1. Benzodiazepines
Rachel Anderson

2. Introduction Benzodiazepines (BZD, BZs) "benzos” Psychoactive drugs
Chemical structure is the fusion of a benzene ring and a diazepine ring
Central nervous system depressants that are commonly known as tranquilizers, sedatives, or anxiolytics
Due to the sedative effects they produce, they are often used as “date rape” drugs
Approximately 2,000 benzodiazepines have been produced but only 15 are marketed in the U.S
Schedule IV
Twice as many women as men taking them
CNS depressants
They are the most commonly prescribed medications in the U.S. and are mainly used to treat anxiety and insomnia
Second most frequently abused prescription
Combination with other CNS depressants can cause dangerous drug interactions, and contribute to death via overdose

3. History As we learned in class:
1800’s looking for something other than alcohol to be used as CNSD
Bromides 1800s helpful but toxic
Barbiturates 1900s initially safe/effective; eventual problems with tolerance, safety and dependence
Benzodiazepines 1950s safe for short periods of time; long term use cause dependence and withdrawal
However, they are less toxic than their predecessors, (the barbiturates) and death rarely results when a benzodiazepine is the only drug taken.

4. Benzodiazepines History
1955 – Synthesis of the first benzodiazepine, Chlordiazepoxide (Librium) 1960 – Librium (Chlordiazepoxide) made available
1963 – Valium (Diazepam) made available
1970s – Benzodiazepines had replaced barbiturates
million prescriptions written
1977- Benzodiazepines were globally the most prescribed medications
1978 – 2.3 billion tablets of Valium sold
1980 – Researchers issued one of the earliest warnings against long term use

5. Reason for Use
Benzodiazepines possess sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant, and amnesia actions, which are useful in a variety of indications:
Generalized anxiety disorder (GAD)/ Panic Attacks / Acute Anxiety,
Insomnia
Psychiatric Emergencies
Muscle Spasms
Epileptic seizures
Alcohol Dependence
Sedate patients

6. Mechanism of Action
Most are administered orally; however, they can also be given intravenously, or intramuscularly
Mechanism of Action:
Affect neurons that have receptors for neurotransmitter gamma- aminobutyric acid (GABA)
GABA is the most common inhibitory transmitter in brain regions
Limbic System (alter mood)
RAS (cause Drowsiness)
Motor Cortex (relax muscles)
Distinguished primarily by duration of action: (short acting) hypnotics, (long acting) sedatives
Benzos are categorized as either short-, intermediate-, or long-acting:
longer-acting benzodiazepines are recommended for the treatment of anxiety
Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia
High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and dissociation

8. Contraindications
Respiratory depression - myasthenia gravis, sleep apnea, bronchitis, and COPD.
Increase suicidal tendencies – major depression
Life Threatening interactions – history or current drug comorbidity
Not safe – Pregnancy

9. Side Effects
The most common side-effects of benzodiazepines are related to their sedating and muscle-relaxing action:
Drowsiness
Dizziness
Decreased alertness
Decreased concentration
Lack of coordination
Driving impairment
Decreased libido
Depression
Less common side effects:
Nausea
Blurred vision
Confusion
Euphoria
Nightmares

10. ADDICTION/ DEPENDENCE /TOLERANCE AND WITHDRAWALS
Main Sign of Physical Dependence
Rebound Symptoms
Withdrawal Symptoms
Most Frequent Symptoms of Withdrawal
Insomnia
Gastric problems
Tremors
Agitation
Anxiety
Difficulty breathing
Headaches
Fear
Muscle spasms
Less Frequent Symptoms of Withdrawal
Irritability
Sweating
Depersonalization
Hypersensitivity
Depression
Suicidal behavior
Psychosis
Seizures
Abrupt Withdrawal can be dangerous – gradual reduction regimen/ tapering is recommended

12. Some Benzos to Know
Of the 15 FDA-approved benzodiazepines in the U.S., the most commonly known include:
Versed (midazolam) & Halcion (triazolam), which are ultra-short acting
[These are often prescribed to help a person sleep or to calm a person down before surgery]
Xanax (alprazolam), Klonopin  (clonazepam), & Ativan (loraz epam), which are short-acting
Librium (chlordiazepoxide) & Valium (diazepam), which are long-actin

14. Prescribing rates per 100 persons (in quartiles), by state and drug type — IMS Health, United States, 2012
Wide variation exists from one state to another in prescribing rates for these drugs. High rates of prescribing these controlled substances are important determinants of rates of fatal overdose and drug abuse, especially when prescribed with opioids
Alabama, Tennessee, and West Virginia were the three highest-prescribing states

15. Charts/ Graphs
National Overdose Deaths—Number of Deaths from Benzodiazepines. The figure is a bar chart showing the total number of U.S. overdose deaths involving benzodiazepines from 2002 to 2015.  The chart is overlayed by a line graph showing the number of deaths of females and males. From 2002 to 2015 there was a 4.3-fold increase in the total number of deaths.

16. Other/Interesting
Toxicology screen - A toxicology screen refers to various tests that determine the type and approximate amount of legal and illegal drugs a person has taken.
Benzodiazepines: up to 6 weeks with high level use
1966 hit “Mothers Little Helper” by Rolling Stones is a song written about Valium
“What a drag it is getting old ‘kids are different today’ I hear every mother say. Mother needs something to calm her down. And though shes not really ill. Theres a little yellow pill. She goes running for the shelter of a mothers little helper

17. Current Awareness
for-world-benzodiazepine-day/
in a new video for World Benzodiazepine Awareness Day (W-BAD) people from all over the world share about the iatrogenic harm they sustained from taking benzodiazepines as prescribed.

18. Summary Benzodiazepines are psychoactive drugs
They are classified as depressants and act on the Central Nervous System
Benzodiazepines possess sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant, and amnesia actions
They are the most commonly prescribed medications in the U.S. and are mainly used to treat anxiety and insomnia.
Combination with other CNS depressants can cause dangerous drug interactions, and contribute to death via overdose

19. Resources http://wickedsober.com/benzodiazepines/
meta?query=benzodiazepine&v%3Aproject=nlm-main-website
death-rates
bendodiazepines/