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1214 SECTION 15: Toxicology DISPOSITION Admission decisions are made by considering acuity of the toxicity and the circumstances that led to the toxicity.39 Asymptomatic patients with acute ingestions should be monitored for 4 to 6 hours, with measure ment of serial serum lithium levels. Admit patients with serum lithium levels of >1.5 mEq/L (>1.5 mmol/L) after an acute ingestion. Any patient with an acute ingestion of a sustained-release preparation should be admitted regardless of serum lithium level and observed for signs and symptoms of lithium toxicity. Patients with mild toxicity who have no additional risk factors may be managed with IV saline treatment for 6 to 12 hours, often in an obser vation unit. Once repeated serum lithium levels decrease to <1.5 mEq (<1.5 mmol/L), patients can be discharged after psychiatric evaluation, if needed. Patients with moderate toxicity require admission, and patients with severe toxicity require intensive care and consideration for extracorporeal removal. Patients taking lithium may seek care in the ED for conditions not related to mental health or lithium toxicity. Take care to avoid prescribing any drugs that negatively impact glomerular filtration and renal function. Thiazide diuretics, loop diuretics, NSAIDs, angiotensinconverting enzyme inhibitors, and angiotensin receptor II blockers are common agents with potential for lithium interaction promoting toxicity. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Barbiturates Chip Gresham Frank LoVecchio INTRODUCTION Barbiturates are still the most common class of antiepileptic drugs used in developing countries, but their use is declining due to the introduc tion of safer, less toxic sedative-hypnotics (e.g., benzodiazepines) and second-generation anticonvulsants. 1 Status epilepticus, 2 severe ethanol and sedative withdrawal syndromes,3-5 and toxicologic seizures6 are typically managed with benzodiazepines, but barbiturates have a useful role as second-line agents. They are still used in combination drugs (e.g., butalbital) and alone (e.g., secobarbital) for the treatment of tension and migraine headaches 7-9 and for refractory intracranial hypertension from focal and diffuse brain injury.10 CHAPTER TABLE 182-1 Selected Properties of Commonly Used Barbiturates in Adults Long Acting* Intermediate Acting* Short Acting* Ultrashort Acting* Agent Phenobarbital† Amobarbital Butalbital Pentobarbital Secobarbital Thiopental Methohexital Duration of action (hours) >6 3–6 3–4 <3 <3 5–10 min 5–7 min Elimination half-life (hours) 24–96 14–42 35–88 21–42 20–28 6–26 1–2 Hypnotic dose PO (milligrams) 300–500 100–200 50–200 100–200 50–100 100–200 50–100 IV Fatal dose, approximate (grams)‡ 5 3–6 2–5 3–6 3–6 ND ND Abbreviation: ND = no data. *This classification scheme is a convention only; it preceded the discovery that the elimination half-lives do not conform to the apparent duration of action. †Only drug responsive to extracorporeal removal. ‡In nontolerant individuals. PHARMACOLOGY Barbiturates are generally classified according to their duration of action, which is primarily dependent on lipid solubility and tissue distribution rather than the elimination half-life (Table 182-1). Barbiturates readily distribute throughout the body to most tissues, crossing the blood–brain barrier and placenta, and are excreted in breast milk.

sified according to their duration of action, which is primarily dependent on lipid solubility and tissue distribution rather than the elimination half-life (Table 182-1). Barbiturates readily distribute throughout the body to most tissues, crossing the blood–brain barrier and placenta, and are excreted in breast milk. Fetal blood barbiturate concentrations closely reflect maternal plasma levels, creating the potential for fetal withdrawal syndrome. Most barbiturates are metabolized in the liver to inactive metabolites, primarily through routes involving the cytochrome P450 system. The elimination half-life of barbiturates can be greatly shortened in infants and children and very prolonged in the elderly and in patients with liver or renal disease. Chronic barbiturate use induces activity of the cytochrome P450 enzymes and may accelerate the metabolism of concurrently taken therapeutic drugs such as oral contraceptives, antico agulants, and corticosteroids. Barbiturates’ main action is the depression of activity in the CNS and musculoskeletal system. In the CNS, this is accomplished by enhancing the action of the primary inhibitory neurotransmitter γ-aminobutyric acid at its receptor. 11 When γ-aminobutyric acid binds to its chloride channel receptor, it causes it to open, resulting in a depolarization; the depolarization temporarily stabilizes the resting membrane potential and inhibits the firing of new action potentials. Barbiturates bind to the α subunit of the γ-aminobutyric acid receptor, causing an increase in the duration of opening of the cell membrane chloride channel; this results in prolonged depolarization and prolonged inactivity. Benzodiazepines bind to a different site on the α subunit of the γ-aminobutyric acid receptor and increase the frequency with which the chloride channel opens. Increased duration, as opposed to increased frequency, is one of the reasons cited for increased morbidity and mortality with barbiturate overdoses compared to benzodiazepines. Barbiturates inhibit both the activity of the excitatory neurotransmitter glutamate at the glutamate receptor and calcium-mediated excitatory neurotransmitter release at the presynaptic terminal. Blockade of the calcium channel may contribute to the cardiac contractility impairment seen with barbiturate overdoses. Barbiturates also have effects on voltage-dependent sodium and potassium channels, but in concentrations typically far above the therapeutic range. 12 These effects may contribute to the toxicity or paradoxical actions seen with some barbiturate drugs in overdoses. CLINICAL FEATURES Mild to moderate barbiturate intoxication closely resembles alcohol intoxication and toxicity of other sedative-hypnotics. Drowsiness, dis inhibition, ataxia, slurred speech, and mental confusion are common features that escalate with increasing dose. The progressive neurologic depression seen with severe barbiturate intoxication predictably manifests as a range from stupor to coma to complete neurologic unrespon siveness, including the absence of a corneal reflex, deep tendon reflexes, and even brainstem reflexes (in patients who ultimately completely recover). Tintinalli_Sec15_p1187-1332.indd 1214 8/2/19 8:39 PM