Respiratory Pharmacology 2

Question 1

Muscarinic system: Cholinergic receptors

Answer 1

• Nicotinic - somatic NS and autonomic ganglia
• Muscarinic - Parasympathetic effector

Question 2

Smooth muscle : M3 receptor

Answer 2

• Exocrine salivary gland, smooth muscle and GI
• Bladder, blood vessel and endothelium
• Increase IP3 stimulation which stimulates Ca2+

Question 3

Muscarinic receptor mechanism

Answer 3

• Neurone in Vagus nerve parasympathetic preganglionic nerve binds to M1
• Parasympathetic postganglionic nerve M2 releasing Ach binding to M3 receptor releases Ca2+ causing contraction

Question 4

Muscarinic antagonist

Answer 4

• Effects are limited by lack of selectivity binding to M2 autoreceptor
• They aim to inhibit acetylcholine

Question 5

Why are muscarinic receptors used

Answer 5

• Non-specific limit effect on smooth muscle contraction
• Cause bronchodilatory effect
• reduces mucus build up (M3 increases gland secretion)
  – may increase muco-cillary clearance

Does effect late phase asthma

Question 6

Ipratropium

Answer 6

• Derivative of N-isopropylatropine
• Onset of action 30 mins; lasts 3-5 hours
• Not selective for M receptor subtypes
• Used as short term reliever COPD longer onset than salbumol

SABA

Question 7

Tiotropium

Answer 7

• longer-acting and slightly more selective
• once daily dosing
• More lipophilic
• Used more in COPD than asthma

LAMA

Question 8

Adverse effects common muscarinic antagonist

Answer 8

• Miinimal when inhaled
• Anti-muscarininc side effects such as GI tract and dry mouth as effects M3

Question 9

Adverse effects uncommon muscarinic antagonist

Answer 9

• Exacerbation of angle glaucoma
• Urinary retention

Question 10

Asthma

Answer 10

• May be used as an adjunct to Beta 2 agonists and steroids
  – Bronchospasm - precipitated by B2 antagonist

Question 11

Xanthines mechanism

Answer 11

• Phosphodiesterase enzyme regulating intracellular levels of cAMP and cGMP
• Methylxanthines inhibit PDE maintaining cAMP levels
• MLCK inactivated
• Myosin not phosphorylated
• Achieves bronchial smooth muscle
  relaxation

Mechnism unclear

Question 12

Xanthines Mechanisms Adenosine receptor antagonism

Answer 12

• Methylxanthines are antagonist of A1 and A2 receptors
• A1 stimulates in airways causing bronchoconstriction in asthmatics

Question 13

Xanthines Mechanisms Anti-inflammatory effect

Answer 13

• Increase cAMP to prevent inflammatory cell activation
• May potentiate effects of corticosteroids

Question 14

Xanthines Mechanisms CNS stimulation

Answer 14

• Stimulate respiratory control centre in COPD

Question 15

Theophyline

Answer 15

• Quite insoluable
• Narrow theraputic index
• Many drug-drug interactions
  CytP450

Question 16

Aminophyline

Answer 16

• More soluable version of Theophyline it is the ester

Question 17

Xanthines formulation and uses

Answer 17

• Both Orally (modified release formulas)
• Aminophyline IV in acute severe asthma

Question 18

Xanthines Unwanted effects

Answer 18

• Effecting CNS, CVS causing Nervousness, insomnia
• Narrow theraputic window :
• Serious CVS CNS
  – Cardiac dysrhythmia (can be fatal)
  – Seizures (at only slightly above therapeutic range)
  – Monitor

Question 19

Xanthines Unwanted effects on pKa

Answer 19

• Absorption from gut unpredictable due to variable plasma half life as modified release

Question 20

Xanthines Unwanted effects when metabolising p450 enzyme

Answer 20

• Plasma decreased by drugs that induce P450 enzymes
• Eg carbamazepine, phenytoin
  Plasma concentration increased by drugs that inhibit P450 enzymes
• Eg erythromycin

Question 21

Leukotriene receptor antagonists mechanism: Leukasts

Answer 21

• Cysteinyl leukotrienes LTD4 act on CysLT1 receptor in
  respiratory mucosa
  Airway inflammation and hyper activity
• Montelukast & Zafirlukast antagonise the CysLT1 receptor

Question 22

Leukotrienes

Answer 22

• Arachidonic acid metabolites
• Synthesized from arachidonic
  acid and bind to receptors on
  target tissues
• Formed by leukocytes including activated mast cells and eosinophils

Question 23

Activation of cysteinyl leukotriene receptor

Answer 23

• Leukocyte recruitment
• mucus secretion
• vascular permeability / airway
  oedema
• smooth muscle contraction

Question 24

Mechanism Leukotriene receptor antagonists

Answer 24

• Prevention of bronchoconstriction mediated by LTs
• Inhibit early & late phase responses to irritants in asthma
• Taken orally with inhaled corticosteroid
• Relax airways in mild asthma not as effective as salbutamol or ICS

Question 25

Histamine H1 receptor antagonists

Answer 25

• Mast cell degranulation and release of histamine - required early phase allergic asthma
• Histamine binds to H1 Mucus secretion cause some Bronchoconstriction
• Mildly effective in mild atopic asthma