23A10: Exam Report

Describe the pharmacology of salbutamol (70% of Marks), including the principles and efficacy of methods of delivery (30% of Marks)

20% of candidates passed this question.

Good candidates answered this question in 4 parts; pharmaceutics, pharmacokinetics, pharmacodynamics and delivery devices.

The most common reason for not passing this question was providing vague statements without explanation or the specific information required.

Candidates were expected to comment on importance of particle size and drug delivery, patient compliance, the effect of a spacer and systemic effects of different routes of administration. Whilst some candidates did make reference to this it lacked the detail required to demonstrate that they understood the concepts.

F1ii / 23A10: Describe the pharmacology of salbutamol (70% of Marks), including the principles and efficacy of methods of delivery (30% of Marks)



Synthetic symphathomimetic amine

Chiral drug with R and S isomers, R is thought to bind to human B2 adrenoceptor.

  • Tablets – 2/4/8 mg
  • Syrup – 0.4/2.5 mg/ml
  • Aerosol – 100 microgs/puff
  • Dry powder (inhalation) in capsules – 200/400 microgs
  • Solution (nebulisation) – 2.5/5 mg/ml
  • IV – colourless solution – 1mg/ml of salbutamol sulfate


  • Exacerbation of Obstructive airway disease – Asthma, Chronic obstructive pulmonary disease
  • Bronchospasm
  • Hyperkalemia
  • Tocolytic

Mechanisms of Action

  • Pre-dominantly Beta-2 agonist (with minor effect at B1)
  • G-protein coupled receptor (S)
  • Activates Adenylate Cyclase
  • Increases [cAMP]
  • Activates Protein Kinase A
  • Inactivates myosin-light chain kinase and activates myosin light-chain phosphatase
    • = smooth muscle relaxation


  • PO: 2-4 mg Q6-8H
  • Inhalation: 1-2 metered puffs of 200-400 microgs of powder Q6-8H
  • Nebulised solution: 2.5-5 mg inhaled Q6H
  • SC/IM: 0.5 mg Q4H
  • IV: diluted in glucose or saline, rate not exceeding 0.5 microgs/kg/min
  • Burst therapy: 12 puffs salbutamol MDI via spacer and mask every 20 minutes for 3 doses


  • Resp – bronchodilation, increases ciliary clearance of mucous, interferes with hypoxic pulmonary vasoconstriction

  • CVS – higher doses lead to increased inotropy/chronotropy, can cause vasodilatation resulting in decreased diastolic BP

  • Genitourinary – tocolytic, 10% of administered dose crosses placenta and may lead to fetal tachycardia

  • Metabolic – may increase plasma concentrations of free fatty acids and glucose


    • Lactataemia, palpitations, anxiety, tremor, sweating, palpitations, ketosis, hypokalemia, postural hypotension


  • A – 10% of inhalation dose reaches bronchial tree, minimal reaches systemic circulation. Oral administration is rapidly and well-absorbed (50% oral bioavailability due to significant first pass metabolism in liver and intestinal mucosa)

  • D – 8-64% protein-bound in the plasma, Vd is 156L or ~ 2L/kg

  • M – significant first pass metabolism in liver, mainly metabolised by sulfate conjugation, main metabolite is salbutamol-4-o-sulfate which is inactive.

  • E – 30% excreted unchanged in urine, remainder in faeces, sulfate derivates in the urine

    • Clearance 28L/h, elimination half-life – 2.7-5 hours

Special points

Long-term use downregulates B2-receptors (loss of bronchodilator responses, increased airway hyperresponsiveness and increased airway inflammation) and should not be used in monotherapy in asthmatics.

Appears to potentiate non-depolarising muscle relaxants by hyperpolarisation.

Methods of delivery

Inhalation is the preferred mode of delivery as direct effect on airways, as well as reducing systemic side effects.

Only 10-20% of drug is inhaled, while the rest is swallowed and undergoes absorption from the GI tract before entering systemic circulation.

Optimum size for particles to settle in airways is 2-5 micrometers.

Larger particles settle out in upper airways, smaller particles remain suspended and are therefore exhaled.

Pressurised metered-dose inhalers

Drugs propelled from a canister in the pMDI with the aid of a propellant.

  • Convenient, portable
  • Typically delivers 50-200 doses of drugs

Space chambers

Large-volume spacer devices between the pMDI and the patient reduce the velocity of particles entering the upper airways and the size of the particles by allowing evaporation of liquid propellant.

  • Reduces the amount of drug that impinges on the oropharynx and increases the proportion of drug inhaled into lower airways.
  • Useful in children who are not able to use a pMDI.

Dry powder inhalers

Delivered as a micronized dry powder, using devices delivering a fine powder dispersed by air turbulence on inhalation, which requires a minimum inspiratory flow.


Useful in treating acute exacerbations where obstruction is extreme, or for delivering inhaled drugs to infants and small children who cannot use other inhalation devices.

  • Nebulised drug may be inspired during tidal breathing
  • Possible to deliver much higher doses of drug compared with a pMDI

Two forms:

  1. Jet nebuliser – driven by a stream of gas (air or oxygen)
  2. Ultrasonic nebulisers – rapidly vibrating piezoelectric crystal


Oral dose much higher than inhaled dose to achieve same effect (20:1), so systemic effects are more common.


Immediate delivery for patients where other delivery routes are not possible.

Greatest risk of systemic side effects.


Although inhaled delivery devices decrease the risk of systemic adverse events they require patient education & compliance in order to correctly administer and deliver the dose and this needs to be considered when selecting the appropriate route

Author: Michael Wu