Resp Part 1 Flashcards
Beta 2 agonists, anti-muscarinincs, ICS, oral corticosteroids
Indications of β2-agonists (short-acting and long-acting)?
Asthma:
- SABA (relieve breathlessness)
- LABA (used alongside ICS for chronic asthma; ALWAYS give LABA with ICS)
COPD:
- SABA (relieve breathlessness)
- LABA (2ND LINE to reduce exacerbations + improve symptoms)
Hyperkalaemia
- nebulised salbutamol
Mechanism of action of β2-agonists?
Activates beta2 receptors in smooth muscle of bronchi/gut/uterus/blood vessels.
→ stimulates GPCR (G protein-coupled receptor) signalling cascade.
→ causes smooth muscle relaxation.
→ As a result, improves airflow in constricted airways and reduces breathlessness.
β2-agonists stimulate Na/K ATPase pumps.
→ causes K+ to move from outside of cells to inside.
Examples of SABA?
Salbutamol
Terbutaline
Examples of LABA?
Salmeterol
Formoterol
Adverse effects of β2-agonists?
Tachycardia
Palpitations
Anxiety
Tremor
Promote glycogenolysis →increase serum glucose conc
At high doses →serum lactate may rise
LABA -muscle cramps
Warnings of β2-agonists?
ALWAYS offer LABA + ICS
- LABA alone is associated with increased asthma deaths.
CVD pts:
- tachycardia may provoke angina/arrhythmias
→occurs in tx of hyperkalemia when high doses are given.
Important interactions of β2-agonists?
Effectiveness may be reduced by β-blockers.
Concomitant use of high-dose nebulised β2-agonists with theophylline and corticosteroids can cause hypokalemia
→ so monitor serum K conc
How are β2-agonists monitored?
Asthma:
- monitor disease severity by assessing their symptoms and serial measurements of PEFR (peak expiratory flow rate).
COPD:
- monitor disease severity by assessing their symptoms and exacerbation rate.
Patient education on β2-agonists?
Aim to make their airways relax and improve breathing.
Seek medical advice if they use the inhaler very frequently
- increase other tx (e.g. ICS) according to their written action plan.
Ensure they know how and when to take the inhaler (e.g. for acute episode, before exercise, or regular long-acting medication).
Multiple doses in a short time period can cause pt to feel shaky and anxious.
Indications of anti-muscarinics (short-acting and long-acting)?
Asthma:
- SAMA (relieve breathlessness during acute exacerbation; given in addition to SABA).
- LAMA (offered to pts one or more severe asthma exacerbation in the past year; given alongside ICS + LABA).
COPD:
- SAMA (relieve breathlessness during acute exacerbation/exercise).
- LAMA (prevent breathlessness and exacerbation)
Mechanism of action of anti-muscarinics?
BRONCHODILATORS
Anti-muscarinics bind to muscarinin receptor by acting as a competitive inhibitor of acetylcholine
→ increases HR and conduction
→ reduces smooth muscle tone and secretions from glands in the resp and GI tract
In the eye:
→ causes relaxation of the pupillary constrictor, hence results pupillary dilation.
→ causes relaxation of ciliary muscles, hence prevents accommodation.
Adverse effects of anti-muscarinics?
Irritation of resp tract:
- Nasopharyngitis
- Sinusitis
- Cough
GI disturbance:
- Dry mouth
- Constipation
- Urinary retention
Blurred vision
Headaches
Warnings of anti-muscarinics?
Use with caution in pts:
- susceptible to acute angle closure glaucoma (can increase intraocular pressure)
- with/at risk of arrhythmias/urinary retention
Important interactions on anti-muscarinics?
Not generally a problem due to LOW SYSTEMIC ABSORPTION.
Monitoring of anti-muscarinics?
Effectiveness assessed by:
- improvement of symptoms
- review PEFR (for asthma)
Check inhaler technique at every review and correct it to optimise potential tx benefits.
Pt education on anti-muscarinics?
Aims to open airways and improve breathing.
Ensure they know how and when to take the inhaler (e.g. for acute episode, before exercise, or regular long-acting medication).
Discuss SEs e.g. dry mouth →advise pt to keep a bottle of water or chew gum or suck sweet to relieve this symptom.
Examples of SAMA (shorting-acting anti-muscarinics)?
ipratropium
Examples of LAMA?
tiotropium
Indications of ICS (inhaled corticosteroids)?
Asthma:
- for airway inflammation and control symptoms if SABA not effective alone
COPD:
- for symptom control and prevent exacerbation in severe airflow obstruction on spirometry and/or recurrent exacerbation
Adverse effects of ICS?
Oral candidiasis
Hoarse voice
In COPD:
- risk of pneumonia
In high dose ICS:
- adrenal suppression
- growth retardation (in CHILDREN)
- osteoporosis
MOA of ICS?
Corticosteroids pass through the plasma membrane and activate receptors in the cytoplasm.
→ activated receptor passes into the nucleus and DOWNREGULATES interleukins/cytokines/chemokines and UPREGULATES anti-inflammatory proteins.
→ this reduces mucosal inflammation, widens the airways, reduces mucus secretion
→ hence improve symptoms and reduce exacerbation in asthma and COPD
Warnings of ICS?
High dose ICS (specifically FLUTICASONE)
Use with caution in:
- COPD pts with a hx of pneumonia
→ children due to growth retardation (suppression) risk.
Important interactions of ICS?
None significant.
Monitoring ICS?
Asthma:
- monitor disease severity by assessing their symptoms and serial measurements of PEFR.
COPD:
- monitor disease severity by assessing their symptoms and exacerbation rate.
- review after 3-6months tx to see if tx needs to be adjusted or maintained.
Pt education on ICS?
Aims to reduce inflammation in the lung.
Steroid is unlikely to be absorbed into the body except in high dose tx.
Advise rinse mouth and gargle after taking inhaler to prevent development of a sore mouth or hoarse voice.
Ensure they know how to use the inhaler at each review, correct if needed.
Examples of ICS?
beclometasone
budesonide
fluticasone
Indications of oral corticosteroids?
Allergic or inflammatory disorders (e.g. anaphylaxis, asthma)
Suppression of autoimmune disease (e.g. IBD, inflammatory arthritis)
Cancer (reduces tumour-associated swelling)
Hormonal replacement (in adrenal insufficiency or hypopituitarism)
MOA of oral corticosteroids?
Drug binds to glucocorticoid receptors, which then translocate to the nucleus and bind to glucocorticoid-response elements.
→this regulates gene expression.
Drug modifies the immune response by:
→UPREGULATES anti-inflammatory genes.
→DOWNREGULATES pro-inflammatory genes (e.g. cytokines, TNFα)
→this suppresses circulating monocytes and eosinophils.
Metabolic effects include:
- INCREASED gluconeogenesis (due to increased AA and fatty acids, released by catabolism of muscle and fat)
-MINERALOCORTICOID EFFECTS (stimulating sodium and water retention AND potassium excretion in renal tubule)
Adverse effects of oral corticosteroids?
Immunosuppression (increase risk of infection, alters host response)
Metabolic effects:
- DM
- Osteoporosis
Mood and behavioural changes:
- Insomnia
- Confusion
- Psychosis
- Suicidal thoughts
Mineralocorticoids actions results in:
- Hypertension
- Hypokalemia
- Oedema
Prolonged tx causes:
- adrenal atrophy (prevents endogenous cortisol secretion)
Sudden tx withdrawal causes:
- acute Addisonian crisis with CVS collapse
→hence easing off tx is required.
Chronic glucocorticoid deficiency can occur during tx withdrawal:
- fatigue
- wt loss
- arthralgia
Warnings of oral corticosteroids?
Prescribe with caution in people with:
- Infection
- children (can suppress growth)
Important interactions of oral corticosteroids?
Corticosteroids + NSAIDs:
- peptic ulceration
- GI bleeding
Corticosteroids + β2-agonists/loop or thiazide diuretics/theophylline:
- hypokalaemia
Efficacy of corticosteroids REDUCED by cytochrome P450 inducers.
Corticosteroids REDUCE immune response to vaccines.
Monitoring of oral corticosteroids?
Efficacy monitored:
- peak flow for asthma
- blood inflammatory markers
In prolonged tx, monitor for adverse effects:
- glucose and HbA1c (diabetes)
- DEXA (bone density)
Pt education on oral corticosteroids?
Tx should suppress the underlying process.
Start to feel better within 1-2 days.
Prolonged tx -advise pt to not stop tx suddenly.
Give pts a steroid card to carry with them at all time and show if they need tx.
Discuss benefits and risks, including osteoporosis, bone fractures, and diabetes so that pt can make an informed decision.
