1. asthma: diagnosis....

Question 1

define asthma

what is it characterised by

Answer 1

reversible increases in airway resistance, involving bronchoconstriction and inflammation

• Characterised by reversible decreases in the FEV₁:FVC (less than 70-80% suggests increased airway resistance)
• Variations in PEF which improve with a b₂ agonist (+ morning dipping: asthma worse in morning PEF drops)
• May be managed pharmacologically: but under treated or poor compliance (poor inhaler technique)
• Hygiene hypothesis

Question 2

COPD

conditions

chracterisation

Answer 2

• Chronic bronchitis + Emphysema: spectrum covering these two conditions
• Chronic bronchitis: increased mucus, airway obstruction, intercurrent infections
• Emphysema: destruction of alveoli
• Smoking related
• FEV₁ reduced, little PEF variation

Question 3

PNS on bronchi

Answer 3

• A.Ch. acts on muscarinic M₃–receptors: bronchoconstriction
• Increase mucus

Question 4

SNS on bronchi

Answer 4

• Circulating adrenaline act on beta₂-adrenoceptors on bronchial smooth muscle->relaxation.
• Plus sympathetic fibres releasing NA, acting at adrenoceptors on parasympathetic ganglia- inhibit transmission.
• Beta₂-adrenoceptors also on mucus glands- inhibit secretion.

Question 5

what other type of nerve innervate bronchial smooth muscle aside from PNS and SNS?

Answer 5

sensory: reflex eg. dust- constriction

Question 6

asthma: predisposition and what is it provoked by

what two phases are there

Answer 6

genetic

• allergens
• cold air
• viral infections
• smoking
• exercise

early (immediate) and late (inflammatory) phase

Question 7

clinical features of asthma

Answer 7

• Wheezing (high pitched whistling sound normally heard when exhaling)
• Breathlessness
• Tight chest
• Cough (worse at night /exercise)
• Decreases in FEV₁, reversed by a b₂-agonist

Question 8

how are spasmogens related to asthma?

Answer 8

causes bronchospasm

released by mast cells

• Histamine
• Prostaglandin D₂
• Leukotrienes (C₄ & D₄)

Question 9

how are chemotaxins involved in asthma?

Answer 9

late phase

released by mast cells

• Leukotriene B₄, PAF triggered release
• Attract leukocytes, esp. eosinophils and mononuclear cells
• Leading to inflammation + airway hyper-reactivity- more sensitive to spasmogens

Question 10

treatment of asthma: inhalers

Answer 10

Bronchodilators: Reverse bronchospasm (early phase), rapid relief (“Relievers”)

Prevention: Used to prevent an attack-may be anti-inflammatory (‘Preventers)

Question 11

Beta₂-adrenoceptor agonists in asthma

use

downfall

what can overcome this

Answer 11

• e.g. salbutamol (Ventolin)
• Agents of 1st choice
• Increases FEV₁
• Act on b₂-adrenoceptors on smooth muscle to increase cAMP:
• Reduce parasympathetic activity
• Given by inhalation: 1 or 2 puffs when SoB
• Prolonged use may lead to receptor down-regulation: less responsive
• Long acting beta agonists (LABA) (e.g. salmeterol) given for long term prevention & long-term control (overnight)

Question 12

Xanthines in asthma

Answer 12

• e.g. theophylline
• Bronchodilators, not as good as beta-adrenoceptor agonists (2nd line use)
• Oral (or i.v. aminophylline in emergency)
• Phosphodiesterase inhibitors

Question 13

Muscarinic receptor antagonists in asthma

Answer 13

• Block parasympathetic bronchoconstriction
• Inhalation: prevents antimuscarinic side effects- selective
• Limited/little value in asthma, used in COPD

Question 14

anti-inflammatory agents in asthma

Answer 14

• Preventative: do not reverse an attack

Corticosteroids:

• activation of intracellular receptors, leading to altered gene transcription (decrease cytokine production) and production of lipocortin: delayed effect
• binds to intracellular receptor, steroid- receptor complex goes to nucleus
• Proteins inhibit LTs and PGs by inhibiting PLA2

Question 15

how do you prescribe steroids in asthma

Answer 15

Given with b₂-agonists – reduce receptor down-regulation

Side effects: throat infections, hoarseness (inhalation), adrenal suppression (oral)

• Rinse mouth to reduce side effects
• bronchodilaters given before

Question 16

Leukotriene receptor antagonists (LTRAs) in asthma

Answer 16

• New – increased role as add on therapy, good for eczema and allergic rhinitis
• Preventative AND bronchodilators, limited side effects
• Antagonise actions of LTs

Question 17

BTS guidelines for asthma

Answer 17

Question 18

treatments for COPD

Answer 18

• Stop smoking
• Bronchodilators (b₂-agonist + ipratropium)
• ‘Trial of steroids’
• Antibiotics for intercurrent infections
• Oxygen therapy

Question 19

NSAIDS and asthma

Answer 19

Non-steroidal anti-inflammatory drugs (NSAIDs) e.g. aspirin, ibuprofen may provoke asthma by increasing LT production: inhibit COX enzyme reduce prostaglandins

Question 20

which type of beta blocker is contraindicated with asthma

Answer 20

block beta2 receptors so no relaxation NEVER prescribe even if selective / COPD (?)

Question 21

mechanism of beta 2 adrenoreceptors

Answer 21

β adrenergic receptors are coupled to a stimulatory G protein of adenylyl cyclase

cAMP decreases calcium concentrations within cells and activates protein kinase A (phosphorylated MLCK). Both of these changes inactivate myosin light-chain kinase (phosphorylated) and activate myosin light-chain phosphatase (dephosphorylates MLC)

β2 agonists open large conductance calcium-activated potassium channels and thereby tend to hyperpolarize airway smooth muscle cells