Diazepam
Systematic (IUPAC) name
7-chloro-1-methyl- 5-phenyl-1,3-dihydro-2H- 1,4-benzodiazepin-2-one
Identifiers
CAS number	439-14-5
ATC code	N05BA01 N05BA17
PubChem	3016
DrugBank	APRD00642
Chemical data
Formula	C16H13ClN2O
Mol. mass	284.7 g/mol
Pharmacokinetic data
Bioavailability	93%
Metabolism	Hepatic
Half life	20-100 hours
Excretion	Renal
Therapeutic considerations
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Routes	Oral, IM, IV, suppository

Diazepam (IPA: /daɪˈæzɨpæm/), first marketed as Valium by Hoffmann-La Roche) is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, sedative, skeletal muscle relaxant and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, alcohol withdrawal, and muscle spasms. 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.^[1][2] In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Intramuscular injection is the injection of a substance directly into a muscle. ... Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... Four 500mg acetaminophen/paracetamol suppositories A suppository is a medicine that is inserted either into the rectum (rectal suppository) or into the vagina (vaginal suppository) where it melts. ... Hoffmann-La Roche, Ltd. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... In medicine, a muscle relaxant is a drug that causes skeletal muscle contraction to cease. ... Amnesia (or amnaesia in Commonwealth English) is a condition in which memory is disturbed. ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... This article is about the sleeping disorder. ... This article is about epileptic seizures. ... Withdrawal, also known as withdrawal syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes physical dependence is regularly used for a long time and then suddenly discontinued or decreased in dosage. ... A Spasm is a sudden, involuntary contraction of a muscle, a group of muscles, or a hollow organ, or a similarly sudden contraction of an orifice. ... Endoscopic images of a duodenal ulcer A flexible endoscope. ... For other uses, see Amnesia (disambiguation). ...

Diazepam is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.^[3] Diazepam is used to treat a wide range of conditions and has been one of the most frequently prescribed medications in the world for the past 40 years. WHO redirects here. ... The World Health Organization (WHO) Model List of Essential Medicines is a guideline for national governments that want to ensure they have an inventory of medicines needed by every health system. ...

History

Diazepam was the second benzodiazepine to be invented by Leo Sternbach of Hoffmann-La Roche, and was approved for use in 1963. It is two and a half times more potent than its predecessor, chlordiazepoxide, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.^[4] Dr Leo Henryk Sternbach (May 7, 1908 – September 28, 2005) was a Polish-Jewish chemist who is credited with inventing the benzodiazepine, a class of tranquilizers. ... Hoffmann-La Roche, Ltd. ... For other uses, see 1963 (disambiguation). ... Chlordiazepoxide (pronounced [ˈklɔːrˌdaɪəzepˈoksaɪd], marketed under the trade name Librium®) is a sedative/hypnotic drug which is a benzodiazepine derivative. ...

The benzodiazepines gained popularity among medical professionals as an improvement upon barbiturates, which have a comparatively narrow therapeutic index, and are far more sedating at therapeutic doses. The benzodiazepines are also far less dangerous; death rarely results from diazepam overdose, except in cases where it is consumed with large amounts of other depressants (such as alcohol or other sedatives).^[5] Barbituric acid, the basic structure of all barbiturates Barbiturates are drugs that act as central nervous system depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ... The therapeutic index of a medication is a comparison of the amount that causes the therapeutic effect to the amount that causes toxic effects. ... See also sedative. ...

Diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak sales in 1978 of 2.3 billion pills.^[4] Diazepam along with oxazepam, nitrazepam and temazepam represent 82% of the benzodiazepine market in Australia.^[6] While psychiatrists continue to prescribe diazepam for the short-term relief of anxiety, neurology has taken the lead in prescribing diazepam for the palliative treatment of certain types of epilepsy and spastic activity, e.g., forms of paresis. It is also the first line of defense for a rare disorder called stiff-person syndrome.^[7] Palliative care is any form of medical care or treatment that concentrates on reducing the severity of the symptoms of a disease or slows its progress rather than providing a cure. ... Paresis is a condition typified by partial loss of movement, or impaired movement. ... First described by Moersch and Woltman at the Mayo Clinic in 1956, stiff person syndrome (SPS) is a rare neurologic disorder of unknown etiology. ...

Diazepam is also found in nature. Several plants, such as potato and wheat, contain trace amounts of naturally occurring diazepam and other benzodiazepines.^[8] For other uses, see Potato (disambiguation). ... Species T. aestivum T. boeoticum T. dicoccoides T. dicoccon T. durum T. monococcum T. spelta T. sphaerococcum T. timopheevii References:   ITIS 42236 2002-09-22 Wheat Wheat For the indie rock group, see Wheat (band). ...

Physical properties

Diazepam occurs as solid white or yellow crystals and has a melting point of 131.5 to 134.5°C. It is odorless, and has a slightly bitter taste. The British Pharmacopoeia lists diazepam as being very slightly soluble in water, soluble in alcohol and freely soluble in chloroform. The United States Pharmacopoeia lists diazepam as soluble 1 in 16 of ethyl alcohol, 1 in 2 of chloroform, 1 in 39 of ether, and practically insoluble in water. The pH of diazepam is neutral (i.e. pH = 7). Diazepam has a shelf-life of 5 years for oral tablets and 3 years for IV/IM solution.^[9] Diazepam is structurally related to quinazolines and is a hapten.^[10] The British Pharmacopoeia is the authoritative collection of standards for UK medicinal substances. ... The United States Pharmacopoeia is a compendium of drugs published every five years by the United States Pharmacopoeial Convention. ... For other uses, see PH (disambiguation). ... Quinazoline is a compound made up of two fused six-membered simple aromatic rings, a benzene ring and a pyrimidine ring. ... A hapten is a small molecule which can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one which also does not elicit an immune response by itself. ...

Diazepam should be stored at room temperature (15°-30°C). The solution for parenteral injection should be protected from light and kept from freezing. The oral forms should be stored in air-tight containers and protected from light.^[11]

Diazepam can absorb into plastic, and therefore diazepam solution is not stored in plastic bottles or syringes. It can absorb into plastic bags and tubing used for intravenous infusions. Absorption appears to be dependent on several factors such as temperature, concentration, flow rates and tube length. Diazepam should not be administered if a precipitate has formed and will not dissolve.^[11]

Pharmacology

Diazepam and other benzodiazepines may influence neurosteroid metabolism and progesterone levels which in turn may adversely influence the functions of the brain and reproductive system. The pharmacological actions of benzodiazepines at the GABAa receptor are similar to those of neurosteroids. Neuroactive steroids are positive allosteric modulators of the GABAa receptor, enhancing GABA function. Many benzodiazepines (diazepam, medazepam, estazolam, flunitrazepam and nitrazepam) potently inhibit the enzymes involved in the metabolism of neurosteroids. Long-term administration of benzodiazepines may influence the concentrations of endogenous neurosteroids, and thereby would modulate the emotional state. Factors which effects benzodiazepines ability to alter neurosteroid levels depend on the molecular make up of the individual benzodiazepine molecule. Presence of a substituent at N1 position of the diazepine ring and/or the chloro or nitro group at position 7 of the benzene ring contribute to potent inhibition of the isoenzymes, and in turn a bromo group at position 7 (for bromazepam) and additional substituents (3-hydroxy group for oxazepam and tetrahydroxazole ring for cloxazolam and oxazolam) decrease the inhibitory potency of benzodiazepines on neurosteroids.^[12] Benzodiazepine tablets The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsant, amnestic and muscle relaxant properties. ... Apart from exerting effects on the genome via intracellular steroid receptors, neuroactive steroids (or neurosteroids) rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. ... Progesterone is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. ... The human brain In animals, the brain (enkephalos) (Greek for in the skull), is the control center of the central nervous system, responsible for behavior. ... The reproductive system is the ensembles and interactions of organs and/or substances within an organism that strictly pertain to reproduction. ... Pharmacology (in Greek: pharmacon is drug, and logos is science) is the study of how chemical substances interfere with living systems. ... Apart from exerting effects on the genome via intracellular steroid receptors, neuroactive steroids (or neurosteroids) rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. ... Neuroactive is a synthpop/EBM group from Finland. ... In biochemistry, an enzyme or other protein is allosteric if its activity or efficiency changes in response to the binding of an effector molecule at a so-called allosteric site. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... Medazepam is a drug of the Benzodiazepine family. ... Estazolam (ProSom®) is a benzodiazepine commonly prescribed for short-term treatment of insomnia. ... Flunitrazepam (IPA: ; is marketed by Roche under the trade name Rohypnol. ... Nitrazepam (marketed under the trade names Mogadon®, Nitredon®, Nilandron®) is a powerful hypnotic drug, which is a benzodiazepine derivative. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism. ... Look up Endogenous in Wiktionary, the free dictionary. ... For benzine, see petroleum ether. ... General Name, Symbol, Number bromine, Br, 35 Series halogens Group, Period, Block 17 (VIIA), 4, p Density, Hardness 3119 kg/m3 (300 K), NA Appearance Gas: red-brown solid: metallic luster Atomic properties Atomic weight 79. ... Oxazepam (marketed under brand names Alepam, Murelax, Oxascand, Serax, Serepax, Seresta, Sobril) is a drug which is a benzodiazepine derivative. ... Cloxazolam (marketed under brand name Sepazon) is a drug which is a benzodiazepine derivative. ... Oxazolam is a drug which is a benzodiazepine derivative. ... Inhibitory Postsynaptic Potential is commonly abbreviated to Impulses are transmitted from neuron to neuron by the release of a chemical transmitter across synaptic clefts from the synaptic vesicles along the axon to the postsynaptic receptors of another neuron. ...

Diazepam at high doses has been found to decrease histamine turnover via diazepam's action at the benzodiazepine-GABA receptor complex.^[13]

Mechanism of action

See also: Benzodiazepine

Diazepam is a benzodiazepine that binds to a specific subunit on the GABA_A receptor at a site that is distinct from the binding site of the endogenous GABA molecule.^[14][15]The GABA_A receptor is an inhibitory channel which, when activated, decreases neurologic activity. Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... The GABAA receptor is one of the three ligand-gated ion channels responsible for mediating the effects of Gamma-AminoButyric Acid (GABA), the major inhibitory neurotransmitter in the brain. ... Look up Endogenous in Wiktionary, the free dictionary. ... The GABAA receptor is one of the three ligand-gated ion channels responsible for mediating the effects of Gamma-AminoButyric Acid (GABA), the major inhibitory neurotransmitter in the brain. ...

Due to the role of diazepam as a positive allosteric modulator of GABA, when it binds to benzodiazepine receptors it causes inhibitory effects. This arises from the hyperpolarization of the post-synaptic membrane, due to the control exerted over negative chloride ions by GABA_A receptors.^[14][16] In biochemistry, allosteric regulation is the regulation of an enzyme or protein by binding an effector molecule at the proteins allosteric site (that is, a site other than the proteins active site). ... Inhibitory Postsynaptic Potential is commonly abbreviated to Impulses are transmitted from neuron to neuron by the release of a chemical transmitter across synaptic clefts from the synaptic vesicles along the axon to the postsynaptic receptors of another neuron. ... In biology, hyperpolarization is any change in a cells membrane potential that makes it more polarized. ... Illustration of the major elements in a prototypical synapse. ... The chloride ion is formed when the element chlorine picks up one electron to form an anion (negatively-charged ion) Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. ... This article is about the electrically charged particle. ...

Diazepam appears to act on areas of the limbic system, thalamus and hypothalamus, inducing anxiolytic effects. Its actions are due to the enhancement of GABA activity.^[1][14] The limbic system is a historically defined set of brain structures that support a variety of functions including emotion and memory. ... The thalamus (from Greek θάλαμος = bedroom, chamber, IPA= /ˈθæləməs/) is a pair and symmetric part of the brain. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model...

The anticonvulsant properties of diazepam 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 be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.^[17]

The muscle relaxant properties of diazepam are produced via inhibition of polysynaptic pathways in the spinal cord.^[18]

Pharmacokinetics

Diazepam can be administered orally, intravenously, intramuscularly, or as a suppository.^[9] Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... Intramuscular injection is the injection of a substance directly into a muscle. ... Four 500mg acetaminophen/paracetamol suppositories A suppository is a medicine that is inserted either into the rectum (rectal suppository) or into the vagina (vaginal suppository) where it melts. ...

When diazepam is administered orally, it is rapidly absorbed and has a fast onset of action. The onset of action is 1-5 minutes for IV administration and 15-30 minutes for IM administration. The duration of the diazepam's main pharmacological effects is 15 minutes to 1 hour for both routes of administration.^[19]

Peak plasma levels are achieved 30 minutes to 2 hours after oral administration. When diazepam is administered as an intramuscular injection, absorption is slow, erratic and incomplete.^[20][11]

Diazepam is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses both the blood-brain barrier and the placenta, and is excreted into breast milk. After absorption, diazepam is redistributed into muscle and adipose tissue. Continual daily doses of diazepam will quickly build up to a high concentration in the body (mainly in adipose tissue), which will be far in excess of the actual dose for any given day.^[9][11] The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ... The placenta is a sack of fat present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy). ... For other uses of Muscles, see Muscles (disambiguation). ... Adipose tissue is an anatomical term for loose connective tissue composed of energy in the form of fat, although it also cushions and insulates the body. ...

There is preferential storage of diazepam in some organs including the heart. Absortion by any administered route and the risk of accumulation is significantly increased in the neonate and there is clinical justification to recommend the withdrawal of diazepam during pregnancy and breast feeding.^[21] A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ...

Diazepam is metabolised via oxidative pathways in the liver via the cytochrome P450 enzyme system. It has a biphasic half-life of 1-2 and 2-5 days, and has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam). Diazepam's other active metabolites include temazepam and oxazepam. These metabolites are conjugated with glucuronide, and are excreted primarily in the urine. Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug.^[20][11][22] For the bird, see Liver bird. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Half-Life For a quantity subject to exponential decay, the half-life is the time required for the quantity to fall to half of its initial value. ... Nordazepam (Calmday®, Stilny®, Madar®), formerly known as nordiazepam, is a 1,4-benzodiazepine derivative. ... Temazepam (marketed under brand names Restoril®, Normison®, Planum®, Tenox® and Temaze®) is a benzodiazepine derivative with powerful hypnotic properties. ... Oxazepam (marketed under brand names Alepam, Murelax, Oxascand, Serax, Serepax, Seresta, Sobril) is a drug which is a benzodiazepine derivative. ... Glucuronide is a substance produced by attaching glucuronic acid to another substance with glycosidic bonds. ...

Diazepam has a half-life (t1/2α) of 20-50 hours, and desmethyldiazepam has a half-life of 30-200 hours and is considered to be a long acting benzodiazepine.^[11]

Most of the drug is metabolised; very little diazepam is excreted unchanged.^[9]

In humans, the protein binding of diazepam is around 98.5%.^[20]

The elimination half life of diazepam and also the active metabolite desmethyldiazepam increases significantly in the elderly which may result in prolonged action as well as accumulation of the drug during repeated administration.^[23] Nordazepam (marketed under brand names Stilny®, Madar®, Vegesan®, and Calmday®), also known as nordiazepam and desmethyldiazepam, is a 1,4-benzodiazepine derivative. ...

Indications

Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol or opiate withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia prior to certain medical procedures (e.g. endoscopy).^[20] This article does not cite any references or sources. ... Scoring the poppy pod. ... Withdrawal, also known as withdrawal syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes physical dependence is regularly used for a long time and then suddenly discontinued or decreased in dosage. ... Premedication refers to a drug treatment given to a patient before a (surgical or invasive) medical procedure. ... Endoscopic images of a duodenal ulcer A flexible endoscope. ...

Diazepam is rarely used for the long-term treatment of epilepsy. This is due to the fact that tolerance to the anticonvulsant effects of diazepam usually develops within 6 to 12 months of treatment, effectively rendering it useless for this purpose and also due to side effects in particular sedation.^[9][24]

Diazepam has a broad spectrum of indications (most of which are off-label), including:

• Treatment of anxiety, panic attacks, and states of agitation^[20]

• Treatment of status epilepticus, adjunctive treatment of other forms of epilepsy^[20]

• Treatment of the symptoms of alcohol and opiate withdrawal^[20]

• Short-term treatment of insomnia^[20]

• Treatment of tetanus, together with other measures of intensive-treatment^[25]

• Initial management of mania, together with firstline drugs like lithium, valproate or other antipsychotics^{[citation needed]}

• Adjunctive treatment (with antidepressants) of depression with symptoms of anxiety^{[citation needed]}

• Adjunctive treatment (with antipsychotics), in patients who develop early extrapyramidal side-effects^{[citation needed]}

• Adjunctive treatment of painful muscle conditions^[7]

• Adjunctive treatment of spastic muscular paresis (para-/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, spinal cord injury (long-term treatment is coupled with other rehabilitative measures)^[7]

• Palliative treatment of stiff person syndrome^[16]

• Used to alleviate the symptoms of Lesch-Nyhan Syndrome

• Pre-/postoperative sedation, anxiolysis and/or amnesia (e.g. before endoscopic or surgical procedures)^[7]

• Treatment of overdosage with hallucinogens or CNS stimulants^[9]

• Adjunctive treatment of drug-induced seizures, resulting from exposure to sarin, VX, soman (or other organophosphate poisons; See CANA), lindane, chloroquine, physostigmine, or pyrethroids^[9]

• Emergency treatment of eclampsia, along with IV magnesium sulfate

• Prophylactic treatment of oxygen toxicity during hyperbaric oxygen therapy.^[26]
• Used in the treatment for irritable bowel syndrome. ^[27]
• Used to treat pain resulting from muscle spasms caused by various spastic dystonias, including blepharospasm, spasmodic dysphonia and Meige's Syndrome.

Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... A panic attack is a period of intense fear or discomfort, typically with an abrupt onset and usually lasting no more than 30 minutes. ... Agitation may have the following special meanings Agitation, an emotional state Agitation, putting into motion (by shaking or stirring) Agitation, a term from the lexicon of Communists: political activities aimed at urging people to do something This is a disambiguation page — a navigational aid which lists other pages that... This article is about the sleeping disorder. ... Tetanus is a medical condition that is characterized by a prolonged contraction of skeletal muscle fibers. ... This article is an expansion of a section entitled Mania from within the main article Bipolar disorder. ... This article discusses the pharmacological uses of lithium salts; for information on the chemistry of individual lithium salts, see Category:Lithium compounds. ... Valproic acid or 2-Propylpentanoic acid is CH3CH2CH2CH(CH2CH2CH3)COOH . ... The term antipsychotic is applied to a group of drugs used to treat psychosis. ... An antidepressant is a medication used primarily in the treatment of clinical depression. ... On the Threshold of Eternity. ... The term antipsychotic is applied to a group of drugs used to treat psychosis. ... In human anatomy, the extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. ... Paresis is a condition typified by partial loss of movement, or impaired movement. ... The Spinal cord nested in the vertebral column. ... For other uses, see Stroke (disambiguation). ... Stiff person syndrome (SPS) (or occasionally, stiff-man syndrome) is a rare neurologic disorder of unknown etiology. ... -1... Endoscopy means looking inside and refers to looking inside the human body for medical reasons. ... Hallucinogenic drugs or hallucinogens are drugs that can alter sensory perceptions, elicit alternate states of consciousness, or cause hallucinations. ... A stimulant is a drug which increases the activity of the sympathetic nervous system and produces a sense of euphoria or awakeness. ... For other uses, see Sarin (disambiguation). ... This article does not cite any references or sources. ... Boiling point 198 °C (388 °F) Freezing/melting point −42 °C (−44 °F) Vapor pressure 0. ... An organophosphate (sometimes abbreviated OP) is the general name for esters of phosphoric acid and is one of the organophosphorus compounds. ... This article refers to a place mentioned in the New Testament. ... Lindane is an insecticide, also known as gamma-Hexachlorocyclohexane (HCH) and benzene hexachloride (BHC). ... Chloroquine is a 4-aminoquinoline drug long used in the treatment or prevention of malaria. ... Physostigmine is a parasympathomimetic, specifically, an irreversible cholinesterase inhibitor obtained from the Calabar bean. ... A pyrethroid is a synthetic chemical that kills most insects. ... Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... Magnesium sulfate (or sulphate) is a chemical compound containing magnesium and sulfate, with the formula MgSO4. ... This page is a candidate to be moved to Wiktionary. ... Oxygen toxicity or oxygen toxicity syndrome is severe hyperoxia caused by breathing oxygen at elevated partial pressures. ... This article does not cite any references or sources. ...

Veterinary uses

• Diazepam is used as a short term sedative and anxiolytic for cats and dogs. It is also used for short-term treatment of seizures in dogs and short-term and long-term treatment of seizures in cats. For emergent treatment of seizures, the typical dose is 0.5 mg/kg intravenously or 1-2 mg/kg per rectum of the injectable solution.^[28]
• Diazepam is also used as a muscle relaxant for horses, to be given intravenously, the usual dose is 0.02 - 0.1 mg/kg in conjunction with or just after induction of general anesthesia.

Dosage

Dosages should be determined on an individual basis, depending upon the condition to be treated, the severity of symptoms, the body weight of the patient, and any comorbid conditions the patient may have.^[9] In medicine and in psychiatry, comorbidity is either The presence of one or more disorders (or diseases) in addition to a primary disease or disorder; or The effect of such additional disorders or diseases. ...

Typical dosages for healthy adults range from 2mg per dose to 30mg per dose, depending on such factors as body weight and condition being treated. For the elderly or people with liver disorders, initial dose is at the low end of the range, with the dose being increased as required.^[16]

Availability

Diazepam is supplied in the following forms: Image File history File links No higher resolution available. ...

• For oral administration:
  • Tablets - 2mg, 5mg, 10mg^[16]. Generic versions available.
  • Capsules, time-release - 15mg (marketed by Roche as Valrelease®)^[11]
  • Liquid solution - 1mg/ml in 500ml containers and unit-dose (5mg & 10mg); 5mg/ml in 30 ml dropper bottle (marketed by Roxane as Diazepam Intensol®)^[11]

• For parenteral administration:
  • Solution for IV/IM injection - 5mg/ml. 2ml ampoules and syringes; 1ml, 2ml, 10ml vials; 2 ml Tel-E-Ject; also contains 40% propylene glycol, 10% ethyl alcohol, 5% sodium benzoate and benzoic acid as buffers, and 1.5% benzyl alcohol as a preservative.^[29][11]

Notice : IM injection is largely less effective as the drug is injected into a tetanic muscle with compressed muscular veins . This does not allow the drug to reach the circulation rapidly.

• For rectal administration:
  • Solution^[9]
  • Suppositories - 5mg and 10mg^[30][9]
  • Rectal tubes
• For inhalation administration:This method uses heating diazepam to form a vapor later producing an aerosol. This allows the drug to be passed through an inhalation route during an inhalation therapy. Provided in doses 2mg-20mg either in a single inhalation or multiple small inhalations ^[31]

Side effects

Diazepam has a range of side effects which are common to most benzodiazepines. Most common side effects include:

• Somnolence
• Suppression of REM sleep or dreaming
• Addiction
• Impaired motor function
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Depression
• Impaired learning
• Anterograde amnesia (especially pronounced in higher doses)
• Cognitive deficits^[32]
• Reflex tachycardia^[19]

Rare paradoxical side effects can include: nervousness, irritability, insomnia, muscle cramps, and in extreme cases, rage, and violence.^[33][34][35] If these side effects are present, diazepam treatment should be immediately terminated. Somnolence (or drowsiness) is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods. ... // Pre-syncope is a sensation of feeling faint. ... In everyday language depression refers to any downturn in mood, which may be relatively transitory and perhaps due to something trivial. ... Anterograde amnesia is a form of amnesia, or memory loss, in which new events are not transferred from short-term memory to long-term memory. ... Cognitive The scientific study of how people obtain, retrieve, store and manipulate information. ... This article or section does not cite any references or sources. ...

Benzodiazepines such as diazepam impair learning and memory via their action on benzodiazepine receptors which causes a dysfunction in the cholinergic neuronal system.^[36]

It has been shown in a clinical study that 100% of patients on low dose diazepam therapy long term are physically dependent on their medication.^[37] Increased ratings of dizziness, blurred vision, heart pounding, feelings of unreality, pins and needles, nausea, sweatiness, noises louder than usual, jitteriness, things moving, sensitivity to touch and panic attacks may be experienced as withdrawal symptoms in low therapeutic dose long term users of diazepam when discontinuing their diazepam medication.^[38] Diazepam is therefore only recommended for short term therapy at the lowest possible dose due to risks of severe withdrawal problems from low doses even after gradual reduction.^[39] There is a significant risk of pharmacological dependence on diazepam and patients experiencing the benzodiazepine withdrawal syndrome if it is taken for 6 weeks or longer.^[40] Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ...

Diazepam may impair the ability to drive vehicles or operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants.^[16]

During the course of therapy, tolerance to the sedative effects usually develops, but not to the anxiolytic and myorelaxant effects.^[41]

Patients with severe attacks of apnea during sleep may suffer respiratory depression (hypoventilation) leading to respiratory arrest and death. Apnea, apnoea, or apnœa (Greek απνοια, from α-, privative, πνεειν, to breathe) is a technical term for suspension of external breathing. ... In medicine, hypoventilation exists when ventilation is inadequate to perform gas exchange. ...

Organic changes such as leukopenia^[42] and liver-damage of the cholostatic type with or without jaundice (icterus) have been observed in a few cases.^{[citation needed]} Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). ... Icterus can mean: Icterus is the genus name for orioles in the Americas. ...

Diazepam in doses of 5 mg or more causes significant deterioration in vigilance performance combined with increased feelings of sleepiness.^[43] Vigilance is the act of watching for something to happen, of watching for danger. ...

Interactions

If diazepam is to be administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that enhance the effects of diazepam, such as barbiturates, phenothiazines, narcotics and antidepressants.^[16] Phenothiazines are the largest of the 5 main classes of antipsychotic drugs. ... The term narcotic, derived from the Greek word for stupor, originally referred to a variety of substances that induced sleep (such state is narcosis). ... An antidepressant is a medication used primarily in the treatment of clinical depression. ...

Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. There is no evidence that would suggest diazepam alters its own metabolism with chronic administration.^[9]

Agents which have an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable.^[9]

• Diazepam increases the central depressive effects of alcohol, other hypnotics/sedatives (e.g. barbiturates), narcotics, and other muscle relaxants. The euphoriant effects of opioids may be increased, leading to increased risk of psychological dependence.^[44][45]
• Cimetidine, omeprazole, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine and valproic acid prolong the action of diazepam by inhibiting its elimination.^[9][11]
• Alcohol (ethanol) in combination with diazepam may cause a synergistic enhancement of the hypotensive properties of benzodiazepines and alcohol.^[46]
• Oral contraceptives ("the pill") significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam.^[45][47]

• Rifampin, phenytoin, carbamazepine and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects.^[9]

• Nefazodone can cause increased blood levels of benzodiazepines.^[45]

• Cisapride may enhance the absorption, and therefore the sedative activity, of diazepam.^[48]

• Small doses of theophylline may inhibit the action of diazepam.^[49]

• Diazepam may block the action of levodopa (used in the treatment of Parkinson's Disease).^[44]

• Diazepam may alter digoxin serum concentrations.^[9]

• Other drugs that may have interactions with diazepam include: Antipsychotics (e.g. chlorpromazine), MAO inhibitors, ranitidine.^[45]

• Smoking tobacco can enhance the elimination of diazepam and decrease its action.^[44]
• Because it acts on the GABA receptor the herb Valerian may produce an adverse effect.^[50]
• Foods that acidify the urine can lead to faster absorption and elimination of diazepam, reducing drug levels and activity.^[44]
• Foods that alkalinize the urine can lead to slower absorption and elimination of diazepam, increasing drug levels and activity.^[9]
• There are conflicting reports as to whether food in general has any effects on the absorption and activity of orally administered diazepam.^[44]

Hypnotic drugs are a class of drugs that induce sleep, used in the treatment of severe insomnia. ... A muscle relaxant is a drug which decreases the tone of a muscle. ... Cimetidine is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. ... Omeprazole (INN) (IPA: ) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD) and Zollinger-Ellison syndrome. ... Ketoconazole is a synthetic antifungal drug used to prevent and treat skin and fungal infections, especially in immunocompromised patients such as those with AIDS. Due to its side-effect profile, it has been superseded by newer antifungals, such as fluconazole and itraconazole. ... Itraconazole (marketed as Sporanox® by Janssen Pharmaceutica) is a triazole antifungal agent that is prescribed to patients with fungal infections. ... Disulfiram is a drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. ... Fluvoxamine (brand name as Luvox®, Faverin®, Fevarin® and Dumyrox®) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. ... Isoniazid (also called isonicotinyl hydrazine or isonicotinic acid hydrazide); abbreviated INH or just H. Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. ... Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. ... Probenecid is a uricosuric drug, primarily used in treating gout or hyperuricemia, that increases uric acid removal in the urine. ... Propranolol (INN) (IPA: ) is a non-selective beta blocker mainly used in the treatment of hypertension. ... This article does not cite any references or sources. ... Ciprofloxacin is the generic international name for the synthetic antibiotic manufactured and sold by Bayer Pharmaceutical under the brand names Cipro, Ciproxin and Ciprobay (and other brand names in other markets, e. ... Prozac redirects here. ... Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder. ... Grain alcohol redirects here. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... Rifampicin (INN) or rifampin (USAN) is an antibiotic drug of the rifamycin group. ... Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK, by Parke-Davis, now part of Pfizer) is a commonly used antiepileptic. ... Carbamazepine (CBZ) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. ... Phenobarbital (INN) or phenobarbitone (former BAN) is a barbiturate, first marketed as Luminal by Farbwerke Fr. ... Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. ... Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist. ... Theophylline is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. ... Levodopa (INN) or L-DOPA (3,4-dihydroxy-L-phenylalanine) is an intermediate in dopamine biosynthesis. ... Digoxin (INN) (IPA: ) is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. ... The term antipsychotic is applied to a group of drugs used to treat psychosis. ... Chlorpromazine was the first antipsychotic drug, used during the 1950s and 1960s. ... Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. ... Ranitidine (INN) (IPA: ) is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). ... Shredded tobacco leaf for pipe smoking Tobacco can also be pressed into plugs and sliced into flakes Tobacco is an agricultural product processed from the fresh leaves of plants in the genus Nicotiana. ... Valerian may mean: Valerian, two genera of garden plants Emperor Valerian I, Roman emperor 253-260 Valerian II, son of Gallienus (d. ...

Contraindications

Use of diazepam should be avoided, when possible, in individuals with the following conditions:

• Ataxia
• Severe hypoventilation
• Acute narrow-angle glaucoma
• Severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
• Severe renal deficiencies (e.g. patients on dialysis)
• Severe sleep apnea
• Severe depression, particularly when accompanied by suicidal tendencies
• Acute intoxication with alcohol, narcotics, or other psychoactive substances (with the exception of some hallucinogens, where it is occasionally used as a treatment for overdose)
• Myasthenia gravis
• Hypersensitivity or allergy to any drug in the benzodiazepine class

For other uses, see Ataxia (disambiguation). ... In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo means below) to perform needed gas exchange. ... The liver is an organ in vertebrates including humans. ... Hepatitis (plural hepatitides) implies injury to liver characterised by presence of inflammatory cells in the liver tissue. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... In medicine, dialysis is a type of renal replacement therapy which is used to provide an artificial replacement for lost kidney function due to renal failure. ... Sleep apnea, sleep apnoea or sleep apnœa is a sleep disorder characterized by pauses in breathing during sleep. ... On the Threshold of Eternity. ... Hallucinogenic drugs or hallucinogens are drugs that can alter sensory perceptions, elicit alternate states of consciousness, or cause hallucinations. ... Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ...

Special caution needed

• Pediatric patients
  • Less than 18 years of age - Treatment usually not indicated, except treatment of epilepsy, and pre-/postoperative treatment. The smallest possible effective dose should be used for this group of patients.^[45]
  • Under 6 months of age - Safety and effectiveness have not been established; diazepam should not be given to individuals in this age group.^[16][45]

• Elderly and very ill patients - Possibility that apnea and/or cardiac arrest may occur. Concomitant use of other central nervous system depressants increases this risk. The smallest possible effective dose should be used for this group of patients.^[16][45][51]

Diazepam may also be dangerous in geriatric patients due to a significant increased risk of falls.^[52]

• I.V. or I.M. injections in hypotensive individuals or those in shock should be administered carefully and vital signs should be monitored.^[51]

• Benzodiazepines such as diazepam are lipophilic and rapidly penetrate membranes and therefore rapidly crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines including diazepam in late pregnancy, especially high doses, may result in floppy infant syndrome.^[53]

Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ...

Patients at a high risk for abuse and dependence

Diazepam can lead to physiological tolerance, and psychological and/or physical dependence^{[citation needed]}. At a particularly high risk for diazepam misuse, abuse, and dependence are: In physiology, tolerance occurs when an organism builds up a resistance to the effects of a substance after repeated exposure. ...

• Patients with a history of alcohol or drug abuse or dependence^[16][54]
• Emotionally unstable patients^{[citation needed]}
• Patients with severe personality disorders, such as Borderline Personality Disorder^[55]
• Patients with chronic pain or other physical disorders^{[citation needed]}

Patients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.^[16][54] The American Society of Addiction Medicine has policy indicating that patients with addictive disease should not be prescribed benzodiazepines such as diazepam. Borderline Personality Disorder (DSM-IV Personality Disorders 301. ... This page is a candidate for speedy deletion, because: it is patent nonsense. ...

Pregnancy

There is inconclusive evidence that diazepam 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 new borns, however the data is inconclusive. Diazepam when taken during late in pregnancy, the third trimester, causes a definite risk of a severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the new born may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.^[56] For the term trimester used in academic settings, see Academic term The human gestation period of approximately 40 weeks between the time of the last menstrual cycle and delivery is traditionally divided into three periods of three months, or trimesters. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ... Apnea (British spelling - apnoea) is the absence of external breathing. ... Cyanosis refers to the bluish coloration of the skin due to the presence of deoxygenated hemoglobin in blood vessels near the skin surface. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος(metavallo), the Greek word for change), in the most general sense, is the ingestion and breakdown of complex compounds, coupled...

Dependence

Diazepam as with other benzodiazepine drugs can cause physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from diazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. 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 regime.^[57] Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. ... Heroin bottle An addiction is a recurring compulsion by an individual to engage in some specific activity, despite harmful consequences to the individuals health, mental state or social life. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Barbituric acid, the basic structure of all barbiturates Barbiturates are drugs that act as central nervous system depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ...

The Committee on the Review of Medicines

The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence and benzodiazepine withdrawal problems and other adverse effects. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are therefore unsuitable treatments for conditions such as depression, tension headaches and dysmenorrhoea. Benzodiazepines are also not benefitial in the treatment of psychosis due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of anxiety or insomnia in children. The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long-term use of benzodiazepine hypnotics were beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep-promoting properties within 3 to 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more short acting benzodiazepine. Withdrawal effects could occur however after treatment lasting only 2 weeks at therapeutic dose levels; however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the central nervous system depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the neonate high single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate and irregularities in the fetal heart. Benzodiazepines should be avoided in lactation. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhoea.^[58] Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant, is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... Tension headaches, which were recently renamed tension type headaches by the International Headache Society, are the most common type of headaches. ... Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen. ... Psychosis is a generic psychiatric term for a mental state often described as involving a loss of contact with reality. Stedmans Medical Dictionary defines psychosis as a severe mental disorder, with or without organic damage, characterized by derangement of personality and loss of contact with reality and causing deterioration... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... This article is about the sleeping disorder. ... The Institute of Medicine, a part of the National Academy of Sciences, is an American organization whose purpose is to provide national advice on issues relating to biomedical science, medicine, and health (National Academy of Sciences, n. ... Cover of a NIDA educational booklet. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... In psychology, apprehension (Lat. ... For the film see Tremors (film). ... This article is about the sleeping disorder. ... For other uses, see Nausea (disambiguation). ... Emesis redirects here. ... A diagram showing the CNS: 1. ... A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ... Hypothermia is a condition in which an organisms temperature drops below that Required fOr normal metabolism and Bodily functionS. In warm-blooded animals, core [[body Temperature]] is maintained nEar a constant leVel through biologic [[homEostasis]]. But wheN the body iS exposed to cold Its internal mechanismS may be unable... A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ... Fetus at eight weeks A fetus (alternatively foetus or fœtus) is an embryo in later stages of development, from the third month of pregnancy until birth in humans. ... Kittens nursing Lactation describes the secretion of milk from the mammary glands, the process of providing that milk to the young, and the period of time that a mother lactates to feed her young. ... Look up Confusion in Wiktionary, the free dictionary Confusion can have the following meanings: Unclarity or puzzlement, e. ... Psychosis (not to be confused with psychopathy) is a generic psychiatric term for a mental state in which thought and perception are severely impaired. ... This article is about the medical condition. ... For the beer, see Delirium Tremens (beer). ... Anxiety is a complex combination of the feeling of fear, apprehension and worry often accompanied by physical sensations such as palpitations, chest pain and/or shortness of breath. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Irritability is an excessive response to stimuli. ... Perspiration (also called sweating or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... Diarrhoea is the correct way to spell the word Diarrhoea. ...

Overdose

An individual who has consumed too much diazepam will display one or more of the following symptoms^[16][59]:

• Drowsiness
• Mental confusion
• Hypotension
• Impaired motor functions
  • Impaired reflexes
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Coma

Although not usually fatal when taken alone, a diazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil (Anexate®). This drug is only used in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug and the effects of diazepam can last for days, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary. Although not routinely indicated, activated charcoal can be used for decontamination of the stomach following a diazepam overdose. Emesis is contraindicated. Dialysis is minimally effective. Hypotension may be treated with levarterenol or metaraminol.^{[9][5][16][59]} In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... For other uses, see Coma (disambiguation). ... An antidote is a substance which can counteract a form of poisoning. ... Flumazenil (flumazepil, Anexate®, Lanexat®, Mazicon®, Romazicon®) is a benzodiazepine antagonist, used as an antidote in the treatment of benzodiazepine overdose. ... Wikibooks has a book on the topic of First Aid Artificial respiration is a technique for providing air for a person who is not breathing on their own, but whose heart is still beating. ... Activated carbon (also called activated charcoal) is the more general term which includes material mostly derived from charcoal. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... In medicine, dialysis is a type of renal replacement therapy which is used to provide an artificial replacement for lost kidney function due to renal failure. ... Norepinephrine (INN) or noradrenaline (BAN) is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ... Metaraminol (INN, trade name Aramine®) is a potent sympathomimetic amine used in the prevention and treatment of hypotension, particularly as a complication of anesthesia. ...

The oral LD₅₀ (lethal dose in 50% of the population) of diazepam is 720mg/kg in mice and 1240mg/kg in rats.^[16] D. J. Greenblatt and colleagues reported in 1978 on two patients who had taken 2000 and 500 mg of diazepam, respectively, went into moderately deep comas, and were discharged within 48 hours without having experienced important complications in spite of having high concentrations of diazepam and its metabolites—desmethyldiazepam, oxazepam, and temazepam—according to samples taken in the hospital and as follow-up.^[60] An LD50 test being administered In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. ...

Overdoses of diazepam with alcohol, opiates and/or other depressants may be fatal.^[5][61]

Misuse and abuse

Diazepam is a drug of potential dependence and addiction. Between 50 and 64% of rats will self administer diazepam.^[62] Benzodiazepines including diazepam in animal studies have been shown to increase reward seeking behaviours by increasing impulsivity which may suggest an increased risk of addictive behavioural patterns with usage of diazepam or other benzodiazepines.^[63] Diazepam is often found as an adulterant in heroin.^[64] This may be because diazepam greatly amplifies the effects of opioids. Adulterants are chemical substances which should not be contained within other substances (eg. ... For other uses, see Heroin (disambiguation). ... An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. ...

Sometimes diazepam is used by stimulant users to 'come down' and sleep and to help control the urge to binge^[65]

Benzodiazepines, including diazepam, temazepam, nitrazepam and flunitrazepam account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines.^[66] Temazepam (marketed under brand names Restoril®, Normison®, Planum®, Tenox® and Temaze®) is a benzodiazepine derivative with powerful hypnotic properties. ... Nitrazepam (marketed under the trade names Mogadon®, Nitredon®, Nilandron®) is a powerful hypnotic drug, which is a benzodiazepine derivative. ... Flunitrazepam (IPA: ; is marketed by Roche under the trade name Rohypnol. ...

Diazepam was detected in 26% of cases of people suspected of driving under the influence of drugs in Sweden and its active metabolite nordazepam was detected in 28% of cases. Other benzodiazepines and zolpidem and zopiclone also were found in high numbers. Many drivers had blood levels far exceeding the therapeutic dose range suggesting a high degree of abuse potential for benzodiazepines and zolpidem and zopiclone.^[67] In Northern Ireland in cases where drugs were detected in samples from impaired drivers who were not impaired by alcohol, benzodiazepines were found to be present in 87% of cases. Diazepam was the most commonly detected benzodiazepine.^[68] Zolpidem is a prescription short-acting nonbenzodiazepine hypnotic that potentiates gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by binding to gamma-aminobutyric acid receptors. ... Zopiclone (trade names: Imovaneâ„¢ and Zimovaneâ„¢) is a novel hypnotic agent used in the treatment of insomnia. ... Northern Ireland (Irish: , Ulster Scots: Norlin Airlann) is a constituent country of the United Kingdom lying in the northeast of the island of Ireland, covering 5,459 square miles (14,139 km², about a sixth of the islands total area). ...

It is sometimes referred to by street names, including 'blues', 'mother's little helper', 'drunk pills', 'vals', 'V', and occasionally 'ludes', mistaken for quaaludes. As well as less specific street terms, 'candy'(pills), 'benzos' (benzodiazepines), or downers(depressants). Methaqualone1 is an addictive, sedative drug. ...

Legal status

Internationally, diazepam is a Schedule IV drug under the Convention on Psychotropic Substances.^[69] In the UK, it is classified as a Class C drug. Convention on Psychotropic Substances Opened for signature February 21, 1971 in Vienna Entered into force August 16, 1976 Conditions for entry into force 40 ratifications Parties 175 The Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. ... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ...

Toxicity

Laboratory tests assessing the toxicity of diazepam, nitrazepam and chlordiazepoxide on mice spermatozoa found that diazepam produced toxicities in sperm including abnormalities involving both the shape and size of the sperm head. Nitrazepam however caused more profound abnormalities than diazepam.^[70] Nitrazepam (marketed under the trade names Mogadon®, Nitredon®, Nilandron®) is a powerful hypnotic drug, which is a benzodiazepine derivative. ... Chlordiazepoxide (pronounced [ˈklɔːrˌdaɪəzepˈoksaɪd], marketed under the trade name Librium®) is a sedative/hypnotic drug which is a benzodiazepine derivative. ... Schematic diagram of a sperm cell, showing the (1) acrosome, (2) cell membrane, (3) nucleus, (4) mitochondria, and (5) flagellum (tail) A sperm cell, or spermatozoon ( spermatozoa) (in Greek: sperm = semen and zoon = alive), is the haploid cell that is the male gamete. ...

Further reading

• Fachinformationen (German) for Valium, provided by Roche Pharmaceuticals
• Bandelow, Borwin et al. Handbuch der Arzneimitteltherapie, Bd.1, Psychopharmaka, 2nd edition. Enke, 2004. ISBN 3-13-113041-5.
• Benkert, Otto et al. Kompendium der Psychiatrischen Pharmakotherapie, 5th edition. Springer, 2003. ISBN 3-540-21893-9.

References

PubChem is a database of chemical molecules. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 70th day of the year (71st in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 71st day of the year (72nd in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 70th day of the year (71st in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 102nd day of the year (103rd in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 70th day of the year (71st in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 70th day of the year (71st in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 82nd day of the year (83rd in leap years) in the Gregorian calendar. ... is the 138th day of the year (139th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 267th day of the year (268th in leap years) in the Gregorian calendar. ... is the 262nd day of the year (263rd in leap years) in the Gregorian calendar. ... Year 1975 (MCMLXXV) was a common year starting on Wednesday (link will display full calendar) of the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 268th day of the year (269th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... March 10 is the 69th day of the year (70th in leap years) in the Gregorian calendar. ... is the 293rd day of the year (294th in leap years) in the Gregorian calendar. ... Year 1978 (MCMLXXVIII) was a common year starting on Sunday (link displays the 1978 Gregorian calendar). ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 70th day of the year (71st in leap years) in the Gregorian calendar. ...

External links

• Roche Pharmaceuticals (US) - Valium Product Information

There are several sulphonamide-based groups of drugs. ... Acetazolamide, sold under the trade name Diamox®, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, benign intracranial hypertension and altitude sickness. ... Ethoxzolamide (6-ethoxybenzothiazole-2-sulfonamide, alternatively known as Ethoxyzolamide) is a sulfonamide medication that functions as a carbonic anhydrase inhibitor. ... Sultiame (rINN, also known as sulthiame) is a sulfonamide and inhibitor of the enzyme carbonic anhydrase. ... Zonisamide (brand name Zonegran®) is an anticonvulsant used as an adjunctive therapy in adults with partial-onset seizures. ... The propionate (also propanoate) ion is C2H5COO− (propionic acid minus one hydrogen ion). ... Beclamide (marketed as Chloracon, Hibicon, Posedrine, Nydrane, Seclar, and other names) is a propionate and was used as a sedative and as an anticonvulsant. ... An aldehyde. ... Paraldehyde is the cyclic form of three acetaldehyde molecules (a trimer). ... A bromide is a phrase, or person who uses phrases, which have been used and repeated so many times as to become either insincere in their meaning, or seem like an attempt at trying to explain the obvious. ... Potassium bromide (KBr) is a salt, used as an anticonvulsant and a sedative in the 1800s. ... Sodium bromide is the chemical compound with the formula NaBr. ... In pharmacology, a psycholeptic is a medication which produces a calming effect upon the patient. ... An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ... A section of the Anatomical Therapeutic Chemical Classification System. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... Adinazolam is a benzodiazepine derivative. ... Alprazolam, also known under the trade names Xanax and Niravam, is a short-acting drug in the benzodiazepine class used to treat severe anxiety disorders and as an adjunctive treatment for anxiety associated with clinical depression. ... Bretazenil was originally developed as an anti-anxiety drug, but never commercialised. ... Bromazepam (marketed under brand names Calmepam, Compendium, Creosedin, Durazanil, Lectopam, Lexaurin, Lexilium, Lexomil, Lexotan, Lexotanil, Normoc, Somalium)[1] is a drug which is a benzodiazepine derivative. ... Camazepam (marketed under the brand name Albego) is a drug which is a benzodiazepine derivative. ... Chlordiazepoxide (pronounced [ˈklɔːrˌdaɪəzepˈoksaɪd], marketed under the trade name Librium®) is a sedative/hypnotic drug which is a benzodiazepine derivative. ... Clobazam is triazolobenzodiazepine, also known as a 1,5-benzodiazepine, meaning that its diazepine ring has its nitrogen atoms at the 1 and 5 positions instead of the usual 1 and 4. ... Clorazepate (marketed under the brand names Tranxene® and Tranxilium®) is a drug which is a benzodiazepine derivative. ... Clonazepam (marketed by Roche under the trade-names Klonopin in the United States and Rivotril in Europe, South America, Canada, India, and Australia) is a drug which is a benzodiazepine derivative. ... Clotiazepam (marketed under brand name Trecalmo) is a drug which is a benzodiazepine derivative. ... Cloxazolam (marketed under brand name Sepazon) is a drug which is a benzodiazepine derivative. ... Ethyl loflazepate (marketed under brand name Meilax®) is a drug which is a benzodiazepine derivative. ... Etizolam (marketed under brand name Sedekopan) is a drug which is a benzodiazepine derivative. ... Fludiazepam (marketed under the brand name Erispan) is a drug which is a benzodiazepine derivative. ... Halazepam is a benzodiazepine derivative. ... Imidazenil is an anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil and bretazenil. ... Ketazolam (marketed under brand names Anseren, Anxon, Contamex, Loftran, Marcen, Sedotime, Solatran, Unakalm) is a drug which is a benzodiazepine derivative. ... Lorazepam is a benzodiazepine tranquilizer with short to medium duration of action. ... Medazepam is a drug of the Benzodiazepine family. ... Nordazepam (Calmday®, Stilny®, Madar®), formerly known as nordiazepam, is a 1,4-benzodiazepine derivative. ... Oxazepam (marketed under brand names Alepam, Murelax, Oxascand, Serax, Serepax, Seresta, Sobril) is a drug which is a benzodiazepine derivative. ... Pinazepam (marketed under the brand name Domar®) is a drug which is a benzodiazepine derivative. ... Parazepam belong to the group of medicines called central nervous system depressants (medicines that slow down the nervous system). ... Tofisopam (marketed under brand name Emandaxin) is a drug which is a benzodiazepine derivative. ... The nonbenzodiazepines are comparatively new drugs whose actions are very similar to those of the benzodiazepines, but are structurally unrelated to the benzodiazepines and are believed to have fewer side effects. ... Alpidem is a prescription drug used for the treatment of moderate to severe anxiety. ... Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs. ... This article or section is not written in the formal tone expected of an encyclopedia article. ... Panadiplon (U-78875) is an anxiolytic drug with a novel chemical structure that is not closely related to other drugs of this type. ... Pipequaline (PK-8165) is an anxiolytic drug with a novel chemical structure that is not closely related to other drugs of this type. ... Diphenylmethane is a compound consisting of two phenyl groups joined to a single carbon. ... Hydroxyzine is a piperazine derivative that is used as an antihistamine (especially for itches), anti-emetic (nausea reducing), and anxiolytic (anxiety reducing) drug. ... Captodiame (INN, also known as captodiamine) is an anxiolytic. ... Carbamates are a group of organic compounds sharing a common functional group with the general structure -NH(CO)O-. More precisely the carbamate group is considered an amide group with an alkoxy or hydroxy functional group next to the carbonyl group. ... Meprobamate (marketed under the brand names Miltown® by Wallace Laboratories and Equanil® by Wyeth) is a carbamate derivative which is used as an anxiolytic drug. ... Emylcamate (marketed as Striatran® by Merck) is an anxiolytic and muscle relaxant. ... Mebutamate is an anxiolytic. ... β-Carboline (9H-pyrid-[3,4-b]-indole) is an organic amine that is the prototype of a class of compounds known as β-Carbolines. ... Abecarnil (ZK-112119) is an anxiolytic drug from the β-Carboline family. ... Gedocarnil is an anxiolytic. ... Benzoctamine is an anxiolytic. ... Azaspirodecanediones are a class of drugs with anxiolytic effects used in the treatment of anxiety. ... A serotonin receptor agonist is a compound that activates serotonin receptors, mimicking the effect of the neurotransmitter serotonin. ... Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Buspisal, Narol, Spitomin, Sorbon) is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. ... Gepirone (BMY 13805, MJ 13805, ORG 13011, Ariza®, Variza) is a pyridinyl piperazine partial 5-HT1A agonist that has anxiolytic effects. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Mephenoxalone is an anxiolytic. ... Etifoxine (or etafenoxine) is an anxiolytic. ...