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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. Muscarinic ACh. Ad Cyclase. G.Cyclase. +. _. GTP. ATP. cAMP. Kinases. cGMP. PDE. 5’AMP.

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Pharmacology of respiratory drugs

PHARMACOLOGY OF RESPIRATORY DRUGS

Susanne Young

May 04’


Content
content

  • Physiology/ sites of action

  • Review drugs in use

  • Main considerations in anaesthesia


Control of bronchial tone
Control of bronchial tone+++

ß2

Muscarinic ACh

Ad Cyclase

G.Cyclase

+

_

GTP

ATP

cAMP

Kinases

cGMP

PDE

5’AMP


Prostaglandin synthesis
Prostaglandin Synthesis

Phospholipids

PLA2

Arachidonic Acid

Lipoxygenase

COX

PGG2

5HPETE

Leukotrienes

IgE

TXA2

PGI2


Common respiratory drugs
Common Respiratory Drugs

  • ß2 agonists

  • Long acting ß2 agonists

  • Anti-cholinergics

  • Inhaled steroids


Less common
Less common

  • Leukotriene receptor antagonist

  • Methylxanthines

  • Sodium cromoglycate


2 agonists
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
Side Effects

  • ß2 Muscle tremor

  • Hypokalaemia (Na+/K+ ATPase)

  • ß1 Anxiety

  • Nausea and vomitting

  • Hypertension

  • Tachyarryhthmias

  • Dizziness/ Headache


Anticholinergics
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


Inhaled steroids
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
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
Methylxanthines (cont)

  • Proposed mechanisms:

  • PDE Inhibition

  • Adenosine (causes mast cell degranulation) Receptor Antagonism

  • Prostaglandin Inhibition

  • Endogenous CA release


Leukotriene receptor antagonists
Leukotriene Receptor Antagonists

  • Good in rhinitis

  • Not better than but additive to steroids

  • Steroid sparing

  • Preventer


Sodium cromoglycate
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
Considerations/ Conclusions

  • ? Avoid Histamine releasing drugs

  • ? Avoid NSAID’s

  • ß2 agonists, corticosteroids, Theophylline (and Sux) all cause Hypokalaemia

  • Arrythmias are potentiated by hypoxia


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