pulmonary Flashcards
NANC
Non adrenergic non-cholinergic receptors. Present in bronchial smooth muscle. Release NO and VIP (nitric oxide) (vasoactive intestinal peptide) will relax smooth muscle
Activation of M3 receptors in bronchial smooth muscle
By PSNS (acetylcholine) leads to bronchoconstriction via activation -> increase IP3, increase Ca, BRONCHOCONSTRICTION + mucous secretion
growth factors r/t bronchial smooth muscle hypertrophy
Growth factors are released from inflammatory cells on smooth muscle cells and the smooth muscle itself can release pro inflammatory mediators and growth factors
epithelial loss in bronchioles means that
irritant receptors and C fibers are more accessible to irritant stimuli
gold standard of asthma is to
get inflammation under control, usually done via inhaled glucocorticoid
even with great technique, MDIs deliver
10% of the dose to the lungs
DPIs deliver
20% of dose to lungs, don’t require spacers
MOA of inhaled glucocorticoids
suppress inflammation by altering genetic transcription
target: glucocorticoid receptor alpha in cytoplasm of airway epithelial cells
- increase transcription of B2 receptors and receptor responsiveness
- increase transcription of genes for ANTI-inflammatory proteins
- DECREASE transcription of genes for PRO-inflammatory proteins
- decrease airway mucous production
- decrease vascular pemeablity
- induce APOPTOSIS in inflammatory cells
- eoisinophils, TH2 lymphocytes
- indirect inhibtion of mast cells over time
- REVERSES many features of asthma, especially bronchial hyperreactivity
Most effective/important preventative treatment for asthma
Glucocorticoids
used as suppressive therapy, not curative
Inhaled Corticosteriods (4)
Budesonide
Beclomethasone
Triamcinolone
Fluticasone
IV corticosterids (2)
hydrocrotisone
methylprednisone
PO corticosteroids
Prednisone
Prednisolone
Adrenal Suppression r/t taking steroids
when discontinuing, must taper dose!
because adrenal suppresion happens
systemic (IV/PO) adverse effects of
CORTICOSTEROIDS
minor when taken <10 days
can be severe when used long term
- myopathy/weakness
- adrenal suppresion (must taper dose)
- may require extra dose during times of physiological stress, may even need months after tapering off
- infection risk is higher
- suppression of growth and development (avoid in young kids)
- Peptic Ulcer Disease (NSAIDs incresae the risk)
- Weight gain, edema,
- hypokalemia (some diuretics increase risk)
- hyperglycemia - cortisol
- mobilizing FFA - cortisol, advances atherosclerosis
Cromolyn
MOA:
Uses:
Dosing:
SE:
Cromolyn
MOA:
- Stabilizes pulmonary mast cells
- prevents antigen binding that would lead to antigen induced release of histmaine and inflammatory mediators
Uses:
- prophylatic therapy of bronchial asthma
- atopic individuals, i.e. exercise induced asthma
- SUPPRESSES inflammation, not a rescue inhaler
Dosing:
- must be taken 4 times per day
- administed via inhalation - 8-10% enters systemic circulation
- route: neb or MDI
SE:
- safest of all, rare but serious SE
- cough and/or bronchospasm
- laryngeal edema
- angioedema
- urticaria
- anaphylaxis
Leukotriene Modifiers (3)
Zileuton (Zyflo)
Zafirlukast (Accolate)
Montelukast (Singulair)
leukotrienes C4, D4, and E4
- Promote bronchoconstriction
- Promote eosinophil infiltration
- Promote mucus production and
- Promote airway edema
Leukotriene modifers compared to gluccocorticoids
LESS effective than inhaled gluccocorticoids
Also not effective in tx of acute asthma
Zileuton (Zyflo)
class:
MOA:
Uses:
Dosing:
SE:
Zileuton (Zyflo)
Class:
- leukotriene inhibitor/modifer?
MOA:
- Lipoxygenase inhibtor which blocks the biosynthesis of luekotriens from arachidonic acid, produces bronchodilation,
Uses:
- improves asthma symptoms, has shown long term improvements in PFTs
Dosing:
- low bioavailabiliity, low potency
SE:
- Hepatotoxic 2-4%
- monitor LFTs regualrly, early in tx
- once a month for 3 months
- Neuropyschiatric
- depression, anxiety, suicidal ideation, hallucinations,
- Cytochrome 450 interactions!
- warfarin, propanolol, theophylline
NOT WIDELY USED
Montelukast (Singulair)
Class:
MOA:
Uses:
Dosing:
SE:
Montelukast (Singulair)
Class:
- leuktriene inhibitor
MOA:
- blocks the ability of leukotrienes to bind ot leukotriene-1 receptor (blocks CystLT1)
- improves bronchial tone, pulmonary function, asthma sypmtoms
- MAX EFFECT 24 HRS AFTER 1ST DOSE
Uses:
- used to tx patients <1 year old
- exercise induced asthma >15 y/o
- treat allergic rhinitis
Pk:
- 99% PB
- undergoes extensive cYP450
SE:
- Rare psyschatric effects
*
Omalizumab
Class
MOA:
Uses:
Pk:
Dosing:
SE:
Omalizumab
Class:
- Anti-IgE antibodies
MOA:
- binds to IgE in blood, inactivating it, decrease IgE levels for up to a year
- in response to lower IgE levels, decrease receptors on mast cells, basophils, and dendritic cells. This reduces the stimulation of T2 lymphocytes and decreases the late phase asthmatic reponse than would be expected with IgE alone
Uses:
- decreases quantity of circulating IgE
- only used in allergy induced asthma when inhaled glucocorticoids have failed
Pk:
- given SQ for 2-4 weeks or IV
- very expensive
- 1/2L = 26 days
SE:
- Injection site reactions
- viral infection
- URI and sinusitis
- HA
- pharyngitis
- increase CV complications, increased MI, stroke, HF, dysrhytmias, thromboembolism,
- possible increased risk of Ca
Rare adverse effect: triggering of an immune rsponse, anaphylaxis. Monitor 2 hours after 1st 3 doses, monitor 30 minutes after all subsequent doses
drug binding to B2 receptor leads to
binding to GPCR -s
increase in cAMP
decrease in calicum
increase in conductance of potassium
bronchodilatin
inhibits mast cells
increase clearance of mucous
most effective drugs for relief of acute bronchospasm and prevention of exercise induced bronchospasm
beta 2 adrengeric agonists
short acting beta 2 agonists
albuterol, levalbuterol
