Pulmonary Pharmacology

Question 1

Provide two examples of why pulmonary pharmacology is of clinical importance

Answer 1

Feline Asthma
-similar to huma asthma (delayed hypersensitivity
to inhaled allergens)

Equine recurrent airways obstruction (RAO)

Question 2

What is NANC?

Answer 2

Non-cholinergic non-adrenergic

Modulators of pulmonary circulation that are not inhibited by adrenergic or cholinic blockades

Question 3

What is NO?

Answer 3

Nitric Oxide

Regulator of pulmonary vasomotor tone

Question 4

How do muscarinic mediated bronchospasms occur?

Answer 4

Muscarinic receptors control smooth muscle tone, mucus secretion, vasodilation and inflammation

Possible some Alpha 1…

Question 5

Define respiritory disease

Answer 5

Respiratory disease is often characterized by abnormal production of secretions and exudates and by a reduced ability to remove them

Question 6

Outline the primary goal of the body during respiratory disease and how this is accomplished

Answer 6

Reduce volume and viscosity of the secretions & facilitate their removal.

Accomplished by controlling infection, modifying the 
    secretions, and when possible, improving postural 
    drainage and mechanically removing the material. 
	
Therapeutic methods include altering the inspired air and 
    administering expectorants, antitussives (suppress 
    coughing), bronchodilators, antimicrobials, diuretics 
    (remove salt?), and other drugs.

Question 7

List the characteristics of airway inflammation

Answer 7

Prolonged exposure to irritants:
- Narrowed airways
- Increased smooth muscle constriction
- Increased resistance
- Number of inflammatory mediators

Question 8

What are the potential targets of respiritory disease?

Answer 8

Airway inflammation
Bronchoconstriction
Irritation and cough
Infection

Question 9

Which division of the ANS is the adrenergic system apart of?

Answer 9

Sympathetic

Question 10

Name the different types / subtypes of adrenoreceptor system

Answer 10

α1, α2, β1, β2, and β3-receptors - (these have therapeutic relevance)

Question 11

In which cardio-respiratory structures are these different adrenoreceptors found?

Answer 11

Smooth muscle of the bronchioles and heart muscle

Question 12

How does bronchodilation occur by sympathetic stimulation

Answer 12

Beta2 adrenoreceptors
- (Nor)Adrenaline / (Nor)Epinephrine acting as agonist
- relax smooth muscle in lung
- dilation via increased cAMP
a1 mediated constriction in diseased airway

Question 13

Which division of the ANS is the cholinergic system apart of?

Answer 13

Parasympathetic

Question 14

Name the different types / subtypes of cholinergic system

Answer 14

Muscarinic receptors
M1, M2, M3

Question 15

In which cardiorespiratory structures are these different cholinergic receptors found?

Answer 15

Bronchiole and heart muscle

Question 16

How does bronchoconstriction occur by parasympathetic stimulation

Answer 16

Muscarinic receptors

M3 receptors:
		Decrease cellular cAMP, 
		Increased mucus secretion
		Contraction of bronchial smooth muscle
				
M1 receptors:
                     Increased mucus secretion

Question 17

What class of drugs acting on the autonomic nervous system could be used to reduce airway resistance?

Answer 17

Beta 2 agonists and M3 antagonists

Question 18

Outline the host defence system in the lungs (parasympathetic control)

Answer 18

Airway inflammation signal is sent to CNS via C fibre

CNS send information to parasympathetic airway ganglion via Vagal nerve.

Ganglion stimulates releases of Ach which will bind to M3 trigger mucus secretion or M1 which trigger bronchoconstriction

Question 19

Which of the following drugs would be most suitable and why?

Beta agonists: Epinephrine; Isoprenaline (isoproterenol); Salbutamol or Clenbuterol
Muscarinic antagonists: Atropine; Tiotropium or Ipratropium

Answer 19

Salbutamol or Clenbuterol

Tiotropium or Ipratropium

Question 20

Provide an overview of the peripheral nervous systems response to respiritory disease

Answer 20

Non-adrenergic non-cholinergic (NANC) neurotransmitter in many tissues

Released at same time as acetylcholine / noradrenaline

Primarily slower response

Excitatory or inhibitory

    Potential therapeutic targets: limited research

Question 21

How is control of airway muscle tone maintained?

Answer 21

Parasympathetic release of ACh stimulates M3 & M1 which causes constriction and increase in glandular secretions

Sympathetic/adrenal medulla both act to release noradrenaline which acts on B2 receptors leading to relaxation of smooth muscle

NANC can both relax (by use of VIP, NO) and contract (by use of SP, NK-A)

Question 22

What therapeutics are used to decrease inflammation?

Answer 22

Antihistamines

Glucocorticoids

Question 23

Outline how antihistamines work

Answer 23

Act to block effects of histamine as an H1antagonist by binding with H1 receptors on smooth muscle. Due to this blocking it prevents mast cells from degranulating releasing their histamine

Question 24

Outline the characteristics of corticosteroids

Answer 24

Control the signs of respiritory disease and not the cause

Reduce mucosal oedema

Reduce release of inflammatory mediators

Sensitise membranes to beta agonists

Prolong half life of adrenaline – slows uptake

Question 25

Outline other pulmonary therapeutic goals

Answer 25

• Modify airway resistance (less common pulmonary target)
• Decrease inflammatory and immune responses (less common pulmonary target)
• Stimulate respiration
• Suppress cough
• Increase watery component of secretions
• Inhibit infections - secondary

Question 26

List three other types of pulmonary drug and provide a brief overview of their mechanisms

Answer 26

Respiratory stimulants
(Doxapram hydrochloride)
Stimulate peripheral chemoreceptors and CNS
Used in CPR, delivery

Mucolytics
(e.g. Expectorants: Oils, turpentine)
Stimulate glandular cells
Breakdown mucus à decreased viscosity
Increases expulsion

Cough suppressants
(antitussives e.g. Opioids/opiates)
Non-productive coughs
Mechanical irritation (bronchi)
Inhibit medullary oblongata cough centre

Question 27

Outline the summary for pulmonary targets

Answer 27

Bronchodilators
- b2 agonists / Muscarinic antagonists

Inflammation
- Antihistamines
- Glucocorticoids

Irritation and cough
- Opioids
- Mucolytics

Infection
- Antibiotics