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Block 2: Pathophysiology and Pharmacology > Pharmacology of airway diseases > Flashcards

Pharmacology of airway diseases Flashcards

1
Q

List the classes of drugs used in the management of chronic airway diseases

A

Bronchodilators: “BAM”
Beta2-andrenoreceptor agonists
Anti-cholinergics
Methylxanthines

Anti-inflammatory: “LU-GLU”
Leukotriene receptor antagonists
Glucocorticoids (corticosteroids)

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2
Q

What is the treatment pathway for severe acute asthma?

A 
O..SHIT! 
Oxygen 
Salbutamol (beta2-agaonist) 
Hydrocortisone (glucocorticoid) 
Ipratropium (anticholinergic 
Theophylline (methylxanthine)
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3
Q

How does the sympathetic nervous system influence lung function?

A

Drives bronchodilation, mostly via adrenergic nerve fibres and noradrenaline

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4
Q

How does the parasympathetic nervous system influence lung function?

A

Drives bronchoconstriction, mostly via cholinergic nerve fibres and acetylcholine

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5
Q

What is the mechanism of action of Beta2 Agonists?

A

Stimulate adrenergic responses in the bronchiolar smooth muscle cells in the lungs.

  1. Bind directly (or indirectly) to Beta2 Receptor on cell membrane
  2. Activates G protein associated to receptor
  3. Activates adenylate cyclase enzyme which drives generation of cAMP from ATP
  4. cAMP activates PKA (Protein Kinase A enzyme)
  5. PKA acts specifically on cells to bring about bronchodilation
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6
Q

What specific actions does Protein Kinase A enzyme have on the bronchiolar smooth muscle cells to bring about bronchodilation?

A

Reduces intracellular calcium

Reduces smooth muscle contractions

Reduces activity of myosin light chain kinase

Dephosphorylation of myosin light chain via MLCP (part of contractile pathway)

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7
Q

Give 2 short-acting and 2 long-acting examples of Beta2 adrenoreceptor agonists?

A

Short acting: Salbutamol + Terbutaline

Long acting: Salmeterol + Formoterol - enter proximal plasma membranes and interact with sites at different point to sustain effect

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8
Q

What are the key side effects of Beta2-adrenoreceptor agonists?

A

Tremor, tachycardia, cardiac arrhythmia

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9
Q

What is the mechanism of action for anticholinergic drugs in the lungs?

A
  1. Binds to M3 Muscarinic Acetylcholine Receptor on cell membrane of smooth muscle cells in lungs
  2. Prevents acetylcholine from stimulating pathway that eventually leads to bronchoconstriction

[Nb. normal bronchoconstriction pathway - G protein stimulated, phospholipase C enzyme activated, calcium released, bronchoconstriction]

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10
Q

What are the key side effects of anti-cholinergics?

A

Dry mouth, constipation, urinary retention

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11
Q

Give 1 short-acting and 1 long-acting example of anticholinergics

A

Short acting: Ipratropium

Long acting: Tiotropium

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12
Q

What is the mechanism of action for methylxanthines?

A

Inhibit enzyme phosphodiesterase (PDE) - this enzyme normally inactivates cAMP so by inhibiting the actions of this enzyme this is sustaining cAMP action (allowing for bronchodilation)

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13
Q

Give 2 examples of methylxanthines?

A

Theophylline and Aminophylline

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14
Q

What are the key side effects of methylxanthines?

A

Cardiac arrhythmias, seizures

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15
Q

What is the mechanism of action for leukotriene receptor antagonists?

A
  1. Blockade of CysLT1 Leukotriene Receptors on Eosinophils and smooth muscle cells in lungs
  2. Reduction of inflammatory response in early and late phases of asthma

[Nb. Often used in conjunction with other drugs to provide an additive effect and given orally as a ‘preventer’ in asthma management]

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16
Q

What is a leukotriene?

A

Lipid-based signalling molecule with multiple effects in lungs:

Leukotriene receptors on Eosinophils guide Eosinophil chemotaxis to site of inflammation
Leukotriene receptors on bronchiolar smooth muscle cells stimulate constriction similar to Acetylcholine (via phospholipase C activation)

17
Q

What are the key side effects for leukotriene receptor antagonists?

A

Abdominal pain, headache

18
Q

What are the key examples of glucocorticoids used in the lungs?

A

Inhaled:
Beclomethasone
Fluticasone

Oral:
Prednisolone

IV:
Hydrocortisone

19
Q

What is the mechanism of action for glucocorticoids?

A
  1. Targets intracellular glucocorticoid receptors in immune cells in the lungs (e.g. macrophages, T-lymphocytes and eosinophils)
  2. Activated glucocorticoid receptor interacts with selected nuclear DNA sequences and influences the expression of many key genes:
  • Suppression of pro-inflammatory mediators
  • Expression of anti-inflammatory products
20
Q

What are the key side effects for glucocorticoids?

A

Many side effects including moon face, weight gain, osteoperosis, hyperglycaemia

21
Q

What are the common examples of leukotriene receptor antagonists?

A

Montelukast and Zafirlukast

Block 2: Pathophysiology and Pharmacology (11 decks)

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