VIVA: Pharmacology - Respiratory

Question 1

Outline the groups of drugs that might be used in asthma and give an example of each

Answer 1

Sympathomimetics* (e.g. salbutamol)
Corticosteroids* (e.g. dexamethasone)
Muscarinic antagonists* (e.g. ipatropium)
Other bronchodilators (e.g. magnesium)
Antihistamines (for allergic asthma)
Methylxanthines (e.g. aminophylline)
Cromolyns (mast cell stabilisers; e.g. sodium cromoglycate)
Leukotriene inhibitors (e.g. montelukast)
Heliox (changes airflow dynamics)
Other smooth muscle dilators (e.g. ketamine, calcium channel blockers)
IgE monoclonal antibodies (e.g. omalizumab)

*needed to pass + one other with one correct drug example per group

Question 2

Outline the mechanism of action of corticosteroids in asthma

Answer 2

Increase in airway calibre by:
- Reduce bronchial reactivity*
- Inhibit lymphocytic and eosinophilic airway mucosal inflammation*
- Local immune suppression

*needed to pass

Question 3

Outline the types of drugs used as preventers in the management of asthma

Answer 3

Corticosteroids* (e.g. budesonide, fluticasone)
Cromolyn* / nedocromil
(+/- long-acting cromolyn - tilade)
Leukotriene pathway inhibitors (e.g. montelukast)
Long-acting anticholinergic
Long-acting B2 agonist
Anti-IgE monoclonal Ab (omalizumab)
Calcium channel blockers
NO donors

*needed to pass

Question 4

What are the potential adverse clinical effects of inhaled corticosteroid therapy?

Answer 4

Oropharyngeal candidiasis*
Hoarseness
Osteoporosis
Cataracts
Slows rate of growth in children

*needed to pass + one other

Question 5

Describe the mechanism of action of sodium cromoglycate?

Answer 5

Mast stell stabilisation*
Inhibits cellular activation of airway neurones (responsible for cough), mast cells, and eosinophils
Changed function of delayed Cl channels

*needed to pass

Question 6

What are the clinical uses of cromoglycate?

Answer 6

1. Asthma:
   - Antigen-induced
   - Exercise-induced
   - Occupational
   - In young children with extrinsic asthma
2. Systemic mastocytosis
3. Allergic rhinoconjunctivitis

Question 7

What B receptor types are there?

Answer 7

B1 *, B2 *, B3

*needed to pass

Question 8

What cellular processes do B-agonist - B-receptor coupling initiate?

Answer 8

Activation of all three receptor types results in stimulation of adenylyl cyclase*, and increased conversion of ATP to cAMP
Mediated by stimulatory coupling protein (Gs) via GDP and GTP

*needed to pass

Question 9

What are the clinical uses of B2 selective agonists?

Answer 9

Respiratory*, uterine (tocolytic) and vascular smooth muscle relaxation
Skeletal muscles K+ uptake

*needed to pass + one other

Question 10

What are the actions of B2 agonists in the treatment of asthma?

Answer 10

Smooth muscle relaxation/bronchodilation*
Inhibits mast cell release
Increases mucociliary activity
Acts via Gs protein, adenylyl cyclase and cAMP

*needed to pass

Question 11

Compare salmeterol and salbutamol

Answer 11

Salbutamol:
- IV, oral or inhaled
- Short-acting (4hrs)
- Partial agonist

Salmeterol:
- Inhaled
- Long-acting (12hrs) due to high lipid solubility (dissolves in smooth muscle membrane)
- Partial agonist
- Not useful for acute asthma

Question 12

What are the side effects of B2 agonists?

Answer 12

Need any two to pass:
- Skeletal muscle tremor
- Lactic acidosis
- Tachycardia
- Tachyphylaxis
- Hypokalaemia
- Transient hypoxaemia

Question 13

Describe the cellular mechanisms by which corticosteroids are believed to exert their effects in asthma acutely

Answer 13

2/5 needed to pass:
- Decreased activation of lymphoid cells/eosinophils
- Decreased cytokine production and action
- Decreased production of vasodilator prostaglandins
- Decreased histamine release
- Decreased production of IgE and IgG

Question 14

What class of drug is salbutamol?

Answer 14

Selective B2 agonist* used as a bronchodilator

*needed to pass

Question 15

What are the different routes of administration of salbutamol?

Answer 15

Inhaled: nebulised, puffer +/- spacer*
Oral, IV*, IM, subcut

*needed to pass

Question 16

What are the advantages of the different methods of administration of inhaled salbutamol?

Answer 16

Nebulised:
- Rapidly absorbed
- No coordination required
- Not much education required
- No first pass metabolism

Puffer +/- spacer:
- As effective as nebulised* when used properly
- Targeted
- Lower dose
- Less side effects*

*needed to pass

Question 17

Describe the pharmacokinetics of salbutamol

Answer 17

Absorption:
- Fast and complete (all routes including inhaled)*
- Rapidly absorbed in GIT, respiratory tract slower
- For inhaled: rapid onset with bronchodilation maximal within 15-30mins* and persists for 3-4hrs

Metabolism:
- 50% first pass metabolism: sulphated in the liver with metabolites excreted in kidneys
- Rest excreted unchanged in kidneys
- No metabolism in lungs
- Half-life 3-6hrs*

*needed to pass

Question 18

Describe the pros and cons of the different routes of delivery of salbutamol?

Answer 18

Spacer/inhaler*:
- Pros: targeted, low dose, minimise systemic side effects, as effective as nebulised, no first pass metabolism
- Cons: coordination and education required

Nebulised*:
- Pros: less coordination required and minimal education
- Cons: larger particles and hence dose required, noisy (children may get frightened), higher incidence of systemic side effects

Oral:
- Pros: easier in very young/disabled, longer half-life
- Cons: big doses, high side effect profile (tachycardia, tremor, nervousness, weakness), minimal advantage to inhaled, 50% first pass metabolism

IV/IM/subcut (useful in severe asthma):
- Pros: no first pass metabolism
- Cons: needle, painful, higher cost and side effect profile

*need to describe pros and cons of inhaled + one other route

Question 19

What are the organ system effects of theophylline?

Answer 19

CNS:
- Mild cortical arousal with increased alertness and deferral of fatigue
- Nervousness, tremor
- Overdose causes medullary stimulation, convulsions and death

CVS*:
- Positive chronotropic and inotropic effects by inhibiting presynaptic adenosine receptors in sympathetic nerves and increasing catecholamine release at nerve endings
- Increased HR, BP and CO
- May cause arrhythmias

GIT:
- Stimulates gastric acid and digestive enzymes secretion

Kidney:
- Weak diuretic from increased glomerular filtration and reduced tubular sodium reabsorption

Lung*:
- Bronchodilation by relaxing airway smooth muscle
- Inhibits antigen-induced release of histamine from lung tissue

*needed to pass

Question 20

How do the organ effects of theophylline correlate to its serum concentrations?

Answer 20

Theophylline has a narrow therapeutic window *, and its therapeutic and toxic effects are related to its blood level:
- 5-20mg/L: improvement in pulmonary function *, anorexia, nausea
- 15-20mg/L: vomiting, abdominal discomfort, headache, anxiety
- >40mg/L: seizures, arrhythmias *

*needed to pass

Question 21

What are the advantages and disadvantages of IV salbutamol in asthma?

Answer 21

2/4 needed to pass

Advantages:
- No first pass metabolism
- May be useful in severe/life-threatening asthma

Disadvantages:
- Requires IV access (disadvantage particularly in children)
- More systemic side effects