Core pharmacology

Class Group

BRONCHODILATORS - ANTIMUSCARINIC

Legacy Cicm Level

Level 2

Introduction

quaternary ammonium derivative of atropine that acts as an anticholinergic agent.

Indications Uses

in combination with inhaled beta-agonist systemic corticosteroids for the management of severe exacerbations of asthma flares requiring treatment
bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema
Studied for Rhinorrhoea and Sialorrhea

Chemical Pharmaceutics

Synthetic quaternary ammonium compound derived from atropine

Presentation

Isotonic solution containing 0.25mg/ml for nebulization (100-500mcg Q6hr) or as a MDI of 200mcg/dose (1-2 puffs Q6)
Maximum effect achieved in 1.5-2 hours and lasts 4-6 hours

Main Action

Competitive inhibition of cholinergic receptors

Mechanism of action

- Competitive inhibition of cholinergic receptors in bronchial smooth muscle leading to inhibition of the bronchoconstrictor effect and vagal efferent impulses
- M3 are receptors for bronchial smooth muscle contraction and mucous production
- Inhibition of M3-R leads to decreased IP3/DAG and therefore decreased calcium required for bronchoconstriction

Physiological effects

CVS
- Cardiovascular effects are minimal after inhaled
- M2 effects may lead to tachycardia, increased CO and increased BP particularly when given IV
Resp
- Bronchodilation
- May cause a small decreased mucous production
GIT
- Dry mouth
- Decreased gastric secretions when given orally
CNS
- Unable to cross BBB

Adverse Effects Toxicity

Paradoxical bronchospasm
headache, dizziness,
nausea, dry mouth,
shaking (tremors),
nervousness, or.
cold symptoms such as stuffy nose, sneezing, cough, or sore throat.

Absorption

Inh
Poor bioavailability PO: 30% Inh: 5%

Protein binding

Very weak protein binding

Volume of distribution

Vd 4.6L/kg

Metabolism

Metabolized by GIT by CYP450 enzymes.

Excretion

80-100% urine (unchanged), rest faeces
Mostly in faeces if given orally

Half-life

T1/2 1.6hrs

Route And Dose

Inh/Neb