pharmacology of respiratory drugs susanne young may 04’
TRANSCRIPT
PHARMACOLOGY OF RESPIRATORY DRUGS
Susanne Young
May 04’
content
Physiology/ sites of actionReview drugs in useMain considerations in anaesthesia
Control of bronchial tone+++
ß2
Ad Cyclase
ATPcAMP Kinases cGMP
G.Cyclase
Muscarinic ACh
GTP
5’AMPPDE
+ _
Prostaglandin Synthesis
Arachidonic Acid
PGG2 5HPETE
LeukotrienesTXA2 PGI2
COX Lipoxygenase
Phospholipids
PLA2
IgE
Common Respiratory Drugs
ß2 agonistsLong acting ß2 agonists
Anti-cholinergicsInhaled steroids
Less common
Leukotriene receptor antagonistMethylxanthinesSodium cromoglycate
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
Side Effects
ß2 Muscle tremor Hypokalaemia (Na+/K+ ATPase)ß1 Anxiety Nausea and vomitting Hypertension Tachyarryhthmias Dizziness/ Headache
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
Inhaled steroids
Becotide/ Flixotide/ PulmicortDose range 100 mcg to 1g per dayPeak effect 6-12hrsAnti- inflammatorySensitise ß2 receptorsPrevent tachyphlaxis
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
Methylxanthines (cont)
Proposed mechanisms:PDE InhibitionAdenosine (causes mast cell degranulation)
Receptor AntagonismProstaglandin InhibitionEndogenous CA release
Leukotriene Receptor Antagonists
Good in rhinitisNot better than but additive to steroidsSteroid sparingPreventer
Sodium Cromoglycate
Mast cell stabiliser, closes Ca++ channelsMay be of use in allergic asthma in kidsPreventer, butNot as effective as inhaled steroid
Considerations/ Conclusions
? Avoid Histamine releasing drugs? Avoid NSAID’sß2 agonists, corticosteroids, Theophylline
(and Sux) all cause HypokalaemiaArrythmias are potentiated by hypoxia