W6 25 respiratory pharmacology

Question 1

What is flow equal to?

Answer 1

Flow = pressure gradient / resistance
Pressure gradient is generated by pressure in the alveolar space compared with the atmospheric pressure outside, giving a gradient for flow, which goes through the airways which gives resistance to flow.

Question 2

What reduces peak expiratory flow?

Answer 2

A normal elastic recoil, so normal pressure gradient, but an increased airway resistance, will reduce flow.
A reduced elastic recoil means a reduced ability to generate the pressure gradient, but a normal resistance, will reduce flow.

Question 3

Will peak expiratory flow test distinguish between an increased airway resistance or a decreased pressure gradient?

Answer 3

No, test won’t distinguish between airway resistance and pressure gradient

Question 4

Do restrictive lung diseases affect pressure gradient or airway resistance?

Answer 4

They affect the generation of pressure gradient
Affects the lung parenchyma, affecting the ability to stretch that tissue

Question 5

Do obstructive lung diseases affect pressure gradient or airway resistance?

Answer 5

Will affect the airway resistance, a disease of the airways.

Question 6

What can induce restrictive diseases?

Answer 6

Drug induced, dust infections, pneumonia etc

Question 7

Give examples of obstructive diseases

Answer 7

Asthma, COPD

Question 8

What happens to the lungs in restrictive diseases?

Answer 8

Reduced vital capacity

Question 9

What happens to the lungs in obstructive diseases? (Graph pg278)

Answer 9

Reduced FER (forced expiratory ratio). FEV1/FVC
FEV1 measures how much air blown out in first second.
Insignificant effect on vital capacity.

Question 10

What are the pathological symptoms of asthma?

Answer 10

Chronic airway inflammation
Increased airway responsiveness
Bronchoconstriction
Airway obstruction
Wheeze, cough and dyspnoea

Question 11

Immediate phase asthma causes bronchospasm. How can this be treated?

Answer 11

Reversed by bronchodilators, eg b2 adrenoceptor agonists

Question 12

Late phase asthma causes inflammatory responses and hypereactive airway. How might this be treated?

Answer 12

Inhibited by glucocorticoids

Question 13

Can we treat the airway remodelling that occurs in asthma?

Answer 13

Chronic inflammation causes remodelling. Drug treatments will control the condition, not reverse this.

Question 14

Where can we intervene with drugs in in acute asthma attack?

Answer 14

Mast cell stabilisers to prevent mast cell degranulation and generation of inflammatory response.
Target smooth muscle to cause a bronchodilatation and reduce airway resistance
Target underlying inflammatory response as glucocorticoids as potent anti-inflammatories

Question 15

What prevents and what relieves in asthma?

Answer 15

Anti-inflammatories are preventers - brown inhaler
Bronchodilators are relievers - blue inhaler

Question 16

What anti-inflammatory drugs can be used to prevent asthma?

Answer 16

Steroids - eg inhaled beclometasone ; oral prednisolone
Leukotriene receptor antagonists - eg oral montelukast
(chronic reduction in inflammation and airway responsiveness)

Question 17

What is the action of steroids in asthma?

Answer 17

Glucocorticoids counteract airway inflammation
Affects inflammatory cells to reduce the underlying problem.
Inhaling will go directly to the site of action, or can be taken orally.
Take regularly to keep inflammatory cells in check

Question 18

What is the action of leukotriene receptor antagonists in asthma?

Answer 18

Leukotrienes (generating arachidonic acid to generate this) are pro-inflammatory and bronchconstrictors, so can block leukotriene receptors with an antagonist. Will help constriction, changes in permeability and fluid accumulation. Targets smooth muscle, endothelial, goblet cells and leukocytes.

Question 19

What is the main action we want to happen in an acute asthma exacerbation?

Answer 19

An acute reduction in airway resistance

Question 20

What do we have in smooth muscle cells during bronchoconstriction?

Answer 20

In a smooth muscle cell we will have a calcium-mediated constriction in that cell

Question 21

What are the 3 reliever strategies by bronchodilators and give examples of the drugs?

Answer 21

1st - b2 agonist eg salbutamol (short acting) or salmeterol (long acting)
2nd - theophyllines eg aminophylline (long acting)
3rd - anti-muscarinics eg ipratropium bromide (short acting)

Question 22

What is the average time for short acting vs long acting?

Answer 22

Short acting is about 4-6 hrs
Long acting is about 12hrs

Question 23

What do b2 agonists do in asthma?

Answer 23

Sympathomimetic effect on airway smooth muscle.
Stimulating the b2 adrenoceptors on the airway smooth muscle with promote formation of cAMP. cAMP will inhibit myosin light-chain kinase and interfere with this calcium calmodulin complex that causes the constriction.
Short or long acting.

Question 24

What do theophyllines do in asthma?

Answer 24

cAMP is broken down by phosphodiesterase (PDE). Theophyllines will inhibit PDE.
If we inhibit PDE, we inhibit the breakdown of cAMP, so we have more cAMP, interfering with the constriction.

Question 25

What do anti-muscarinics do in asthma?

Answer 25

Cholinergic receptors do the opposite to adrenoceptors, so we want to inhibit cholinergic receptors. M3 muscarinic receptors on airway smooth muscle, so want to block these muscarinic effects. Block vagal/parasympathetic effect on airway smooth muscle.

Question 26

What is the order of drug delivery devised for asthma?

Answer 26

(Oral too but not in order)
Aerosol/gas-type = quickest - inhalers. Can use a spacer to increase effectiveness.
More severe - nebulisers - or fine nebulised spray - give a high dose very quickly. More expensive tho.
Might be quite severe, requiring acute oxygen therapy to keep alveolar PO2 up when unable to ventilate too much.

Question 27

What is aspirin-induced asthma?

Answer 27

A medical emergency, quickly onset. Anaphylactic reaction, aspirin hypersensitivity, redness of skin is an early sign. Precipitates asthma attack.
Can develop ‘aspirin triad’ - nasal polyps, asthma, aspirin sensitivity

Question 28

How can aspirin induce asthma, what mechanisms?

Answer 28

PGs and leukotrienes involved. The involvement of arachidonic acid derivatives in the control of airway smooth muscle might suggest that COX1 inhibitors might impact the pathway.
Some people are tolerant and some are sensitive. Might be due to inhibition of PGE2 formation (bronchodilator). Inhibiting this switches the balance of arachidonic acid derivatives, allowing more leukotriene E4 production in mast cells, stimulating them more giving an inflammatory response and thus bronchoconstriction. Only happens in sensitive individuals when you inhibit COX1.

Question 29

What should you do in an acute asthma attack?

Answer 29

Sit the patient upright and give a short-acting bronchodilator. If don’t recover quickly, stabilise them. Use a spacer to get higher doses. If not responding, call an ambulance.

Question 30

What are the pathological symptoms of COPD?

Answer 30

Alveolar destruction (emphysema) - loss of elastic recoil and airway traction and reduced SA for diffusion
Airway obstruction (increased resistance)
Air trapping
Hyperinflation

Question 31

What does loss of elastic recoil in COPD do to the lungs?

Answer 31

Elastic recoil holds the airways open, reducing resistance. So losing alveolar elastic recoil means airways can collapse more easily. As they collapse more easily, they rap air in the lungs and no more is expelled. Increases airway resistance.

Question 32

How do you treat COPD?

Answer 32

Not treatable - cant restore the alveolar once destroyed

Question 33

How can you prevent deterioration of COPD?

Answer 33

Smoking cessation - removal of airway irritants
Slows increase in airway resistance

Question 34

How can we alleviate the symptoms and reduce exacerbations of COPD?

Answer 34

Alleviate symptoms by reducing airway resistances and work of breathing with bronchodilators
Reduce exercerbations - vaccinations eg prevent influenza; corticosteroids to reduce neutrophil infiltration and inflammatory cell activations

Question 35

What other methods of management are there for COPD?

Answer 35

Pursed lip breathing
Long term O2 therapy
Improve quality of life
Improve exercise capacity

Question 36

What is pursed lip breathing for COPD?

Answer 36

Patient purses lips to reduce size of hole breathing out of, to create a resistance breathing out, upstream to where the air is coming from. This will increase pressure in the airways slightly, helping keep open for a little bit longer, so better able to ventilate our alveoli and do gas exchange.
(not a problem breathing in, since they’ve lost elastic recoil it’s issues breathing out)

Question 37

How can long term oxygen therapy help COPD patients?

Answer 37

With severe COPD patients might have chronic hypoxaemia (<7.3kPa)
To increase partial pressure in the alveoli, increase gradient for diffusion, to get arterial PO2 to about 8kPA, about 90% saturated.

Question 38

How can you improve quality of life in COPD patients?

Answer 38

Rehabilitation - eg training in pursed lip breathing
Increased alveolar ventilation
Reduce dyspnoea
Decrease airway trapping and hyperinflation

Question 39

How can we increase airway capacity in COPD patients?

Answer 39

Bronchodilators - reduce airway resistance
O2 therapy - increase partial pressure gradient for diffusion

Question 40

What is allergic rhinitis?

Answer 40

Hay fever, might have a stimulus eg pollen, which when inhaled stimulates the release of IgEm which will sensitise mast cells and activate them, to produce an inflammatory response.

Question 41

What is the management order for allergic rhinitis?

Answer 41

Generally - antihistamine treatment
More severe - anti-IgE therapy - allergic asthma eg omalizubab. Inhibits the action of IgE binding to the mast cells and prevents sensitisation, having an anti inflammatory response. Tends to be used with glucocorticoids can’t be used.

Question 42

What early intervention can be used to help respiratory depression?

Answer 42

Verbal stimulation - keeping pt awake and consciously thinking
O2 therapy
CPAP

Question 43

What pharmacological intervention can be used in respiratory depression?

Answer 43

Respiratory stimulants (analeptic agents)
Carotid body stimulants

Question 44

What do carotid body stimulants do for respiratory depression?

Answer 44

They sense hypoxia and stimulate breathing.

Question 45

Give examples of carotid body stimulants

Answer 45

Doxapram - post-op stimulation, drug overdoses, COPD patients. Can maintain analgesia whilst stimulating breathing.
Almitrine - COPD patients (unlicensed in UK)