S9 L2 Respiratory Pharmacology Flashcards
What is the pathophysiology behind asthma?
- TH2 and eosiniphil driven inflammation resulting in mucosal oedema, bronchoconstriction, mucus plugging and bronchial hyperresponsiveness
- Chronic inflammatory, intermittent, reversible
- Parasympathetic M3 causes bronchoconstriction
What does asthma control mean?
- Minimal symptoms during day and night
- Minimal need for reliever medication
- No exacerbations
- No limitation of physical activity
- Normal lung function (FEV1 and/or PEF >80% predicted or best)
What should you check with a patient before you step them up or down the asthma treatment ladder?
- Adherance
- Inhaler technique
- Eliminate trigger factors
What is the stepwise approach for the treatment of asthma?
- Step 1 – short acting β2 agonists as needed, consider low dose ICS
- Step 2 – regular low dose ICS
- Step 3
A. LABA + low dose ICS
B. LABA + ↑ dose ICS / stop LABA if no effect
- Step 4 – LABA + high dose ICS (can add LTRA/aminophylline)
- Step 5 – daily oral steroid + high dose ICS + consider others
Should you add LABA or LTRA after low dose ICS?
NICE suggests LTRA as this is cheaper but BTS/SIGN says LABA and most patients do end up on this
How do SABA’s act to help mild/intermittent asthma?
- Bronchodilation by agonising beta-2 receptors
- Gs protein so activate adenyl cyclase, and then PKA which phosphorylates myosin light chain kinase to inhibit smooth muscle contraction.
- Also increases mucus clearance by action of cilia
- Symptom relief by reversing bronchoconstriction, only use as required
What are some examples of beta agonists and when are they used?
SABA: as needed
LABA: add on therapy with ICS and p.r.n SABA. Can be used as a preventer before exercise to prevent exacerbations and improve lung function
(formoterol has rapid onset of action similar to salbutamol but long acting. More potent and efficacious than salmeterol)
What are some adverse affects that can occur when using B2 agonists and what drugs cannot be used alongside it?
- May generate a tolerance if constantly using
- Tachycardia
- Palpitations
- Anxiety
- Tremor
- Muscle cramps (LABA)
- Increased renin and glycogenolysis so could raise b.p
- Don’t use with beta blockers as may reduce effects of beta agonist
What should LABA always be taken with and why is it taken as a combined inhaler?
ICS - increased risk of death when prescribed alone
- Adherance
- Ease of use
- Less prescriptions
- Safer
When are inhaled corticosteroids added on to asthma treatment and what is their mechanism of action?
- When reliever alone not sufficient and using more than 3 times a week or waking up with symptoms
- Reduces mucosal inflammation, widens aiway and reduces mucus to reduce symptoms, exacerbations and death
- Lipid soluble so activate intracellular GC receptor alpha and cause gene activation of B2 receptors and inactivation of inflammatory mediators and cytokines
What are some side effects of ICS being used as a regular preventer therapy?
- Can have local immunosuppressive action e.g oral candidiasis, hoarse voice
- Pneumonia risk with COPD
- Very few ADRs if taken correctly
What are some examples of ICS’s and what are their pharmacokinetic properties?
- Poor oral bioavailability which is why little side effects and you inhale.
- Slow dissolution in aqueous bronchial fluid but high affinity for glucocorticoid receptor
- When inhaling some will go to stomach and some will sta in mouth
After a an ICS and a LABA have been added to an asthma treatment and this is still not controlling the patient’s condition, what can be added next?
- Increase dose of ICS to medium by having two puffs a day
- Add LTRA (montelukast)
What is the mechanism of action of leukotriene receptor antagonists like montelukast?
- Leukotrienes are released by mast cells/eosinophils, induce bronchoconstriction, mucus secretion and mucosal oedema and promote inflammatory cell recruitment through GPCR CysLT1
- LTRAs block the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor
- Only works in 15% of asthmatics
What are the side effects of using a LTRA?
- No major drug interactions but:
- Headache
- GI disturbance
- Dry mouth
- Hyperactivity
- Angiooedema
- Anaphalyxis
- Fever
How do long acting muscarininc antagonists (antimuscarinics) act as an addition controller therapy for asthma and what are the side effects of this drug?
- Tiotropium bromide and Ipratropium bromide
- Selective for M3 (SAMA are less selective) and have anticholinergic effects but not as effective as beta agonists in dilating
- Dry mouth, urinary retention, dry eyes
- Given in severe asthma and COPD
When diagnosing a patient with asthma what should you give them apart from pharmacological agents?
- Self management plan for better day to day management and reduce exacerbations
- Useful for children and carers
- Instructions on when to step up and down. Need to review after exacerbation
What are the characteristics of acute sever and life threatening asthma?
- Only need one bold to be classed as life threatening
- Fatal when CO2 starts to increase as patient is tiring. They need mechanical ventilation
What is the treatment plan when someone presents with acute severe/life threatening asthma?
OSHIT ME
Oxygen: get them to 94-98%
Salbutamol: high dose nebulised oxygen driven
Hydrocortisone/Prednisolone: IV or oral
Ipratropium Bromide: nebulised SAMA not LAMA like tio.
Theophylline/Aminophylline: I.V if life threatening and no success with above
What are the five tasks needed for management of stable COPD?
What is the treatment plan when someone presents with an acute exacerbation of their COPD?
- Nebulised salbutamol and/or ipratropium
- If hypercapnic or acidotic give air in nebuliser not oxygen
- Antibiotics
- Oral steroids: sometimes but not as effective as in asthma as not effective on neutrophils like eosinophils
- Review chronic treatment and aciton plan
What are the different inhaler options?
- Pressured metered dose inhalers: slow breath in and hold. can be used with a spacer
- Breath actuated MDI: automatic actuation
- Dry power inhalers: fast deep inhalation
NEED THE RIGHT TECHNIQUE TO GET THE RIGHT PARTICLE SIZE AND RIGHT DEPOSITION
How can you check someone is using the right inhaler technique?
In-check DIAL device measures inspiratory flow for different devices
What is the difference between a metered dose and dry powdered dose inhaler?
(google more)
- Dry powder has more pharyngeal deposition
Why are inhalers prescribed by brand name not class like other drugs?
Patients may have incorrect inhaler technique with a different brand, even if same mixture in the inhaler
What can help to improve a patient’s inhaler technique?
Spacer for MDIs gets it straight to lungs and not in mouth
