Pharmacology of Asthma Flashcards
Describe the pathophysiology of asthma.
Th 2 - driven and eosinophilic inflammation causing mucosal oedema, bronchoconstriction, mucus plugging, and bronchial hyperresponsiveness.
What can we target in asthma therapy?
Smooth muscle function
Inflammation
Mast cell stablisation
What can make asthma worse, and how?
NSAIDs in some pts. NSAIDs prevent arachadonic acid from -> COX1 -> prostaglandins. More AAs are available to form cys LT1 which causes bronchospasm etc.
How do we manage asthma?
In a stepwise fashion
Who gives guidelines for asthma therapy?
NICE and the BTS
Which guidelines will I use here?
NICE
What is the first step on the NICE pathway?
Offer a SABA as reliever therapy to all adults with newly diagnosed asthma
Who can you consider SABA only in?
Adults with infrequent, short-lived wheee and normal lung function
Who is low dose ICS offered to first line?
Maintenance therapy if symptoms present 3 times a week or more, or causing waking at night, or if it is uncontrolled with only a SABA.
What is th enext step up from low dose ICS, and when do we escalate?
Escalate if asthma uncontrolled on low dose ICS.
Add on a LTRA to ICS and SABA
A pt is on SABA + ICS + LTRA, and their asthma is still uncontrolled. What is the next step?
SABA + Low dose ICS, and add on LABA.
Review LTRA according to how the pt feels and their response (or not) to LTRAs.
What is the step up from low dose ICS and LABA +- LTRA?
Change LABA to MART ( with low dose ICS +- LTRA)
If MART + low dose ICS +- LTRA doesnt work, what is the next step?
Increase ICS maintenance dose.
Also consider continuing MART or switching back to ICS with LABA.
After a moderate dose of ICS, what is the next step up?
Consider:
- High maintenance dose (fixed dose regimen) with SABA
- Trialling an additional drug such as LAMA or theophylline
- Referal to asthma specialist.
What is considered controlled asthma?
Minimal symptoms during the day and night
Minimal need for reliever inhalers
No limitations or exacerbations on physical activity
Normal lung function
What is a key thing to check before initiating new treatment?
Compliance and technique with existing therapies
What lifestyle things can pts do the prevent asthma exacerbations?
Avoidance of triggers
What are SABAs?
Short acting Beta2 agonists
Name 2 SABAs.
Salbutamol
Terbutaline
What are the ADRs associated with B2 agonists?
Tachycardia
Palpitations
Tremor
How do SABAs work to relieve asthma?
Reverse bronchoconstriction and inhibiting mast cell degranulation in response to an allergen.
What is the issue with using SABAs too much?
Decreased asthma control as mast cell degranulation becomes more sensitive to allergen.
What are the other options for B2 agonists, other than SABAs?
LABAs!
Fast onset long duration, or slow onset long duration.
Which LABAs are fast onset with long duration?
Formoterol
Olodaterol
Indacaterol
Which LABAs are slow onset with long duration?
Salmeterol
Vilanterol
How frequently do we review the response to treatment?
Every 4-8 weeks.
How do ICS work (broadly speaking)?
Inhaled corticosteroids target inflammation, and reduce eosinophil count.
What is the molecular action of steroids?
Bind to intracellular receptors (glucocorticoid receptor alpha) causing chaperone proteins to dissociate. The complex goes to the nucleus where it binds to DNA.
What effect do steroids causes complexes on the DNA to have?
- Transactivation of anti-inflammatory genes nd increase B2 receptors expression.
- Transrepression by inhibiting proinflammatory gene transcription.
What are pro-inflammatory genes normally triggered by for transcription?
Cytokines
LPs
Viruses
Who responds best to ICS?
Pts with eosinophilic asthma
What can happen with ICS?
ICS can be absorbed and join systemic circulation via the lungs causing the potential for systemic side effects A small fraction is also likely to be swallowed.
What local side effect can ICS have, and how do we avoid it?
Candida infection in the throat. Avoid this by rinsing throat after using ICS inhaler, and having good inhaler technique.
What ICSs are used in asthma?
Beclomethasone
Budesonide
Fluticasone
Which 2 LABAs are the most commonly used?
Formoterol and salmeterol
How frequently do pts take formoterol?
BD
How frequently do pts take salmeterol?
BD
Why must LABAs be prescribed alongside an ICS?
They have no anti-inflammatory effect, unlike ICSs.
How can we make it easier for a pt on LABAs and ICSs?
Give a combination therapy, so ony have to use one inhaler for 2 drugs.
What is an LTRA?
Leukotriene receptor antagonist
What are the LTRAs?
Montelukast
Zafirlukast
How do LTRAs work?
Block LTC4 released by mast cells and eosinophils, preventing broncoconstriction, mucus secretion, and mucosal oedema.
What % of pts are LTRAs effective in?
15%
What are the ADRs of LTRAs?
Angioedema Dry mouth Anaphylaxis Arthralgia Fever Gastric disturbance Nightmares
What kind of drug are theophylline and aminophylline?
Methylxanthines
How do theophylline and aminophylline work?
Antagonise adenosine receptors, inhibit phosphodiesterase, and increase cAMP.
What are the downsides to theophylline and aminophylline?
Poorly efficacious
Narrow therapeutic window
Bad ADRs
What are the ADRs associated with theophylline and aminophylline?
Nausea Headache Reflux Arrhythmias Seizures
What are theophylline and aminophylline metabolised by?
CYP450, so increase in bioavailability when taken alongside cyp450 inhibitors such as erythromcin and ciprofloxacin.
When are LAMAs indicated?
COPD and severe asthma (after a moderate ICS dose has been trialed) and asthma excerbations
What is the main LAMA liscenced for asthma?
Tiotropium bromide
What are the LAMAs liscenced for COPD, as well as tiotropium bromide?
glycopyrronium
usually used as part of a triple therapy inhaler
When giving an oral corticosteroid, what dose is usually used?
10mg OD or more
What is a MART?
Maintenace and Reliever therapy
What biological therapies are there available for asthma?
Anti-IgE such as Omalizumab
Anti-IL-5 such as Mepolizumab/Reslizumab
What can cause exaccerbations of asthma?
Allergens
Viral infection
Cold weather
Exercise
What is there good evidence for, in terms of achieving the best outcomes in asthma?
Pts having a personal self-management plan with written instructions on when to step up or down.
How do we identify acute severe asthma?
1 of:
- Unable to complete sentances
- Pulse over 110 bpm
- RR over 25/min
- Peak flow 33-50% of best/predicted.
What is life threatening asthma classified by?
Any of the criteria for severe, plus any of:
- PEF less than 33%
- spO2 less than 92%
- Silent chest
- Cyanosis
- Feeble resp effort
- Hypotension
- Bradycardic
- Arrhythmia
- Exhaustion
- Confusion
- Coma
How do we treat a severe/life threatening acute asthma attack?
High flow O2
Nebulised salbutamol/ipratorpium bromide
Oral prednisolone
IV aminophlline if no response
What is the difference between tiotropium and ipratropium bromide?
Ipratropium has a shorter duration of action.
