Pharm - Asthma and COPD Flashcards
Structure vs. function of sweat glands
Anatomically SNS (long postganglionic fiber) Functionally PNS (releases ACh)
Non-specific beta agonists
Epi, ephedrine, isoproterenol
Fast acting, short lived beta 2 agonists
Albuterol, levalbuterol, terbutaline
LABAs
Salmeterol, formoterol
used with steroid
Antiinflammatory meds
Steroids
Cromolyn
Leukotriene inhibitors
Leukotriene receptor blockers
Montelukast, zafirlukast
Leukotriene synthesis blocker
Zileuton
IgE mab
Omalizumab
What has highest density of B2R?
Bronchial smooth muscle cells
Bronchial SMCs don’t have ___ innv, while blood vessels don’t have ___ innv
Symp
Parasymp
What is unique about the adrenergic receptors in bronchial SMCs?
Epinephrine is their endogenous ligand rather than NE like other adrenergic receptors
What type of cholinergic receptors are present on bronchial SMCs?
M2 and M3
M2R responsible for ___ using what G protein?
Decreased ACh release (M2R is autoreceptor)
Gi
M3R responsible for ___ using what G protein?
Bronchoconstriction
Gq –> increased Ca2+
Relationship between eosinophils and asthma/COPD
Major basic protein of eo’s causes bronchoconstriction by inhibiting M2R (so increasing ACh)
When would an M2R AGONIST cause bronchoconstriction?
In presence of a B2R agonist which would increase levels of cAMP and cause relaxation; by working through Gi, an M2R agonist would inhibit this effect and cause constriction.
How do B2 agonists cause bronchial SMC relaxation?
Increase cAMP –> PKA –> phosphorylation of MLCK –> relaxation
Which nerve is stimulated in asthma pts? Effect?
Vagal afferents –> sends messages to vagal afferents –> release ACh (parasymp) –> constriction of bronchial SMC
Affinity of epi vs. ephedrine vs. isproterenol
Epi - B1, B2, alpha
Ephedrine - B1, B2, some alpha
Isoproterenol - B1, B2
4 MOA beta agonists
- Increase cAMP –> relaxation
- Increase mucociliary transport
- Decrease mast cell release of mediators
- Decrease microvascular permeability
How do LABAs cause increased mortality?
Through Gq –> PLC –> inflammation
(beta2 agonists do NOT treat inflammation of asthma/COPD; they might exacerbate it
AE of sympathomimetics
N/V, HA, hypotension, arrhythmias, agitation, coma, convulsions, respiratory and vasomotor collapse
Density of B2R vs. muscarinic receptors
B2R - bronchioles
MR - lower airways
2 antimuscarinics
Atropine
Ipratropium
2 MOA antimuscarinics
- COMPETITIVE muscarinic block –> SMC relaxation
2. Decrease mucus secretion
AE atropine
Pupil dilation
Cycloplegia (paralysis of ciliary muscle causing loss of accommodation = blurry near vision)
Combo beta2 agonist and antimuscarinic indicated for:
COPD
List the methylxanthines
Theophylline
Aminophylline
Dyphylline
Oxtriphylline
Actions of methylxanthines
- Increase cAMP –> SMC relaxation
- Inhibit adenosine –> antiinflammatory
- Weak diuretic
- Increase skeletal muscle (diaphragm) strength
- Positive inotropic and chronotropic effects
- Increase gastric acid secretions
- Decrease release of mediators
Unique AE of methylxanthines
Hypokalemia
Hyperglycemia
Neuromuscular irritability
Indications for cromolyn
Exercise or allergen induced asthma
Actions of cromolyn
- Inhibit mast cell degranulation*******
- Inhibit Cl- channels
- Inhibit eosinophilic inflammatory pathway
- Reduce cough by action on airway nerves
- Reduce bronchial hyperactivity
AE cromolyn
- Bad tase
- Cough and bronchospasms after inhalations
- CNS depression
- Anorexia
MOA of glucocorticoids
Cause dissociation of HSO90 –> recruitment of HDAC:
- Decreased synthesis of pro-inflammatory cytokines
- TRANSACTIVATION of anti-inflammatory cytokines
- Recruitment of TTP, which decreases stability of mRNA of pro-inflammatory cytokines
Overall effects of glucocorticoids
- Reduce bronchial hyperactivity
- Reduce mucus secretion
- Reduce pro-inflammatory cytokines
- Synergism with beta 2 agonists
Which GC’s are oral? IV?
PO - dexamethasone, prednisone
IV - dexamethasone
(rest are inhaled)
AE of GC’s
Cushingoid syndrome Bone demineralization Retarded growth in children Oral candidiasis/immunosuppression Weight gain Glucose intolerance HTN Cataracts
Indication for leukotriene antagonists
Aspirin-induced asthma
What does LTB4 do? LTC4 and D4?
LTB4 = neutrophil chemoattractant LTC4/D4 = mimic asthma; mucus secretion, bronchoconstriction, bronchial hyper-reactivity, edema
MOA zileuton vs. montelukast/zafirlukast
ZiLeuton = Lipoxygenase inhibitor ZafiRlukast/montelukast = LTD4 receptor antagonist
Which leukotriene inhibitor prevents neutrophil recruitment?
Zileuton = inhibits LTB4
AE zafirlukast
Hepatic enzyme elevation
Bladder, liver, histocytic cancer
AE montelukast
Infections
Suicidal ideations
AE zileuton
Increase liver enzymes
Inhibit CYP1A2
Which other asthma drug may interact with zileuton?
Theophylline (levels would increase if also taking zileuton)
Name the IgE mab
Omalizumab
Indication for omalizumab
ABPA (IgE > 700)
AE of omalizumab
Severe allergic reaction (SOB, closing of throat, swelling of face, lips, tongue, hives)
6 steps of therapy for asthma
- SABA PRN
- Low-dose ICS
- Low-dose ICS + LABA or medium-dose ICS
- Medium-dose ICS + LABA
- High-dose ICS +LABA
- High-dose ICS + LABA + PO CS
Are steroids helpful in COPD?
Not really; poor response
CI in COPD
Sedatives Beta blockers ACE inhibitors ASA/cox inhibitors Local anesthetics with epi
MOA doxapram
Stimulate peripheral carotid receptors –> respiratory stimulant
Indications for doxapram
COPD exacerbation
Post-anesthesia or drug-induced respiratory depression