Lecture 16 - Pharmacology of the Respiratory System

Question 1

in a diseased airway what is airflow like?

Answer 1

higher resistance to airflow –> smaller lumen size

Question 2

what are the two treatment classes of drugs for feline asthma?

Answer 2

• bronchodilators

- anti-inflamamtory

Question 3

what are the aims of respiratory drugs/treatment?

Answer 3

• control inflammation
• minimis bronchoconstriction
• minimise long term damage

Question 4

what are the steps in smooth muscle contraction and relation?

Answer 4

CONTRACTION
–> stimulus –> Ca2++ release –> calcium bind to calmodulin –> activates MLCK –> phosphorylates myosin –> only phosphorylated myosin can bind to actin

RELAXATION STEPS
withdrawal of stimulus –> Ca2+ uptake SR –> myosin looses P –> thin filament/thick filament disengagement –> relaxation (lattice normal shape)

Question 5

what are the three classes of bronchodilators?

Answer 5

1. beta-2 adrenoreceptor agonists
2. phosphodiesterase inhibitors
3. muscarinic receptor antagonists

Question 6

what is the mechanism of action for beta 2 adrenoreceptor agonists?

Answer 6

normally ATP –> cAMP via adenyl cyclase
beta 2 adrenoreceptor agonists bind to adrenergic receptors increasing activity of adenyl cyclase
= increased cAMP –> increased cAMP dependent protein Kinase
=> Inactivation of MLCK
=> increased mucociliary clearance

Question 7

what is an example of a b2 adrenoreceptor agonist?

Answer 7

Clenbuterol

Question 8

in what circumstances does clenbuterol work best?

Answer 8

when used in conjunction with allergen and just avoidance, and/or anti-inflammatory adminisatrion

Question 9

what are side effects of b2 adrenoreceotor agonists such as clenbuterol?

Answer 9

at high doses = beta 1 effects: tachycardia, excitement and sweating.
AND b2 effects in preg. mares inhibit uterine contractions

Question 10

what is the mechanism of phosphodiesterase inhibitors?

Answer 10

block phosphodiesterase mediated breakdown of cAMP

therefore high levels of cAMP remain –> increased PKA –> inactivation of MLCK

Question 11

what do phosphodiesterase inhibitors cause?

Answer 11

• relaxation of airways
• increased HR and increased cardiac output
• CNS stimulation

Question 12

are phosphodiesterase inhibitors as effective as beta agonists at bronchodilation?

Answer 12

no - useful adjunct therapy in asthma and COPD

Question 13

what are unwanted side effects of phosphodiesterase inhibitors?

Answer 13

• CNS stimulation - tremor, nervousness
• Dieuresis as a result of increased blood flow
• they have a NARROW THERAPEUTIC WINDOW: GI symptoms, nausea, vomiting, anorexia w/ increasing dose

Question 14

what are two types of phosphodiesterase inhibitors?

Answer 14

• Theophylline

- Aminophylline

Question 15

what are the effects of the phosphodiesterase inhibitor theophylline on airways? (inflammatory and structural cell populations)

Answer 15

structural cells - decreases leak from endothelial cells, may increase strength of respiratory skeletal muscles, causes bronchodilation of airway smooth muscle

inflammatory cells - anti-inflam effects on inflammatory cells

Question 16

what is the mechanism for muscurinic receptor antagonists?

Answer 16

block the parasympathetic nerve reflex causing airways to constrict
bind to muscurinic receptors, competitively inhibiting acetylcholine –> stop bronchospasm

Question 17

when are muscurininc receptor antagonists used

Answer 17

often used when B2 agonists haven’t worked or need combination drugs

Question 18

what are the classes of other drugs used in airway disease?

Answer 18

• anti-inflammatory: sodium cromoglycate
• antitussives (Cough suppressants): opioids, antihistamines
  mucolytics: increase mucus clearance, change character of mucus eg/ bromhexine