New drugs and therapies

Saturday 3 June, 14h00-15h30, Room 4

This 3-part session during Saturday’s Euroanaesthesia will cover new anaesthetic agents. The first presentation on new intravenous anaesthetics will be given by Professor J Robert Sneyd, Dean and Professor of Anaesthesia, Plymouth University Peninsula Schools of Medicine and Dentistry, UK.

“In order to prosper in a market dominated by low-cost propofol formulations, a new intravenous hypnotic must offer improvements on the ‘problems’ of propofol, such as pain on injection, lipid accumulation, support of bacterial growth and a degree of cardiorespiratory depression,” explains Prof Sneyd.

One way to justify a higher price, he says, would be to develop a hypnotic suitable for use by non-anaesthetists, typically for sedation during colonoscopy. Such a compound would require a “cleaner” profile than propofol, specifically a marked reduction in airway compromise and hypotension. If this profile can be achieved then the commercial “business opportunity” is generated by the ability to avoid paying for medically qualified anaesthesiologist administration, thereby making it easier to rationalise the high price of the drug. This approach failed for fospropofol as the US regulator insisted on anaesthesiologist administration.

Prof Sneyd’s talk will explore several new intravenous anaesthetics, including remimazolam, an esterase metabolised benzodiazepine with a shorter duration of action than midazolam; cyclopropyl-methoxycarbonylmetomidate (ABP-700), an esterase metabolised etomidate derivative which produces short duration anaesthesia with minimal haemodynamic challenge; and alfaxalone, well known from previous use as an active component within Althesin which was withdrawn because of allergic reactions to the vehicle within which it was presented. Professor Sneyd says: “A reformulation of alfaxalone in a beta-cyclodextrin had a markedly superior haemodynamic profile to propofol when studied in volunteers. Whether this improved profile will justify a full development programme to achieve regulatory approval is uncertain.”

He will discuss the problems faced in developing these and other compounds, with a major obstacle in most cases being that taking these compounds to market has not been seen as commercially attractive.

New analgesics will then be covered by Professor David Lambert, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester. “Opioid receptors are part of a family that are all capable of producing some form of analgesia – at least in animals,” he explains. “Despite this the mu or MOP receptor is the main clinical target responsible for the actions of the familiar analgesics like morphine and fentanyl.”

There is growing evidence that multi-targeting (MOP plus another member of the family) may offer advantages in reducing side effect profile. In this lecture, Prof Lambert will concentrate on the opioid family and pose the question ‘Is the design of highly selective MOP agonists the way forward’. The current state of play in the clinic is the use of mixtures and these will be reviewed.  Prof Lambert says: “We know if MOP is activated and delta receptors (or DOP) are blocked in animals, this results in good quality analgesia with reduced tolerance. In addition, there is currently ongoing preclinical development of mixed MOP and nociceptin receptor (NOP) agonists with a number of registered trials on the internet.”

The final presentation, on novel local anaesthetics and peripheral antinociceptive drugs, will be given by Dr Philipp Lirk, Attending Anaesthesiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.

He will discuss how local anaesthetics are indispensable in modern perioperative patient management, and are essential for local, regional or neuraxial anaesthesia, or for intravenous administration. “Current research into new substances has focused on prolonging the duration of action, with extended-release bupivacaine now available in several countries,” explains Dr Lirk. “Secondly, the specific tailoring of local anaesthetics to block specific sodium channels or sodium channels on specific neurons (nociceptors) has been pursued. Lastly, biophysical targeting of local anaesthetics into specific cells has been experimentally demonstrated.”

He concludes:  “The ultimate goal of these avenues of research would be a sensory-selective or even nociceptor-selective block without affecting motor function. This lecture will also focus briefly on new developments on peripheral antinociceptive drugs. It is fascinating to see local anaesthetic research evolve and new ideas being continuously brought forward.”