Benzodiazapines

  • Act in limbic system & reticular activating system (RAS) (blocking brain’s response to incoming stimuli)
  • make GABA more effective (opens Cl- channels, hyperpolarizing cells - becomes more difficult to depolarize, reducing excitability)
  • most widely used anxiolytic drugs – safer, more effective, less potential for addiction & does not cause much sedation
    - Lower doses cause anxiolytic effects – reduction in anxiety w/o causing much sedation
    - Higher doses cause sedation and hypnosis
  • Other uses:
    - Anticonvulsants
    - Muscle relaxants

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Indications:
  • Relieve S&S of anxiety disorders 
  • Alcohol withdrawal 
  • Hyperexcitability / agitation 
  • Pre-op relief of anxiety & tension (lower dose)
  • Balanced anesthesia 
  • Seizures (anticonvulsant effect) 
  • Conscious sedation (Producing IV anesthetic)
  • Muscle spasms (Producing skeletal muscle relaxation)
  • Anxiety, insomnia


Contraindications:
  • Psychosis 
  • Acute narrow angle glaucoma (May ↑ IOP) 
  • Shock 
  • Coma 
  • Acute alcohol intoxication
  • pregnancy & lactation
    - fetus can develop dependency in utero & experience withdrawal Sx


Caution:
  • 15% - 20% of African Americans genetically predisposed to delayed metabolism of benzodiazepines (leading to eventual buildup &↑ AE)
  • Older Adults – ↑ CNS effects 
  • Effects on fetus and neonate: 
    - Cleft lip and/or palate
    - Cardiac defects


Adverse Reactions:
  • Sedation, DrowsinessLethargy 
  • DepressionConfusion
  • Blurred Vision 
  • Dry Mouth
  • Hypotension
  • urinary retention
  • N/V, Constipation
  • loss of libido 


Interactions:
  • ↑ CNS depression when taken with alcohol 
  • ↑ in effect when taken w/ cimetidine, oral contraceptives, or disulfiram (Antabuse) 
  • ↓ in effect if given with theophylline or ranitidine (Zantac) 


Kinetics:
  • Well absorbed from GI tract; Lipid soluble and distributes well throughout the body 
  • Peak levels achieved in 30 minutes to 2 hours 
  • Metabolized in the liver; Excretion is primarily in the urine

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Drugs:

1. Diazepam (Valium) & Clorazepate (Tranxene) - fast onset (30min)


2. Oxazepam (Serax) - slow onset (~ 2hrs)


3. Lorazepam (Ativan), Alprazolam (Xanax), Clonazepam (Klonopin) - intermediate onset


Drugs by Use:

  • Anxiety Disorders:
    - alprazolam (Xanax), chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), lorazepam (Ativan), midazolam 

  • Seizure Disorders
    - clonazepam (Klonopin), clorazepate (Tranxene), and diazepam (Valium)

  • Insomnia
    - estazolam, flurazepam, quazepam (Doral), temazepam (Restoril), triazolam (Halcion)

  • Anesthesia
    - midazolam, lorazepam (Ativan), and diazepam (Valium) 

  • Muscle Relaxation
    - diazepam (Valium)

  • Alcohol Withdrawal
    - chlordiazepoxide (Librium) 

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Nursing Mgmt
  • Avoid alcohol & other CNS depressants during therapy (to avoid severe drowsiness, respiratory depression, apnea)
  • Do not drive or engage in other potentially hazardous activities or those requiring mental precision until reaction to drug is known. 
  • Tell physician if you become or intend to become pregnant during therapy; drug may need to be discontinued. 
  • Take drug as prescribed; do not change dose or dose intervals. 
  • Check with physician before taking any OTC drugs. 
  • Do not breast feed while taking this drug without consulting physician. 
  • Psychic & physical dependence may occur in pt on LT high dosage therapy, in pt w/ Hx alcohol or drug addiction, or in pt who self-medicates
  • Abrupt stop may lead to withdrawal syndrome (nausea, headache, vertigo, malaise and nightmares)
  •  dec dose in elderly (dec liver/kideny function)
  • before using these drugs try: exercise, good sleep hygiene, relaxation techniques
  • IV - do not mix with other agents; slowly - connection closest to the vein – rate (5mg/minute)– hypotension, bradycardia, cardiac arrest. BR x 3 hours post administration 
  • No intra-arterial administration – IV only w/ caution 
  • No driving or operation of heavy mechanical equipment
  • Antidote:
    - Flumazenil (Romazicon) a benzodiazepine receptor antagonist antidote for overdose; indicated to reverse sedative effects of benzos 

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