’s and narrow TI
methylxanthine PDI SE’s (general)
headache n/v irritability, restlessness insomnia cardiac arrhythmias seizures SJS
Inhaled corticosteroids MOA, use
alter genetic transcription by:
- increasing transcription of genes for B2 receptor and anti inflammatory proteins
- decreasing transcription of genes for pro inflammatory proteins
- induce apoptosis in inflammatory cells (eosinophils, TH2, lymphocytes)
- indirect inhibition of mast cells over time
- reducing number of inflammatory cells in airways reduced damage to epithelium
- vascular permeability is reduced which decreases airway edema
- overall reduction in airway hyper-responsiveness
- used as suppressive therapy, major preventive tx for patients with asthma (most important asthma mgmt)
Inhaled Corticosteroid Examples (4)
beclomethasone
traimcinolone
fluticasone
budesonide
Inhaled corticosteroid anesthesia considerations (periop use)
may consider use of corticosteroid 1-2h postop
prolong response of B agonists
may consider 5 day course of combined corticosteroid and albuterol to minimize risk of intubation invoked bronchospasm
Corticosteroid inhaled and PO route considerations
80-90% of inhaled dose reaches oropharynx and is swallowed
higher airway concentration than same dose given PO
systemic effects decreased through inhalation
Inhaled Corticosteroid SE’s
oropharyngeal candidiasis osteopenia/osteoporosis delayed growth in children hoarseness hyperglycemia
Cromolyn MOA
stabilizes mast cells
inhibits antigen induced release of histamine
including release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, leukotrienes from pulmonary mast cells
inhibits immediate allergic response to antigen but not allergic response once it has been activated
Cromolyn use, administration, SE’s
prophylactic therapy of bronchial asthma (does not relieve allergic response after initiation, and is therefore not to be used as a rescue inhaler)
-administered via inhalation, take 4x daily
SE are rare but include laryngeal edema, angioedema, urticaria, anaphylaxis
Leukotriene Inhibitors use
useful for bronchial asthma
synthesis of leukotriene
from arachidonic acid when inflammatory cells are activated
Zileuton class MOA, use, bioavailability, potency, SE
leukotriene inhibitor
lipoxygenase inhibitor which blocks biosynthesis of leukotrienes from arachidonic acid
produces bronchodilation, improves asthma symptoms, has shown long term improvement in PFT
low bioavailability and potency
hepatotoxicity is SE, not widely used because of many adverse effects
Monteuklast-Singulair class, MOA, co administration considerations
leukotriene inhibitor
block mechanism of bronchoconstriciton and smooth muscle effects by blocking ability of leukotrienes to bind to cysteinyl leukotriene 1 receptor
improves bronchial tone, pulmonary function, and asthma symptoms
caution with co admin with warfarin which would prolong PT
Anti IgE Antibodies and Asthma
since asthma is an IgE mediated allergic response, the idea is that the removal of the IgE antibodies from circulation would mitigate acute response of inhaled allergen
Omalizumab class, use, route of administration, duration of administration, SE, drug considerations
monoclonal antibody derived from DNA, binds to IgE to decrease the quantity of IgE and prevent binding of IgE to mast cells. in response to lower levels of IgE, mask cells, basophils, and dendritic cells are down regulated
- given in early and late phase of asthmatic response
- given SQ for 2-4w/parenterally infused
- SE: rare but triggering of immune response
- high cost and inconvenience
which drug class is most utilized for COPD
anticholinergics
what are the two ways in which leukotriene inhibitors work
block synthesis of leukotriene via arachidonic acid or block receptors
Methylxanthine examples
theophylline, aminophylline
