Chapter 8 - Depressants Flashcards
What is a depressant?
drug that diminishes physiological activity
Therapeutic uses of depressants
anxiety, sleep management, seizures, anesthesia
-most produce positive subjective effects (activate reward pathways); high abuse liability
What are some common depressants?
alcohol, barbiturates, benzodiazepines, opioids
Most depressants act through increased activity of ____
GABA
Depressants and GABAA receptor
Ionotropic receptor that allows entry of Cl- ions; hyperpolarizes neurons which decreases their firing rate; five subunits; two binding sites for GABA
There are ____ sites on the GABAA receptor that enhance GABA transmission
allosteric
What are barbiturates?
became available after development of barbital from barbituric acid; became widely used for insomnia, nervousness, sedation, anesthesia; first effective anti-seizure medication
Barbiturates are ____ depressants and are sometimes referred to as ____
CNS; sedatives
barbiturates are classified by their…
speed of onset and duration of action
speeds and durations of barbiturates
ultra-shortacting: effects in 20-30s, lasts ~30min ex. thiopental
short-acting/intermediate: ex. pentobarbital
long-acting: effects in ~1hr, last ~12hr ex. phenobarbital
Barbiturate as a drug of abuse
positive reinforcing effects; reduce feelings of stress and anxiety; produce feelings of well-being and lower inhibitions
depressants enhance GABA inhibition at sites of action such as…
cerebral cortex, amygdala, thalamus, and medulla
HOWEVER as doses increase the effects reach deeper into brain cortex>amygdala>medulla
cortex: disinhibition
amygdala: red. anxiety
medulla: resp. depression
Inhibition of ____ accounts for
the effects on seizures, memory, attention, and other cognitive functions
cortical activity
the ____ effects of barbiturates are due to the inhibition of the amygdala
anti anxiety
The effects on ____ result from inhibition of the medulla
respiratory function
overdose potential of barbiturates
main concern is respiratory depression; memory blocking effects (forgetting if they took a dose); long term use can lead to shrinking therapeutic index
chronic use of barbiturates causes tolerance to the ____ but not to the ____
therapeutic effects: respiratory depressant effects
withdrawling from barbiturates
Withdrawal should be done gradually; abrupt withdrawal causes a Barbiturate Abstinence Syndrome (anxiety, muscle weakness, abdominal pain seizures)
-think of it like the opposite of what theyre used for
What are benzodiazepines?
produces less drowsiness and cognitive inhibition than barbiturates; relatively common for anxiety disorders
short-acting benzodiazepines are used as..
“as needed” acute anxiety situations
intermediate/long-lasting benzodiazepines are used as…
relief for or to prevent generalized anxiety disorder
Long-lasting benzodiazepines produce ____
active metabolites
Benzodiazepines abuse
High abuse potential; positive subject effects but less than barbiturates
Benzodiazepine withdrawal syndrome
Characterized by depression, anxiety, mania; can last several months; avoiding withdrawal could be main reason to continue use
Risks of using benzodiazepines
Accidental injury; poor decision making; most misuse is from combining with alcohol;
Benzodiazepines serve as positive modulators by ____
binding to an allosteric site known as the benzodiazepine site (separate from barbiturate site)
What are the two types of benzodiazepine sites?
BZI site: high affinity
BZII site: low affinity
What are Z-drugs?
non-benzodiazepine hypnotics (sleep aids); generic names typically start w Z; high binding affinity for GABAA receptors
Risks of Z-drugs
Sleep-related complex behaviours (walking, driving, cooking, eating, conversing while asleep); recommends 8hrs of sleep for effects to wear off
What is Gamma-Hydroxybutyrate (GHB)?
a drug (white, tasteless, dissolves in water) and a NT; used instrumentally (narcolepsy, schedule II) and recreationally (abused, schedule I); associated with sexual assault
What two precursor drugs is GHB easily produced from?
GBL (gamma-butyrolactone, immediate precursor of GHB); 1,4 butanediol (readily converted to GHB); biotransformation occurs in “alcohol” metabolic pathway in liver
GHB is also produced naturally in the brain from ____
GABA
-GHB is stored and released with GABA; GABA is the product of GHB metabolism
How many GHB receptors are there?
one, with evidence of another
-G-protein-coupled receptor
-inhibitory effects on hippocampus, cerebral cortex, & basal ganglia
Pharmacokinetics of GHB
concentrated within 45 mins, onset of effects after about 15-20; metabolized into GABA in liver and brain; about 30min half life
Pharmacological effects of GHB
longer time in deep sleep; subjective effects are time dependent (similar to alcohol; good at first but later effects mood, memory, drowsiness, etc)
Overdosing on GHB
nausea; decreased BP; decreased HR; unconsciousness
-most emergency room visits related to GHB involve polydrug use, often alcohol
What are inhalants?
vaporous chemicals with psychoactive effects
What are some compounds of inhalants?
amyl nitrate (“poppers,” warmth, enhances sexual experiences); nitrous oxide (laughing gas, aerosol spray cans, euphorogenic but can also be a depressant); volatile solvents (hydrocarbon chemicals, toluene, gasoline, acetone)
Who uses inhalants?
mainly adolescents; mainly bc none of the compounds are legal (easily accessible) and wear off quickly
Ways to administer inhalants
sniffing (direct inhalation); huffing (soaking a cloth); bagging (inhaling from a bag)
Pharmacological actions of inhalants
most are depressants (share some mechanisms of actions with alcohol); After several days of use there is an upregulation of NMDA receptors to compensate for this antagonism (tolerance to subjective effects); positive modulation of GABAA receptors
4 stages of inhalant effects
- stimulant like positive subj effects
- behaviours resembling alcohol intoxication
- enhanced depressant effects
- overdose (unconsciousness, seizures, cardiac arrest)
How is inhalant overdose dangerous?
cardiac arrest is the primary cause of sudden sniffing death syndrome due to poor oxygen availability (occurs when vapors complete with oxygen inhalation and absorption)
-Chronic use of inhalants can lead to loss of brain tissue: ventricular enlargement and white matter degeneration
