Question 17

College Answer

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

Discussion

It is clear from the college comments that the college wanted the trainees to be able to treat oxygen as a drug in this discussion. Thus:

Physico-chemical properties of oxygen

• Oxygen (O₂)is a diatomic gas with a density and viscosity slightly higher than that of air. 
• Conventional "wall" oxygen is delivered at approximately 4 atmospheres of pressure (415 kPa) and is close to 0°C at the wall outlet.

Administration:

• As an inhaled agent via a selection of fixed or variable performance delivery devices
• As intravenous or intra-arterial infusion of well-oxygenated blood (i.e. ECMO)
• Externally (as in hyperbaric oxygen therapy)

Absorption:

• Pulmonary absorption (250ml/min with 21% FiO₂, at rest)
• Cutaneous absorption (under 1ml/min at normal atmospheric pressure)
• Oral (and other) mucosal absorption (usually, nil)

Metabolism

• Metabolised in all tissues (mainly brain, heart and skeletal muscle)
• Mainly metabolised by cytochrome c mitochondrial enzymes (90%)
• Zero-order clearance kinetics, roughly 200ml/minute
• Main metabolites are CO₂ and H₂O, cleared via the lung and renally. 

Indications for use

• Supplementation (in hypoxemia)
• Prophylaxis (in pre-oxygenation for anaesthesia)
• As an antidote (carbon monoxide toxicity)
• Therapeutic uses:
  • As an antibiotic (hyperbaric oxygen for deep anaerobic infections)
  • To decrease the volume of air-filled body cavities by denitrogenation (eg. pneumothorax and pneumoencephalus)
  • In management of decompression sickness

Contraindications

• Bleomycin use (leads to pulmonary fibrosis)
• Paraquat toxicity (worsens ARDS)
• Aspiration of acid (worsens ARDS)

Complications

• Drying of mucous membranes and inspissation of secretions
• Inflammatory tracheobronchitis
• Decreased central respiratory drive (minimally)
• Hypecapnoea in "CO₂ retainers" mainly by virtue of V/Q mismatch and Haldane effect
• Absorption atelectasis
• Increased left-to-right shunting in ASDs
• Increased peripheral vascular resistance
• Cerebral and coronary vasoconstriction
• Euphoria
• Retrolental fibroplasia of the newborn
• Decreased erythropoiesis

Toxicity

• Visual changes and seizures (hyperbaric) 
• Toxicity from free radicals (worsening ARDS)

O'Driscoll, B. R., et al. "BTS guideline for oxygen use in adults in healthcare and emergency settings." Thorax 72.Suppl 1 (2017): ii1-ii90.

Tibbles, Patrick M., and John S. Edelsberg. "Hyperbaric-oxygen therapy." New England Journal of Medicine 334.25 (1996): 1642-1648.

Cherniack, NEIL S., and G. S. Longobardo. "Oxygen and carbon dioxide gas stores of the body." Physiological reviews50.2 (1970): 196-243.

RAHN, HERMANN. "Oxygen stores of man." Oxygen in the Animal Organism. 1964. 609-619.

Farhi, L. E., and H. Rahn. "Gas stores of the body and the unsteady state." Journal of Applied Physiology 7.5 (1955): 472-484.

Chawla, Anuj, and A. K. Lavania. "Oxygen toxicity." Medical Journal Armed Forces India 57.2 (2001): 131-133.

Sackner, Marvin A., et al. "Pulmonary effects of oxygen breathing: a 6-hour study in normal men." Annals of internal medicine 82.1 (1975): 40-43.