Asthma/ COPD Flashcards
therapy for Asthma/ COPD affects the physiology by doing what? (2 things)
1) decreasing airway resistance: (1/radius^4)
2) decreasing airway response to irritants (allergen, cold air, exercise)
Methylprednisolone
systemic corticosteroid (along with prednisone)
Flucasone
Aerosol corticosteroid (local acting)
Albuterol
Short acting Beta2 adrenergic agonists
(SABA), along with levabuterol
Salmeterol
long acting Beta2 agonist (LABA), along with formoterol
Ipatropium Bromide
Short acting Muscarinic antagonist (SAMA)
Tiotroipum
Long acting muscarinic antagonist (LAMA)
Theophylline
Phosphodiesterase inhibitor which is non-selective aka
Methylxanthine drug
(selective is ODE4 inhibitor: roflumilast (don’t need to know)
Montelukast
leukotriene pathway inhibitor (also zileuton* don’t need to know)
Omalizumab
IgE inhibitor (“alergEEEE” inhibitor)
asthma’s two mechanisms for decreased radius
1) increased constriction of airway,
2) increased mucus production (disabling epithelial cilia)
asthma acts on CNS by
inflammatory response that constricts the bronchioles.
…inflammatory response also increases plasma leak and epithelial shedding via TH2 cells,,dendrites, eosinophils, and sensory nerves)
6 asthma stimuli
allergens viral infections ^ pollutants^ cold air* exercise* stress*
^ mucosal inflammation
*non-specific hyperreactivity
Process of allergenic asthma
Early response
1) Mast cell captures Allergen
2) Mast cell degranulates and releases histamine (etc other mediators).
3) Histamine contracts airway by acting on smooth muscle.
4) –> forced expiration volume is restricted.
Late response
5) Mast cells also recruit T-lympthocytes, which releaes ILs etc. to call Eosinophils, which increase inflammation and increases Neutrophils (hallmark of asthma)
Which stage (early or late) do maintainace drugs work on?
Late stage. Affect airway responsiveness to allergens.
What affects early stage?
Bronchidilators (rescue drugs, “SA-“ drugs) IV corticosteroids
most asthma drugs are IV
most are inhaled, so they don’t target the GI, can be IV in hospital
tone of airways is mostly maintained by which part of NS, so we use anti-_______
parasympathetic mediated (vagus) use anti-muscarinic to block and relax
optimal particle size for asthma meds
2-5ums 10-20%inhaled to lungs (less than 2.5um stays in mouth, more goes to GI, liver, systemic)
Asthma meds target
1) corticosteroids, leukotriene inhibitors and IgE antibodies target the inflammatory immune cascade
2) Muscarinic antagonists target muscarinic receptors
3) Beta2 adrenergic receptors and methylxanthines target bronchoconstriction
what drug is a methylxanthine?
Theophilline
target B2 adrenergic agonists
2 pneumonic for Beta1 and Beta2 sites
One heart
two lungs
(and “Be” my “#1” <3 valentine)
Most effective treatment for preventing asthma attack according to Ceriak
Inhaled Corticosteroids (ICS) For example Fluticasone.
decrease exacerbations
Fast anti-inflammatory effect (hrs), but max benefit is wks-mths after daily use.
Adding a LABA even more effective (better than increasing steroid dose)
inflammation in cell starts when…
NF-kappa-B activated
with a captivator, it binds in nucleus to acetylate (enhances gene transcription)
Good Corticosteroid effects
1) suppress inflammatory gene transcription
2) 17a substitution increases topical activity of ICS
3) no effect on mediator release, but increase B2 receptors in lung structual cells
Adverse Effects:
1) thrush (oral candidiasis) (gargle to prevent)
2) suppresses hypothalamic pituitary axis–> bone resorption, skin thinning, growth retardation (mostly for high dose ICS/systemic effects)
3) doesn’t help with COPD because it COPD is not about inflammation
dx of COPD means they have…
FEV1<50% with exacerbations
MC asthma control is a combo of
ICS + SABA
1st pass metabolism of ICS
1st pass metabolism in liver once in systemic circulation (80-90% swallowed to GI tract)
10-20% to lungs.
COPD is reversible True or false?
false… includes emphysema and/or chronic bronchitis, usually a combo
Astha is reversible True or False?
true. chronic inflammatory disease increasing airway resistance is temporarily reversible (avoiding triggers, and through medication,) but not curable
types of inhalers
1) metered dose inhalers (MDI) pressurized cannister
2) MDI with spacer (decreases amt to GI/ posterior pharynx)
3) Dry powder (released by fast deep breath)
4) MDI with facemask (infant kids)
5) Nebulizer with mouthpiece/mask (mist for infants, kids, people who can’t use inhaler)
Methylprednisolone category
systemic corticosteroid
adverse effect of methylprednisolone
bone resorption, skin thinning, growth retardation
indications for methylprednisolone
asthma exacerbation
SHORT TERM 3-10days then switch to ICS.
IV use for status asthmaticus
Flucanisone
aerosol corticosteroid
indications for flucanisone
controversial use in COPD
only used if FEV1 is <50% with exacerbations
No anti-inflammatory effect
contraindications for flucasone
oropharyngeal andidaisis, dysphonia (gargle and spit to prevent)
high dose the same as methyl prednisolone (bone resorption, skin thinning, growth retardation)
Albuterol
SABA used for rescue
bronchodilation (use less than 2x/wk or step up drugs)
timing of SABA
albuterol works in 3-5min, peaks at 30min, lasts for 3-6 hours
timing of LABA
12 hours (salmeterol)
ultra LABA used for COPD 36hrs
Methylanthines mechanism of action
which drug is associated
work though preventing C-AMP –> 5AMP and PKA (downstream targets to relax smooth muscle, by decreasing Ca into cell via K-channel de-activation to prevent depolarization)
Basically do opposite of phosphodiesterase which changes C-AMP –> 5amp
Theophylline is a phosphodiesterase inhibitor
contraindications for LABA and SABA
SABA: tolerance, rarely:tachycardia
LABA: tremor, tachycardia, hypokalemia
(need to also take ICS if asthma but can be alone in COPD)
Ipatropium Bromide
Muscarinic antagonist which blocks effect of Ach release from vagus nerve to M3 receptors to stop muscle contraction: i.e. they bronchodilate, AND they reduce mucus secretion.
Ipa is Short acting SAMA
pneumonic for remembering which is LAMA and which is SAMA
SAMA: sam is an IPA rat (IPrAtropium) (ipRATropium)
LAMA: Is your momma a llama? “No, es mi tio” (Spanish for, “No, it’s my uncle”)
other pneumonic for SABA,LABA, SAMA, LAMA
SABA is the shorter word of the two Beta AGONISTS, but SABA is longer word…
Albuterol
Salmeterol
…
But with Muscarinic ANTAGONISTS, since they are anti- it’s backwards…SAMA is a longer word, and LAMA is shorter…
Ipratropium Bromide
Tiotropium
indication for SAMA/LAMA
COPD (sometimes effective)
Asthma if intolerant of B2 agonists or in combo with B2 agonists
Adverse effects of SAMA/LAMA
dry mouth, urinary retention (caution with BPH in elderly men),
Few other systemic side effects because poorly absorbed
Theophylline
Phosphodiesterase inhibitor that works to block cAMP from being changed to 5AMP and PKA. this is also how Beta2 agonists work, BUT theophylline does it INSIDE the cell. (effect is relaxed and open bronchioles)
side effect of Theophyline
NARROW THERAPEUTIC WINDOW, monitor plasma levels taken PO
- CV effects (vasodilation, tachycardia, arrhythmias
- CNS stimulation: anxiety, tremor, convulsions
- GI effects: N/V
MOA for theophylline
COPD (improves diaphragm contraction)
Asthma
blocks activation of adenosine receptor on smooth muscle (decreased contraction) and mast cells (decreased histamine release)
increases histone deacetylation (decreasing cytokine production/release)
how does Theophylline work with other drugs
in COPD, increase muscle contractility, improving ventilatory function may increase ICS effect
Montelukast
PO
leukotriene receptor agonist
LT pathway inhibitor so inhibits bronchoconstriction
indication for montelukast
add on for mild-moderate asthma who aren’t compliant with ICS, or not well-controlled.
not used with COPD
negative side effects of montelukast
hepatic dysfunction
neuropsychiatric events
Omalizumab
SQ
IgE Inhibitor
humanized anti IgE monoclonal AB that binds to Fc portion so it can’t bind to mast cells
Indication for Omalizumab
reduces use of corticosteroids used for allergy rhinitis prophylaxis
problems with omalizumab
expensive, possible anaphylaxis within 2 hours
WIDE variation in response
NEEDS TO BE MONITORED
