A benzodiazepine medication used to treat anxiety disorders, trouble sleeping, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting.
Has anxiety-reducing effects and its best-known indication is the short-term management of severe anxiety.
Has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant properties.
Acts fast, and useful in treating fast onset panic anxiety.
Trade name Ativan.
Can be used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated.
It can be given by mouth or intravenously or intramuscularly, sublingual and transdermal.
Pregnancy category US: D (Evidence of risk if taken during the first trimester of pregnancy.
Bioavailability 85% when taken by mouth.
Liver metabolism is by glucuronidation.
Excretion by kidneys
Common side effects include weakness, sleepiness, low blood pressure, and a decreased effort to breathe.
May be associated with increased risk of suicide among depressed.
With long-term use, increased dosage may be required for the achieve the same effect.
Physical dependence and psychological dependence may a occur with prolonged use.
Sudden cessation after long-term use, may result in a withdrawal syndrome.
The elderly often develop adverse effects.
It is associated with falls and hip fractures in the older age groups.
It is generally only recommended for up to two to four weeks of use.
It is an appropriate choice for the short-term treatment of insomnia, especially in the presence of severe anxiety or night t2242ors.
It can effectively reduce agitation and induce sleep.
It has a fairly short duration of action.
After seven days of use, withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur.
Intravenous diazepam or lorazepam are first-line treatments for convulsive status epilepticus.
It is more effective than diazepam and intravenous phenytoin in the treatment of status epilepticus and has a lower risk of continuing seizures.
Its anticonvulsant and CNS depressant properties are useful for the treatment and prevention of alcohol withdrawal syndrome.
In critically ill people, propofol has been found to be superior to lorazepam in effectiveness.
It is administered before a general anesthetic to reduce the amount of anesthetic required, or before unpleasant awake procedures, such as in dentistry or endoscopies, to reduce anxiety, to increase compliance, and to induce amnesia for the procedure.
Orally it is given 90 to 120 minutes before procedures, and intravenous lorazepam as late as 10 minutes before procedures.
Sometimes used as an alternative to midazolam in palliative sedation.
In intensive care units lorazepam is sometimes used to produce anxiolysis, hypnosis, and amnesia.
It is sometimes used as an alternative to haloperidol when there is the need for rapid sedation of violent or agitated individuals,
Acute delirium and catatonia are sometimes treated with lorazepam, but as it can cause paradoxical effects.
Sometimes used in chemotherapy in addition to medications used to treat nausea and vomiting, and as adjunct therapy for cyclic vomiting syndrome.
It is only slowly absorbed intramuscularly.
Adverse effects include: sedation, low blood pressure, confusion, ataxia, inhibiting the formation of new memories, and hangover effects.
Adverse effects are increased in combination with other CNS depressant drugs.
Its cognitive deficits persist for at least six months after withdrawal.
It impairs both explicit and implicit memory.
Falls in elderly ay occur.
The elderly have more adverse effects, and they appear at lower doses than in younger patients.
Can worsen depression, as can other benzodiazepines.
It may have paradoxical effects: worsening of seizures, or paradoxical excitement.
Paradoxical excitement is more likely to occur in children and elderly, in those with a history of alcohol abuse, and in people with a history of aggression or anger problems.
Has pupil dilating effect and may worsen narrow-angle glaucoma.
Lorazepam’s effects are dose-dependent.
Associated with an increased risk of death.
Most common side effect is sedation, followed by dizziness, weakness and unsteadiness.
Cognitive impairment, behavioural disinhibition and respiratory depression and hypotension may occur.
Side effects increase with age.
Paradoxical effects can occur: increased hostility, aggression, angry outbursts, and psychomotor agitation, and are more likely to occur with higher doses, in patients with pre-existing personality disorders and those with a psychiatric illness.
Paradoxical effects appear to be dose-related, and usually subside on dose reduction or on complete withdrawal of the drug.
Benzodiazepines like lorazepam are associated with increased risk of suicide.
It has a relatively strong amnesic effects, but tolerance to this develops with regular use.
Amnesic effects are not correlated to the degree of sedation present.
Prolonged parenterally administered lorazepam , at high dose is sometimes associated with propylene glycol poisoning.
It should be avoided in people with:
Allergy or hypersensitivity.
Severe respiratory failure
Acute intoxication
Ataxia
Acute narrow-angle glaucoma
Sleep apnea
Myasthenia gravis
Pregnancy and breastfeeding
Lorazepam given to pregnant women antenatally may cause floppy infant syndrome or respiratory depression in the newborn.
Use during the third trimester, carries a definite risk of benzodiazepine withdrawal syndrome in the neonate.
Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.
It may lead to neonatal jaundice, as it inhibits fetal liver bilirubin glucuronidation.
Breast milk contains lorazepam.
Dosing must be individualized, especially in the elderly and debilitated patients in whom the risk of oversedation is greater.
May lead to cognitive deficits with prolonged use, especially in the elderly.
Cognitive deficits may only be partially reversible.
Associated with falls and fractures in the elderly.
Dosage recommendations for the elderly are about half of those used in younger individuals.
The use in the elderly should be limited to no longer than two weeks.
It may be cleared more slowly in the elderly, with potential for accumulation.
Can cause impairments in body balance and standing steadiness in individuals who wake up at night or the next morning.
Impaired liver or renal function is unlikely to result in accumulation to an extent causing adverse reactions.
The risk of abuse of this drug is increased in dependent patients.
With its use the risk of dependence and paradoxical adverse effects are increased with comorbid psychiatric disorders.
Withdrawal syndrome occurs in about one-third of individuals who are treated for longer than four weeks.
Higher doses and longer periods of use increase the risk of developing dependence.
Benzodiazepines with a relatively short half life, such as lorazepam, have the highest risk of causing a dependence.
Tolerance develops with regular use.
The development of dependence is relatively high with lorazepam compared to other benzodiazepines.
It is best used only short-term, at the smallest effective dose.
Physical withdrawal have been observed on abrupt or overly rapid discontinuation of lorazepam.
It can cause physical dependence, addiction, withdrawal syndrome.
Withdrawal symptoms can range from mild anxiety, insomnia to seizures and psychosis, and are increased with long-term use, use of high doses, abrupt or over-rapid reduction, among other factors.
Withdrawal symptoms can occur after taking the drug for as little as one week.
Withdrawal symptoms include: headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia.
Overdoses with alcohol can be fatal due to respiratory impairment, but otherwise is not.
Adverse effects may also occur when coadministered with other drugs, such as opioids or other hypnotics..
Its metabolism is inhibited by valproate, whereas carbamazepine, lamotrigine, phenobarbital, phenytoin, and rifampin increase its rate of metabolism.
Sedative effects may be worsened by antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opiates, antipsychotics and alcohol when taken concomitantly with lorazepam.
Overdose symptoms: mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia, ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression, and death.
Management of overdose includes: emetics, gastric lavage, and activated charcoal, and vital sign support.
It may be quantitated in blood or plasma to confirm poisoning.
Blood or plasma concentrations are usually in a range of 10–300 μg/l in persons either receiving the drug therapeutically.
Approximately 300–1000 μg/l of lorazepam is found in people after acute overdosage.
It may not be detected by commonly-used urine drug screenings.
Has a relative potency 1 mg is equal in effect to diazepam 10 mg
The biological half-life is 10–20 hours.
Highly protein bound and is extensively metabolized into inactive metabolites.
It is absorbed relatively slowly by mouth, and its volume of distribution is mainly the vascular compartment, causing relatively prolonged peak effects.
Its anticonvulsant effects are durable, lasting 12–24 hours.
It is an intravenous agent of choice in status epilepticus.
On regular administration, maximum serum levels are attained after three days.
On discontinuation, serum levels become negligible after three days and undetectable after about a week.
It is metabolized in the liver by conjugation into inactive lorazepam-glucuronide.
It is thought to have high affinity for GABA receptors, probably explaining its amnesic effects.
It enhances the effects of the neurotransmitter GABA at the GABAA receptor.
Enhancing the effects of GABA at the GABAA receptor via increases the frequency of opening of the chloride ion channel on the GABAA receptors, resulting in the therapeutic actions of benzodiazepines.
The magnitude and duration of it effects are dose-related.
The brain has spare benzodiazepine drug receptor capacity, with single, clinical doses leading only to an occupancy of some 3% of the available receptors.
Its anticonvulsant properties may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.
It s mainly available as tablets and a solution for injection, but, in some locations, it is also available as a skin patch, an oral solution, and a sublingual tablet.
Parenteral, it can be administered either by intramuscular injection or by intravenous injection.
Peak effects occur 10 minutes after intravenous injection, up to 60 minutes after intramuscular injection, and 90 to 120 minutes after oral administration.
It is normally effective for six to 12 hours, so it is usually prescribed as two to four daily doses when taken regularly.
Of drugs used in attempted suicide, it is a commonly used pharmaceutical drug.
Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S.