Archive for the ‘pharmacology/physiology’ Category

Black Box Warnings

April 18th, 2011
by reuben in pharmacology/physiology

I have watched droperidol disappear from my ED’s formulary and it makes me sad. So good for so many purposes, so convenient to use, so safe, so cheap. It had to go. The black box stamp of death. Except that I just learned that there has been a black box warning on all fluoroquinolones since July 2008. Not only has cipro and levaquin use continued unabated, no one is even talking about their black box, I hadn’t even heard of it until just now. What else has a black box that I didn’t know about? Well, it’s an impressive list of drugs. Here are some highlights for the emergency doc: Clindamycin: “Clindamycin phosphate therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS and USAGE section.” Clopidogrel: “Poor metabolizers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function.” Factor VIIa: “Clinical studies have shown increased risk of arterial thromboembolic adverse events with this product when administered outside the current approved indications. Fatal and non-fatal thrombotic events have been reported.” Dihydroergotamine: “Serious and/or life threatening peripheral ischemia has been reported with coadministration of this drug with potent CYP 3A4 inhibitors (including protease inhibitors and macrolide antibiotics).” Flumazenil: “Has been associated with seizures.” Haloperidol: “Elderly patients with dementia related psychosis treated with atypical antipsychotic drugs are at an increased…

For RSI, all drugs are based on total (actual) body weight rather than ideal body weight, except ketamine, for which you are supposed to use ideal body weight. You can remember this by keeping in mind that ketamine is the ideal RSI agent. So ideal, that if you give it based on TBW rather than IBW as recommended, it doesn’t matter. Propofol is a little funky, they recommend IBW+TBW(.4). Morphine is dosed based on IBW, whereas you’re supposed to use TBW for fentanyl. I doubt that these recommendations are based on much science, but when you have to pick a dose, it’s something. From Brunette, AmJEM, 2004. doi:10.1016/S0735-6757(02)42250-4 Thanks to Erin Robey for finding this for me.

When you don’t have an IV, use midazolam for seizures and agitation. The dose is 0.2 mg/kg IM. “…The time to maximum plasma concentrations (Cmax) was shorter for midazolam (17.5 ± 6.5 min) than for diazepam (33.8 ±7.5 min). (P < 0.05, Table II) The IM absorption profiles for midazolam and diazepam demonstrate that there is more variability in the absorption rates of IM diazepam than those of IM midazolam (Figure 2). The mean time to peak absorption rate was shorter for midazolam (9 ±2 min) than for diazepam (13.8 ±7.5 min). The absorption of midazolam was almost complete within one hour following the im administration. However, for diazepam, considerable drug absorption continued, with larger variability, beyond one hour after the IM injection.” Hung, Dyck, Varvel et al. Comparative absorption kinetics of intramuscular midazolam and diazepam. Can J Anaesth 1996;43:5 pp 450-5. “Midazolam is the only benzodiazepine stable in aqueous solution and suitable for intramuscular injection. A delayed onset of action might be expected, as shown by Jawad et al., but this was not confirmed by Chamberlain et al. Intramuscular midazolam may be useful in patients when attempts to introduce an intravenous line are unsuccessful. It appeared to be well tolerated and rapidly effective for treatment of acute seizures.” Wermeling, Archer, Manaligod et al. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol 2001;41:1225-1231. “We found that midazolam is superior to haloperidol and lorazepam in the sedation of violent and severely agitated patients (VSAPs) with respect to time to sedation…

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