Lecture 18- Respiratory pharmacology Flashcards
(42 cards)
1
Q
Asthma pathophysiology
A
- Chronic inflammatory airway disease often caused by exposure to allergens or other environment exposure
- Causes intermittent airway obstruction and hyper-reactivity in small airways
- Non allergic around 30-40%
- Reversible
- A heterogeneous disease (don’t know everything about asthma)
2
Q
What does good Asthma control look like:
A
- Minimal symptoms during the 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)
- Aim is for early control with stepping up OR down as required
3
Q
what does uncontrolled asthma look like
A
4
Q
Before stepping up or down asthma treatment check…
A
- Adherence
- Inhaler technique
- Eliminate/reduce trigger factors
5
Q
Chronic asthma management 2 slightly different guidelines
A
BTS vs NICE
BTS
- low dose ICS (preventrer) + SABA prn
- add on LABA
- then consider increasing ICS and adding LTRA
NICE
- low dose ICS + SABA prn
- option 1: add on ICS/LABA
- or option 2: add on LTRA
Can step up and step down therapy
- LTRA cheaper than LABA
- Most end up on LABA anyway
6
Q
name some Steroids- inhaled corticosteroids (ICS) used to treat athma (as preventer)
A
- Beclomethasone
- Budesonide
- Fluticasone
7
Q
uses of ICS in asthma
A
- First line treatment
- Regular preventer when reliver alone not sufficient
8
Q
Pharmacokinetics steroids
A
- Poor bioavailability
- Due to lipophilic side chain added
- Slow dissolution in aqueous bronchial fluid
- High affinity for glucocorticoid receptor
- Local effect
- Most IC are substrate of CYP450 3A4
- If steroids absorbed po transported from stomach to liver via hepatic portal system (almost complete first pass metabolism)
- But at high doses all ICS potential to produce systemic side effects
- If steroids absorbed po transported from stomach to liver via hepatic portal system (almost complete first pass metabolism)
9
Q
MOA of ICS
A
- Pass through plasma membrane, activate cytoplasmic receptors, activated receptor then passes in to nucleus to modify transcription
- Reduces mucosal inflammation, widens airways, reduces mucus
- Reduces symptoms, exacerbations and prevents death
10
Q
Adverse drug response ICS
A
- If taken correctly very few significant ADRS
- Local immunosuppressive action e.g. candidiasis, horse voice (in pharynx)
- Wash mouth out after
- Pneumonia risk at high doses
11
Q
Drug-drug interactions ICS
A
CYP450 3A4 inhibitors e.g. budesonide
12
Q
name some drugs under B agonists
A
SABA and LABAs
13
Q
SABA uses
*
A
- ‘reliever’
- Symptom relief through reversal of bronchoconstriction
- Only to be use prn (when required)
- May be used prior to exercise to prevent bronchoconstriction
- When used regularly can reduce asthma control – tolerance?
- Seen as a quick fix esp in young adults
14
Q
uses of LABA taken with ICS
A
Add on therapy to ICS and prn SABA
15
Q
Mode of action B agonists
A
- Bind to B2 receptors (GPCR)
- Increase cAMP
- Increase PKA
- Cause airway smooth muscle to relax
- Also increase mucus clearance by action of cilia
16
Q
Adverse drug response B agonists
*
A
- Adrenergic- fight or flight effects
- Tachycardia
- Palpitations
- Anxiety
- Tremor
- Increase glycogenolyis (liver)
- Increased renin (kidney
- Supraventricular tachycardia
17
Q
Contraindication B agonist
A
- Should only be prescribed alongside ICS
- Alone can mask airways inflammation in near fatal and fatal attacks (LABA now always prescribed mixed with ICS)
- CVD- tachycardia may provide angina
18
Q
Drug-drug interactions B agonist
A
B-blockers may reduce effects of B2 agonists
19
Q
Additional asthma controller therapies:
A
- leukotriene receptor antagonist (LTRA) e.g. Montelukast (PO)
- Long acting muscarinic antaognist (LAMA) e.g. tiotropium
- theophylline
20
Q
Uses of LTRA
A
- Alternative to LABA in NICE guidelines
- Only useful in 15% of asthmatics- most end up moving up to LABA
21
Q
MOA of LTRA
A
- Inhibit leukotrienes released by mast cells/eosinophils by blocking CysLT1 receptor
- Reducing bronchoconstriction
- Reducing mucus
- Reducing oedema
22
Q
Adverse drug response LTRA
A
- Headache
- GI disturbance
- Dry mouth
- hyperactivity
23
Q
A
24
Q
uses of LAMA e.g. tiotropium
A
- Severe asthma and COPD
25
**Mode of action LAMA**
* Relatively antagonistic for M3 receptor (SAMA much less selective)
* Block vagally mediated contraction of airway smooth muscle
26
**Adverse drug response LAMA**
* Infrequent
* Anticholingeric effects
* Dry mouth
* Urinary retention
* Dry eyes
27
**uses of theophylline**
* Chronic poorly controlled asthma
28
29
MOA theophylline
* Adenosine receptor antagonist
* Reduce bronchoconstriction
30
**Adverse drug response theophylline**
* Narrow therapeutic index
* Life threatening complications inc arrhythmia – must measure [plasma]
31
**Drug-drug interactions theophylline**
CYP450 inhibitors- will increase theophylline
32
**Self management plans**
* Important for all asthmatics
* Written instruction on when and how to step up AND step down treatment
* Better day to day management and reduced exacerbations
* Think about who is involved
* Adult
* Child
* Cognitively impaired
* Carer
* **Should be reviewed following treatment for exacerbation and on discharge from hospital following acute attack**
33
define features of acute severe asthma
* Unable to complete sentences
* Peak flow 33-50% best or predicted
* Respiratory rate ≥ 25/min
* Heart rate ≥ 110/min
**Plus any of the following considered life-threatening:**
* Peak flow \< 33% best or predicted (if recordable)
* Arterial oxygen saturation (SpO2) \< 92%
* Partial arterial pressure of oxygen (PaO2) \< 8 kPa
* Normal partial arterial pressure of carbon dioxide (PaCO2) (4.6–6.0 kPa)
* Silent chest, Cyanosis, Poor respiratory effort, Arrhythmia, Exhaustion, Altered conscious level, Hypotension
34
treatment of acute severe and life threatening asthma
* Oxygen!!
* Increase to 94-98%
* High dose (nebulised) B2 agonist- continuous if necessary
* Driven in with oxygen
* Oral steroid (**prednisolone**) should be prescribed for minimum 5 days (IV if not oral- preferably oral)
* Continuous IC alongside
* Nebulised ipratropium bromide (**ipratropium**) – short acting muscarinic antagonist (SAMA) alongside b2 agonist if poor response alone
* Ipratropium less selective for M3 receptors compared to tiotropium, M2 activity too
* Consider IV aminophylline if life threatening/near fatal and no success with above
* Caution with taking PO theophylline
35
name a SAMA (short acting muscarinic antagonist
ipratropium bromide
Ipratropium is in a class of medications called bronchodilators. It works by relaxing and opening the air passages to the lungs to make breathing easier
36
COPD management
37
management of acute COPD exacerbations
**In acute exacerbations – requiring hospitalisation**
* nebulised **salbutamol** and/or ipratropium should be prescribed
* *If patient is hypercapnic or acidotic nebuliser should be driven by air and not oxygen**
* Oral steroids
- they can be less effective than in eosinophilic asthma due to reduced action on neutrophils
* Antibiotics (narrow spectrum – less severe, broad spectrum – greater severity)
* Review of chronic treatment and action plan
38
inhaler selection and prescribing
39
**Inhaler options**
* **Pressurised metered dose inhalers (pMDI)**
* **Breath-actuated pMDI**
* **Dry powder inhalers (DPI)**
40
**Pressurised metered dose inhalers (pMDI)**
* Inhalation and actuation of device
* Slow breath in and hold
* Can be used with a spacer to improve delivery
41
* **Breath-actuated pMDI**
* Newer
* Automatic actuation upon inspiration
42
* **Dry powder inhalers (DPI)**
* Micro ionised drug plus carrier powder
* Own inspiratory flow- fast deep inhalation (vs pressure metered dose inhalers)
