Lorazepam dosing

Since volume of blood in the body is inadequate for holding the complete lorazepam dose at the observed Cp, what volume of blood would hypothetically be required to contain the full 2-mg dose at a Cp of 20 ng/mL The required volume is 100 L (2,000 /jlg -t- 20 /xg / l.j. This volume—the volume of blood required to contain the drug within a body at an observed concentration—is called the volume of distribution (V dj. Volume of distribution is a purely hypothetical value and is sometimes called apparent volume of distribution to hammer home the idea that Vd is not a physiologically real number. A human does not have 100 L of blood, but a V d of 100 L for a drug is completely acceptable. 

A 57-year-old man with a history of alcohol abuse developed acute respiratory failure and was given lorazepam up to 18 mg/hour during alcohol withdrawal (17). On day 43 (cumulative intravenous lorazepam dose 4089 mg, containing about 220 ml of polyethylene glycol 400), he developed oliguric acute tubular necrosis with proteinuria and granular casts. 

Yahwak JA, Riker RR, Fraser GL, Subak-Sharpe S. Determination of a lorazepam dose threshold for using the osmol gap to monitor for propylene glycol toxicity. Pharmacotherapy 2008 28(8) 984—91. 

Caille G, Spenard J, Lacasse Y, et al Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses. Biopharm Drug Dispos 4 31—42, 1983... 

Monitor osmolar gap in patients receiving prolonged or high doses of above intravenous medications (e.g., lorazepam >10 mg/h infusion for >48 h). 

Must evaluate volume of medication administered to determine total propylene glycol exposure. High-dose lorazepam (i.e., >8-10 mg/h), phenytoin loading doses, and phenobarbital are the most likely offenders. 

Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,10 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.10 Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines. 

Midazolam Midazolam is water-soluble and can be administered intravenously, intramuscularly,13 buccally,14,15 and nasally.16,17 At physiologic pH, it becomes more lipophilic and can diffuse into the CNS. Compared to diazepam and lorazepam, it has fewer effects on the respiratory and cardiovascular systems. Its short half-life requires that it be re-dosed... 

It has been forty-five minutes since CH s arrival, and he has been given lorazepam 4 mg twice and loaded with 1500 mg of phenytoin. He received another 400 mg dose of phenytoin 15 minutes ago, but is still unarousable. His jerking movements have slowed down, but his temperature is now 39.9°C (103.8°F), and his blood pressure has dropped to 124/62 mm Hg. His oxygen saturation is 91% on 4 L oxygen via nasal cannula. Bilateral crackles are heard upon auscultation of his lungs. A CT scan of his head is obtained which shows no evidence of hemorrhage, tumor, or mass effect. 

In contrast to chlordiazepoxide and diazepam, lorazepam and oxazepam are not metabolized into active compounds in the liver. Instead, they are excreted by the kidneys following glucuronidation. This is important because many alcohol-dependent patients have compromised liver function. Therefore, when treatment is initiated before the results of blood tests for liver function are known, as is often the case in outpatient clinics, lorazepam and oxazepam may be preferred. Patients with liver disease may still be treated with diazepam and chlordiazepoxide, but at lower doses. This can be accommodated with the loading technique, although hourly dosing with 5 mg of diazepam or 25 mg of chlordiazepoxide may be sufficient. 

Cocaine or stimulant intoxication may require administration of a small dose of a short-acting benzodiazepine (e.g., lorazepam 1 to 2 mg) for agitation or severe anxiety. Antipsychotics (e.g., haloperidol 2 to 5 mg) should be used only if psychosis is present. If hyperthermia is present, initiate cooling measures. 

Additional doses of atropine and 2-PAMC1 depending on severity. Diazepam or lorazepam to prevent seizures if >4 mg atropine given ventilatory support. 

L The answer is a. (Hardman, p 922) Lactulose is a synthetic disaccharide (galactose-fructose) that is not absorbed. In moderate doses, it acts as a laxative. In higher doses, it is capable of binding ammonia and other toxins that form in the intestine in severe liver deficiency and that are believed to cause the encephalopathy. Loperamide is an antidiarrheal opioid lorazepam is a CNS depressant loxapine is a heterocyclic antipsychotic. 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

A benzodiazepine (BZ) should be administered as soon as possible if the patient is actively seizing. Generally one or two IV doses will stop seizures within 2 to 3 minutes. Diazepam, lorazepam, and midazolam are equally effective. If seizures have stopped, a longer-acting anticonvulsant should be given. 

Lorazepam is currently considered the BZ of choice. It takes longer to reach peak brain levels than diazepam but has a longer duration of action (12 to 24 hours). Patients chronically on BZs may require larger doses. The administration rate of diazepam and lorazepam should not exceed 5 and 2 mg/min, respectively, because the propylene glycol in the vehicle can cause dysrhythmia and hypotension. 

Refractory GCSE has also been treated with large-dose continuous infusion lorazepam or diazepam. Lorazepam contains propylene glycol, which can accumulate and cause marked osmolar gap, metabolic acidosis, and renal toxicity. 

Pregabalin produced anxiolytic effects similar to lorazepam, alprazolam, and venlafaxine in acute trials. Sedation and dizziness were the most common adverse effects, and the dose should be tapered over 1 week upon discontinuation. 

Lorazepam Ativan Tablet 0.5, 1,2 mg Oral solution 2 rrig/rri Injection 2,4 mg/mL 2-40 mg/day in divided doses or one dose at bedtime. Dosage should be slowly adjusted up and down according to response and adverse effects. 

Intramuscular (IM) lorazepam, 2 mg, as needed in combination with the maintenance antipsychotic may actually be more effective in controlling agitation than using additional doses of the antipsychotic. 

Treatment includes IM or IV AChs (Table 71-4) or benzodiazepines. Benztropine mesylate, 2 mg, or diphenhydramine, 50 mg, may be given IM or IV, or diazepam, 5 to 10 mg slow IV push, or lorazepam, 1 to 2 mg IM, may be given. Relief usually occurs within 15 to 20 minutes of IM injection or within 5 minutes of IV administration. The dose should be repeated if no response is seen within 15 minutes of IV injection or 30 minutes of IM injection. 

Lorazepam 0,5-2 mg ria, seizures (CIWA-Ar or equivalent) dosing is more common than over- ... 

Lorazepam The PK-PD modeling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers showed that the parameter values derived from PK/PD modeling, and especially the EC values, may provide sensitive indices that can be used, rather than the raw data derived from PD measurements, to compare CNS effects of benzodiazepines... 

Hanks GW, O Neill WM, Simpson P, Wesnes K. (1995). The cognitive and psychomotor effects of opioid analgesics II. A randomized controlled trial of single doses of morphine, lorazepam, and placebo in healthy subjects. EurJ Clin Pharmacol. 48(6) 455-60. 

Benzodiazepines are preferred by many for the management of agitation in nonpsychotic bipolar patients, though antipsychotics are effective as well. The most widely used benzodiazepines for this purpose are lorazepam and clonazepam. Lorazepam is perhaps the most versatile of the benzodiazepines. It has an intermediate duration of action, does not tend to accumulate and thereby cause confusion or excessive drowsiness, and can be administered by mouth, intramuscular injection, or intravenous injection. Lorazepam should be administered on an as-needed basis several times daily at 0.5-2mg per dose. The calming effects of lorazepam are usually evident within 20-30 minutes and will last for several hours. 

By contrast, clonazepam is an especially long-acting benzodiazepine that is only available in an oral preparation. Clonazepam can be started at 0.5-1 mg/day given in one or two doses per day. Whereas lorazepam provides a relatively quick onset of its tranquilizing effects, clonazepam offers a calming effect that lasts throughout the day. 

Benzodiazepines. Like the barbiturates, benzodiazepines bind to the GABA receptor and are therefore cross-tolerant with alcohol. As a result, they also make suitable replacement medications for alcohol and are widely used for alcohol detoxification. Theoretically, any benzodiazepine can be used to treat alcohol withdrawal. However, short-acting benzodiazepines such as alprazolam (Xanax) are often avoided because breakthrough withdrawal may occur between doses. Intermediate to long-acting benzodiazepines including chlordiazepoxide (Librium), diazepam (Valium), oxazepam (Serax), lorazepam (Ativan), and clonazepam (Klonopin) are more commonly utilized. 

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