Clinically significant drug interactions with agents specific for migraine attacks

The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-MT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When egopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.

A study of large-bowel volvulus in urban Australia

Background: Large-bowel volvulus is a rare cause of bowel obstruction in the industrialized world. We analyzed the presentation and outcome of 49 patients at the Princess Alexandra Hospital, Brisbane, Australia, who received a diagnosis of colonic volvulus from 1991 to 2001. Methods: A retrospective chart study was carried out. Results: Twenty-nine patients had sigmoid volvulus (59%), 19 patients had cecal volvulus (39%) and 1 patient had a transverse colon volvulus (2%). The diagnosis of sigmoid volvulus was made accurately on plain abdominal radiography or contrast enema in 90% of cases (n = 26), compared with only 42% of cases (n = 8) of cecal volvulus. Twenty-two patients with sigmoid volvulus were treated initially with endoscopic decompression. The success rate was 64% (n = 14). There was a high early recurrence rate of sigmoid volvulus for those treated by endoscopic decompression alone (43%) during a mean period of 32 days. Of the 14 patients with cecal volvulus who were treated with right hemicolectomy, 12 had primary anastomosis and 2 had end ileostomy with mucous fistula formation. There was no anastomotic leak following right hemicolectomy with primary anastomosis, even though 6 of these patients had an ischemic cecum. Conclusions: Endoscopic decompression of the sigmoid volvulus was safe and effective as an initial treatment but has a high early recurrence rate. Any patient who is fit enough to undergo operation should have a definitive procedure during the same admission to avoid recurrence. Cecal volvulus is associated with a higher incidence of gangrene and is treated effectively by right hemicolectomy with or without anastomosis. The need for swift operative intervention is emphasized.