PHARMACOLOGY OF RESPIRATORY DRUGS

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PHARMACOLOGY OF RESPIRATORY DRUGS

• Susanne Young
• May 04

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content

• Physiology/ sites of action
• Review drugs in use
• Main considerations in anaesthesia

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Control of bronchial tone
ß2
Muscarinic ACh
Ad Cyclase
G.Cyclase
GTP

_
ATP
cAMP
Kinases
cGMP
PDE
5AMP
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Prostaglandin Synthesis
Phospholipids
PLA2
Arachidonic Acid
Lipoxygenase
COX
PGG2
5HPETE
Leukotrienes
IgE
TXA2
PGI2
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Common Respiratory Drugs

• ß2 agonists
• Long acting ß2 agonists
• Anti-cholinergics
• Inhaled steroids

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Less common

• Leukotriene receptor antagonist
• Methylxanthines
• Sodium cromoglycate

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ß2 AGONISTS

• Salbutuamol, Bricanyl, Terbutaline
• Less selective in hi dose- get ß1effect
• 100mcg per puff lasts 4hrs or so.
• Salmeterol, Eformoterol
• Last 12 hrs or so
• 15x more potent at ß2 than Salbutamol

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Side Effects

• ß2 Muscle tremor
• Hypokalaemia (Na/K ATPase)
• ß1 Anxiety
• Nausea and vomitting
• Hypertension
• Tachyarryhthmias
• Dizziness/ Headache

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Anticholinergics

• 200 yrs ago Datura plants were smoked!
• Atropine later
• Then more selective agents
• Ipatropium
• Peak effect 30-60 mins
• Lasts 6hrs or so
• Spireva Tiotropium- longer acting o.d egg

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Inhaled steroids

• Becotide/ Flixotide/ Pulmicort
• Dose range 100 mcg to 1g per day
• Peak effect 6-12hrs
• Anti- inflammatory
• Sensitise ß2 receptors
• Prevent tachyphlaxis

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Methylxanthines

• Caffeine related!
• In use since 1930
• Very alkaline- never give im
• Therapeutic range 10-20mg/l
• Half life increased in CCF, elderly
• Decreased in smokers, enzyme induction
• Side Effects incl
• Inc HR, FOC, arrythmias.
• Inc GORD. Hypokalaemia, seizures

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Methylxanthines (cont)

• Proposed mechanisms
• PDE Inhibition
• Adenosine (causes mast cell degranulation)
  Receptor Antagonism
• Prostaglandin Inhibition
• Endogenous CA release

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Leukotriene Receptor Antagonists

• Good in rhinitis
• Not better than but additive to steroids
• Steroid sparing
• Preventer

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Sodium Cromoglycate

• Mast cell stabiliser, closes Ca channels
• May be of use in allergic asthma in kids
• Preventer, but
• Not as effective as inhaled steroid

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Considerations/ Conclusions

• ? Avoid Histamine releasing drugs
• ? Avoid NSAIDs
• ß2 agonists, corticosteroids, Theophylline (and
  Sux) all cause Hypokalaemia
• Arrythmias are potentiated by hypoxia