Treatment of asthma and COPD

Question 1

Management of acute asthma

Answer 1

Oxygen: get sats to >94%

bronchodilator: b2-agonist
glucocorticoids: prednisolone (oral) or hydrocortisone (IV, hospital). Continue for 5 days

Also:
ipatropium via nubuliser if initial response is poor
IV aminophylline
Antibiotics if cause is infective

Question 2

Mechanism of b2 agonists

Answer 2

beta-2 receptors are coupled to adenylate cyclase. b2-agonists bind to their receptors and activate adenylate cyclase, increasing cAMP.

cAMP activates PKA which phosphorlyates MLCK and inactivates it. It also phosphorylates the IP3 receptor which reduces Ca2+ release from the ER, and causes hyperpolarisaation of the cell by activating a K+ channel.

These reduce smooth muscle contraction and results in relaxation of the airway

Question 3

Common adverse effects of beta-2 agonists

Answer 3

Tremor

Tachycardia

Arrhythmias

Vasodilation

Headache

hypokalemia

Question 4

How does desensitisation of B2-agonists occur?

Answer 4

Repeated over-activation of beta2-Rs increases expression of phosphodiesterase which breaks down cAMP into AMP. This means that the drug has less of a bronchodilator effect.

Question 5

Difference between short acting and long acting beta2 agonists

Answer 5

Short acting: salbutamol - given by inhalation to prevent or treat wheeze in patients with reversible obstructive airway disease. Maximum effect in 30mins, and duration of 3-5hrs.

Long acting: salmeterol - given by inhalation but tke longer to bind to the receptor, either because they are stored in the lipid bilayer of the cell membrane or because they take longer to diffuse. Given to prevent bronchospasm in patients requiring long term therapy

Question 6

Mechanism of ipratropium bromide

Answer 6

Ipratropium is a muscarinic receptor antagonist.

It blocks M3 receptors on smooth muscle in the airway, which reduces the activity of PLC. Less Ca2+ is released from the endoplasmic reticulum. (less IP3 induced Ca2+ release)

Absent or reduced Ca2+ reduces the activity of MLCK and therefore reduces smooth muscle contraction. Airways are relaxed.

N.B. does not discriminate between muscarinic receptors. Side effects

Question 7

Mechanism of methylxanthine drugs

Answer 7

e.g. theophylline, aminophylline

Bronchodilator drugs

Inhibit PDE enzymes, increasing cAMP levels and promoting muscle relaxation.

Very toxic side effects: insomnia, arrythmias, seizures, nausea, vomiting,

narrow theraputic window.

Plasma concentration decreased by drugs that induce P450 enzymes.

Question 8

Effects of leukotriene antagonists

Answer 8

Reduces exercise-induced symptoms of asthma

Reduced inflammatory response in early and late ashma

Additive effect with other drugs

Side effects: abdo pain, headache, thirst, restlessness

Question 9

Theraputic use of glucocorticoids

Answer 9

Inhibit pro-inflammatory products and increase expression of anti-inflammatory mediators

prednisolone (oral)

Hydrocortisone (IV)

Question 10

Name 4 side effects of glucocorticoids

Answer 10

Cental obesity

Muscle wasting of the limbs

Interscapular adiposity (buffalo hump)

Moon face

Brusing

Thinning of the skin

Osteoporosis