Anti-inflammatory Drugs & Cough

Question 1

Use of Anti-inflammatory Drugs

Answer 1

• Reduce severity and frequency of asthma attacks
• Limit progression of disease by inhibiting remodelling
• Reduce night-time asthma attacks by preventing late-phase

Question 2

Glucocorticoids

Answer 2

• Mainly used anti-inflammatory
  properties in asthma
• Not a bronchodialator not relieving early phase
• Prevents progression of chronic asthma
• Effective in acute severe asthma
• Add-on inhalational therapy in asthma when bronchodilator is used more than once daily

Question 3

Glucocorticoid mechanism

Answer 3

• Glucicorticoids drugs bind to the glucocorticoid receptors in the cytoplasm
• Complex migrates into nucleaus and binds to glucocorticoid response elements
• • effects inhibit glucocorticoid response element - decrease pro inflammatory COX-2
• • effect stimulatory glucocorticoid response element increase anti-inflammatory gene products IL-10

Question 4

Immunosupression response of Glucocorticoids

Answer 4

• IL-10 Decreases cytokine formation
  decreases recruitment and activation of inflammatory T cells
• Inhibit esponses responsible for production of IgE and its receptors and for recruiting eosinophils
• Effect early phase and causes late phase of asthma

Question 5

Anti-inflammatory response of Glucocorticoids

Answer 5

• inhibits phospholipase A2
• decreased inflammatory mediators
  also suppress COX-2 induction ↓inflammatory prostanoid production
• Reduce severity of early phase response and prevent late phase response

Question 6

Glucocorticoids impact on inflammatory cascade

Answer 6

• Upregulate Beta 2 adrenoreceptors - regular use of beta 2 adenorecptor agonist (LABA) use with ICS
• Eventually reduce number of mast cells
  – May have some effect on early phase

Question 7

Formulation of corticosteroids: Inhaled

Examples

Answer 7

• Beclometasone dipropionate (BDP)
• Budesonide
• Fluticasone propionate (2 x potent as BDP)
• Mometasone

Question 8

Formulation of corticosteroids: oral

Examples

Answer 8

• Prednisolone
• Given as a single dose in the morning to mimic the body’s
  cortisol secretion

Question 9

Formulation of corticosteroids: IV

Example

Answer 9

• Hydrocortisone

Question 10

Glucocorticoids Unwanted effects that are uncommon with inhaled

Answer 10

• Systemic effects only in high doses
  – Spacers minimise

Question 11

Glucocorticoids unwanted side effects: Oropharyngeal candidiasis

Answer 11

• Suppress T-lymphocytes important
  against fungal infection
  – Spacer devices reduce

Question 12

Glucocorticoids unwanted side effects: Regular high doses

Answer 12

• Adrenal suppression esp in
  children

Question 13

Other unwanted side effects of Glucocorticoids

Answer 13

• Iatrogenic Cushings
• Osteoporosis
• Increased risk of pneumonia in elderly with COPD
• Poor absorption from GI tract
  – Fluticasone / mometasone unwanted effects less likely
  Steroid card

Question 14

Mast cell stabilisers

Answer 14

• Variable efficacy shown in antigen, exercise and irritant induced asthma - not a bronchodialator
• Weak anti-inflammatory effects
• Reduce immediate & late-phase responses
  – Reduce bronchial hyper-reactivity

Question 15

How is the mast cell stablisation mechanism unclear

Answer 15

• Mast cell stablisation plays no part in oral anti-histamines
• Drepresses signal from irritant receptors
• May inhibit cytokine release

Question 16

Immunotherapies: Omalizumab

Answer 16

• Monoclonal antibody
• Anti-IgE antibody –
• Once binds to IgE these are
  removed from circulation
• IgE receptors also reduced
• Reduces mediator release from
  mast cells
• Gradually reduces inflammation
• prophylaxis severe and persisitant
• Risk of anaphylaxis with injection

Question 17

Reflex cough action

Answer 17

• Afferent sensory stimulus to an efferent motor response
• A forceful movement of respiratory muscles to affect the reflex
• essential reflex response of the airways under both physiological and pathophysiological conditions

Question 18

Two roles of a cough

Answer 18

• The final pathway of mucociliary clearance
• Part of the defence mechanisms against inhaled particles and
  noxious substances

Question 19

Causes of a cough

Answer 19

• Irritants-smokes, fumes, dusts, etc.
• Diseased conditions like COPD, tumors of thorax, etc.
• Pressure on respiratory tracts
• Infections

Question 20

Components of cough reflex

Answer 20

• Cough receptors
• Afferent nerves
• Cough center (medulla)
• Efferent nerves
• Effector muscles

Question 21

Irritation

Answer 21

A stimulus irritates the upper
airways and results in a reflex action leading to cough

Question 22

Inspiration

Answer 22

Occurs to achieve optimum
thoracic gas volume thus allowing the
most efficient use of the expiratory muscles

Question 23

Compression

Answer 23

With the glottis closed, the
abdominal muscles and the thoracic cage actively contracts, leading to high
intrathoracic pressures

Question 24

Expulsion

Answer 24

The glottis opens and a high airflow results. The force of expression is increased by collapsing the airways following the explosive decompression caused by glottic opening

Question 25

Relaxation

Answer 25

At the end of the cough,
the intrathoracic pressure decreases
as the expiratory muscles relax and a
transient bronchodilatation occurs

Question 26

Mechanism of ACE

Answer 26

• ACE metabolises bradykinin which is potent vasodialator peptide that exerts its vasodialatory action via B2 receptors
• Aterioles dilate due to the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor

Question 27

ACE inhibitor effect on bradykinin

Answer 27

• Increase in bradykinin levels contributing to vasodilator action

Question 28

What is bradykinin

Answer 28

• Chemical irritation of c fibres of
  respiratory tract – through release of proinflammatory peptides
• Substance p and histamine – these stimulate hyper stimulate
  the cough reflex

Question 29

Classification of cough

Answer 29

• Dry or chesty
• Classified as acute, subacute or chronic

Question 30

Acute cough

Answer 30

• Been present for less than three weeks and can be divided into infectious and non-infectious causes

Question 31

Subacute cough

Answer 31

Resolves over three to eight weeks

Question 32

Chronic Cough

Answer 32

• Coughs are those present for more than eight
  weeks

Question 33

Chronic Cough cause

Answer 33

• Environmental irritants
• Conditions within the lungs
• Conditions in the upper airways
• Conditions within the chest cavity
• Digestive causes
• Asthma and COPD common

Question 34

Antitussives

Answer 34

• Cough suppressants
• All in clinical use are opioid analgesics
• Suppress cough in doses below those required
  for pain relief
• Action is poorly defined
• Suppress cough centre

Question 35

What do dry cough drugs do

Answer 35

• Increase bronchial secretion or reduce its viscosity to facilitate removal

Question 36

Secretion enhancers

Answer 36

Sodium citrate, potassium iodide, guaiacol, tolu
balsam, ammonium salts

Question 37

Mucolytics: Acteylcysteine

Answer 37

• Actively breaking down sulphide bonds thinning mucus
• Useful in cystic fibrosis and COPD

Question 38

COPD treatment efficacy: ICS

Answer 38

• Very effective in asthma but may only reduce exacebations in COPD

Question 39

Side effects of ICS

Answer 39

• Adrenocortical suppression
• Bone mineral density reduced – osteoporosis
• Candidiasis of mouth and throat
• Resistance in certain individuals

Question 40

Phosphodiesterase type 4 inhibitors

Answer 40

• Inhibition of PDE results in cAMP accumulation e.g. Roflumilast
• found in airways smooth muscle and inflammatory cells in COPD
• Reduced cytokines released from neutrophils
  – Reduced accumulation of T-cells in lungs
  – Reduced cell death of airway cells

Question 41

Treatment of acute exacerbations of oxygen

Answer 41

• use low strength O2 in COPD 24%
• Become tolerant to prolonged CO2 retention & respiratory drive is maintained by low levels of O2
• High strength O2 will cause respiratory arrest