asthma Flashcards
Episodic narrowing of airway walls thought to be caused by an underlying chronic inflammatory disorder
Asthma
SYMPATHOMIMETIC AGENTS
Bind to β receptors on airway smooth
muscle cells → stimulate adenylyl cyclase →
increase cyclic AMP →
relaxing airway smooth muscle
Bronchodilation is promoted by__
Camp (adenylyl cyclase or PDE)
Epinephrine_ max bronchodilati
15 minutes and last about 60-90 minutes
● Potent, non-selective β1 and β2 bronchodilator
● Inhalation of 80-120 mcg as aerosol with maximal
bronchodilation in 5 mins and duration of 60-90 mins
● Increased mortality in the UK (1960s) due to cardiac
dysrhythmias
● Now rarely used for asthma
isoproterenol
Non-selective adrenergic
Epinephrine, isoproterenol, ephedrine
S/e of epinephrine
Tachycardia, arrhythmia, worsening angina pectoris
Isoproterenol: ___ mcg as aerosol with maximal broncodilation in _ min and duration of -
80-120mcg, 5 min. 60-90 min
Longer duration than epinephrine, lower potency, central effects
Ephedrine
Results from frequent or overuse of LABA and SABA
Tachyphylaxis
SABA
Salbutamol terbutaline levalbuterol metaproterenol pributerol
Optimal size
1-5um
LABA
Salmeterol
Formoterol
Fenoterol
clenbuterol
Given as an add-on for inhaled steroids
LABA
Neurotransmitter in the parasympathetic NS (released by vagus nerves) that promotes bronchoconstriction
Acetylcholine
Blocks bronchoconstrictive effects of histamine, bradykinin, and eicosanoids
(mediators released during asthma attacks)
atropine (Datura stramonium)
Inhaled irritants are sensed by the _____ pathways of the vagus nerve
Efferent
Parasympathetic - 2 possible mechanisms
Triggers chemical mediators, initiate reflex bronchoconstriction or release tachykinins
May last up to 6 hrs, quaternary ammonium derivative of atropine
Ipatropium Br
Particular good response in subgroup of asthmatics with psychogenic exacerbations
Also useful in patient intolerant of β2 agonists
ipatropium br
Drug of choice for rapid symptomatic relief of
dyspnea in asthma bronchoconstriction
SABA
Longer duration of action
Maintenance therapy for COPD
Tiotropium br
Dissociates most rapidly from M2 receptors
some degree of receptor selectivity
Tiotropium br, Aclidinium
Tiotropium: __mcg OD (24hr duration)
18mcg
Aclidinium: ___ mcg BID (12hr duration)
Aclidinium
T or F
Antocholinergic agents have only modest inhibition to histamine, bradykinin or PGF2a
T
Anticholinergics only frequent side effect
dry mouth
prototype drug of methylxanthines
Aminophylline
Theophylline-ethylenediamine complex, commonly used in IV preparation
aminophylline
METHYLXANTHINES USED IN ASTHMA: BRONCHODILATOR
DRUGS
(Phosphodiesterase inhibitors)
o THEOPHYLLINE
o AMINOPHYLLINE
o DOXOFYLLINE
Methylxanthines toxicity
- adverse cns effects
- urticaria
Do not directly relax airway smooth muscles, no
value in acute bronchoconstriction – central to the
pathophysiology of asthma is that it is a chronic
inflammatory disease so steroids are very important
because of their anti-inflammatory action.
glucocorticoids
Greatly enhances therapeutic index of these drugs
(Can be given higher doses with very little side
effects), targets the drug directly to site of inflamm
inhale glucocorticoids
Inhaled glucocorticoids includes:
o Fluticasone
o Budesonide
o Betamethasone
o Fluticasone Furoate
For acute and chronic severe asthma
Glucocortiloid:systemic
prednisolone, methylprednisolone
Dose for exacerbations:
Prednisolone:
40-60mg/day
children: 1-2mg/kg/day
5-10 days max
for persistent asthma
alternate-day therapy with oral prednisolone
better tx (gold standard)
inhaled glucocorticoids
Inhaled steroids systemic adverse effect
HPA axis suppression Bone resorption Carbohydrate and lipid metab Cataracts Skin thinning Purpura Dysphonia Candidiasis Growth retardation
Known adverse effects of systemic steroids:
o Consequences that result from PA suppression o Fluid and electrolyte abnormalities o Hypertension o Hyperglycemia o Increased susceptibility to infection (due to decreased immunity) o Osteoporosis -myopathy -behavioural disturbances -cataracts -growth arrest -cushing syndrome
Inflammatory mediators produced from the
lipoxygenase pathway
Cysteinyl Leukotrienes (CysLTs)
∼1000 times more potent than Histamine
as a bronchoconstrictor.
LTD4
LTRAs
Montelukast
Zafirlukast
Potent and selective inhibitor of 5-
lipoxygenase Not commonly prescribed due to hepatic
toxicity Not locally available
Leukotriene Synthesis Inhibitors
o Zileuton
o Selective high-affinity competitive antagonists for
the CysLT1 receptor
o Orally active
o Antagonists of LTC4 and LTD4
LTRA
has effectiveness in asthma-induced asthma, and exercised-induces asthma
LTRAs
LEUKOTRIENE PATHWAY INHIBITORS: TOXICITY
Very rarely: systemic eosinophilia and vasculitis with
features similar to Churg-Strauss syndrome.
o Often associated with a reduction in
glucocorticoid therapy, may represent the unmasking of a pre-existing disease.
may interact with warfarin and increase
prothrombin times.
Zafirlukast
First biological agent approved for the treatment of asthma
Omalizumab
Indicated for adults and adolescents >12 years of age
with allergies and moderate-to-severe persistent
asthma
Omalizumab
Oxygen therapy: GOAL
02 saturation of atleast 95%
