Abstract
Dear sir Silberstein and McCrory are to be congratulated on their important review on opioids (1). In the United States, and possibly elsewhere, the use of these drugs is probably not well-taught to generalists, quite apart from their specific use, under appropriate conditions, in patients with headache.
An additional point is that, quite apart from their differential receptor selectivity, opioids can have different chronopharmacology. This may be illustrated by comparing, for example, remifentanil, buprenorphine and, levo-alpha-acetyl methadol (LAAM) (2).
Chronopharmacology may or may not be dependent upon pharmacokinetics. Among the three example drugs cited, this is clearly the case for remifentanil, whose principal metabolite is inactive, and results from relatively rapid hydrolysis in plasma and tissues; indeed, its offset of effect after terminating an infusion is about as fast as when a dose of naloxone is adminstered (3, 4). In contrast, buprenorphine evidently sequestrates in the central nervous system, has a slow onset of effect, and is effective after detectable plasma concentrations have disappeared (5, 6); its chronopharmacology may be governed by a slow receptor dissociation rate, and not by its metabolism. The effects of LAAM last for three days, for reasons which are probably more complex (7). These three drugs do not differ in their receptor selectivity (they are all pure mu-opioid receptor agonists); their clinical uses differ because of their differential chronopharmacology.
As a pharmaceutical physician and pharmacologist, please may I suggest that headache specialists could include, when they match drugs with the often difficult clinical situations that they face, consideration of the chronopharmacology of the candidate opioids?