Respiratory Medicine Flashcards
what is the pathophysiology of Asthma ?
Type 1 hypersensitivity reaction leads to TH2/ Eosinophilic inflammation via degranulation .
Leads to airway remodelling via -
Mucosal oedema , Bronchoconstriction and mucus plugging
what specially do B2 agonists target in Asthma ?
what about steroids ?
SM dysfunction
Inflammation
why is Asthma difficult to manage ?
heterogeneous disease
pathologically can vary (Eosinophils and neutrophils)
Symptom paterns and triggers vary
response to treatment vary
how do you define asthma control ?
Minimal symptoms during day + night Minimal need for reliever No exacerbations no limitations of physical activity normal lung function
what should you check before starting therapy ?
Check compliance with existing therapy
inhaler technique
eliminate trigger factors
what is Step 1 on Management of Asthma ?
What drug ?
what do you need to be aware of ?
Short acting B2 agonists - Salbutamol, Terbutaline
Only for relief
if used regularly = reduce asthma control
what is site of action of B2 agonist if only for symptom relief ? what can happen on overuse?
Predominant action on SM in airway
also inhibit mast cell degranulation but if overuse happens this can reverse and sensitivity increases
how does B2 adrenorecpetor work in smooth muscle ?
Alpha s Subunit phosphorylates GDP to GTP and activates Adenyl cyclase to increase cAMP =
Inhibits Myosin light chain
activates PKA-
relaxation
name 1 fast onset long duration B2 agonist and its uses
Formoterol -
Reliever
reduce sever asthma Exacerbation
name 1 long onset long duration B2 agonist and its use
Salmeterol
prophylaxis
what are side effects of B2 Agonists ?
Tachy , palpitation and tremor
when should you use step 2 therapy ?
- using inhaler more than 3 times a wek
- symptoms 3 times a week
- waking up once a week
- Exacerbations requiring oral steroids in the last 2 yrs
(symptoms more than x2 a mnth)
what is step 2 therapy?
regular preventer via inhaled corticosteroids
how do steroids work ?
Attaches to transcription factor (GCS receptor) and chaperones disassociate allows gene transactivation of Anti-inflammaotries and also increase B2 receptor production
also Transrepression of inflammatory mediators
name 2 inhaled steroids
Beclomethasone dipropionate, Budesonide, Fluticasone,
What chemical changes were done to previous steroids and what changes therefore happened to new ones ?
Lipophilic side chain added
a higher affinity for GCS receptor . increased uptake and dwell time in tissue
inactivates hepatic metabolism
how does inhaled steroids enter circulation ?
Lung depsostion and absorption
Swallowed fraction and gut absorption and phase 1 met in liver
what asthma do you have to be aware of when giving steroids ?
Non - eosinophlic patients do not respond as well to inhaled steroids than eosinophilic
what is step 3 therapy?
when is it indicated ?
what drugs ?
add-on
long acting B2 Agonists
Over 400 mcg/day of ICS
Formoterol and salmeterol
which of the LABA is the most potent ?
Formoterol and then Salmeterol
how do you measure potency ?
the dose at causing half the max response
which of the LABA is the most efficacy ?
foametrol = 100% repsonse Salmeterol = 50%
how do you measure efficacy ?
the dose at which the max response is occurring
what are features of LABAs?
reduce asthma exacerbations , improve symptoms and lung functions
not anti-inflammatory
what are good Steroid combinations ?
Budesonide/formoterol
• Beclomethasone/formoterol
• Fluticasone/formoterol
• Fluticasone/salmeterol
what is a major benefit of LABA and ICS in single inhaler ?
increase compliance
reduce cost
what does the evidence suggest LABA and SABA as as a reliever ?
LABA are better relievers when on step 3 management
what are alternative in step 3 to LABA ?
Higher dose ICS (eosoniphilic)
luekotriene receptor antagonist
Theophylline- methylxanthines
tiotropium
how do LRAs work ?
name 1
LTC4 released by mast cells and eosinophils = induce bronchoconstriction, mucus secretion and oedema
LRA block LTs by blovking CysLT1 receptor
Montelukast
what are side effects of LRAs?
angioedema , dry mouth
insomnia , nightmares
how does Theophylline work ?
methylxanthine that anatagonosies the adenosine receptor - inhibit PDesterase increase cAMP
What disadvatages and side effects of theophylline ?
Poorly efficacious , narrow therapeutic window with freequnet side effects:
Nausea , headaches and reflux, Arrhythmias , fits
levels increase from CYP450 inhibitors
name 2 long acting Anticholingerics
Ipratropium bromide, Tiotropium bromide
what are indications for tritropium bromide ?
what does it work on?
COPD and sever step 4/5 asthma
Reduces exacerbations
M3 receptor
side effects of LAMAs?
Dry mouth, urinary retention and glaucoma
what is step 5 management ?
Oral steroids - prednisolone
biological therapies
what biological therapies are used? how do they work ? what is the main advantage ?
Anti-IgE
attached to IgE receptor and tops cross linking of mast cells
Anti-IL 5 - must have high eosinophil number
Reduce esoniophil numbers
reduce exacerbations
what could you implement to asthma patients to help with asthma control ? what do they include ?
self management plan
when and how to step up and step down treatment
why should patients step down?
may be receive too high dose of steroid
what is particle size of inhalers ? what is important of this ?
1-5 microns
the closer to this number the more is deposited in the lungs / small airways
define acute severe asthma
any one of :
- unable to complete sentence
- pulse >= 110 bpm
- respiration rate >= 25 min
- peak flow 33-50%
define life threatening asthma
any one of acute sever plus PEF <33% • sPO2 <92 • PaO2 <8 kPa • PaCO2 >4.5 kPa • Silent chest • Cyanosis • Feeble respiratory effort • Hypotension, bradycardia, arrhythmia • Exhaustion, confusion, coma
define Near-fatal asthma
PaCO2 >6 kPa, mechanical
ventilation
what is treatment of acute severe asthma ?
- oxygen 94-98%
- nebulised salbutamol
- oral prednisolone for 10-14 days
what is treatment of life threatening asthma ?
same as sever but add nebulised Ipratropium bromide
IV aminophyline
