Lorazepam, initially marketed under the brand names
Ativan and
Temesta, is a
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
drug with short to medium duration of action. It has all five intrinsic benzodiazepine effects:
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
,
amnesicAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
,
sedativeA sedative is a substance that induces sedation by reducing irritability or excitement.At higher doses it may result in slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes...
/
hypnoticHypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia. Because drugs in this class generally produce dose-dependent effects, ranging from anxiolysis to production of unconsciousness, they are...
,
anticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers. The goal of an anticonvulsant is to suppress the rapid and...
and
muscle relaxantA muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
. It is a powerful anxiolytic, and, since its introduction in 1977, lorazepam's principal use has been in treating the symptom of
anxietyAnxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry....
. Among benzodiazepines, lorazepam has a relatively high addictive potential.
Uses
Lorazepam has relatively potent
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
effects and its best known indication is the short-term management of severe chronic anxiety, though in fact the FDA advises against this usage. It is fast acting, and useful in treating fast onset panic anxiety.
Lorazepam has strong
sedativeA sedative is a substance that induces sedation by reducing irritability or excitement.At higher doses it may result in slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes...
/
hypnoticHypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia. Because drugs in this class generally produce dose-dependent effects, ranging from anxiolysis to production of unconsciousness, they are...
effects, and the duration of clinical effects from a single dose makes it an appropriate choice for the short term treatment of
insomniaInsomnia is a symptom of any of several sleep disorders, characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both"...
, particularly in the presence of severe anxiety. Withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur after only 7 days' administration of lorazepam.
Its relatively potent amnesic effect, with its anxiolytic and sedative effects, makes lorazepam useful as
premedicationPremedication refer to a drug treatment given to a patient before a medical procedure. These drugs are typically sedative or analgesic....
. It is given before a general anaesthetic to reduce the amount of anaesthetic agent 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. Oral lorazepam is given 90 to 120 minutes before procedures, and intravenous lorazepam as late as 10 minutes before procedures.
The marked anticonvulsant properties of lorazepam, and its pharmacokinetic profile, makes intravenous lorazepam a reliable agent for terminating
acute seizuresStatus epilepticus refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between...
, but it has relatively prolonged sedation aftereffects. Oral lorazepam, and other benzodiazepines, have a role in long-term prophylactic treatment of resistant forms of
petit mal epilepsyEpilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures...
but not as first-line therapies, mainly because of the development of
resistanceDrug resistance is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance...
to their effects.
Lorazepam's anticonvulsant, or CNS depressant, properties are useful for the prevention and treatment of
alcohol withdrawal syndromeAlcohol Withdrawal Syndrome is the set of symptoms seen when an individual reduces or stops alcohol consumption after prolonged periods of excessive alcohol intake. Excessive abuse of alcohol leads to tolerance, physical dependence, and an alcohol withdrawal syndrome. The withdrawal syndrome is...
. In this setting it is relevant that impaired liver function is not a hazard with lorazepam since lorazepam does not require oxidation, hepatic or otherwise, for its metabolism.
Where there is need for
rapid sedationSedation is a medical procedure involving the administration of sedative drugs, generally to facilitate a medical procedure with local anaesthesia.- Uses :...
of violent or agitated patients, including acute
deliriumDelirium is an acute and debilitating decline in attention-focus, perception, and cognition that produces an altered form of semi-consciousness. It is a systemic syndrome caused by a chemical or disease-process which is disrupting the neurons of the cerebral cortex...
, lorazepam may be used, but as it can cause paradoxical effects, it is preferably given together with
haloperidolHaloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
. Lorazepam is absorbed relatively slowly if given intramuscularly, a common route in restraint situations.
CatatoniaCatatonia is a syndrome of psychological and motorological disturbances. Karl Ludwig Kahlbaum first described it in 1874: Die Katatonie oder das Spannungirresein...
with inability to speak is responsive and sometimes controlled with a single 2 mg oral, or slow intravenous, dose of lorazepam. Symptoms may recur and treatment for some days may be necessary. Catatonia due to abrupt or too rapid withdrawal from benzodiazepines, as part of the
benzodiazepine withdrawal syndromeBenzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or reduces the dosage too rapidly...
, should also respond to lorazepam treatment. As lorazepam can have paradoxical effects,
haloperidolHaloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
is sometimes given concomitantly.
It is sometimes used in
chemotherapyChemotherapy, in its most general sense, is the treatment of disease by chemicals especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a cytotoxic standardized treatment regimen...
as an adjunct to
antiemeticAn antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics and chemotherapy directed against cancer.-Types of Antiemetics:...
s for treating anticipatory
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
and
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Undesired vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure...
, i.e. nausea and vomiting caused or worsened by psychological sensitisation to the thought of being sick. It is also used as adjunct therapy for
cyclic vomiting syndromeCyclic vomiting syndrome or cyclical vomiting syndrome is a condition whose symptoms are recurring attacks of intense nausea, vomiting and sometimes abdominal pain and/or headaches or migraines. Cyclic vomiting usually develops during childhood usually ages 3–7; although it often remits during...
.
Formulation and administration
Pure lorazepam is an almost white powder that is nearly insoluble in water and oil. In medicinal form, lorazepam is 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
sublingualSublingual, literally 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue...
tablet.
Lorazepam tablets and syrups are administered by mouth only. The tablets contain 0.5 mg, 1 mg, or 2 mg lorazepam, with some differences between countries. Lorazepam tablets of the Ativan brand also contain
lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
,
microcrystalline celluloseCellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
, polacrilin potassium,
magnesium stearateMagnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula Mg2. It is a salt containing two equivalents of stearate and one magnesium cation...
and colouring agents (indigo carmine—E132—in blue tablets and tartrazine—E102— in yellow tablets).
Lorazepam injectable solution is administered either by deep
intramuscular injectionIntramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
or by
intravenousIntravenous therapy or IV therapy is the giving of liquid substances directly into a vein. It can be intermittent or continuous; continuous administration is called an intravenous drip. The word intravenous simply means "within a vein", but is most commonly used to refer to IV therapy...
injection. The injectable solution comes in 1 mL
ampouleAn ampoule is a small sealed vial which is used to contain and preserve a sample, usually a solid or liquid. Ampoules are commonly made of glass, although plastic ampoules do exist....
s containing 2 mg or 4 mg lorazepam. The solvents used are
polyethylene glycol 400Poly , also known as poly , polyoxyethylene and under the tradename Carbowax is the most commercially important type of polyether. PEG, PEO or POE refers to an oligomer or polymer of ethylene oxide...
and
propylene glycolPropylene glycol, known also by the systematic name propane-1,2-diol, is an organic compound , with a faintly sweet taste, and is a colorless, nearly odorless, clear, viscous liquid that is hygroscopic and miscible with water, acetone, and chloroform...
. As a preservative, the injectable solution contains
benzyl alcoholBenzyl alcohol is an organic compound with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn", thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid with a mild pleasant aromatic odor. It is a useful solvent due to its...
. Toxicity from propylene glycol has been reported in the case of a patient receiving a continuous lorazepam infusion. Intravenous injections should be given slowly and patients closely monitored for side-effects, such as respiratory depression, hypotension, or loss of airway control.
Peak effects roughly coincide with peak serum levels, which occur 10 minutes after intravenous injection, up to 60 minutes after intramuscular injection, and 90 to 120 minutes after oral administration, but initial effects will be noted before this. A clinically relevant lorazepam dose will normally be effective for 6 to 12 hours, making it unsuitable for regular once-daily administration, so it is usually prescribed as two to four daily doses when taken regularly.
Adverse effects
Any of the five intrinsic benzodiazepine effects possessed by lorazepam (sedative/hypnotic, muscle relaxant, anxiolytic, amnesic and anticonvulsant) may be considered as "adverse effects," or "side-effects," if unwanted. Lorazepam's effects are dose-dependent, meaning that the higher the dose the stronger the effects (and side-effects) will be. Using the smallest dose needed to achieve desired effects lessens the risk of adverse effects.
Sedation is the most complained-of side-effect. In a group of around 3500 patients treated for anxiety, the most common side-effects complained of from lorazepam were sedation (15.9%), dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). Side-effects such as sedation and unsteadiness increased with age.
- Paradoxical effects: In some cases there can be paradox
A paradox is a statement or group of statements that leads to a contradiction or a situation which defies intuition. The term is also used for an apparent contradiction that actually expresses a non-dual truth...
ical effects with benzodiazepines, such as increased hostility, aggression, angry outbursts, and psychomotor agitation. Paradoxical effects are more likely to occur with higher doses, in patients with pre-existing personality disorderPersonality disorders, formerly referred to as character disorders, are a class of personality types which deviate from the contemporary expectations of a society....
s and those with a psychiatric illness. It is worth noting that frustrating stimuli may trigger such reactions, even though the drug may have been prescribed to help the patient cope with such stress and frustration in the first place. As paradoxical effects appear to be dose related, they usually subside on dose reduction or on complete withdrawal of lorazepam.
- Suicidality: Benzodiazepines may sometimes unmask suicidal ideation in depressed patients, possibly through disinhibition or fear-reduction. Though relatively non-toxic in themselves, the concern is that benzodiazepines may inadvertently become facilitators of suicidal behaviour. Lorazepam should, therefore, not be prescribed in high doses or as the sole treatment in depression but only together with an appropriate antidepressant.
- Amnesic effects: Among benzodiazepines, lorazepam has relatively strong amnesic
Anterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
effects, but patients soon develop tolerance to this with regular use. To avoid amnesia (or excess sedation) being a problem, the initial total daily lorazepam dose should not exceed 2 mg. This also applies to use for night sedation. Five participants in a sleep study were prescribed lorazepam 4 mg at night, and the next evening three subjects unexpectedly volunteered memory gaps for parts of that day, an effect that subsided completely after 2–3 days' use. Amnesic effects cannot be estimated from the degree of sedation present, since the two effects are unrelated.
Full lists of Lorazepam side-effects:
For lists of lorazepam side-effects, refer to the manufacturers' data sheets. Please note that some may list side-effects for the entire benzodiazepine class, not the specific side-effect profile for lorazepam.
Contraindications
Lorazepam must be avoided in patients with the following conditions:
- Allergy
Allergy is a disorder of the immune system often also referred to as atopy. Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type...
or hypersensitivityHypersensitivity refers to undesirable reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification was expounded by P. H. G...
. Past hypersensitivity or allergy to lorazepam, to any benzodiazepine or to any of the ingredients in lorazepam tablets or injections.
- Severe respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
. Benzodiazepines, including lorazepam, may depress central nervous system respiratory drive and are contraindicated in severe respiratory failure. An example would be the inappropriate use to relieve anxiety associated with acute severe asthmaStatus asthmaticus is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids. Symptoms include chest tightness, rapidly progressive dyspnea , dry cough, use of accessory muscles, labored breathing and extreme wheezing. It is a...
. The anxiolytic effects may also be detrimental to a patient's willingness and ability to fight for breath. However, if mechanical ventilationIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
becomes necessary, lorazepam may be used to facilitate deep sedation.
- Acute intoxication
Intoxication is the state of being affected by one or more psychoactive drugs. It can also refer to the effects caused by the ingestion of poison or by the overconsumption of normally harmless substances.Some types of intoxication:*A mechanism of disease....
. Lorazepam may interact synergistically with the effects of alcohol, narcotics, or other psychoactive substances. It should, therefore not be administered to a drunk or intoxicated person.
- Ataxia
Ataxia is a neurological sign and symptom consisting of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum...
. This is a neurological clinical sign, consisting of unsteady and clumsy motion of the limbs and torso, due to failure of gross muscle movement coordination, most evident on standing and walking: It is the classic way in which acute alcohol intoxication may affect a person. Benzodiazepines should not be administered to already-ataxic patients.
- Acute narrow-angle glaucoma
Glaucoma is a group of diseases that affect the optic nerve and involves a loss of retinal ganglion cells in a characteristic pattern. It is a type of optic neuropathy. Raised intraocular pressure is a significant risk factor for developing glaucoma...
. Lorazepam has pupil-dilating effects, which may further interfere with the drainage of aqueous humour from the anterior chamber of the eye, thus worsening narrow-angle glaucomaGlaucoma is a group of diseases that affect the optic nerve and involves a loss of retinal ganglion cells in a characteristic pattern. It is a type of optic neuropathy. Raised intraocular pressure is a significant risk factor for developing glaucoma...
.
- Sleep apnea
Sleep apnea is a sleep disorder characterized by pauses in breathing during sleep. Each episode, called an apnea , lasts long enough so that one or more breaths are missed, and such episodes occur repeatedly throughout sleep...
. Sleep apnea may be worsened by lorazepam's central nervous system depressant effects. It may further reduce the patient's ability to protect his or her airway during sleep.
- Myasthenia gravis
Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. This condition is characterised by muscle weakness and a muscle relaxant such as lorazepam may exacerbate symptoms.
- Pregnancy
Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets. Human pregnancy is the most studied of all mammalian pregnancies. Obstetrics is the surgical field...
and breast feeding. Lorazepam belongs to the Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) pregnancy category D, which means that it is likely to cause harm to the developing baby, if taken during the first trimester of pregnancy. There is inconclusive evidence that lorazepam, if taken early in pregnancy, may result in reduced IQ, neurodevelopmental problems, physical malformations in cardiac or facial structure, as well as other malformations in some newborns. Lorazepam given to pregnant women antenatally may cause floppy infant syndromeHypotonia is a disorder that causes low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
in the neonate, or respiratory depression necessitating ventilation. Regular lorazepam use during late pregnancy (the third trimester), carries a definite risk of benzodiazepine withdrawal syndromeBenzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or reduces the dosage too rapidly...
in the neonate. Neonatal benzodiazepine withdrawal may include hypotoniaHypotonia is a disorder that causes low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, reluctance to suck, apneic spells, cyanosisCyanosis is a blue coloration of the skin and mucous membranes due to the presence of > 5g/dl deoxygenated hemoglobin in blood vessels near the skin surface....
, and impaired metabolic responses to cold stress. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. Lorazepam may also inhibit foetal liver bilirubin glucuronidation, leading to neonatal jaundice. Lorazepam is present in breast milk, so caution must be exercised about breast feeding.
Special groups and situations
- Children and the elderly. The safety and effectiveness of lorazepam is not well determined in children under 16 years of age, but it is used to treat serial seizures. Dose requirements have to be individualized, especially in the elderly and debilitated patients in whom the risk of oversedation is greater. Long term therapy may lead to cognitive deficits, especially in the elderly, but this is reversible after a period of discontinuation. Benzodiazepines, including lorazepam, have been found to increase the risk of falls and fractures in the elderly.
- Liver or Kidney failure. Lorazepam may be safer than most benzodiazepines in patients with impaired liver function
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
. Like oxazepamOxazepam , is a drug which is a benzodiazepine derivative...
, it does not require hepatic oxidation, but only hepatic glucuronidation into lorazepam-glucuronide. Therefore, impaired liver function is unlikely to result in lorazepam accumulation to an extent causing adverse reactions. Lorazepam-glucuronide and a small amount of unchanged lorazepam are excreted by the kidneys, so in renal failure small increases in lorazepam levels may theoretically occur.
- Surgical Premedication. Informed consent
Informed consent is a legal condition whereby a person can be said to have given consent based upon a clear appreciation and understanding of the facts, implications and future consequences of an action. In order to give informed consent, the individual concerned must have adequate reasoning...
that was given only after receiving lorazepam premedicationPremedication refer to a drug treatment given to a patient before a medical procedure. These drugs are typically sedative or analgesic....
could have its validity challenged later. Staff must use chaperoneIn clinical medicine a chaperone is a person whose has a role to witness both a patient and a medical practitioner and to be a safeguard for both parties during a medical examination or precedure. The exact role of a chaperone will vary according to the clinical situation.Chaperones are widely...
s to guard against allegations of abuse during treatment. Such allegations may arise because of incomplete amnesia, disinhibition, and impaired ability to process cues. Because of its relative long duration of residual effects (sedationSedation is a medical procedure involving the administration of sedative drugs, generally to facilitate a medical procedure with local anaesthesia.- Uses :...
, ataxiaAtaxia is a neurological sign and symptom consisting of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum...
, hypotensionIn physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the opposite of hypertension, which is high blood...
and amnesiaAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
), lorazepam premedication is best suited for hospital inpatient use. Patients should not be discharged from hospital within 24 hours of receiving lorazepam premedication, unless accompanied by a caregiver. They should also not drive, operate machinery, or use alcohol within this period.
Tolerance and dependence
Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative effects, undesirable with anxiolytic, hypnotic, and anticonvulsant effects. Patients at first experience drastic relief from anxiety and sleeplessness, but symptoms gradually return, relatively soon in the case of insomnia but more slowly in the case of anxiety symptoms. After four to six months of regular benzodiazepine use, there is little evidence of continued efficacy. If regular treatment is continued for longer than this, dose increases may be necessary to maintain effects, but treatment resistant symptoms may in fact be benzodiazepine withdrawal symptoms.
On abrupt, or overly rapid discontinuation of lorazepam, anxiety and signs of physical withdrawal have been observed, similar to those seen on withdrawal from alcohol and barbiturates. Lorazepam as with other
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
drugs can cause
physical dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction. Physical dependence can develop from low-dose therapeutic use of certain medications as...
,
addictionThe term "addiction" is used in many contexts to describe an obsession, compulsion, or excessive psychological dependence, such as: drug addiction The term "addiction" is used in many contexts to describe an obsession, compulsion, or excessive psychological dependence, such as: drug addiction The...
and what is known as the
benzodiazepine withdrawal syndromeBenzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or reduces the dosage too rapidly...
. The higher the dose and the longer the drug is taken for the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur from standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regimen.
The likelihood of dependence is relatively high with lorazepam compared to other
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s. Lorazepam's relatively short serum half-life, its confinement mainly to the vascular space, and its inactive metabolite results in interdose withdrawal phenomena and next-dose cravings. This may reinforce psychological dependence. Because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose reduction (in the UK, the smallest tablet strength is 1.0 mg, which further accentuates this difficulty). To minimise the risk of physical/psychological dependence, lorazepam is best used only short-term, at the smallest effective dose. If any benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of weeks, months or longer, according to dose and duration of use, degree of dependence and the individual. Coming off long-term lorazepam may be more realistically achieved by a gradual switch to an equivalent dose of diazepam, a period of stabilization on this and only then initiating dose reductions. The advantage of switching to diazepam is that dose reductions are felt less acutely, because of the longer half lives (20–200 hours) of diazepam and its active metabolites.
Withdrawal
Withdrawal symptoms can occur after taking therapeutic doses of Ativan 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. It takes approximately 18–36 hours for the benzodiazepine to remove itself from your body. The ease of addiction to Lorazepam, (the Ativan brand was particularly cited), and its withdrawal were brought to the attention of the British public during the early 1980s in Esther Rantzen's BBC TV series "
That's Life!That's Life! was a magazine-style television series on BBC One between 26 May 1973 and 19 June 1994, presented by Esther Rantzen throughout the entire run, with various changes of co-presenters. The show was generally recorded about an hour prior to transmission, which was originally on Saturday...
", in a feature on the drug over a number of episodes.
Pharmacology
Lorazepam is high-potency and an intermediate-acting benzodiazepine and its uniqueness, advantages and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and non-oxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency (lorazepam 1 mg is equal in effect to
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, restless legs...
10 mg). The half life of lorazepam is 10–20 hours.
Pharmacokinetics
Because of its poor lipid solubility lorazepam is absorbed relatively slowly by mouth and is unsuitable for rectal administration. But its poor lipid solubility and high degree of protein binding (85-90%) mean that lorazepam's volume of distribution is mainly the
vascular- [Headline text]--75.137.171.242 01:21, 21 October 2009 :bThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, nitrogen waste products, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pHb to maintain...
compartment, causing relatively prolonged peak effects. This contrasts with the highly lipid-soluble
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, restless legs...
which, although rapidly absorbed orally or rectally, soon redistributes from the serum to other parts of the body, particularly body fat. This explains why one lorazepam dose, despite lorazepam's shorter serum half-life, has more prolonged peak effects than an equivalent diazepam dose. On regular administration diazepam will however accumulate more, since it has a longer half-life and active metabolites with even longer half-lives.
- Clinical Example: Diazepam has long been a drug of choice for status epilepticus
Status epilepticus refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between...
: Its high lipid solubility means it gets absorbed with equal speed whether given intravenously, orally, or rectally (non-intravenous routes are convenient in non-hospital settings). But diazepam's high lipid solubility also means it does not remain in the vascular space but soon redistributes into other body tissues. So it may be necessary to repeat diazepam doses to maintain peak anticonvulsant effects, resulting in excess body accumulation. Lorazepam is the opposite case: Its low lipid solubility makes it relatively slowly absorbed by any route other than intravenously, but once injected will not get significantly redistributed beyond the vascular space. Therefore, lorazepam's anticonvulsant effects are more durable, thus reducing the need for repeated doses. If a patient is known to usually stop convulsing after only one or two diazepam doses, diazepam may be preferable because sedative after-effects will be less than if a single dose of lorazepam is given (diazepam anticonvulsant/sedative effects wear off after 15–30 minutes, but lorazepam effects last 12–24 hours). The prolonged sedation from lorazepam may, however, be an acceptable trade-off for its reliable duration of effects, particularly if the patient needs to be transferred to another facility. Although lorazepam is not necessarily better than diazepam at initially terminating seizures, lorazepam is, nevertheless, replacing diazepam as the intravenous agent of choice in status epilepticusStatus epilepticus refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between...
.
Lorazepam serum levels are proportional to the dose administered. Giving 2 mg oral lorazepam will result in a peak total serum lorazepam level of around 20 nanograms/ml around two hours later, half of which is lorazepam, half its inactive metabolite, lorazepam-glucuronide. A similar lorazepam dose given intravenously will result in an earlier and higher peak serum level, with a higher relative proportion of unmetabolised (active) lorazepam. On regular administration, maximum lorazepam serum levels are attained after three days. Longer term use, up to six months, does not result in further accumulation. On discontinuation, lorazepam serum levels become negligible after 3 days and undetectable after about a week. Lorazepam is metabolised in the liver by conjugation into inactive lorazepam-glucuronide. This metabolism does not involve hepatic oxidation and therefore is relatively unaffected by reduced liver function. Lorazepam-glucuronide is more water-soluble than its precursor and therefore gets more widely distributed in the body leading to a longer half-life than lorazepam. Lorazepam-glucuronide is eventually excreted by the kidneys and because of its tissue accumulation it remains detectable - particularly in the urine - for substantially longer than lorazepam.
Pharmacodynamics
Relative to other benzodiazepines, lorazepam is thought to have high affinity for
GABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
s, which may also explain its marked amnesic effects. The main pharmacological effects of lorazepam are the enhancement of
GABAGabâ or gabaa, for the Cebuano people , is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
at the GABA
A receptor. Benzodiazepine drugs including lorazepam increase the inhibitory processes in the cerebral cortex.
The magnitude and duration of lorazepam effects are dose related, meaning that larger doses have stronger and longer-lasting effects. This is 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.
The 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. Sustained repetitive firing seems to get limited, by the benzodiazepine effect of slowing recovery of sodium channels from inactivation in mouse spinal cord cell cultures.
Interactions
- Alcohol. Lorazepam is not usually fatal in overdose, but may cause fatal respiratory depression if taken in overdose with alcohol. The combination also causes synergistic enhancement of the disinhibitory
Disinhibition is a term in psychology used to describe a lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive and perceptual aspects with signs and symptoms...
and amnesicAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
effects of both drugs, with potentially embarrassing or criminal consequences. Some experts advise patients should be warned against taking alcohol while on lorazepam treatment, but such clear warnings are not universal.
Overdose
In cases of a suspected lorazepam overdose, it is important to establish if the patient is a regular user of lorazepam or other benzodiazepines, since regular use causes tolerance to develop. Also, one must ascertain if other drugs were also ingested.
Signs of overdose range through mental confusion,
dysarthriaDysarthria is a motor speech disorder resulting from neurological injury, characterised by poor articulation...
,
paradoxical reactionA paradoxical reaction is when medical treatment, usually a drug, has an opposite effect to an effect normally expected.An example of a paradoxical reaction is when a pain relief medication causes an increase in pain...
s, drowsiness,
hypotoniaHypotonia is a disorder that causes low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
,
ataxiaAtaxia is a neurological sign and symptom consisting of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum...
,
hypotensionIn physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the opposite of hypertension, which is high blood...
, hypnotic state,
comaIn medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
, cardiovascular depression, respiratory depression, and
deathDeath is the termination of the biological functions that define a living organism. It refers to both a particular event and to the condition that results thereby. The true nature of the latter has for millennia been a central concern of the world's religious traditions and of philosophical...
.
Early management of alert patients includes emetics,
gastric lavageGastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...
, and activated charcoal. Otherwise, management is by observation, including of vital signs, support and — only if necessary, considering the hazards of doing so, giving intravenous
flumazenilFlumazenil is a benzodiazepine antagonist....
.
Patients are ideally nursed in a kind, non-frustrating environment since, when given or taken in high doses, benzodiazepines are more likely to cause paradoxical reactions. If shown sympathy, even quite crudely feigned, patients may respond solicitously, but they may respond with disproportionate aggression to frustrating cues. Opportunistic counseling has limited value here, as the patient is unlikely to recall this later, owing to drug-induced
anterograde amnesiaAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
.
Abuse and misuse
Lorazepam is a drug with the potential for misuse. Two types of drug misuse can occur. Recreational misuse, where the drug is taken to achieve a "high," or when the drug is continued long term against medical advice.
Prescribers of lorazepam must be alert to the possibility of abuse or diversion for illegitimate use when prescribing for unsupervised outpatients. This applies particularly to patients with past or present substance abuse disorders, as persons with addictive personalities are more likely to abuse medications such as lorazepam. In addition to recreational use, benzodiazepines may be diverted and used to facilitate crime: Criminals may take them to deliberately seek disinhibition before committing crimes (which increases their potential for violence) or they may give them to unwitting victims as
date rape drugDate rape drug refers to any drug that can be used to assist in the commission of a sexual assault, such as date rape. Drugs used to facilitate rape may have sedative, hypnotic, dissociative, and/or amnesiac effects, and may be added to a food or drink without the victim's knowledge...
s, notably with alcohol.
In
Northern IrelandNorthern Ireland is a part of the United Kingdom of Great Britain and Northern Ireland and it is situated in the north-east of the island of Ireland. It shares a border with the Republic of Ireland to the south and west...
in cases where drivers had low or no alcohol readings but were thought to be impaired through drugs, benzodiazepines were found to be present in 87% of cases.
A large-scale, nationwide, U.S. government study of pharmaceutical-related ED visits by SAMHSA found that sedative-hypnotics in the United States are the most frequently abused pharmaceuticals, with 35% of drug-related emergency room visits involving sedative-hypnotics. In this category, benzodiazepines are most commonly abused. Males abuse benzodiazepines as commonly as women. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drug, with 26% of attempted suicides involving benzodiazepines. Lorazepam was the third most commonly abused benzodiazepine in these ED visit statistics.
History and legal status
Historically, lorazepam is one of the "classical" benzodiazepines. Other classical benzodiazepines include
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, restless legs...
,
clonazepamClonazepam is a benzodiazepine derivative with highly potent anticonvulsant, muscle relaxant, and anxiolytic properties. It is marketed by Roche under the trade-names Klonopin in the United States, and Ravotril in Chile. Other names like Rivotril or Rivatril are known throughout the large majority...
,
oxazepamOxazepam , is a drug which is a benzodiazepine derivative...
,
nitrazepamNitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names - Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos and Somnite...
,
flurazepamFlurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It produces a metabolite with a very long half-life , which may stay in the bloodstream for up to four days...
,
bromazepamBromazepam is a benzodiazepine derivative drug, developed in the 1970s...
and
clorazepateClorazepate , is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Clorazepate was discontinued in February 2006 in the United Kingdom. Clorazepate is a prodrug for desmethyldiazepam which is rapidly produced as...
. Lorazepam was first introduced by Wyeth Pharmaceuticals in 1971 under the brand names of
Ativan and
Temesta. The drug was developed by President of Research, D.J. Richards.
WyethWyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
's original
patentA patent is a set of exclusive rights granted by a state to an inventor or their assignee for a limited period of time in exchange for a public disclosure of an invention....
on lorazepam is expired in the United States but the drug continues to be commercially viable. As a measure of its ongoing success, it has been marketed under more than seventy
generic brandGeneric brands of consumer products are distinguished by the absence of a brand name, although the term is actually improper usage of the word "generic", which actually means "relating to or descriptive of an entire group or class." Furthermore, it is often inaccurate to describe these products...
s since then:
Almazine, Alzapam, Anxiedin, Anxira, Anzepam, Aplacasse, Aplacassee, Apo-Lorazepam, Aripax, Azurogen, Bonatranquan, Bonton, Control, Donix, Duralozam, Efasedan, Emotion, Emotival, Idalprem, Kalmalin, Larpose, Laubeel, Lopam, Lorabenz, Loram, Lorans, Lorapam, Lorat, Lorax, Lorazene, Lorazep, Lorazepam, Lorazin, Lorafen (PL), Lorazon, Lorenin, Loridem, Lorivan, Lorsedal, Lorzem, Lozepam, Merlit, Nervistop L, Nervistopl, NIC, Novhepar, Novolorazem, Orfidal, Piralone, Placidia, Placinoral, Punktyl, Quait, Renaquil, Rocosgen, Securit, Sedarkey, Sedatival, Sedizepan, Sidenar, Silence, Sinestron, Somnium, Stapam, Tavor, Titus, Tolid, Tranqil, Tranqipam, Trapax, Trapaxm, Trapex, Upan, Wintin and
Wypax.
In 2000, the
U.S.The United States of America is a federal constitutional republic comprising fifty states and a federal district...
drug company
MylanMylan Inc. is a U.S.-based generic pharmaceuticals company headquartered in Canonsburg, Pennsylvania. It has production facilities in three states and Puerto Rico....
agreed to pay $147 million to settle accusations by the
F.T.C.The Federal Trade Commission is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act...
that they had raised the price of generic lorazepam by 2600 percent and generic
clorazepateClorazepate , is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Clorazepate was discontinued in February 2006 in the United Kingdom. Clorazepate is a prodrug for desmethyldiazepam which is rapidly produced as...
by 3200 percent in 1998 after having obtained exclusive licensing agreements for certain ingredients.
Lorazepam is a Schedule IV drug under the
Controlled Substances ActThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
in the U.S. and internationally under the United Nations
Convention on Psychotropic SubstancesThe Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. During the 1960 such drugs became widely available. Government authorities opposed this for numerous reasons, arguing that along with...
. Lorazepam is a Schedule IV drug under the
Controlled Drugs and Substances ActThe Controlled Drugs and Substances Act is Canada's federal drug control statute. Passed in 1996 by the Chrétien government, it repeals the Narcotic Control Act and Parts III and IV of the Food and Drug Act and establishes eight Schedules of controlled substances and two Classes of precursors...
in Canada. In the United Kingdom, lorazepam is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001.
In popular culture
Lorazepam has been mentioned in several contemporary media in recent years, with various clinical aspects highlighted. It is seen in medical situations, such as the TV series
House, MDHouse, also known as House, M.D., is an American television medical drama that debuted on the Fox network on November 16, 2004. The program was co-created by David Shore and Paul Attanasio; Fox officially credits Shore as creator. The show's central character is Dr...
as the drug of choice for the cessation of seizures. Usage for seizures is also depicted in the movie
Saw IIISaw III is the third installment in the Saw series, released on October 27, 2006. The film is a joint effort of both the first Saws writers/directors, James Wan and Leigh Whannell, and Saw II's writer/director, Darren Lynn Bousman....
where "Jigsaw" is being operated on and begins to convulse: the character performing the surgery yells many times for Ativan, but discovers that none is available in the limited operating area.
Blue OctoberBlue October is a rock band originally from Houston, Texas. The band was formed in 1995 and currently consists of Justin Furstenfeld , Jeremy Furstenfeld , Ryan Delahoussaye , C.B...
mentions Lorazepam in their song "HRSA", where it is being prescribed in a psychiatric ward for a similar use.
The dependency problem is portrayed in
William GibsonWilliam Gibson is an American-Canadian science fiction author.William Gibson may also refer to:*William Gibson , English Catholic martyr...
's 2007 book
Spook CountrySpook Country is a 2007 novel by William Gibson.Gibson announced the book on October 6, 2006 on his , where fragments of the novel were posted non-sequentially for some time, leading to much speculation on the content and plot of the novel. Spook Country is set in February 2006, and is a...
, in which the character Milgrim is addicted to Ativan and the character Brown exploits Milgrim's addiction, in order to control him, through a steady supply of Ativan and Rize (a brand of the benzodiazepine
clotiazepamClotiazepam is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene ring...
).
In
Martin ScorseseMartin Marcantonio Luciano Scorsese is an American film director, screenwriter, producer, actor, and film historian. He is the founder of the World Cinema Foundation, a recipient of the AFI Life Achievement Award for his contributions to the cinema and has won awards from the Oscars, Golden Globe,...
's recent film,
The DepartedThe Departed is a American crime drama film remake of the 2002 Hong Kong film Infernal Affairs. The Departed was directed by Martin Scorsese, written by William Monahan and stars Leonardo DiCaprio, Matt Damon, Jack Nicholson, Martin Sheen, Alec Baldwin, Ray Winstone, Vera Farmiga and Mark Wahlberg...
,
Billy CostiganWilliam "Billy" Costigan, Jr. was a fictional character and a protagonist in the 2006 film, The Departed. He was portrayed by Leonardo DiCaprio.- Early life and background :...
--an edgy, bitter, intelligent undercover cop for the
Massachusetts State PoliceThe Massachusetts State Police is an agency of the Commonwealth of Massachusetts' Executive Office of Public Safety responsible for criminal law enforcement and traffic vehicle regulation across the state...
--suffers from frequent
anxietyAnxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry....
, claims to have panic attacks, and is prescribed lorazepam by a psychiatrist who counsels both police officers and felons.
Blair WaldorfBlair Cornelia Waldorf is the main character of the Gossip Girl book series, also appearing in the television adaptation of the same name. In addition to being the protagonist of the original novels, she is the most widely publicized figure from the television series, and the most critically...
, of the CW's TV show
Gossip GirlGossip Girl is an American young adult novel series written by Cecily von Ziegesar and published by Little, Brown and Company, a subsidiary of the Hachette Group...
, mentioned Lorazepam and some other drugs in the fifth episode of the first season.
In 2005,
Fall Out BoyFall Out Boy is an American Grammy-nominated rock band from Wilmette, Illinois, formed in 2001. The band consists of vocalist-rhythm guitarist Patrick Stump, lead guitarist Joe Trohman, bassist Pete Wentz and drummer Andy Hurley....
member Pete Wentz attempted suicide by overdosing on lorazepam; he included references to the episode in the songs "I've Got a Dark Alley and a Bad Idea That Says You Should Shut Your Mouth (Summer Song)" and "7 Minutes in Heaven (Atavan Halen)", on the album
From Under the Cork TreeFrom Under the Cork Tree is the third studio album by American rock band Fall Out Boy. The album is Fall Out Boy's first release through Island Records, it was released on May 3, 2005.-Album information:...
.
In Season 6, Episode 2 of
The SopranosThe Sopranos is an American television drama series created and produced by David Chase. It premiered on the premium cable network HBO in the United States on January 10, 1999 and ended its original run of six seasons and 86 episodes on June 10, 2007. The show has also been broadcast on A&E in...
,
Tony SopranoAnthony John "Tony" Soprano, Sr. is a fictional character on the HBO television drama series The Sopranos, portrayed by James Gandolfini and conceived by series creator David Chase. The show's exceedingly complex protagonist, he is the only character to appear in every episode of the show...
is also given Ativan for the seizure when he first awakes from his coma, and is subsequently kept in an induced coma using Ativan.
In the 2009 Broadway musical,
Next to Normal, The song, "My Psychopharmacologist and I" contains the lyrics: "Ativan calms me when I see the bills/These are a few of my favourite pills". Ativan was one of the drugs found in the cabinet in the movie "The Glass House." Dr. Glass was abusing the medication.
In 2009, Lorazepam was said to have been adminstered to pop music icon
Michael JacksonMichael Joseph Jackson , known as the "King of Pop", was an American musician and one of the most commercially successful and influential entertainers of all time...
on the morning of his
deathThe death of Michael Jackson occurred after he suffered cardiac arrest at his home in Holmby Hills, Los Angeles, California on June 25, 2009. He was treated by paramedics at his home, but was pronounced dead at the Ronald Reagan UCLA Medical Center....
by Dr. Conrad Murray as a part of a cocktail of drugs which included Valium and was said to help him wean off of his use of
PropofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
. Mr. Jackson's death was attributed to an overdose of the drug
PropofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
and Lorazepam.
See also
- Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
- Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is the condition when a person is dependent on benzodiazepine drugs. Dependence can either be a psychological dependence or a physical dependence or a combination of the two...
- Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or reduces the dosage too rapidly...
- Long term effects of benzodiazepines
The long-term effects of benzodiazepines include drug dependence as well as the possibility of adverse effects on cognitive function, physical, and mental health. There is evidence that reduction or withdrawal from benzodiazepines can lead to a reduction in anxiety symptoms...
External links