uLorazepam developing world of a typical dose by

uLorazepam sold under the
brand name Ativan among
others is a
benzodiazepine medication is used to treat anxiety disorders, trouble sleeping,
active seizures including status epilepticus.

uIts also used for surgery to
interfere with memory formation and to sedate those who are being mechanically ventilated.

uBenzodiazepines are a class of psychoactive drugs
whose core chemical structure is the combination of a benzene ring and a diazepine ring.

Benzodiazepines enhance the effect of the
neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor,
resulting in sedative, hypnotic, anti-anxiety, anticonvulsant, and muscle
relaxant propertiesuLorazepam was initially patented in 1963, Ativan oral
tablets, made by Valeant Pharmaceuticals, were approved by the Food and Drug
Administration (FDA) 30th of  September
1977 and went on sale in the
United States the
same year.uIt is on the
World Health Organization’s List of Essential Medicines as
one of the most effective
and safe medicines needed in a health system.

uWholesale cost in the
developing world of a typical dose by mouth is between US$0.02 and US$0.16 as
of 2014. In the United States as of 2015 a typical month supply is
less than US$25.

uIn the United
States by 2011 28 million prescriptions for lorazepam were filled making
it the second most prescribed benzodiazepine after alprazolamuLorazepam was initially patented in 1963, Ativan oral
tablets, made by Valeant Pharmaceuticals, were approved by the Food and Drug
Administration (FDA) 30th of  September
1977 and went on sale in the
United States the
same year.

uIt is on the
World Health Organization’s List of Essential Medicines as
one of the most effective
and safe medicines needed in a health system.

uWholesale cost in the
developing world of a typical dose by mouth is between US$0.02 and US$0.16 as
of 2014. In the United States as of 2015 a typical month supply is
less than US$25.

uIn the United
States by 2011 28 million prescriptions for lorazepam were filled making
it the second most prescribed benzodiazepine after alprazolamuLorazepam is accessible in the form of tablets and are available in
strengths of 0.5 mg, 1 mg, and 2 mg.

uAtivan can also be injected intravenously or intramuscularly
though, the
intravenous route is preferred. Care should be taken to avoid injection into small
veins and intra-arterial injection.

uAbsorption from the
injection site is considerably slower if the intramuscular route is used and as
rapid an effect may be obtained by oral administration of lorazepam.

u A 1:1 dilution of Ativan Injection with normal saline or
Sterile Water for Injection BP is recommended in order to facilitate
intramuscular administration
for intravenous
administration, Ativan Injection should always be diluted with saline or
Sterile Water for Injection BP as a 1:1 dilution.

uLorazepam could also be administered sublingually and
trans dermallyuLorazepam is highly
protein bound and is extensively metabolized into pharmacologically inactive metabolites due to its poor
lipid solubility its
absorbed relatively
slowly by mouth and is unsuitable for rectal administration.

uHowever, its poor
lipid solubility and high degree of protein binding (85-90%) mean its
volume of distribution is mainly the vascular compartment, causing relatively
prolonged peak effects. This contrasts with the highly lipid-soluble diazepam,
which, although rapidly absorbed orally or rectally, soon redistributes from
the serum to other parts of the body, in particular, body fat.

uThis explains why
one lorazepam dose, despite its shorter serum half-life, has more prolonged
peak effects than an equivalent diazepam dose.
Lorazepam is rapidly
conjugated at its 3-hydroxy group into lorazepam glucuronide which is then
excreted in the urine.

uLorazepam glucuronide
has no demonstrable CNS activity in animals. The plasma levels of lorazepam are
proportional to the dose given. There is no evidence of accumulation of
lorazepam on administration up to six months. On regular administration,
diazepam will accumulate, since it has a longer half-life and active
metabolites, these metabolites also have long half-livesuRelative to other benzodiazepines, lorazepam is
thought to have high affinity for GABA receptors,
which may also
explain its marked amnesic effects.

u Its main
pharmacological effects are the enhancement of the effects of the
neurotransmitter GABA at the GABAA receptor. Benzodiazepines,
such as lorazepam, enhance the effects of GABA at the GABAA receptor via
increasing the frequency of opening of the chloride ion channel on the GABAA receptors; which results
in the therapeutic actions of benzodiazepines.

u They, however,
do not on their own enhance the GABAA receptors, but
require the neurotransmitter GABA to be present. Thus, the effect of The magnitude
and duration of lorazepam effects are dose-related, meaning larger doses have
stronger and longer-lasting effects, because the brain has spare benzodiazepine
drug receptor capacity, with single, clinical doses leading only to an
occupancy of some 3% of the available receptors.

uThe
anticonvulsant properties of lorazepam and other benzodiazepines may be, in
part or entirely, due to binding to voltage-dependent sodium channels rather
than benzodiazepine receptors. uUsual adult dose for 
anxiety: Tablets:
Initial dose is normally 2 to 3 mg orally
per day administered 2 to 3 times per day and1 to 2 mg orally 2 to 3 times a day for maintenance. If taken intravenously then 2 mg total, or 0.044 mg/kg, whichever is smaller.

uUsual adult dose for insomnia: 2-4 mg orally
administered at bedtime and the dosage should
be increased gradually when needed to help avoid adverse effects.

uUsual pediatric dose for anxiety: similar to adult dose

uUsual pediatric dose for insomnia: similar to adult dose. For elderly or
debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses
is recommended.

The dose of injection should be reduced by 50% when Co-administered with
probenecid or valproate. it may be necessary to increase the dose in female
patients who are taking oral contraceptives
alonguLorazepam metabolises differently compared to other
benzodiazepines as its metabolised in the liver through the process of glucuronidation.uBenzodiazepines that metabolise through glucuronidation- no active
metabolites and they are rarely susceptible to drug-drug interactions unlike
other benzos such as diazepam which are metabolised through the cytochrome p450

u Blood concentrations of unconjugated lorazepam peak
at 1-4 h, significant concentrations persisting for 24 h and decreasing slowly
over the next 24 h.

u About 95% of a dose of lorazepam was accounted for in urine
and faeces over a period of 5 days, 74.5% was excreted in the urine as lorazepam
glucuronide and 13.5% as minor metabolites. The excretory half-life was 12 h.

uThe biological half-life of lorazepam is 10–20 hours.uLorazepam are commonly
prescribed for a wide range of conditions, including use as sleep aides, muscle
relaxants, and anxiolytics. However, dose-related side effects can be seen,
including amnesia and central respiratory depression. Other drugs including opioids,
alcohol, and over-the-counter sleep aids can have additive or synergistic effects on the central
nervous system and respiratory function. 

Certain subpopulations
of patients can have significant and severe benzo-mediated
effects. The prudent clinician should weigh the risks
and benefits of these agents before prescribing