ABSTRACT
BACKGROUND: Cyproheptadine is reported to be effective in treating serotonin syndrome. It is only available as an oral preparation and administration after SSRI overdose treated with activated charcoal is problematic. Sublingual administration may circumvent this problem. The pharmacokinetics of sublingual cyproheptadine are not characterized. This study compares the pharmacokinetics of cyproheptadine following oral and sublingual administration. METHODS: Cross-over, non-blinded, volunteer study using five healthy males. Eight milligrams of oral and sublingual cyproheptadine were administered on separate occasions with a one-week washout period. Sublingual arm subjects were pretreated with 50 g of oral activated charcoal 30 min prior to cyproheptadine, to prevent any gut absorption. Serum cyproheptadine concentration was measured at baseline, 30 min, and 1, 2, 3, 4, 6, 8, and 10 h by liquid chromatography and mass spectroscopy. RESULTS: Mean C(max) for oral and sublingual were 30.0 microg/L and 4.0 microg/L respectively: mean T(max) were 4 h and 9.6 h; mean AUC were 209 and 25 microg x hr/L. Mean +/- SEM within-subject difference between oral and sublingual C(max) was 25.9 +/- 4.1 (p = 0.003) and AUC was 184 +/- 31 (p = 0.004). CONCLUSIONS: Serum concentrations after sublingual cyproheptadine are significantly less than after oral administration. At these concentrations, the sublingual route is unlikely to be effective in treating serotonin syndrome.
Subject(s)
Cyproheptadine/pharmacokinetics , Serotonin Antagonists/pharmacokinetics , Serotonin Syndrome , Administration, Oral , Administration, Sublingual , Adolescent , Adult , Area Under Curve , Chromatography, Liquid , Cross-Over Studies , Cyproheptadine/administration & dosage , Humans , Male , Mass Spectrometry , Middle Aged , Serotonin Antagonists/administration & dosage , Serotonin Syndrome/drug therapy , Serotonin Syndrome/metabolismABSTRACT
We report the case of a 22-year-old female who was bitten on the shoulder by a spider subsequently identified as a female Cupboard spider (Steatoda grossa). She developed nausea, vomiting, and severe local and regional pain, similar to that seen in latrodectism. Symptoms were treated successfully with red-back spider antivenom (RBSAV). We also present in vitro data, which supports this clinical observation, and suggests that S. grossa venom is immunogenically reactive with both RBSAV and latrotoxin (LTx)-specific antibodies by Western blotting. Moreover, the effects of S. grossa venom on the isolated chick biventer cervicis nerve-muscle preparation are dose-dependent and similar to those seen with Latrodectus spp. venoms. S. grossa venom produced a sustained muscle contracture which could be prevented by pre-incubation of venom with RBSAV. Venom effects could also be reversed by the addition of antivenom after application of venom to the preparation. Although severe envenomation is uncommon following the bite of Steatoda spp. it may resemble latrodectism. These results indicate that RBSAV is likely to be effective in reversing symptoms of envenomation and should be considered in the treatment of patients with distressing or persisting symptoms.
