Lec 42-asthma Flashcards
(49 cards)
Definition
- Asthma is a common long term condition that affects the airways
- Central to all definitions is the presence of symptoms (more than one of wheeze, n breathlessness, tight chest, cough and of variable airflow obstruction)
- More recent descriptions of asthma in both children and adults have included airway hyper-responsiveness and airway inflammation as components of disease
Demographics
- 8 million people- over 12% of the population- have been diagnosed with asthma at some point
- Asthma UK states around 5.4 million people receive treatment for the disease
- In 2012, 12,565 females per 100,000 and 12,033 males per 100,000 had asthma. Asthma occurred slightly more frequently in females than males throughout the years 2004-12
- Around 1,200 people a year are recorded as dying from asthma in 2012 (1.1% of total lung disorders
Symptoms
-More than one of the following symptoms: wheezing, breathlessness, chest tightness and coughs (particularly if worse at night or early morning)
-Triggers= irritate, tighten and inflame airways: Common cold; allergies to pollen; air pollution
-The airway lining becomes inflamed causing build up of sputum. This makes the airways even narrower, so harder to get air in and out of the lungs
+Exercise-induced-asthma
+History of atopic disorder
+Family history of asthma and or atopic disorder
Diagnosis
- The amount of air you breathe out is measure by
- Spirometry- measures the total amount of air you can breathe out from your lungs and how fast you can blow it out (presence and severity of airflow obstruction
- Peak flow meter measure how fast you can breathe out after you have taken a full breath in
2 phases of asthma
- Immediate phase reaction: on first exposure to Ag
- Late phase reaction: more sustained occurring 3-12 hours after early reaction
Eosinophils
-Major cells in the LPR Primarily a secreting cell- -Eosinophil granular associated proteins \+Major basic protein (MBP) \+Eosinophil cationic protein \+Eosinophil-derived neurotoxin \+Eosinophil peroxidase -Platelet activating factor (PAF) -Peptido leukotrienes (LTC4,LTD4 , LTE4) -Free radicals species
Inflammatory mediators
-Histamine
-COX products
-Lipooxygenase products
+Bronchoconstriction: powerful response in asthmatics
+Increased vascular permeability: Very potent PAF> LTD4» Histamine
+Increased mucous secretion: v.potent
-Bradykinin
-Platelet activating factor PAF
Drug treatment of asthma
- Asthma is common, incurable but eminently treatable
- Asthma is an inflammatory disorder- the inflammatory basis is an important target
- Relivers (bronchodilators): rapid symptomatic relief in an acute attack
- Preventers- prophylactic therapy to suppress immune component of asthma
- Non-pharmacological and alternative medicine- no convincing data of benefit
Aim in chronic asthma
- Control of symptoms- preferable no chronic symptoms e.g. no nocturnal dyspnoea, best possible pulmonary function with minimal side effects
- Stable long term control- no exacerbations
- Minimal nocturnal symptoms
- Minimal use of relievers
- Peak expiratory flow rate (PEFR) maintained at 80% best. circadian variation on PEFR <20%
- Minimal limitation on exercise
Pathway for drug treatment for asthma
1)Diagnosis and assessment
-Consider monitored initiation of treatment with low dose ICS
2)Evaluation: symptoms, lung function
NB should have short acting B2 agonist prn- consider moving up scale if use 3 or more times a week
-Regular preventer (Low dose ICS)
-Initial add on therapy: add inhaled LABA to low dose- ICS (normally as combo inhaler)
-Additional add on therapies: No response to LABA stop and increase dose of ICS; if benefit from LABA but no control- continue and increase ICS to medium dose; If benefit from LABA but control still inadequate- continue LABA and ICS and consider trial of other therapy (LTRA-MONTELUKAST, theophylline-phosphodiesterase inhibitor)
-High dose therapy: Increasing ICS to high dose; addition of 4th drug (LTRA, theophylline, B-agonist tablets, LAMA) and refer to specialist
-Continuous or frequent use of oral steroids: use daily steroid tablet in the lowest dose to provide adequate control; maintain high dose; consider other treatment to minimise use of steroid tablets (refer to specialist)
Chronic asthma: Step 1- mild intermittent asthma
-Short acting inhaled B2-bronchodilator (SABA) on prn basis (But no evidence against regular dosing)
-Asthma is not controlled at any step is using SABA
+>3 x a week
+Having symptoms 3x a week or more
+Waking at least once a week
-Same strategy for adults and children under 5 years but evidence base best in adults
-Inhaled B-agonist 30 min before exercise is treatment of choice for exercise induced asthma
B-agonsit in asthma
- Bronchodilation- B-receptor on bronchial smooth muscle.M`jor effect. Most quickly effective agents availeble. act as function antagonist
- Cholinergic nerves- some reduction of Ash release (post-ganglionic nerves)
- Mucous secretion- some decrease in viscosity leading to increased clearance
- Mast cells- B-receptors stabilise. No proven anti-inflammatory action. Little change in hyper-reactivity
Adverse effects
- Skeletal muscle tremor- diagnostic use
- Cardiac stimulation- direct B2 and indirect reflex due to peripheral B2-vasodilaiton
- Impaired ventilation/perfusion ratio
- Hyperkalaemia
- Increased glucose metabolism
- Increased lipolysis
- CNS stimulation- variable typically sleep disturbance
Choice of agent (B2)
-All B2-agonist are effective
-Pharmacological differences account for differing profile of action
+Degree of B2-selectivity
+Binding affinity: duration of action
+Binding kinetics: onset of action
-Systemic effects can be clinically significant
+Vascular B2: vasodilation. reflex tachycardia
+In high doses break through B1-agonism
Short acting B2-selective agonist
-None are catecholamines (rapid metabolism)
-Rapid onset of action (<10 minutes, leak 30-90 min) and relatively short duration 4-8 hours when given by MDI
-Some may be used orally for prophylaxis
-Relatively free of CVS effects by inhaled route
+Salbutamol
+Terbutaline
Systemic administration B-agonists
- Some active orally. Increase SE profile and little evidence of benefit (unless unable to use inhaler)
- Parenteral administration used in severe or life threatening asthma
- Caution in hyperthyroidism, CVS disease, diabetes
- Risk of hypokalaemia- may be serious with systemic administration
Chronic asthma Step2: regular preventer therapy
-Low dose inhaled corticosteroids \+Beclomethasone (BEC) 200mcg BD \+Budesonide- 200mcg BD \+Fluticasone- 100mcg BD \+Mometasone- 200mcg BD -NB for dry powder inhaler
CFC free inhalers- HFA propellants
BECLOMETHSAONE (BEC)
-Qvar: extra-fine particles and more potent than traditional CFC containing inhalers and 2x more potent than clenil
-Clenil modulite: Is same potency as dry powder and CFC BEC inhalers
NB: QVAR and CLENIL are NOT interchangeable and should be Rx by brand
-Dose conversion advice in BNF
-Steroid card issued with high dose BEC
Alternative step 2 strategies
- Cromones: DSG ineffective in children, nedocromil not effective <5years
- Long active Beta-Agonist (LABAs)- have effect but should not be used without steroid therapy- so not step 2
- Leukotriene antagonists- have some effect. May be useful in children particularly <5
- Theophylline- may have beneficial effect but side effects. Caution
Glucocorticoids
First used early 1950 by systemic route
-Most powerful agents for asthma therapy
-Major systemic actions
-No direct bronchodilator activity: no immediate relief from symptoms
-6 hours before benefit and even with injection Max benefit only after 12-24 hours
INHALED administration of topically active steroids
+At suitable dosage minimises systemic actions- step 2 ‘standard dose’ regimens
+Now a major component in asthma therapy
Inhaled Administration
-Agents must have potent topical action
-BEC and budesonide equipotent
-No convincing evidence of advantage for any individual agent
-Deposition in oropharyngeal tract is a problem (Candidiasis, dysphoria can occur even at low dose)
+May minimise by use of spacers or prior administration of B-agonist
+Rinse mouth after use. particularly in higher dose schedules
Inhaled steroids- ADRs
-HPA suppression
+No significant risk BDP <800mcg dd adult or 400mcg dd child
-Bone resorption- some controversy
+Modest effects down to 500mcg dd in adults
-Carbohydrate metabolism/ Lipid metabolism
+Effect minor and not significant <800mcg dd
-Growth retardation: possible above 400mcg dd in children- usually short term. Monitor growth and use lowest possible dose
Mode of action in asthma (ICS)
-Major effect in suppression of cytokine synthesis and release and so recruitment of inflammatory cells (particularly eosinophils)
-Affect many components of inflammatory response
+Inhibit PLA2
+Inhibit macrophage activation
+Depress Ab synthesis
+Depress activation and recruitment of T cells and eosinophils
+Depress release of peptide-LTs
+(Little immediate direct effect upon mast cells)
Step 3: initial add on therapy
- Check compliance before action
- Add inhaler LABA to low dose ICS (combination inhaler)
