benzodiazepines Flashcards
what is anxiety?
a common psychiatric disorder found and most people who have anxiety, they have a comorbid disorder
2x more likely in women than men
how has the DSM-5 reclassified anxiety disorders?
into 3 classes:
Anxiety disorders
Obsessive-compulsive disorder (OCD) and related disorders
Trauma related disorders, including post-traumatic stress disorder (PTSD)
what are ways anxiety expressed?
- panic episodes
- phobic avoidance of anxiety-eliciting stimuli
- intrusive thoughts or compulsive behaviors
- damaging negative thinking patterns
is fear and anxiety the same?
NO
Fear: emotional response to current threat
Anxiety: apprehension about possible future events
what could anxiety be a result of in the brain?
an imbalance between emotion generating centers & higher cortical controls
for example:
- Amygdala : emotion - fear
| - Hypothalamus : emotion - activates sympathetic and produces stress response
| - Periaqueductal grey (PAG): emotion - pain and feelings of dread
| - Hippocampus: emotion - memory of fear
| - PFC: higher cortical - uses logic to make judgements and decisions
what is a NT other than serotonin found in anxiety?
GABA
how does GABA act in anxiety?
Impaired GABA function leads to overactive amygdala activity - menacing or dread feelings
GABA receptors found in HIGH concentrations in amygdala, limbic system, & cerebral cortex so we have the ability to shut down our circuit if we get too anxious.
what are the 2 drug groups that are given for anxiety disorders? what do they do?
- anxiolytics: Relieve tension, worry, stress
produce a calm and relaxed state - sedative - hypnotic: drugs are CNS depressants and include barbiturates, benzodiazepines, & alcohol - aides in sleep and sedation
- what are the use of barbiturates?
- what schedule are they?
- what is their route of admin?
- what is their absorption?
- what is their distribution?
- surgical anesthesia, sleep aid, anti-anxiety, anticonvulsant
- 2, 3, 4 - ex. pentobarbital = schedule II; butobarbital = III; luminal = IV
- Oral or IV most common
Short-term use: IV
Long-term use: oral
Intranasal common route for barbiturate abuse - Absorbed rapidly from GI tract depending on lipid solubility
Ultrashort acting = highest lipid solubility
Long acting = lowest lipid solubility - Readily pass through BBB & placental barriers, detectable in milk of nursing mothers
and accumulates in skeletal muscles and adipose tissue (depot binding!)
- what is the metabolism of barbiturates?
- what metabolites are formed?
- how is it excreted?
- broken down in the liver (CYP450 enzymes).
- inactive metabolites
- excreted in urine
what occurs with chronic repeated use of barbiturates?
- metabolic tolerance, cross tolerance, behavioral tolerance
CYP450 enzyme induction associated with increased drug metabolism, lower blood concentration of drug, and reduced drug effectiveness.
how do barbiturates act in the CNS?
- enhance GABA actions
- acts as positive allosteric modulator : increase Increase affinity of the GABAa receptor for GABA
- directly open Cl- ion channel in GABAA receptor without GABA present - causing chances of extreme sedation
- at high doses: antagonists for NMDA, AMPA and Kainate glutamate receptors
what does NOT show tolerance in barbiturates?
Respiratory depression does NOT show tolerance
LOOK at graph on slide 10
what type of dependence does barbiturates cause? what does this implicate
physical dependence so…
- high potential for abuse
- cannot quit cold turkey
Withdrawal syndrome associated with
potentially fatal rebound hyperexcitability
in brain -Similar to alcohol
what effects do we see with high dose of barbiturates?
Poor coordination, slurred speech, life-threatening respiratory depression
what are benzodiazepines used to treat?
anxiety disorders
what are trade names for benzodiazepines?
valium, xanax
what is important about the use of benzodiazepines?
account for ~2/3rds of all medical prescriptions for psychoactive drugs
most are for anxiety and panic disorders
what type of schedule drugs are benzodiazepines?
schedule 4
what is the common suffix for benzodiazepines?
End with suffix azolam or azepam
what are the classes of benzodiazepines and what are their functions?
- Ultrashort-acting
use: IV anesthetic/ surgical preanesthetic
ex: Midazolam (Versed) - Short-acting
use: anxiety disorders/ insomnia
ex: alprazolam (Xanax) & lorazepam (Ativan) - Long-acting
use: chronic anxiety, seizures, or alcohol n
withdrawal
ex: Diazepam (Valium)
how long do people use benzodiazepines?
- women use it more than men
- 80% use it for 4 months or less
- 45% use it for less than a month
- 15% use it for more than a year
- what is the route of admin?
- what is the absorption?
- what is the distribution?
- Oral (most common; xanax),
IV, IM injections (Ativan; Valium)
Intranasal common during abuse (crushed up & snorted - Onset of action determined by lipid solubility
Short-acting BDZs generally more lipid-soluble and reach brain faster than long-acting BDZs
- High blood albumin protein binding (depot binding)
Redistribution from fat & muscle can extend time drug can be detected in a person’s system
what is the metabolism of benzodiazepines?
Short-acting BDZs like lorazepam (Ativan) metabolized in 1 step into INACTIVE metabolites
Ativan: half-life 12 hours
Long-acting BDZs like chlordiazepoxide(Librium) or Diazepam (Valium) metabolized in liver in multiple steps
Valium half-life: ~48 hours
Produce ACTIVE metabolites that re-enter
circulation
Major active : nordiazepam
Minor active: temazepam
