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