2023A 14: 51% of candidates passed this question.
Candidates who approached this question in a structured pharmacology approach were able to score well, outlining the pharmaceutics, pharmacodynamics, and pharmacokinetics. Many candidates limited their pharmacodynamic discussion to adverse effects of oxygen only or listed effects without demonstrating understanding of their mechanism or consequences which limited their ability to score marks.

2014B 17: 35% of candidates passed this question.
Use of a general “pharmacology” structure to answer this question would help avoid significant omissions such as only discussing pharmacokinetics or only discussing pharmacodynamics.
Oxygen has a well described list of pharmacodynamics effects that includes, cardiovascular, respiratory and central nervous system effects. Candidates’ knowledge of the pharmaceutics was limited for a routine drug. It was expected candidates would mention the potential for oxygen toxicity including a possible impact on respiratory drive in selected individuals, retrolental fibroplasia and seizures under some circumstances.
Many candidates did not answer the question asked, and instead focussed on the physiology of oxygen delivery and binding of oxygen to haemoglobin

2009A 06: Pass rate: 20%
Oxygen can be regarded as a ‘drug’ and the best answer will describe oxygen with such a perspective in mind. A good answer would require good understanding and integration of knowledge from different parts of the syllabus.
Most candidates mentioned the oxygen is an odourless and colourless gas and its effects on pulmonary pressure and atelectasis. Common omissions included the clinical uses oxygen other than reversing hypoxia, pharmaceutic properties of oxygen, pharmacodynamic response of different body systems (CVS, CNS, RESP) to hyperoxia, and pharmacokinetics of oxygen including distribution & transfer of oxygen between body systems and the metabolism of oxygen.
Syllabus: B1f, B1h, B1i, B2a, C1f, O1.
Reference: Nunn’s applied respiratory physiology.

Asthma:

1. Airway obstruction that is reversible (completely or partially) either spontaneously or with treatment,
2. Airway inflammation (oedema and hypersecretion)
3. Increased airway responsiveness to a variety of stimuli

General Measures:

• Oxygen.
• Repeated assessment
• ABGs

Specific Pharmacology:

Gladwin 2016

2019B 08: 29% of candidates passed this question.
Answers should have included the most important aspects of the pharmacology of the most commonly used drugs e.g. class, mechanism of action, pharmacodynamics and important adverse reactions. More information on beta-agonists and corticosteroids (mainstays of management) was expected than drugs like magnesium, ketamine and other adjunctive treatments.

2016B 04: 71% of candidates passed this question.
Asthma drugs are typically categorised according to mechanism of action. A reasonable alternative is to categorise by clinical use, e.g. short acting, long acting, preventer, rescue etc. A lot of emphasis in marking was placed on an understanding of the beta-adrenergic pathway, its secondary messenger system and how this medicates smooth muscle relaxation. Candidates whose answers had structure as well those who described the wide range of drugs used to treat asthma scored well.

2014B 11: 54% of candidates passed this question.
Asthma involves reversible bronchospasm, inflammation, and airway hyper-responsiveness to inhaled stimuli. The main classes of drugs for acute therapy include sympathomimetics, antimuscarinic agents, corticosteroids, methylxanthines and magnesium. Candidates should have a detailed knowledge of the mode of action of these mainstream drugs. Information about drugs used for prevention and for chronic asthma was not asked for and answers which provided details about long term inhaled steroids or leukotriene antagonists did not gain extra marks. This question was well covered by some candidates in a semi-table format. A structured approach worked well with details about drug class, mechanism of action and example(s).

2010A 09: 7 (70%) of candidates passed this question
Answers to this question needed to address drugs that target the pathophysiology of asthma: bronchospasm, inflammation (oedema and hypersecretion), and hyperreactivity to inhaled stimuli. Not all drugs used to treat less severe forms of the disease are relevant in the critical care context.
A discussion of efficacy versus toxicity was included in better answers.
As a minimum, sympathomimetics, antimuscarinics, corticosteroids and methylxanthines should have been included. The role of inhaled Adrenaline as a B2-agonist mediating bronchodilatation and an alpha-agonist constricting the bronchial mucosa was relevant to the discussion. Ketamine and volatile anaesthetics could have been discussed as adjuncts to therapy in ventilated patients. More controversial therapies such as Magnesium and Heliox are less commonly prescribed, however marks were awarded for more comprehensive answers.
Syllabus B2a 2a
Reference: Goodman and Gilman’s the Pharmacological Basis of Therapeutics 11th Ed p717-736

2007B 23: 3 candidates (43%) passed this question.
Common drugs listed were: Beta 2 agonists salbutamol and adrenaline, Steroids, Magnesium, Phosphodiesterase inhibitors.
In order to obtain marks for that class of drug the mechanism of action had to be described e.g. for theophylline; acts as a bronchodilator by inhibiting the breakdown of cyclic AMP and cyclic GMP.
There were several excellent answers to this question.

Pharmacology of Salbutamol

Delivery systems (Too much information)

• Dosage forms available
  • Aerosol powder – pMDI (DPI not available)
  • Aerosol solution, Inhalation
  • Nebulization solution, Inhalation
  • Solution, Intravenous (Also IM/Subcut)
  • Syrup and Tablets, Oral
• Inhaled Salbutamol is commonly administered via pressured metered dose inhalors and nebulizers (see below for details)
  • Soft mist inhalers and Dry Powder Inhalers are not available for Salbutamol
• Infused intravenously
  • ​​​​​​​Requires no patient effort or breath syncrony
  • Maximal systemic toxicity
• Ingested orally
  • Excellent patient compliance
  • Slower response of a lower magnitude
  • Gastrointestinal absorption is erratic and unreliable

Pressured Metered Dose Inhalers (pMDI)

• A pMDI consists of a pressurized canister, a metering valve and stem, and a mouthpiece actuator.
• Mechanism:
  • The canister contains the drug suspended in a pressurized mixture of propellants, surfactants, preservatives, flavoring agents, and dispersal agents. The propellent is hydrofluoroalkane (HFA)
  • The medication-propellant mixture is released from the pMDI canister through the metering valve and stem into an actuator boot. Lung deposition ranges between 10 and 40 percent of the nominal dose in adults and is very technique-dependent
  • Difficulty precisely coordinating device actuation with inhalation leads to poor drug delivery, suboptimal disease control, and increased inhaler use
• Devices to optimize usage:
  • Spacer or valved holding chamber:
    •  three basic designs: the open tube, the reservoir or VHC, and the reverse-flow design, in which the pMDI, placed close to the mouth, is fired in the direction away from the patient; adding a one-way valve creates a VHC. They can be used with a mouthpiece or mask, and anti-static devices reduce aerosol losses within the device
  • Breath-actuated inhalers
    • better in patients with incoordination of inhalation with device actuation
    • not available for Salbutamol yet

Nebulizers

• Jet (pneumatic), ultrasonic, mesh
• Factors affecting aerosol delivery by nebulizer
  • Technical factors: Mechanism and manufacturer, Flow rate, Fill volume, Solution characteristics, Characteristics of driving gas, Designs to enhance output, Continuous versus intermittent delivery
  • Patient factors: Breathing pattern, Nose versus mouth breathing, Artificial airway, Airway obstruction, Positive pressure level

Jet Nebulizers

• Mechanism:
  • Air compressor or pressurized gas supply (compressed air or O2) acts as driving force for liquid atomizaiton
  • Compressed gas is delivered as a jet through a small orifice, generating a region of negative pressure above medication reservoid
  • Solution is first entrained, or pulled into the gas stream (Venturi effect), then sheared into a liquid film
  • Film is unstable, and rapidly breaks into droplets due to surface tension forces
• Factors affecting drug delivery
  • Respirable dose – function of mass output of nebulizer and size of droplets (mass median aerodynamic diameter) – should be 2 to 5 µm for bronchodilators
  • Nebulization time – determined by volume of drug and flow of driving gas – lesser the better for patient compliance and need for clinical supervision
  • Dead volume – medication trapped inside nebulizer – typically 1-2ml
  • Driving gas – density of gas (improved with heliox)
  • Breathing pattern – best with slow breathing pattern with a normal tidal volume and occasional deep breaths
  • Nebulizer/compressor combination – more important in portable settings
• Continuous nebulizations
  • HEART Nebulizer (Westmed) and the AirLife Misty Finity (Vyaire), Flo-Mist (Smiths Medical), and Hope (B&B Medical Technologies)
  • Issue with need for frequent refilling ~10-15mins
    • avoided by infusion pump and large volume nebulizer
  • drug delivery over time similar to intermittent
  • better with mesh than jet
  • can be delivered via High Flow Nasal Cannula (not available in most centres)

Mesh Nebulizers

• eFlow (Pari), Aeroneb Solo and Aeroneb Go (Aerogen), MicroAIR/NE-U22 (OMRON), InnoSpire Go (Philips) and the I-neb (Respironics)
• use a mesh or plate with multiple apertures to produce a liquid aerosol
  • Solution or suspension of medication is forced through the mesh to produce an aerosol, without need for an internal baffling system or compressed air source
• Able to generate aerosols with a high fine-particle fraction, which results in more efficient drug delivery compared to conventional nebulizers.
• Portable, battery-operated, minimal residual medication volume
• Precise dosing, minimal wastage
• May not give additional benefit for use with Salbutamol (cost-ineffecient)
• May be incorporated with Adaptive Aerosol delivery
• Blockage with particles may impair drug delivery
• More maintenance – disinfection and sterilization

Ultrasonic Nebulizers

• consist of a power unit and transducer, with or without an electric fan.
  • Power unit converts electrical energy to high-frequency ultrasonic waves. A piezoelectric element in the transducer vibrates at the same frequency as the applied wave.
  • Ultrasonic waves are transmitted to the surface of the solution to create an aerosol.
  • The droplets produced by these devices have a slightly higher MMAD than droplets from a jet nebulizer.
  • A fan is used to deliver the aerosol to the patient, or the aerosol is evacuated from the nebulization chamber by the inspiratory flow of the patient.
• Advantages: quieter medication delivery and shorter treatment time than the jet nebulizers.
• Problems include poor battery life and overheating.
• Drug inactivation by increased temperature a potential issue (but not with bronchodilators)
• With suspensions, the drug particles tend to settle and ultrasonic nebulizers are inefficient

ICU patient populations:

• Not on ventilation
  • Mouthpieces and facemasks
  • mouthpiece interface is generally preferred
  • Bronchodilator response similar with either interface
  • may be based on patient preference
  • Face mask – Significant facial and eye deposition of aerosol, important to instruct the patient to inhale through the mouth to minimize nasopharyngeal deposition of medication.
• Patients with tracheostomy
  • Nebulize either via a mask over the tracheostomy opening or using a T-piece
  • T-piece preferred because more aerosol medication is directed into the tracheostomy tube
  • Special T-shaped connectors for T-piece available for pMDI administation. (Not available for direct administration into tracheostomy)
• Mechanically ventilated patients
  • using either a pMDI or a nebulizer
  • Factors affecting aerosol delivery:
    • Nebulizer: position in circuit, type of nebulizer and volume, treatment time, Duty cycle (I:E), Ventilator brand
    • pMDI: Type of actuator, Timing of actuation
    • Nebulizer and pMDI: ETT size, Humidifaction of inspired gas (deposition, Major factor), use of HME (can filter out aerosol)
  • pMDI: special actuator needed, better with a chamber than in-line, should be synchronized with with inspiratory airflow to optimize drug delivery, more consistent dose than nebulizer. HME is removed, or bypassed using commercially available devices
  • Nebulizer
    • affected by large tidal volume, use of an end-inspiratory pause, and use of a slow inspiratory flow
    • Optimized by placing the nebulizer 30 cm from ETT, rather than at the Y-piece, because the inspiratory ventilator tubing acts as a spacer.
    • Breath-actuated delivery: Operates the nebulizer only during inspiration – 5x more efficient than continuous – available in some ventilators
    • When the humidifier is bypassed the delivered dose increases by a factor of nearly four
  • Jet Nebulizer:
    • circuit contamination due to opening the ventilator tubing circuit (Valved T-piece devices available to avoid this)
    • decreased ability of the patient to trigger the ventilator
    • associated increases in tidal volume and airway pressure due to nebulizer flow
    • A filter in the expiratory limb needed to protect the expiratory valve and flow/pressure monitors.
  • Mesh Nebulizer:
    • can be used effectively – placed between the ventilator outlet and the heated humidifier.
    • Does not interfere with ventilator function (eg, no additional gas flow, no effect on triggering).
• Patients receiving noninvasive ventilation
  • during NIV using devices adapted for inline administration
  • the aerosol generator should be placed between the leak port and the interface.

2023A 10: 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.

2019A 12: 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.

2023B 11: 21% of candidates passed this question.
This question required a detailed description of the many mechanisms of action of aminophylline. This included PDE inhibition and the down stream pathway and its adenosine antagonist and antiinflammatory actions. Important pharmacokinetic concepts included hepatic metabolism with saturable kinetics and thus a narrow therapeutic window/index requiring need for drug monitoring and the risk of metabolic interactions with accelerated or reduced metabolism from inducers or inhibitors of the main enzyme (CYP1A2). Detailed pharacodynamic consequences on the respiratory and cardiovascular systems were prioritised as well as highlighting the neurological, cardiovascular and musculoskeletal consequences of toxicity.

2022A 04: 15% of candidates passed this question.
Most candidates were able to describe the mechanism of action of inhaled nitric oxide (iNO), however many demonstrated very little knowledge about prostacyclin and the adverse effects of both commonly used drugs. General statements about NO, it’s delivery and pharmacological effects did not attract marks candidates are encouraged to read the question and provide information specific to the question.
Methaemoglobin and its effects were reasonably described with many understanding the rational for restricting the concentration of iNO (ppm) because of the risk of N02 formation. The knowledge related to prostacyclin was very limited. Such limited detail as to its mechanism of action prevented any discussion regarding any differences from iNO. Many reasonable answers to the iNO component were limited overall due to a paucity of knowledge and incorrect facts in the prostacyclin section.

2011A 14: 1 (8%) of candidates passed this question.
Many candidates neglected to include oxygen which is also a drug with significant pulmonary vasodilating properties. Accurate detail concerning the receptor and second messenger effects of drugs was expected. The importance of V/Q matching and reduction in systemic effects via inhalational administration needed to be stated.
Better answers included discussion of serious adverse effects such as methaemoglobinaemia, acute lung injury, systemic hypotension, rebound phenomena and heart failure.
Syllabus: B2a, 2b,c,d,e
Recommended sources: Basic and Clinical Pharmacology, Katzung, Chp 18, 19

2020B 17: 24% of candidates passed this question.
Nitric Oxide (NO) is an inorganic colourless and odourless gas presented in cylinders containing 100/800 ppm of NO and nitrogen. Many candidates mentioned oxygen instead of nitrogen. The exposure of NO to oxygen is minimized to reduce formation of nitrogen dioxide and free radicals. Hence it is administered in inspiratory limb close to the endotracheal tube. Many candidates did not mention the contraindications/caution for NO use. Candidates generally did well in mentioning the impact on improving V/Q mismatch by promoting vasodilatation only in the ventilated alveoli and reducing RV afterload. Many candidates did not mention the extra cardio-respiratory effects. The expected adverse effects of NO were nitrogen dioxide related pulmonary toxicity, methemoglobinemia and rebound pulmonary hypertension on abrupt cessation. Pharmacokinetics of NO carried a significant proportion of marks. It was expected that the answers would involve mention of location of delivery of NO in inspiratory limb and reason behind it, the high lipid solubility and diffusion, the dose (5-20ppm), very short half-life of < 5 seconds and combination with oxyhemoglobin to produce methaemoglobin and nitrate. The main metabolite is nitrate which is excreted in urine.