Physiology of Respiration

Question 1

Where is the respiratory centre in the brain?

Answer 1

Medulla

Question 2

Which chemoreceptors control the partial pressure of CO2 on arterial blood?

Answer 2

Medullary chemoreceptors

Question 3

Which chemoreceptors control the partial pressure of oxygen in arterial blood?

Answer 3

Carotid body chemoreceptors

Question 4

Which efferent pathways control airways?

Answer 4

• Cholinergic parasympathetic nerves
• Non-noradrenergic non-cholinergic (NANC) inhibitory nerves
  (inflammatory mediators and other bronchoconstrictors also have a role in diseased airways

Question 5

What is FEV1 and PEFR?

Answer 5

FEV1- forced expiratory volume in 1 second

PEFR- Peak expiratory flow rate- maximal flow (l/min) after a full inhalation

Question 6

The bronchial smooth muscle is predominantly innervated by which autonomic innervation?

Answer 6

Parasympathetic- ganglia are embedded in the walls of the bronchi and bronchioles
Postganglionic fibres innervate airway smooth muscle, vascular smooth muscle and glands

Question 7

Types of M receptors and which type of Muscarinic receptors are pharmacologically more important?

Answer 7

M3-found on bronchial smooth muscle and glands- mediate bronchoconstriction and mucus secretion

• M1- localised in ganglia and on postsynaptic cells and facilitate nicotinic neurotransmission
• M2- Inhibitory autoreceptors mediating negative feedback on Ach

Question 8

Bronchodilators released by NANC

Answer 8

VIP and Nitric oxide

Question 9

Which parts of the lung do sympathetic nerves innervate?

Answer 9

Tracheobronchial blood vessels and glands but not human airway smooth muscle

Question 10

Which B adrenoceptors are in the airways

Answer 10

B2- beta agonists relax bronchial smooth muscle and inhibit mediator release from mast cells- increases mucociliary clearance

Question 11

Location and myelination factor of irritant fibres and C fibres

Answer 11

Irritant fibres- myelinated- Upper airways

C fibres- unmyelinated- low airways

Question 12

Which tachykinins are released with the excitation of sensory nerves?

Answer 12

Substance P and neurokinin A

Question 13

Name two drugs used to treat other conditions which affect the lung and can cause fibrosis

Answer 13

Amiodarone- class III antiarrhythmic drug- potassium channel blocker
Methotrexate- chemotherapy agent and immunosuppressant

Question 14

What is asthma?

Answer 14

It is an inflammatory condition in which there is recurrent reversible airway obstruction in response to irritant stimuli that are too weak to effect non-asthmatic subjects- causes wheezes and needs treatment

Question 15

Characteristics of asthma

Answer 15

• Inflammation of the airway
• Bronchial hyperreactivity
• reversible airways obstruction
  Intermittent attacks of wheezing, shortness of breath and sometimes cough
  Acute asthma causes hypoxaemia

Question 16

Pathogenesis of asthma

Answer 16

Exposure of genetically disposed individuals to allergens: activation of Th2 lymphocytes and cytokine generation promotes:
- differentiation and activation of eosinophils
IgE production and release
- Expression of IgE receptors on mast cells and eosinophils

Question 17

Characteristics of the immediate phase of an asthma attack

Answer 17

Abrupt

• spasm of the bronchial smooth muscle
• allergen interaction with mast cell-fixed IgE causes release of histamine, leukotriene B4 and Prostaglandin D2.

Question 18

Characteristics of the late phase

Answer 18

Late phase or delayed response and may be nocturnal.

Progressing inflammatory reaction, initiation, of which occurred during the first phase, influx of Th2 lymphocytes

Question 19

Two categories of antiasthma drugs

Answer 19

Bronchodilators and anti-inflammatory agents

Question 20

5 steps of treatment

Answer 20

1- mild - salbutamol
2- add ICS
3- uncontrolled add LABA- salmeterol or formoterol- minimises the need for increased doses of inhaled corticosteroid
4- Theophylline and leukotriene antagonists- montelukast- coticosteroid sparring effect
5- prednisolone in addition to oral corticosteroid

Question 21

Bronchodilators other than B2- adrenoceptor agonists

Answer 21

Theophylline, cysteiny leukotriene receptor antagonists and muscarinic receptor antagonists

Question 22

How are B2 adrenoceptor agonists usually given

Answer 22

Inhalation of aerosol, powder or nebulised solution

Question 23

SABA and LABA examples

Answer 23

SABA- Salbutamol - inhalation- max effect within 30 min and duration of action 3-5h

LABA- Salmeterol and formoterol- inhalation- duration of action is 8-12 hours

Question 24

Theophylline characteristics

Answer 24

• Methylxanthine
• Inhibits phosphodiesterase and blocks adenosine receptors
• Narrow therapeutic window
• Antibiotics increase half-life, anti-convulsants

Question 25

Which drugs are third line for asthma?

Answer 25

Cysteinyl leukotriene receptor antagonists

Question 26

Commonest adverse effect of B2 adrenoceptor agonist

Answer 26

Tremor- tachycardia and cardiac arrhythmias

Question 27

Unwanted side effects of Theophyllines

Answer 27

Insomnia, nervousness, seizures - it has a very narrow therapeutic index

Question 28

Main SAMA

Answer 28

Ipratropium bromide- quaternary derivative of atropine

Question 29

Route of administration of ipratropium?

Answer 29

Aerosol inhalation | 30min after inhalation- max effect can be felt

Question 30

Main LAMA used

Answer 30

Tiotropium

Question 31

TWO LTRAs

Answer 31

Montelukast, zafirlukast

Question 32

Which drugs are used for anti-inflammatory action in asthma?

Answer 32

Glucocorticoids

Question 33

MOA of glucocorticoids

Answer 33

Restrain clonal proliferation of Th cells- reduce transcription of gene for IL2 and decrease formation of cytokines (Th2 cytokines that recruit and activate eosinophils and are responsible for production fo IGE)

Question 34

Main compounds of corticosteroids used

Answer 34

Beclomethazone, budesonice, fluticasone (potent), mometasone, ciclesonide- given by inhalation with metered dose or dry powder inhaler

Question 35

Example of higher potency glucocorticoids

Answer 35

Budesonise and fluticasone

Question 36

Glucocorticoids given to patients who have acute exacerbations of asthma

Answer 36

Oral prednisolone and IV hydrocortisone

Question 37

Treatment for acute asthma

Answer 37

- Oxygen >/ 60% - Inhalation of nebulised salbutamol - IV hydrocortisone followed by oral prednisolone - IV magnesium 1.2-2mg for 20 mins - IV theophyliine

Question 38

COPD clinical features

Answer 38

PROGRESSIVE BREATHLESSNESS cough- becomes chronic Pulmonary hypertension- late feature

Question 39

Pathogenesis of COPD

Answer 39

- Fibrosis of small airways - Obstruction/destruction of alveoli and elastin fibres - Emphysema causes resp failure- destroys alveoli- impairs gas transfer

Question 40

Treatment of COPD

Answer 40

``` Stop smoking LABA- modest benefit Combat mucous hypersecretion Look at chest disease lecture LABA and LAMA+ ICS ```