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PHARMACOLOGY OF RESPIRATORY DRUGS
Susanne Young
May 04’
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content
Physiology/ sites of actionReview drugs in useMain considerations in anaesthesia
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Control of bronchial tone+++
ß2
Ad Cyclase
ATPcAMP Kinases cGMP
G.Cyclase
Muscarinic ACh
GTP
5’AMPPDE
+ _
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Prostaglandin Synthesis
Arachidonic Acid
PGG2 5HPETE
LeukotrienesTXA2 PGI2
COX Lipoxygenase
Phospholipids
PLA2
IgE
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Common Respiratory Drugs
ß2 agonistsLong acting ß2 agonists
Anti-cholinergicsInhaled steroids
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Less common
Leukotriene receptor antagonistMethylxanthinesSodium cromoglycate
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ß2 AGONISTS
Salbutuamol, Bricanyl, TerbutalineLess selective in hi dose- get ß1effect100mcg per puff lasts 4hrs or so.Salmeterol, EformoterolLast 12 hrs or so15x 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 laterThen more selective agentsIpatropiumPeak effect 30-60 minsLasts 6hrs or soSpireva= Tiotropium- longer acting o.d egg
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Inhaled steroids
Becotide/ Flixotide/ PulmicortDose range 100 mcg to 1g per dayPeak effect 6-12hrsAnti- inflammatorySensitise ß2 receptorsPrevent tachyphlaxis
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Methylxanthines
Caffeine related! In use since 1930Very alkaline- never give imTherapeutic range 10-20mg/lHalf life increased in: CCF, elderlyDecreased in smokers, enzyme inductionSide Effects incl: Inc HR, FOC, arrythmias. Inc GORD. Hypokalaemia, seizures
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Methylxanthines (cont)
Proposed mechanisms:PDE InhibitionAdenosine (causes mast cell degranulation)
Receptor AntagonismProstaglandin InhibitionEndogenous CA release
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Leukotriene Receptor Antagonists
Good in rhinitisNot better than but additive to steroidsSteroid sparingPreventer
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Sodium Cromoglycate
Mast cell stabiliser, closes Ca++ channelsMay be of use in allergic asthma in kidsPreventer, butNot as effective as inhaled steroid
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Considerations/ Conclusions
? Avoid Histamine releasing drugs? Avoid NSAID’sß2 agonists, corticosteroids, Theophylline
(and Sux) all cause HypokalaemiaArrythmias are potentiated by hypoxia