The serotonin syndrome is a potentially life-threatening drug reaction that may result from therapeutic medication use, self-poisoning, or interactions between drugs.

/pdf/the-serotonin-syndrome-52b0yisqua.pdf

The serotonin syndrome.

AAPCC's 2003 fatality verification process involved the preparation and review of abstracts on 1,390 fatalities reported to poison centers, some of which were eventually determined to be unrelated to a poison exposure.

2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.

The analgesic acetaminophen causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. The initial phases of toxicity were described in Dr. Gillette's laboratory in the 1970s. These findings indicated that acetaminophen was metabolically activated by cytochrome P450 enzymes to a reactive metabolite that depleted glutathione (GSH) and covalently bound to protein. It was shown that repletion of GSH prevented the toxicity. This finding led to the development of the currently used antidote N-acetylcysteine. The reactive metabolite was subsequently identified to be N-acetyl-p-benzoquinone imine (NAPQI). Although covalent binding has been shown to be an excellent correlate of toxicity, a number of other events have been shown to occur and are likely important in the initiation and repair of toxicity. Recent data have shown that nitrated tyrosine residues as well as acetaminophen adducts occur in the necrotic cells following toxic doses of acetaminophen. Nitrotyrosine was postulated to be mediated by peroxynitrite, a reactive nitrogen species formed by the very rapid reaction of superoxide and nitric oxide (NO). Peroxynitrite is normally detoxified by GSH, which is depleted in acetaminophen toxicity. NO synthesis (serum nitrate plus nitrite) was dramatically increased following acetaminophen. In inducible nitric oxide synthase (iNOS) knockout mice, acetaminophen did not increase NO synthesis or tyrosine nitration; however, histological evidence indicated no difference in toxicity. Acetaminophen did not cause hepatic lipid peroxidation in wild-type mice but did cause lipid peroxidation in iNOS knockout mice. These data suggest that NO may play a role in controlling lipid peroxidation and that reactive nitrogen/oxygen species may be important in toxicity. The source of the superoxide has not been identified, but our recent finding that NADPH oxidase knockout mice were equally sensitive to acetaminophen and had equal nitration of tyrosine suggests that the superoxide is not from the activation of Kupffer cells. It was postulated that NAPQI-mediated mitochondrial injury may be the source of the superoxide. In addition, the significance of cytokines and chemokines in the development of toxicity and repair processes has been demonstrated by several recent studies. IL-1beta is increased early in acetaminophen toxicity and may be important in iNOS induction. Other cytokines, such as IL-10, macrophage inhibitory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1), appear to be involved in hepatocyte repair and the regulation of proinflammatory cytokines.

Acetaminophen-induced hepatotoxicity

https://nrr.org/wp-content/uploads/0000/10/07_ERC_Guidelines_2005_Section7.pdf

European Resuscitation Council guidelines for resuscitation 2005. Section 7. Cardiac arrest in special circumstances.

/pdf/european-resuscitation-council-erc-guidelines-for-1vuo3ljag0.pdf

European Resuscitation Council (ERC) Guidelines for Resuscitation 2005

Toxic Exposure Surveillance System (TESS) data are compiled by the American Association of Poison Control Centers (AAPCC) in cooperation with the majority of US poison centers. These data are used to identify hazards early, focus prevention education, guide clinical research, and direct training. TESS data have prompted product reformulations, repackaging, recalls, and bans; are used to support regulatory actions; and form the basis of postmarketing surveillance of newly released drugs and products. From its inception in 1983, TESS has grown dramatically, with increases in the number of participating poison centers, population served by those centers, and reported human exposures (Table 1). 1-15 The cumulative AAPCC database now contains 24.8 million human poison exposure cases. This report includes 2,241,082 human exposure cases reported by 65 participating poison centers during 1998, an increase of 2.2% compared with 1997 poisoning reports.

/pdf/2004-annual-report-of-the-american-association-of-poison-19zajvwfhu.pdf

2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2002 annual report of the American association of poison control centers toxic exposure surveillance system

The purpose of this study was to prospectively compare the effectiveness of three different gut decontamination methods in 51 patients presenting to an emergency department with tricyclic antidepressant overdose. Patients were randomized to three treatments; Group 1 received activated charcoal, Group 2 received saline lavage followed by activated charcoal, and Group 3 received activated charcoal followed by saline lavage followed by activated charcoal. Baseline characteristics of the three groups did not differ, including Glasgow Coma Scores, age, and mean tricyclic antidepressant levels. Average length of stay in admitted patients was 93.3 hours in Group 1, 107.2 hours in Group 2, and 66.7 hours in Group 3. Of those admitted to an ICU, average ICU time was 66.9 hours in Group 1, 54.1 hours in Group 2, and 34.4 hours in Group 3. Average duration of sinus tachycardia was 20.8 hours in Group 1, 30.8 hours in Group 2, and 32.2 hours in Group 3. Of those requiring mechanical ventilation, average ventilator time was 43.4 hours in Group 1, 24.1 hours in Group 2, and 17.8 hours in Group 3. No statistically significant difference could be shown with respect to the clinical endpoints noted. There were no deaths in any of the groups. All three methods of gut decontamination had similar clinical outcomes.

Comparison of three methods of gut decontamination in tricyclic antidepressant overdose

An acellular pertussis vaccine principally containing two purified pertussis antigens, filamentous hemagglutinin and lymphocytosis-promoting factor, combined with diphtheria and tetanus toxoids was compared to conventional diphtheria-tetanus toxoids-whole cell pertussis for adverse effects and serologic responses in a group of 120 children who were from 18 to 24 months of age. Three vaccinations at 2, 4 and 6 months of age with diphtheria-tetanus toxoids-whole cell pertussis had been administered previously. Adverse effects occurred more frequently with the diphtheria-tetanus toxoids-whole cell pertussis than with diphtheria-tetanus toxoids-acellular pertussis vaccine. Fever occurred significantly more often and to a higher degree in the whole cell pertussis vaccine recipients with a peak difference occurring 6 hours after immunization (P = 0.00008). Local swelling, redness, warmth and tenderness at the injection site also occurred significantly more frequently following whole cell pertussis vaccination. No major sequelae were noted in either group. The antibody responses to lymphocytosis-promoting factor were similar for the two vaccines. The diphtheria-tetanus toxoids-acellular pertussis vaccine produced significantly lower pertussis agglutinin titers (P = 0.00001) but significantly higher antibody to filamentous hemagglutinin (P = 0.05) and to diphtheria (P = 0.03). The protective role of antibody to pertussis agglutinins vs. filamentous hemagglutinin and lymphocytosis-promoting factor continues as a central issue in the quest for a new pertussis vaccine. A clinical efficacy trial is needed.

Acellular pertussis vaccine: immunogenicity and safety of an acellular pertussis vs. a whole cell pertussis vaccine combined with diphtheria and tetanus toxoids as a booster in 18- to 24-month old children.

George C. Rodgers

Papers

2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.

2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2002 annual report of the American association of poison control centers toxic exposure surveillance system

Comparison of three methods of gut decontamination in tricyclic antidepressant overdose

Acellular pertussis vaccine: immunogenicity and safety of an acellular pertussis vs. a whole cell pertussis vaccine combined with diphtheria and tetanus toxoids as a booster in 18- to 24-month old children.