Benzodiazepines

Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants; are sedative-hypnotic agents that were first introduced in 1960.

Benzodiazepines commonly are used for a variety of situations that include seizure control (clobazam, clonazepam, clorazepate, diazepam, and lorazepam) , anxiety, alcohol withdrawal (chlordiazepoxide, clorazepate, diazepam, and oxazepam) , insomnia (only effective for a few weeks) , control of drug-associated agitation, as muscle relaxants (diazepam), for panic disorder (a lprazolam and clonazepam) and as preanesthetic agents. They also are combined frequently with other medications for conscious sedation before procedures or interventions.

Benzodiazepines may be habit-forming (causing mental or physical dependence), especially when taken for a long time or in high doses.

Because of their widespread popularity, these drugs commonly are abused. In addition, BZDs frequently are used in overdose, either alone or in association with other substances.

Chlordiazepoxide, Nitrazepam, Oxazepam, Medazepam, Lorazepam, Loprazolam, Clorazepate Dipotassium, Clonazepam,Diazepam, Clobazam, Midazolam, Fluazepam, Triazolam, Lometazepam, Flunitrazepam, Bromazepam, Prazepam, Alprazolam, Ketazolam, Halazepam, Chloral Hydrate, Temazepam.

Librium, Valium, Mogadon, Ativan, Hypnovel, Dalmane, Halcion, Xanax, Tranxene, Klonopin.

D R U G S · T H A T · H A V E · B E N Z O · T Y P E · S I M I L A R · E F F EC T S · W I T H · A D D I C T I V E · P R OP E R T I E S :

There are many other trade names, for example, everyone seems to use the generic name for Temazepam yet some of the trade names are Euhypnos, Restoril, Normison, Sonapam. The names and spellings of drugs may vary in different countries.

Anxiety; confusion; fast, pounding, or irregular heartbeat ; lack of memory of events taking place after benzodiazepine is taken (may be more common with triazolam); mental depression

Abnormal thinking, including disorientation, delusions (holding false beliefs that cannot be changed by facts), or loss of sense of reality ; agitation; behavior changes, including aggressive behaviour, bizarre behaviour, decreased inhibition, or outbursts of anger; convulsions (seizures); hallucinations; hypotension; muscle weakness; skin rash or itching ; sore throat, fever, and chills; trouble in sleeping; ulcers or sores in mouth or throat (continuing); uncontrolled movements of body, including the eyes; unusual bleeding or bruising ; unusual excitement, nervousness, or irritability ; unusual tiredness or weakness (severe); yellow eyes or skin

Confusion (continuing); convulsions (seizures); drowsiness (severe) or coma; shakiness; slow heartbeat; slow reflexes; slurred speech (continuing) ; staggering; troubled breathing ; weakness (severe)

Mortality from a pure benzodiazepine overdose is rare; it usually occurs in conjunction with concomitant alcohol ingestion or use of other sedative-hypnotics. Intravenous administration or overdose of ultrashort-acting benzodiazepines (eg, triazolam [Halcion]) is more likely to result in apnea and death. Elderly individuals and very young persons are more susceptible to the CNS depressant effects of benzodiazepines than people in other age groups.

Intravenous administration is associated with greater degrees of hypotension than other routes of administration and occasional cardiac and respiratory arrest.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Benzodiazepines exert their action by potentiating the activity of GABA. They bind to a specific receptor on the GABA A receptor complex, which facilitates the binding of GABA to its specific receptor site. Benzodiazepine binding causes increased frequency of opening of the chloride channel complexed with the GABA A receptor. Chloride channel opening results in membrane hyperpolarization, which inhibits cellular excitation.

Enhanced GABA neurotransmission results in sedation, striated muscle relaxation, anxiolysis, and anticonvulsant effects. Stimulation of peripheral nervous system (PNS) GABA receptors may cause decreased cardiac contractility, vasodilation, and enhanced perfusion.

The rate of benzodiazepine onset of action is determined by rate of benzodiazepine absorption from the GI tract. The relatively lipophilic BZDs usually are absorbed more rapidly and produce a faster onset of effect than the relatively water-soluble BZDs. Benzodiazepine absorption is especially rapid when ethanol is present and the stomach is empty. Peak blood concentrations of most agents occur within 1-3 hours. After a single dose, the lipophilic agents have a shorter duration of action (shorter CNS effect) than water-soluble agents because rapid redistribution from the CNS to peripheral sites (eg, adipose tissue); thus, lorazepam (water soluble) has a longer CNS duration of action than diazepam (lipophilic).

Benzodiazepines are metabolized predominantly in the liver by oxidation and/or conjugation. Most benzodiazepines are broken down into pharmacologically active metabolites, which may have longer half-lives than the parent compounds.

In the US : In 1998, a total of 40,004 benzodiazepine exposures were reported to US poison control centers, of which 1177 (2.9%) resulted in major toxicity and 53 (0.1%) resulted in death.

Internationally: In the 1980s, an overall rate of 5.9 fatalities per million prescriptions for benzodiazepines occurred in Great Britain ; temazepam and flurazepam appeared to be the most toxic.

	Benzodiazepines
	Based on the National Institute of Drug Abuse Chart:
	Definition Generic Names Trade Names Adverse Effects Mortality/Morbidity Pathophysiology Frequency Bibliography D E F I N I T I O N Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants; are sedative-hypnotic agents that were first introduced in 1960. Benzodiazepines commonly are used for a variety of situations that include seizure control (clobazam, clonazepam, clorazepate, diazepam, and lorazepam) , anxiety, alcohol withdrawal (chlordiazepoxide, clorazepate, diazepam, and oxazepam) , insomnia (only effective for a few weeks) , control of drug-associated agitation, as muscle relaxants (diazepam), for panic disorder (a lprazolam and clonazepam) and as preanesthetic agents. They also are combined frequently with other medications for conscious sedation before procedures or interventions. Benzodiazepines may be habit-forming (causing mental or physical dependence), especially when taken for a long time or in high doses. Because of their widespread popularity, these drugs commonly are abused. In addition, BZDs frequently are used in overdose, either alone or in association with other substances. G E N E R I C · N A M E S : Chlordiazepoxide, Nitrazepam, Oxazepam, Medazepam, Lorazepam, Loprazolam, Clorazepate Dipotassium, Clonazepam,Diazepam, Clobazam, Midazolam, Fluazepam, Triazolam, Lometazepam, Flunitrazepam, Bromazepam, Prazepam, Alprazolam, Ketazolam, Halazepam, Chloral Hydrate, Temazepam. S O M E · T R A D E · N A M E S : Librium, Valium, Mogadon, Ativan, Hypnovel, Dalmane, Halcion, Xanax, Tranxene, Klonopin. D R U G S · T H A T · H A V E · B E N Z O · T Y P E · S I M I L A R · E F F EC T S · W I T H · A D D I C T I V E · P R OP E R T I E S : Zopiclone (Zimovane), Zolpidem (Ambien), Buspirone (Buspar) and Sonata. There are many other trade names, for example, everyone seems to use the generic name for Temazepam yet some of the trade names are Euhypnos, Restoril, Normison, Sonapam. The names and spellings of drugs may vary in different countries. A D V E R S E · E F F E C T S · I N C L U D E: Less common Anxiety; confusion; fast, pounding, or irregular heartbeat ; lack of memory of events taking place after benzodiazepine is taken (may be more common with triazolam); mental depression Rare Abnormal thinking, including disorientation, delusions (holding false beliefs that cannot be changed by facts), or loss of sense of reality ; agitation; behavior changes, including aggressive behaviour, bizarre behaviour, decreased inhibition, or outbursts of anger; convulsions (seizures); hallucinations; hypotension; muscle weakness; skin rash or itching ; sore throat, fever, and chills; trouble in sleeping; ulcers or sores in mouth or throat (continuing); uncontrolled movements of body, including the eyes; unusual bleeding or bruising ; unusual excitement, nervousness, or irritability ; unusual tiredness or weakness (severe); yellow eyes or skin Symptoms of overdose Confusion (continuing); convulsions (seizures); drowsiness (severe) or coma; shakiness; slow heartbeat; slow reflexes; slurred speech (continuing) ; staggering; troubled breathing ; weakness (severe) M O R T A L I T Y / M O R B I D I T Y : Benzodiazepines generally are thought to be safe and death is rare. Mortality from a pure benzodiazepine overdose is rare; it usually occurs in conjunction with concomitant alcohol ingestion or use of other sedative-hypnotics. Intravenous administration or overdose of ultrashort-acting benzodiazepines (eg, triazolam [Halcion]) is more likely to result in apnea and death. Elderly individuals and very young persons are more susceptible to the CNS depressant effects of benzodiazepines than people in other age groups. Intravenous administration is associated with greater degrees of hypotension than other routes of administration and occasional cardiac and respiratory arrest. P A T H O P H Y S IO L O GY: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Benzodiazepines exert their action by potentiating the activity of GABA. They bind to a specific receptor on the GABA A receptor complex, which facilitates the binding of GABA to its specific receptor site. Benzodiazepine binding causes increased frequency of opening of the chloride channel complexed with the GABA A receptor. Chloride channel opening results in membrane hyperpolarization, which inhibits cellular excitation. Enhanced GABA neurotransmission results in sedation, striated muscle relaxation, anxiolysis, and anticonvulsant effects. Stimulation of peripheral nervous system (PNS) GABA receptors may cause decreased cardiac contractility, vasodilation, and enhanced perfusion. The rate of benzodiazepine onset of action is determined by rate of benzodiazepine absorption from the GI tract. The relatively lipophilic BZDs usually are absorbed more rapidly and produce a faster onset of effect than the relatively water-soluble BZDs. Benzodiazepine absorption is especially rapid when ethanol is present and the stomach is empty. Peak blood concentrations of most agents occur within 1-3 hours. After a single dose, the lipophilic agents have a shorter duration of action (shorter CNS effect) than water-soluble agents because rapid redistribution from the CNS to peripheral sites (eg, adipose tissue); thus, lorazepam (water soluble) has a longer CNS duration of action than diazepam (lipophilic). Benzodiazepines are metabolized predominantly in the liver by oxidation and/or conjugation. Most benzodiazepines are broken down into pharmacologically active metabolites, which may have longer half-lives than the parent compounds. F R E Q U E N C Y : In the US : In 1998, a total of 40,004 benzodiazepine exposures were reported to US poison control centers, of which 1177 (2.9%) resulted in major toxicity and 53 (0.1%) resulted in death. Internationally: In the 1980s, an overall rate of 5.9 fatalities per million prescriptions for benzodiazepines occurred in Great Britain ; temazepam and flurazepam appeared to be the most toxic. B I B L I O G R A P H Y : http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202084.html
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