19A12: Exam Report

Compare and contrast the pharmacology of salbutamol and ipratropium bromide.

46% of candidates passed this question.

Overall candidates had a superficial knowledge of these level 1 drugs. To pass candidates needed to identify points of difference and overlap in various areas such as structure, pharmaceutics, pharmacokinetics, pharmacodynamics, mechanism of action, adverse effects and contraindications.

F11i / 19A12: Compare and contrast the pharmacology of salbutamol and ipratropium bromide

Chemical

Salbutamol

Short acting β agonist 2 > β1) synthetic sympathomimetic amine

Ipratropium

A synthetic quaternary ammonium derivative of atropine → muscarinic antagonist

Comments

Different mechanisms of action, may be used synergistically

Use

Salbutamol

bronchoconstriction

Ipratropium

bronchoconstriction

Comments

Presentatation

Salbutamol

Tablets, syrup, aerosol, dry powder for inhalation

Solution for neb & solution for injection

Ipratropium

Solution, nebulised, aerosol inhalation

Comments

Both have variable sites of admin and can be administered to the intubated pt

Salbutamol is a racemic of (R) & (S) isomers

(R) isomer = x 150 more affinity for β2

(S) isomer = assoc. with toxicity

Route

Salbutamol

Neb: 2.5 – 5mg PRN

IV: 0.5mcg/kg/min

INH: 200 – 400mcg PRN

PO: 2 – 4mg TDS

Ipratropium

Neb: 100 – 500mcg QID

Aerosol: 100 – 500mcg BD

Comments

Salbutamol has greater admin capacity

Onset

Salbutamol

Immediate

Ipratropium

Max effect in 1 – 2hrs

Commets

Salbutamol much faster onset

DoA

Salbutamol

Minutes

Ipratropium

Lasts 4 – 6hrs

Comments

And offset

MoA

Salbutamol

b2 receptor agonist

Gs GPCR

  • Activates AC
  • ↑cAMP
  • ↑Protein kinase A
  • Inhibits phosphorylation of myosin = ↓Intrac Ca2+

Smooth m. relaxation & bronchoconstriction

Inhibits MC degranulation “stabilises MC”

Inhibits microvascular leakage

↑mucociliary clearance

Ipratropium

Anticholinergic

Competitive inhibition of cholinergic receptors on bronchial smooth muscle

M3 GPCR (Gq)

↓intrac. Ca2+

Bronchodilation

Commets

Both ultimately minimise Ca++ availability and result in bronchodilation

 

In asthmatics salbutamol has added benefit of stabilisation of MCs

PD

Salbutamol

Resp – bronchodilation; interferes with HPVC

CVS

  • Low dose → β2 predominates → ↓SVR → ↓VP
  • High dose → β1 predominates → +ve inotropy + chronotropy

GU

  • ↓uterine tone
  • 10% dose crosses placenta → foetal tachycardia

Metabolic

  • Hypokalaemia
  • ↑FFAs
  • ↑glucose
  • Stimulates insulin release

Ipratropium

Resp – bronchodilation

CVS – ↑HR when given IV (anticholinergic); no effect inhaled

CNS – can’t cross BBB → quaternary ammonium

GU – @ large doses ↓gastric secretion & salivation

Comments

Ipratropium is longer acting and cannot cross BBB – beneficial for CNS S/E

Salbutamol can cross placenta and affect fetus

Both can cause tachycardia

Salbutamol has a much greater metabolic profile with mobilisation of metabolites

PK

Salbutamol

A

10% inhaled dose reaches site of action → rest is ingested

D

64% PPB

VD 156L

M

Significant 1st pass metabolism → salbutamol 4-O-sulphate

Hydrolysed by esterases in tissue & blood → active compound

E

30% unchanged in urine

Rest as metabolites in urine/faeces

Ipratropium

A

30% (PO) & 5% (inhaled) reaches site of action

D

VD 0.4L/kg

M

8 inactive metabolites. By conjugation & hydrolysis

E

Metabolites via faeces & urine

Comments

Salbutamol has a much larger Vd

 

Salbutamol has active metabolites, Ipra does not

 

Both sets of metabolites excreted in feces & urine

A/E

Salbutamol

Anxiety, insomnia, tremor

Seating, N&V, palpitations

Potentiates muscle relaxants (non-depol)

Ipratropium

20% pts have local effects

Dryness/unpleasant aftertaste in mouth

Local deposition on eye → mydriasis & difficulty with accommodation