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Respiratory Pharmacology. Dr Cathy Armstrong Anaesthetic SpR & Clinical Fellow in Undergraduate Medical Education April 2010. Aims & Objectives. Discuss Oxygen therapy Discuss the pharmacological management of: Asthma COPD Inhaler quiz. OXYGEN. Oxygen Therapy. Fixed performance devices

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Respiratory Pharmacology


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respiratory pharmacology
Applied Clinical Sciences Lecture Programme

Respiratory Pharmacology

Dr Cathy Armstrong

Anaesthetic SpR & Clinical Fellow in Undergraduate Medical Education

April 2010

aims objectives
Aims & Objectives
  • Discuss Oxygen therapy
  • Discuss the pharmacological management of:
    • Asthma
    • COPD
  • Inhaler quiz
oxygen therapy
Oxygen Therapy
  • Fixed performance devices
    • Fi02 constant despite change in inspiratory flow rate
  • Variable performance devices
    • Fi02 varies with inspiratory flow rate
  • Reservoir devices
fixed performance devices
Fixed performance devices

Venturi

HAFOE

High flow oxygen enrichment devices

variable performance devices
Variable performance devices

2 l/min = approx 25-30%

4 l/min = approx 30-40%

oxygen potential concerns
Oxygen -Potential concerns
  • COPD patients dependent on hypoxic drive
  • Atelectasis
  • Retinopathy of prematurity
asthma

Inflammatory response

Intitiated by trigger & mast cell degranulation

Asthma
  • Reversible airways obstruction
    • Bronchoconstriction
    • Bronchial mucosal oedema
    • Mucus plugging
slide15
COPD
  • lung disease characterised by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible.
  • main features include
    • Bronchoconstriction
    • Mucosal oedema
    • Mucosal hypersecretion
slide16
Bronchodilators
  • Anti-inflammatory drugs
  • Mucolytics
agents acting on bronchial smooth muscle

ATP

AC

Β2 agonists

Xanthines

+

+

+

cAMP

Salbutamol

PDE

AMP

Aminophylline

Anticholinergic drugs

Ipratropium bromide

Agents acting on bronchial smooth muscle

Bronchodilation

SNS

Magnesium

Resting Bronchial tone

PNS

Bronchoconstriction

2 agonists
Β2 agonists
  • Short acting
    • Salbutamol
      • Ventolin, airomir, salamol easi-breathe
    • Terbutaline
      • Bricanyl
  • Long acting
    • Salmeterol
      • Serevent
    • Formoterol
      • oxis
2 agonists1

ATP

AC

Β2 agonists

+

+

cAMP

PDE

AMP

Β2 agonists

Bronchodilation

SNS

Resting Bronchial tone

PNS

Agonists at β2 adrenoceptors → activate second messenger system (adenyl cyclase)

Bronchoconstriction

2 agonists2
Β2 agonists
  • Side effects
    • Tachycardia
    • Arrythmias
    • Myocardial ischaemia
    • Tremor
    • Paradoxical bronchospasm
    • Hypokalaemia
anticholinergic drugs
Anticholinergic drugs
  • Short acting
    • Ipratropium bromide
      • Atrovent
  • Long acting
    • Tiotropium
      • spiriva
anticholinergic drugs1

Anticholinergic drugs

Anticholinergic drugs

Bronchodilation

Antagonise muscarinc receptors

SNS

Resting Bronchial tone

PNS

Bronchoconstriction

anticholinergic drugs2
Anticholinergic drugs
  • Side Effects
    • Dry mouth
    • Nausea
    • Headache
  • Cautions
    • Pts with prostatic hyperplasia & bladder outflow obstruction
    • Pts susceptible to glaucoma
xanthines
Xanthines
  • Theophylline
    • Nuelin SA
    • Slo-phyllin
    • Uniphyllin continus
  • Aminophylline
    • Theophylline + ethylenediamine
      • Increased water solubility allowing IV preparation
    • Phyllocontin Continus
      • Modified release tablet

Modified release tablets

xanthines1

ATP

AC

Xanthines

+

+

cAMP

PDE

AMP

Xanthines

Bronchodilation

SNS

Resting Bronchial tone

PNS

Phosphodiesterase inhibitors

Bronchoconstriction

xanthines2
Xanthines
  • Side effects
    • Toxicity can occur
      • Tachycardia
      • Arrythmias
      • Agitation
      • Convulsions
      • Hypokalaemia
      • Levels can increase in sepsis & viral infections
    • Drug interactions (hepatic metabolism)
      • E.g ciprofloxacin & OCP reduce clearance
      • E.g. anticonvulsants increase clearance
anti inflammatory agents
Anti-inflammatory agents
  • Corticosteroids
  • Leukotriene receptor antagonists
  • Sodium cromoglycate
corticosteroids
Corticosteroids
  • Broad anti-inflammatory effect
    • Inhibition of production of inflammatory cytokines
  • Inhaled
    • Beclomethasone
      • becotide
    • Fluticasone
      • Flixotide
    • Budesonide
      • Pulmicort
  • Oral
    • Prednisolone
  • IV
    • Hydrocortisone
corticosteroids1
Corticosteroids
  • Side effects
    • Inhaled fewer systemic effects than oral
      • Candidiasis
      • Hoarseness
      • Adrenal suppression
      • Osteoporosis
      • Growth restriction in children
corticosteroids2
Corticosteroids
  • Combined therapies (with LABA)
    • Seretide
      • Salmeterol & fluticasone
    • Symbicort
      • Budesonide & formoterol
leukotriene receptor antagonists
Leukotriene Receptor antagonists
  • Leukotrienes are synthesized by a variety of inflammatory cells in the airways
    • E.g. eosinophils, mast cells, macrophages & basophils
  • Leukotriene receptor antagonists block the binding of LTD4 to its receptor on target tissues
    • Montelukast
      • singulair
sodium cromoglycate
Sodium cromoglycate
  • Mode of action not completely understood
  • May inhibit degranulation of mast cells
  • Less effective than inhaled corticosteroids
omalizumab
Omalizumab
  • Monoclonal antibody that binds IgE
  • Add on therapy in severe persistent allergic asthma
  • Fortnightly SC injection
  • If no response after 16 weeks then discontinued
management of chronic asthma

BTS Guidelines

Management of chronic asthma
  • Step 1
    • Prn inhaled β2 agonist
  • Step 2
    • Add inhaled steroid (200 – 800mcg/day)
  • Step 3
    • Add LABA, +/- ↑ steroid dose to 800mcg/day
    • Consider leukotriene receptor antagonist or SR theophylline
  • Step 4
    • Further ↑ inhaled steroid to up to 2000mcg/day
    • Add 4th drug (leukotriene receptor antagonist, SR theophylline or β2 agonist tablets)
  • Step 5
    • Daily low dose oral steroid
    • Continue high dose inhaled steroid
    • Refer to specialist
management of chronic copd

NICE Guidelines

Management of chronic COPD
  • Breathlessness & exercise limitation
    • Short-acting bronchodilator
    • Combined therapy (short acting β2 agonist & short acting anticholinergic)
    • Add longer acting bronchodilator
    • Consider combination of long acting bronchodilator & inhaled corticosteroid
    • Add theophylline

salbutamol

Combivent

Tiotropium

salmeterol

Seretide

symbicort

slide36
In a patient having an acute exacerbation of asthma which of the following features would most concern you?
  • RR 28
  • Sats 93% on 15 L/min oxygen
  • Exhaustion
  • Unable to talk in full sentences
assessment of an acute exacerbation of asthma
BTS Guidelines

Moderate exacerbation

Acute severe

Life threatening

Near Fatal

Assessment of an acute exacerbation of asthma
assessment of an acute exacerbation of asthma1
Assessment of an acute exacerbation of asthma
  • Life threatening
    • PEF < 33% best or predicted
    • SpO2 < 92%
    • PaO2 < 8 Kpa
    • Silent chest
    • Cyanosis
    • Poor resp effort
    • Arrythmia
    • Exhaustion, altered conscious level
  • Near Fatal
    • Raised PaCO2 and / or requiring mechanical ventilation
management of an acute exacerbation of asthma
Management of an acute exacerbation of asthma
  • Intial
    • Sit patient up
    • Give High flow oxygen
    • Nebulised β2 agonists every 15 min
    • Nebulised ipratropium (repeat every 4 hours)
    • Steroids
      • Prednisolone 40mg
      • Hydrocortisone 100mg
  • If not reponding
    • Magnesium
      • 1.2 – 2g IV over 20 minutes
    • Consider IV aminophylline or β2 agonists
slide40

Any patient with acute severe or life threatening asthma who is not responding to therapy needs referral to Intensive Care

what is this inhaler
What is this inhaler?
  • Salbutamol
  • Seretide
  • salmeterol
slide43

Long - acting

Short - acting

what is this inhaler1
What is this inhaler?
  • fluticasone
  • beclomethosone
  • symbicort
what is this inhaler2
What is this inhaler?
  • Serevent
  • Seretide
  • combivent
summary
Summary
  • Oxygen therapy
  • Management of asthma & COPD
    • Bronchodilators
    • Anti-inflammatory agents
  • Generic Vs Brand names
slide49

?

BTS Asthma guidelines

www.brit-thoracic.org.uk/ClinicalInformation/Asthma/AsthmaGuidelines/tabid/83/Default.aspx

NICE COPD Guidance

http://guidance.nice.org.uk/CG12