Management of COPD & AsthmaMelissa Brittle & Jessica Macaro

Overview

Drugs used in airway disease

Bronchodilators

A. β2 Agonists

B. Anti-cholinergics

C. Methylxanthines

D. Leukotriene antagonists

Anti-inflammatory agents

A. Glucocorticoids

B. Mast cell stabilisers

Monoclonal Antibodies

Asthma

Acute management

Long term management

COPD management

Bronchodilators

β2 Agonists

1. β2 agonist binds to GPCR

2. This leads to activation of Adenyl cyclase

3. Adenyl cyclase converts ATP to cAMP which activates Protein Kinase A (PKA)

4. PKA phosphorylates myosin light chain kinase (MLCK), inactivating it, and therefore reducing smooth muscle contraction in the airway.

Short acting (SABA) = salbutamol, TerbutalineLong acting (LABA) = salmeterol, Formoterol.

Side effects- Tremor- Tachycardia- Headache- Cardiac arrhythmia - Peripheral vasodilation- Hypokalaemia

Can you name any?

1

2

3

4

Anti-cholinergics1. Blockade of Muscarinic M3 receptors.

2. Reduces action of Phospholipase C (PLC) leading to

a) A reduction in calcium release from endoplasmic reticulum (ER)

b) A reduction in calcium uptake into the cell

Normally, calcium binds to Calmodulin which activates MLCK, which in turn activates myosin leading to smooth muscle contraction.

3. Without Calcium, smooth muscle contraction (i.e. bronchoconstriction) is inhibited.

Short acting (SAMA) = IpratropiumLong acting (LAMA) = Tiotropium

Side effects everything dries up!!- Dry mouth Nausea- Constipation Urinary retention- Cough Glaucoma - Headache

Can you name any?

12

a

b

3

Methylxanthines

1. Methylxanthines inhibit phosphodiesterase (PDE) which normally breaks down cAMP into 5’AMP

2. This allows cAMP levels to rise thus promoting muscle relaxation

AminophyllineTheophylline

Small therapeutic window- take care with dose Multiple drug interactions Side effects…- Insomnia- Nausea and vomiting- Cardiac arrhythmias - Seizures

Can you name any?

What breaks cAMP down?

Leukotriene Antagonists

Leukotrienes cause airway inflammation and bronchospasm

1. Leukotriene antagonists block cysteinyl leukotriene (Cys LT) receptors.

2. This leads to reduced inflammatory response and reduced exercise induced symptoms in asthma

MontelukastZafirlukast

Side effects…- Abdominal pain- Headache- Thirst- Restlessness

Can you name any?

Anti-inflammatory agents

Glucocorticoids1. Glucocorticoids cause

a) Expression of anti-inflammatory products

b) Inhibition of pro-inflammatory products e.g. cytokines, vasodilators, leukotrienes etc

2. This results in reduced oedema and mucous production which contributes to narrowed airways in asthma and COPD.

Inhaled- beclomethasone, fluticasoneOral- PrednisoloneIV- hydrocortisone

Side effects…- Cushings

syndrome- Oral steroids

have more effects than inhaled.

Can you name any?

Mast cell stabilisers

Act by stabilising mast cell membranes therefore preventing histamine release

Unfortunately not very effective but have few side effects

Typically used in children with asthma

Useless in COPD or acute asthma because histamines have already been released.

Sodium cromoglycate, nedocromil.

Side effects…- Bitter taste- Paradoxical

bronchospasm

Can you name any? We can’t…

What do mast cells release?

MONOCLONAL ANTIBODIES

• Anti-IgE antibodies form complexes with free IgE

• Useful to prevent allergic asthma

• Very expensive and not often prescribed

Omalizumab

Mast cell

Can you name any?

ACUTE MANAGEMENT OF ASTHMA

OSHIT…

O – Oxygen S – Salbutamol H – Hydrocortisone (IV) (if in hospital) or Prednisolone (oral) (if in GP)I – Ipratropium T – Theophylline

Reliever

Inhaled SABA e.g salbutamol

Preventer

Add inhaled steroid e.g. fluticasone

Controller

Add inhaled LABA e.g. salmeterol

Higher dose inhaled steroid+Leukotriene antagonist, theophylline or β agonist

Oral steroid e.g. prednisolone

LONG TERM MANAGEMENT OF ASTHMA

Step by step approach

Reliever

Inhaled SABA e.g salbutamol

Preventer

Add inhaled steroid e.g. fluticasone

Controller

Add inhaled LABA e.g. salmeterol

Higher dose inhaled steroid+Leukotriene antagonist, theophylline or β agonist

Oral steroid e.g. prednisolone

MANAGEMENT OF COPD

• Smoking cessation advice• Oxygen• Bronchodilator therapy

o SABA e.g. salbutamolo SAMA e.g. ipratropium

• Combination therapyo LABA e.g. salmeterolo LAMA e.g. tiotropiumo Inhaled steroid e.g. fluticasone

• Oral methylxanthines e.g. theophylline