Diazepam’s Medical Uses

Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia before certain medical procedures (e.g., endoscopy).

Intravenous diazepam or lorazepam are first line treatments for status epilepticus; However, lorazepam has advantages over diazepam, including a higher rate of terminating seizures and a more prolonged anticonvulsant effect. Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to its anticonvulsant effects usually develops within six to 12 months of treatment, effectively rendering it useless for that purpose. Diazepam is used for the emergency treatment of eclampsia, when IV magnesium sulfate and blood pressure control measures have failed. Benzodiazepines do not have any pain-relieving properties of themselves and are generally recommended to be avoided in individuals with pain. However, benzodiazepines such as diazepam can be used for their muscle-relaxant properties to alleviate pain caused by muscle spasms and various dystonias, including blepharospasm. Tolerance often develops to the muscle relaxant effects of benzodiazepines such as diazepam. Baclofen or tizanidine is sometimes used as an alternative to diazepam. Tizanidine has been found to be equally effective as other antispasmodic drugs and have superior tolerability than baclofen and diazepam.

The anticonvulsant effects of diazepam can help in the treatment of seizures due to a drug overdose or chemical toxicity as a result of exposure to sarin, VX, soman (or other organophosphate poisons; See #CANA), lindane, chloroquine, physostigmine, or pyrethroids Diazepam is sometimes used intermittently for the prophylaxis of febrile seizures which occur as a result of a high fever in children and neonates under five years of age. Long-term use of diazepam for the management of epilepsy is not recommended; however, a subgroup individuals with treatment resistant epilepsy benefit from long-term benzodiazepines and for such individuals clorazepate has been recommended due to its slower onset of tolerance to the anticonvulsant effects.

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Some Uses of Phenobarbital

Phenobarbital (INN) or phenobarbitone (former BAN) is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the benzodiazepines for these indications. The World Health Organization recommends its use as first-line for partial and generalized tonic–clonic seizures (those formerly known as grand mal) in developing countries. It is a core medicine in the WHO Model List of Essential Medicines, which is a list of minimum medical needs for a basic health care system. In more affluent countries, it is no longer recommended as a first or second-line choice anticonvulsant for most seizure types, though it is still commonly used to treat neonatal seizures.

Phenobarbital properties can effectively reduce tremors and seizures associated with abrupt withdrawal from benzodiazepines. Phenobarbital is a cytochrome P450 inducer. It's used to reduce the toxicity of some drugs.

Phenobarbital is occasionally prescribed in low doses to aid in the conjugation of bilirubin in patients suffering from Gilbert's Syndrome.

In infants suspected of neonatal biliary atresia, phenobarbital is used in preparation for a 99mTc-IDA hepatobiliary study that differentiates atresia from hepatitis or chondrostasis.

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Lorazepam's Medical Uses

Lorazepam has relatively potent anxiolytic effects and its best-known indication is the short-term management of severe anxiety; the FDA advises against use of benzodiazepines such as lorazepam for longer than 2–4 weeks. It is fast acting, and useful in treating fast onset panic anxiety.

Lorazepam has strong sedative/hypnotic effects, and the duration of clinical effects from a single dose makes it an appropriate choice for the short-term treatment of insomnia, in particular in the presence of severe anxiety. It has a fairly short duration of action (Venable and Aschenbrenner 2009). Withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur after only seven days' administration of lorazepam.

Lorazepam is sometimes used for individuals receiving mechanical ventilation. However, in critically ill patients, propofol has been found to be superior to lorazepam both in effectiveness and overall cost; as a result, the use of propofol for this indication is now encouraged, whereas the use of lorazepam for this indication is discouraged.

Its relatively potent amnesic effect, with its anxiolytic and sedative effects, makes lorazepam useful as premedication. 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. Lorazepam is sometimes used as an alternative to midazolam in palliative sedation. In intensive care units lorazepam is sometimes used to produce anxiolysis, hypnosis, and amnesia.

Intravenous diazepam or lorazepam are first-line treatments for convulsive status epilepticus. Lorazepam is more effective than diazepam in the treatment of status epilepticus. However, phenobarbitol has a superior success rate compared to lorazepam and other drugs, at least in the elderly.

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Midazolam's Indications for Pregnancy

Midazolam ( marketed in English-speaking countries under the trade names Dormicum, Hypnovel, and Versed, is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic, amnestic, hypnotic, anticonvulsant, skeletal muscle relaxant, and sedative properties. Midazolam has a fast recovery time and is the most commonly used benzodiazepine as a premedication for sedation; less commonly it is used for induction and maintenance of anesthesia. Flumazenil, a benzodiazepine antagonist drug, can be used to treat an overdose of midazolam, as well as to reverse sedation. However, flumazenil can trigger seizures in mixed overdoses and in benzodiazepine-dependent individuals, so is not used in most cases.

Midazolam, when taken during the third trimester of pregnancy, may cause severe risk to the neonate, including benzodiazepine withdrawal syndrome, with possible symptoms including hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. Other neonatal withdrawal symptoms include hyperexcitability, tremor and gastrointestinal upset (diarrhea or vomiting). Breast feeding by mothers using midazolam is not recommended.

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Adverse Effects of Zolpidem

From Wikipedia:

Side effects of Zolpidem at any dose may include:

• Nausea
• Vomiting
• Anterograde amnesia
• Hallucinations, through all physical senses, of varying intensity
• Delusions
• Altered thought patterns
• Ataxia or poor motor coordination, difficulty maintaining balance
• Euphoria and/or dysphoria
• Increased appetite
• Increased or decreased libido
• Amnesia
• Impaired judgment and reasoning
• Uninhibited extroversion in social or interpersonal settings
• Increased impulsivity
• When stopped, rebound insomnia may occur
• Headaches
• Short-term memory loss

Some users have reported unexplained sleepwalking while using zolpidem, and a few have reported driving, binge eating, sleep talking, and performing other daily tasks while sleeping. Research by Australia's National Prescribing Service found these events occur mostly after the first dose taken, or within a few days of starting therapy. Rare reports of sexual parasomnia episodes related to zolpidem intake have also been reported. Sleepwalkers can sometimes perform these tasks as normally as they might if they were awake. They can sometimes carry on complex conversations and respond appropriately to questions or statements, so much so that observers may believe them to be awake. This is similar to, but unlike, typical sleep talking, which can usually be identified easily and is characterised by incoherent speech that often has no relevance to the situation or that is so disorganised as to be completely unintelligible. Those under the influence of this medication may seem fully aware of their environments, though they are still asleep. This can bring about concerns for the safety of the sleepwalkers and others. These side effects may be related to the mechanism that also causes zolpidem to produce its hypnotic properties. It is unclear whether the drug is responsible for the behavior, but a class-action lawsuit was filed against Sanofi-Aventis in March 2006 on behalf of those who reported symptoms. It is possible some users believe they were asleep during these events because they do not remember the events, due to the short-term memory loss and anterograde amnesia side effects.

Residual 'hangover' effects, such as sleepiness and impaired psychomotor and cognitive function, after nighttime administration may persist into the next day, which may impair the ability of users to drive safely and increase risks of falls and hip fractures.

The Sydney Morning Herald in Australia in 2007 reported a man who fell 30 meters to his death from a high-rise unit balcony may have been sleepwalking under the influence of Stilnox. The coverage prompted over 40 readers to contact the newspaper with their own accounts of Stilnox-related automatism, and as of March 2007, the drug was under review by the Adverse Drug Reactions Advisory Committee.
In February 2008, the Australian Therapeutic Goods Administration attached a Black Box Warning to zolpidem, stating, that "Zolpidem may be associated with potentially dangerous complex sleep-related behaviours that may include sleep walking, sleep driving, and other bizarre behaviours. Zolpidem is not to be taken with alcohol. Caution is needed with other CNS depressant drugs. Limit use to four weeks maximum under close medical supervision." This report received widespread media coverage after the death of Australian student Mairead Costigan, who fell 20 m from the Sydney Harbour Bridge while under the influence of Stilnox.

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Uses of Estazolam in Elderly

Estazolam (marketed under the brand names ProSom, Eurodin) is a benzodiazepine derivative drug developed by Upjohn in the 1970s. Estazolam possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine.

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including estazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.

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Buspirone's Pharmacology

Buspirone (BEW-spi-rohn; trade name Buspar, pronounced BYOO-spar) is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder (GAD).

Bristol-Myers Squibb (BMS) gained FDA approval of buspirone in 1986 for treatment of GAD. The patent on Buspar by Bristol-Myers Squibb expired in 2001, and buspirone is available as a generic.

Buspirone functions as a serotonin 5-HT1A receptor partial agonist. It is this action that is thought to mediate its anxiolytic and antidepressant effects. Additionally, it functions as a dopamine D2, as well as α1, and α2-adrenergic receptor antagonist to a lesser degree, though these properties are generally undesirable in an anxiolytic and likely only contribute to side effects.

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Indications of Flurazepam

Flurazepam (marketed under the brand names Dalmane and Dalmadorm) 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 (40–250 hours), which may stay in the bloodstream for up to four days. Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next day sedation.

Flurazepam is officially indicated for mild to moderate insomnia and as such it is used for short-term treatment of patients with mild to moderate insomnia such as difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Flurazepam is a long acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep. Intermediate half-life benzodiazepines are also useful for patients with difficulty in maintaining sleep (e.g. loprazolam, lormetazepam, temazepam). Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.


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What Is Halazepam?

Halazepam is a benzodiazepine derivative and is marketed under the brand names Alapryl and Pacinone It is no longer marketed in the United States. It had been marketed under the name Paxipam, but was withdrawn by its manufacturer, Schering Plough, for poor sales. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is a trifluoroethyl derivative of nordazepam. While its structure may be similar to chlordiazepoxide and diazepam, it has both less toxicity and less tendency to cause paradoxical hostility and aggression than either of them. Halazepam has active benzodiazepine metabolites.

Halazepam ( Paxipam ) is an antianxiety agent ( benzodiazepines ). It is primarily used for relief anxiety. Halazepam is also used to relieve anxiety, nervousness, and tension associated with anxiety disorders.

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The History of Meprobamate

Meprobamate was first synthesized by Bernard John Ludwig, PhD, and Frank Milan Berger, MD, at Carter Products in May 1950. Wallace Laboratories, a subsidiary of Carter Products, bought the license and named it Miltown after the borough of Milltown in New Jersey. Launched in 1955, it rapidly became the first blockbuster psychotropic drug in American history, becoming popular in Hollywood and gaining notoriety for its seemingly miraculous effects.

In the mid-1940s, Dr. Berger was working in a laboratory of a British drug company, looking for a preservative for penicillin, when he noticed that a compound called mephenesin had a sedative effect in small laboratory animals (rodents). Dr. Berger subsequently referred to this sedating or “tranquilizing” effect in a now-historic article, published by The British Journal of Pharmacology in 1946. However, there were three major drawbacks to the use of mephenesin as a tranquilizer: a very short duration of action, greater effect on the spinal cord than on the brain, and a weak activity.  After moving to Wallace Laboratories in New Jersey, Dr. Berger and a chemist, Dr. Bernard Ludwig, synthesized a chemically-related tranquilizing compound, meprobamate, that was able to overcome these three drawbacks. It was soon prescribed under the trade name Miltown.

A December 1955 study of 101 patients at the Mississippi State Hospital in Whitfield, Mississippi, found meprobamate useful in the alleviation of "mental symptoms." Three percent of the patients made a complete recovery, 29% were greatly improved, and 50% were somewhat better. Eighteen percent realized little change. Self-destructive patients became cooperative and calmer, and experienced a resumption of logical thinking. In 50% of the cases relaxation brought about more favorable sleep habits. Hydrotherapy and all types of shock treatment were halted. Meprobamate was found to help in the treatment of alcoholics by 1956. By 1957, over 36 million prescriptions had been filled for meprobamate in the US alone, a billion pills had been manufactured, and it accounted for fully a third of all prescriptions written. Dr. Berger, clinical director of Wallace Laboratories (who died on March 16, 2008, aged 94), described it as a relaxant of the central nervous system, whereas other tranquilizers suppressed it. A University of Michigan study found that meprobamate affected driving skills. Though patients reported being able to relax more easily, meprobamate did not completely alleviate their tense feelings. The disclosures came at a special scientific meeting at the Barbizon Plaza Hotel in New York City, at which Aldous Huxley addressed an evening session. He predicted the development of many chemicals "capable of changing the quality of human consciousness," in the next few years. Coincidentally, carisoprodol, a prodrug of meprobamate, was initially marketed under the trade name of "Soma," which was also a fictional drug in Aldous Huxley's Brave New World. Latterly carisoprodol was marketed as a skeletal muscle relaxant under the name of "Carisoma." It was never as popular as the rival products baclofen or dantrolene, and is principally known for having inspired the "Ashworth Scale" to rate the degree of spasticity.

In January 1960 Carter Products, Inc., makers of Miltown and American Home Products Corporation, which marketed Equanil, were charged with having conspired to monopolize the market in mild tranquilizers. It was revealed that the sale of meprobamate earned $40,000,000 for the defendants. Of this amount American Home Products accounted for approximately 2/3 and Carter about 1/3. The U.S. Government sought an order mandating that Carter make its meprobamate patent available at no charge to any company desiring to use it.

In April 1965 meprobamate was removed from the list of tranquilizers when experts ruled that the drug was a sedative instead. The U.S. Pharmacopoeia published the ruling. At the same time the Medical Letter disclosed that meprobamate could be addictive at dosage levels not much above recommended. In December 1967 meprobamate was placed under abuse control amendments to the Food, Drug and Cosmetic Act. Records on production and distribution were required to be kept. Limits were placed on prescription duration and refills.

Production continued throughout the 1960s but by 1970 it was listed as a controlled substance after it was discovered to cause physical and psychological dependence.

On January 19, 2012, the European Medicines Agency recommended suspension throughout the European Union of all medicines containing meprobamate, "due to serious side effects seen with the medicine." The Agency’s Committee for Medicinal Products for Human Use (CHMP) "concluded that the benefits of meprobamate do not outweigh its risks."

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The Uses of Ketazolam

Ketazolam (marketed under the brand names Anseren, Ansieten, Ansietil, Marcen, Sedatival, Sedotime, Solatran and Unakalm) is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, and sedative and skeletal muscle relaxant properties.

It is used for the treatment of anxiety and has similar effectiveness compared to diazepam. Ketazolam also appears to produce a reduced level of side effects such as sedation compared with diazepam and the side effects when they occur tend to be milder. Ketazolam is also an effective antispasmodic drug and is used for the treatment of spasticity

Ketazolam has sedating effects and tends to relax the muscles. Patients can start on a low dose to determine if it controls their anxiety and helps them feel calmer. It can be tapered up if necessary if the patient doesn’t respond on the lower dose, with the goal of finding a balance point between an effective dosage and one that starts to cause side effects. When the patient is ready to stop taking ketazolam, the medication needs to be slowly tapered back down to allow the body to adjust.

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Contraindications of Chlordiazepoxide

Use of chlordiazepoxide should be avoided in individuals with the following conditions:

ž            Myasthenia gravis

ž            Acute intoxication with alcohol, narcotics, or other psychoactive substances
ž            Ataxia
ž            Severe hypoventilation
ž            Acute narrow-angle glaucoma
ž            Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
ž            Severe sleep apnea
Hypersensitivity or allergy to any drug in the benzodiazepine class
Chlordiazepoxide is generally considered an inappropriate benzodiazepine for the elderly due to its long elimination half-life and the risks of accumulation. Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.

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The Tolerance and Withdrawal of Clonazepam

Clonazepam is a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Argentina, Australia, Brazil, Canada, Mexico and Europe. Other names such as Ravotril, Rivatril, Clonex, Paxam, or Kriadex are known throughout the rest of the world. Clonazepam has an unusually long elimination half-life of 18–50 hours, making it generally considered to be among the long-acting benzodiazepines. Clonazepam is a chlorinated derivative of nitrazepam and therefore a chloro-nitrobenzodiazepine.

Like all benzodiazepines, clonazepam is a benzodiazepine receptor agonist. One third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long term use increases the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal and anxiety and insomnia in less severe cases of withdrawal. Gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance but tolerance to the higher dose may occur and adverse effects may increase. The mechanism of tolerance includes receptor desensitisation, down regulation, receptor uncoupling and alterations in subunit composition and alterations in gene transcription coding.

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Pharmacology of Medazepam

Medazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.

It is known by the following brand names: Nobrium, Rudotel, Raporan, Ansilan Medazepam is a long acting benzodiazepine drug. The half-life of medazepam is 36 – 200 hours.

Benzodiazepine drugs including medazepam increase the inhibitory processes in the cerebral cortex by allosteric modulation of the GABA receptor. Benzodiazepines may also act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibited depolarization-sensitive calcium uptake in experiments with cell components from rat brains. This has been conjectured as a mechanism for high dose effects against seizures in a study. It has major active benzodiazepine metabolites which gives it a more prolonged therapeutic effects after administration.


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Nitrazepam' Therapeutic Uses

Nitrazepam is used to treat short-term sleeping problems (insomnia), namely difficulty falling asleep, frequent awakening, early awakenings, or a combination of each.

Nitrazepam is sometimes used for refractory epilepsies. However, long term prophylactic treatment of epilepsy has considerable drawbacks. Most importantly the loss of antiepileptic effects due to tolerance which renders prolonged nitrazepam therapy ineffective. Nitrazepam also has the drawback of significant side effects such as sedation, which is why nitrazepam and benzodiazepines in general are only prescribed in the acute management of epilepsies. Nitrazepam has been found to be more effective than clonazepam in the treatment of West syndrome which is an age dependent epilepsy, affecting the very young. However, as with other epilepsies treated with benzodiazepines, long term therapy becomes ineffective with prolonged therapy and the side effects of hypotonia and drowsiness are troublesome with nitrazepam therapy, other antiepileptic agents are therefore recommended for long term therapy, possibly Corticotropin (ACTH) or vigabatrin. In uncontrolled studies nitrazepam has shown effectiveness in infantile spasms; nitrazepam is sometimes considered as a treatment option for this indication when other drugs fail to control infantile spasms.

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The History of Zopiclone

Zopiclone was first developed and introduced in 1986 by Rhône-Poulenc S.A., now part of Sanofi-Aventis, the main worldwide manufacturer of the drug. Initially it was promoted as being an improvement on benzodiazepines. A recent meta analysis found that zopiclone had no superiority over benzodiazepines in any of the aspects assessed. On April 4, 2005, the United States Drug Enforcement Administration listed zopiclone under Schedule IV, due to evidence that the drug has addictive properties similar to benzodiazepines.

Zopiclone, as traditionally sold worldwide, is a racemic mixture of two stereoisomers, only one of which is active. In 2005, the pharmaceutical company Sepracor of Marlborough, Massachusetts began marketing the active stereoisomer eszopiclone under the name Lunesta in the United States. This had the consequence of placing what is a generic drug in most of the world under patent control in the United States, although it is expected to be available in generic form in that country by 2010[dated info]. It is already available off-patent in a number of European countries as well as Brazil and Canada. The eszopiclone/zopiclone difference is in the dosage—the strongest eszopiclone derivative dosage contains 3 mg of the therapeutic stereoisomer, whereas, the highest zopiclone dosage (7.5 mg) contains 3.75 mg of the active stereoisomer. The two agents have not yet been studied in head-to-head clinical trials to determine the existence of any potential clinical differences (efficacy, side effects, developing dependence on the drug, safety, etc.); the significant possibility that the two drugs have identical effects and only differ in dosing and the simple fact that investing in clinical trials is a very expensive undertaking may be responsible for this line of inquiry thus far remaining unpursued.

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Adverse Effects of Diazepam

Diazepam, first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms (such as in cases of tetanus), restless legs syndrome, alcohol withdrawal, benzodiazepine withdrawal and Ménière's disease. It may also be used before certain medical procedures (such as endoscopies) to reduce tension and anxiety, and in some surgical procedures to induce amnesia. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. The pharmacological action of diazepam enhances the effect of the neurotransmitter GABA by binding to the benzodiazepine site on the GABAA receptor (via the constituent chlorine atom) leading to central nervous system depression.

Adverse effects of diazepam include anterograde amnesia (especially at higher doses) and sedation, as well as paradoxical effects such as excitement, rage or worsening of seizures in epileptics. Benzodiazepines also can cause or worsen depression. Long-term effects of benzodiazepines such as diazepam include tolerance, benzodiazepine dependence and benzodiazepine withdrawal syndrome upon dose reduction; additionally, after cessation of benzodiazepines, cognitive deficits may persist for at least six months and may not fully return to normal; however, it was suggested that longer than six months may be needed for recovery from some deficits. Diazepam also has physical dependence potential and can cause serious problems of physical dependence with long term use. Compared to other benzodiazepines, though, physical withdrawal from diazepam following long term use is usually far more mild due to its long elimination half-life. Nevertheless, urgent action by national governments to improve prescribing practices has been recommended.

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Wikipedia's Definition of Lorazepam

Lorazepam (initially marketed under the brand names Ativan and Temesta) is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all six intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant. Lorazepam is used for the short-term treatment of anxiety, insomnia, acute seizures including status epilepticus and sedation of hospitalized patients, as well as sedation of aggressive patients.

Lorazepam is considered to be a short-acting drug which, similar to other benzodiazepines, exerts its therapeutic as well as adverse effects via its interaction at benzodiazepine binding sites, which are located on GABAA receptors in the central nervous system. After its introduction in 1977, lorazepam's principal use was in treating anxiety. Among benzodiazepines, lorazepam has a relatively high addictive potential. Lorazepam also has abuse potential; the main types of misuse are for recreational purposes or continued use against medical advice.The sedative-hypnotic and anterograde amnesia properties of lorazepam are sometimes used for criminal purposes.

Long-term effects of benzodiazepines include tolerance, dependence, a benzodiazepine withdrawal syndrome, red eye, and cognitive impairments which may not completely reverse after cessation of treatment; however, for most patients, cognitive impairment is not severe. Withdrawal symptoms can range from anxiety and insomnia to seizures and psychosis. Due to tolerance and dependence, lorazepam is recommended for short-term use, 2–4 weeks only. Adverse effects including anterograde amnesia, depression and paradoxical effects such as excitement or worsening of seizures may occur. Children and the elderly are more sensitive to the adverse effects of benzodiazepines. Lorazepam impairs body balance and standing steadiness and is associated with falls and hip fractures in the elderly.

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Indications of Midazolam

From Wikipedia:

Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for preoperative sedation, for the induction of general anesthesia, and for sedation of ventilated patients in critical care units. Midazolam is superior to diazepam in impairing memory of endoscopy procedures, but propofol has a quicker recovery time and a better memory-impairing effect. It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion. However, for long-term sedation, lorazepam is preferred due to its long duration of action, and propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation. There is evidence buccal and intranasal midazolam is easier to administer and more effective than rectally administered diazepam in the emergency control of seizures. In the final stages of end-of-life care, midazolam is routinely used at low doses via subcutaneous injection to alleviate agitation, myoclonus, restlessness or anxiety in the last hours or days of life. At higher doses during the last weeks of life, midazolam is considered a first line agent in palliative continuous deep sedation therapy when it is necessary to alleviate intolerable suffering not responsive to other treatments, but the need for this is rare. Midazolam is also sometimes used in neonates who are receiving mechanical ventilation, although morphine is preferred, owing to its better safety profile for this indication.

Oral midazolam is indicated for the short-term treatment of moderately severe insomnia in patients who have not reacted adequately to other hypnotics, and who have persistent trouble in falling asleep. Because of midazolam's extremely short duration, it is not used for patients who have trouble staying asleep through the night; moderate- to long-acting benzodiazepines, such as temazepam, nitrazepam, flunitrazepam and lormetazepam, are used for those purposes. Like other benzodiazepines, midazolam produces a decrease in delta activity, though the effect of benzodiazepines on delta may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; it is thought to reflect sleep quality, with lower levels of delta sleep reflecting poorer sleep. Thus, midazolam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to nitrazepam in the treatment of insomnia, as it enhances sleep quality based on EEG studies.
Midazolam in combination with an antipsychotic drug is indicated for the acute management of schizophrenia when it is associated with aggressive or out of control behaviour. It is also sometimes used for the acute management of seizures such as status epilepticus. Long-term use for the management of epilepsy is not recommended, however, due to the significant risk of tolerance (which renders midazolam and other benzodiazepines ineffective) and the significant side effect of sedation. A benefit of midazolam is that in children it can be administered buccally or intranasally at home or at school for emergency control of acute seizures, including status epilepticus. Midazolam is effective for refractory status epilepticus, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle, which occurs with other benzodiazepines. Drawbacks include a high degree of breakthrough seizures—due to the short half-life of midazolam—in over 50% of people treated, as well as treatment failure in 14–18% of people with refractory status epilepticus. Tolerance develops rapidly to the anticonvulsant effect, and the dose may need to be increased by several times to maintain anticonvulsant therapeutic effects. With prolonged use, tolerance and tachyphylaxis can occur and the elimination half-life may increase, up to days.

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Tolerance, Dependence and Withdrawal of Triazolam

From Wikipedia:

A review of the literature found that long term use of benzodiazepines including triazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. It recommended that benzodiazepine hypnotics are used at their lowest possible dose and for a short period of time. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality. The risk of withdrawal reactions and drug dependence is much higher with triazolam than with other benzodiazepines. Triazolam has a very high risk of dependency with chronic users often taking exceedingly high daily doses. Regular use of triazolam may cause a hypnotic drug dependence. Withdrawal symptoms typically appear when triazolam dosage is reduced or stopped altogether. Withdrawal symptoms including a worsening of insomnia (rebound insomnia) compared to baseline typically occurs after discontinuation of triazolam even after short term single nightly dose therapy.

Daytime withdrawal symptoms are commonly associated with triazolam. This is due to its very short half-life. After only 10 nights of triazolam use, patients report anxiety, become distressed, display weight loss, experience panics, and experience depression, feel unreal, and develop paranoia. These reactions occurred more commonly with triazolam than lormetazepam, which has an intermediate half-life. Thus the more short-acting a benzodiazepine hypnotic the more severe the daytime withdrawal symptoms. This phenomenon of day time withdrawal anxiety from nightly hypnotic use does not seem to be exclusive to triazolam but occurs with other hypnotic drugs although reactions are not as severe as those seen with triazolam.
Abrupt withdrawal after long-term use from therapeutic doses of triazolam may result in a severe benzodiazepine withdrawal syndrome. A psychotic state was reported in a patient, developing after abrupt withdrawal from triazolam and nitrazepam. The withdrawal symptoms included auditory hallucinations and visual cognitive disorder. Gradual and careful reduction of the dosage was recommended to prevent severe withdrawal syndromes from developing.

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