PHARMACOLOGY OF RESPIRATORY DRUGS Susanne Young May 04’

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

Control of bronchial tone+++ ß2 Ad Cyclase ATP cAMPKinasescGMP G.Cyclase Muscarinic ACh GTP 5’AMP PDE + _

Prostaglandin Synthesis Arachidonic Acid PGG25HPETE Leukotrienes TXA2PGI2 COX Lipoxygenase Phospholipids PLA2 IgE

Common Respiratory Drugs  ß2 agonists  Long acting ß2 agonists  Anti-cholinergics  Inhaled steroids

Less common  Leukotriene receptor antagonist  Methylxanthines  Sodium cromoglycate

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

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 later  Then more selective agents  Ipatropium  Peak effect mins  Lasts 6hrs or so  Spireva= Tiotropium- longer acting o.d egg

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

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

Methylxanthines (cont)  Proposed mechanisms:  PDE Inhibition  Adenosine (causes mast cell degranulation) Receptor Antagonism  Prostaglandin Inhibition  Endogenous CA release

Leukotriene Receptor Antagonists  Good in rhinitis  Not better than but additive to steroids  Steroid sparing  Preventer

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

Considerations/ Conclusions  ? Avoid Histamine releasing drugs  ? Avoid NSAID’s  ß2 agonists, corticosteroids, Theophylline (and Sux) all cause Hypokalaemia  Arrythmias are potentiated by hypoxia