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lorazepam / AtivanTM
ANTI-ANXIETY
Description: Lorazepam is an
oral and parenteral benzodiazepine used in the treatment of
anxiety and status epilepticus. Other uses include perioperative
sedation induction and anterograde amnesia. Intravenous lorazepam
has replaced intravenous diazepam as the drug of choice for the
treatment of status epilepticus because lorazepam persists in the
CSF longer than diazepam. Some clinicians also prefer lorazepam
over chlordiazepoxide or diazepam for controlling anxiety and
agitation during ethanol withdrawal because lorazepam is not
metabolized to active metabolites. Lorazepam was approved by the
FDA in September 1977. It is a DEA schedule IV controlled
substance. (Continued below video)
Mechanism of Action:
Benzodiazepines act at the level of the limbic, thalamic, and
hypothalamic regions of the CNS, and can produce any level of CNS
depression required including sedation, hypnosis, skeletal muscle
relaxation, anticonvulsant activity, and coma. The action of
these drugs is mediated through the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA). Central benzodiazepine receptors
interact allosterically with GABA receptors, potentiating the
effects of GABA and thereby increasing the inhibition of the
ascending reticular activating system. Benzodiazepines block the
cortical and limbic arousal that occurs following stimulation of
the reticular pathways.
As an anticonvulsant, lorazepam has become the
preferred parenteral benzodiazepine. Although lorazepam has a
shorter elimination half-life than diazepam, lorazepam persists
in the CNS longer than diazepam.
Pharmacokinetics: Lorazepam is
administered orally and parenterally. It is absorbed rapidly
following an oral dose, with wide distribution throughout the
body tissues. Approximately 91% of lorazepam present in the blood
is protein- bound. Lorazepam is conjugated to glucuronide by the
liver to inactive metabolites. The half-life of lorazepam is
approximately 42, 10.5, and 13 hours in neonates, older children,
and adults, respectively. The plasma half-life is much longer in
neonates because their glucuronidation pathways are not mature.
The metabolites are excreted in the urine.
CONTRAINDICATIONS/PRECAUTIONS:
Lorazepam should not be used in patients with preexisting
respiratory depression or in cases of acute ethanol intoxication,
shock, or coma because the drug can worsen CNS depression.
Lorazepam should not be used in patients with diseases that
decrease respiratory function such as chronic obstructive
pulmonary disease (COPD).
Large quantities of lorazepam should not be
prescribed for patients with known suicidal ideation or
tendencies.
Lorazepam can impair mental ability and
alertness, so patients should be warned not to drive a motor
vehicle or operate heavy equipment while taking this drug.
Lorazepam is contraindicated in cases of acute
closed-angle glaucoma because benzodiazepines can have
anticholinergic effects.
Lorazepam is rarely beneficial for patients
with depressive neurosis or psychosis and can induce paradoxical
effects in these patients; the drug should therefore be
administered very cautiously, if at all, to such patients.
Lorazepam can cause harm to the fetus when
administered to pregnant women, so the drug is contraindicated
during pregnancy.
Benzodiazepines should be administered
cautiously to patients with renal impairment or hepatic disease;
liver and renal function should be monitored regularly during
prolonged therapy.
Abrupt discontinuation of lorazepam after
prolonged use can cause seizures in susceptible patients. Abrupt discontinuation of benzodiazepine
therapy has been reported to cause withdrawal symptoms including
irritability, nervousness, and insomnia.
Benzodiazepine withdrawal is more likely to occur following
abrupt cessation after excessive or prolonged doses, but it can
occur following the discontinuance of therapeutic doses
administered for as few as 1-2 weeks. Benzodiazepine withdrawal
also can be more intense if the benzodiazepine involved possesses
a relatively short duration of action such as lorazepam.
Abdominal cramps, confusion, depression, perceptual disturbances,
sweating, nausea, vomiting, parasthesias, photophobia,
hyperacusis, tachycardia, and trembling also occur during
benzodiazepine withdrawal, but the incidence of these reactions
is lower. Convulsions, hallucinations, delirium, and paranoia
also can occur. Benzodiazepines
should be withdrawn cautiously and slowly, using a very gradual
dosage-tapering schedule.
The clearance and/or elimination of many drugs
are reduced in the elderly. Delayed elimination can either
intensify or prolong the actions of adverse reactions of the
drug. Benzodiazepines have been associated with falls in the
elderly and the consumer advocate group, Public Citizen, has
recommended these drugs not be used in the elderly.
DRUG INTERACTIONS: Phenytoin
can increase the hepatic metabolism of lorazepam, reducing
lorazepam serum concentrations.
Patients receiving levodopa for
Parkinson's disease can experience decreased control of the
symptoms of this disease when benzodiazepines are added to their
regimen. Benzodiazepines should be
administered cautiously to such patients.
Cimetidine, erythromycin, or disulfiram can
decrease the hepatic metabolism of lorazepam if administered
concomitantly. Probenecid has also been shown to decrease
lorazepam clearance and increase its elimination half-life
although the clinical significance of this is unclear. Patients
receiving lorazepam should be monitored for signs of altered
benzodiazepine response when cimetidine, erythromycin,
disulfiram, or possibly probenecid is initiated or discontinued.
Concomitant administration of lorazepam with
CNS-depressant drugs, including opiate agonists, phenothiazines,
barbiturates, ethanol, HA-blockers, general anesthetics, and
tricyclic antidepressants, can potentiate the CNS effects (i.e.,
increased sedation or respiratory depression) of either agent.
Diazepam has reportedly decreased the
elimination of digoxin in some patients. Digoxin toxicity has
occurred in a patient receiving alprazolam and digoxin. This
interaction may be the result of increased protein binding of
digoxin and/or an effect of benzodiazepines at the renal tubules
that decreases the elimination of digoxin. Pending further
clarification of this interaction, patients receiving a
benzodiazepine and digoxin concurrently should be monitored for
increased serum digoxin levels.
Oral contraceptives can increase the effects of
lorazepam because oral contraceptives inhibit oxidative
metabolism, thereby increasing serum concentrations of
concomitantly administered benzodiazepines that undergo
oxidation. Patients receiving oral contraceptive therapy should
be observed for evidence of increased response to lorazepam.
Flumazenil and benzodiazepines are
pharmacological opposites. Flumazenil is specifically used to
reverse the actions of benzodiazepines. Clinicians should note
that the duration of action for some benzodiazepines may be much
longer than that of flumazenil and repeat doses of flumazenil may
be necessary.
ADVERSE REACTIONS: Most of the
CNS-related adverse effects associated with lorazepam therapy are
dose-dependent. These include headache, drowsiness, ataxia,
dizziness, confusion, depression, slurred speech, syncope,
lightheadedness, fatigue, tremors, and vertigo. Occasionally,
paradoxical CNS stimulation can occur, particularly in
psychiatric patients and hyperactive children. Symptoms of
paradoxical CNS stimulation include hostility, nightmares,
talkativeness, excitement, mania, tremulousness, sleep
disturbances, increased muscle spasticity, acute rage reactions,
anxiety, restlessness, euphoria, and hyperflexia. Benzodiazepine
therapy should be discontinued if any of the signs of paradoxical
CNS excitement occur.
Other less frequently reported adverse
reactions to lorazepam therapy include bradycardia, hypotension,
rash, urticaria, blurred vision, diplopia, flushing,
constipation, nausea/vomiting, libido decrease, hepatic
dysfunction, and abdominal pain.
Apnea, hypotension, and cardiac arrest have
been reported following parenteral administration of
benzodiazepines to the elderly, to severely ill patients, or to
patients with compromised respiratory function. Respiratory
depression also has occurred in these pateints during
benzodiazepine therapy, occasionally resulting in death.
Even after short-term use of lorazepam, there
is evidence of physiological dependence and consequent adverse
withdrawal symptoms. Abrupt withdrawal of benzodiazepine therapy
has been reported to cause withdrawal symptoms including
irritability, nervousness, and insomnia. Benzodiazepine
withdrawal is more likely to occur following abrupt cessation of
excessive or prolonged doses, but it can occur following the
discontinuance of therapeutic doses that have been administered
for as few as 1- 2 weeks. Abdominal cramps, confusion,
depression, perceptual disturbances, sweating, nausea/vomiting,
parasthesias, photophobia, hyperacusis, tachycardia, and
trembling also occur during benzodiazepine withdrawal, but these
reactions are less frequent. Convulsions, hallucinations,
delirium, and paranoia also can occur. Benzodiazepines should be
withdrawn cautiously and gradually, using a very gradual
dosage-tapering schedule.
PATIENT INFORMATION:
What do lorazepam tablets do?
Lorazepam (AtivanTM ) is a benzodiazepine.
Benzodiazepines belong to a group of medicines that slow down the
central nervous system. Lorazepam relieves anxiety and
nervousness. Federal law prohibits the transfer of clonazepam to
any person other than the patient for whom it was prescribed. Do
not share this medicine with anyone else. Generic lorazepam
tablets are available.
What should my doctor or pharmacist know before
I take lorazepam?
They need to know if you have any of these
conditions:
- an alcohol or drug abuse problem
- glaucoma
- kidney disease
- liver disease
- lung disease or breathing difficulties
- psycotic illness
- shock
- suicidal thoughts
- an unusual or allergic reaction to
lorazepam, other benzodiazepines, foods, dyes, or
preservatives
- pregnant or trying to get pregnant
- breast-feeding
How should I take this medicine?
Take lorazepam tablets by mouth. Follow the
directions on the prescription label. Swallow the tablets with a
drink of water. If lorazepam upsets your stomach, take it with
food or milk. Take your doses at regular intervals. Do not take
your medicine more often than directed. Do not stop taking except
on your doctor's advice.
Special precautions for use in
children:
The safe use of lorazepam in children under 12
years old has not been established.
Elderly patients over 65 years old may have a
stronger reaction to this medicine.
What if I miss a dose?
If you miss a dose and remember within an hour,
take it as soon as you can. If it is more than an hour since you
missed a dose, skip that dose and go back to your regular
schedule. Do not take double or extra doses.
What other medicines can interact with
lorazepam?
- alcohol
- barbiturate medicines for inducing sleep
or treating seizures (convulsions)
- cimetidine
- digoxin
- disulfiram
- erythromycin
- female hormones, including contraceptive
or birth control pills
- flumazenil
- levodopa
- medicines for hay fever and other
allergies
- medicines for mental depression
- medicines for mental problems and
psychotic disturbances
- medicines for pain
- probenecid
Tell your doctor or pharmacist: about all other
medicines you are taking, including non-prescription medicines;
if you are a frequent user of drinks with caffeine or alcohol; if
you smoke; or if you use illegal drugs. These may affect the way
your medicine works. Check before stopping or starting any of
your medicines.
What side effects may I notice from taking
lorazepam?
Serious side effects with lorazepam include:
- confusion
- depression
- double vision or abnormal eye movements
- hallucinations (seeing and hearing things
that are not really there)
- lightheadedness or fainting spells
- mood changes, excitability or aggressive
behavior
- movement difficulty, staggering or jerky
movements
- muscle cramps
- restlessness
- tremors
- weakness or tiredness
Call your doctor as soon as you can if you get
any of these side effects.
Minor side effects with lorazepam include:
- constipation or diarrhea
- difficulty sleeping, nightmares
- dizziness, drowsiness, clumsiness, or
unsteadiness; a "hangover" effect
- headache
- loss of memory
- nausea, vomiting
Let your doctor know about these side effects
if they do not go away or if they annoy you.
What do I need to watch for while I take
lorazepam?
Visit your doctor for regular checks on your
progress. Your body may
become dependent on lorazepam, ask your
doctor if you still need to take it. However, if you have been
taking lorazepam regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get
severe side effects. Ask your doctor for advice before increasing
or decreasing the dose. Even after you stop taking lorazepam it
can still affect your body for several days.
You may get drowsy or dizzy. Do not drive, use
machinery, or do anything that needs mental alertness until you
know how lorazepam affects you. To reduce the risk of dizzy and
fainting spells, do not stand or sit up quickly, especially if
you are an older patient. Alcohol may increase dizziness and
drowsiness. Avoid alcoholic drinks.
Do not treat yourself for coughs, colds or
allergies without asking your doctor or pharmacist for advice.
Some ingredients can increase possible side effects.
If you are going to have surgery, tell your
doctor or dentist that you are taking lorazepam.
Where can I keep my medicine?
Keep out of the reach of children in a
container that small children cannot open.
Store at room temperature, approximately 25C
(77F). Protect from light. Keep container tightly closed. Throw
away any unused medicine after the expiration date.
The P-I-E-N-O Parkinsn's List Drug Database Index
John Cottingham is the
webmaster of this site.
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