Week 11 - Anxiolytics & Sedatives Flashcards

(59 cards)

1
Q

anxiolytics & sedative-hynotics

A

used to reduce anxiety, sedate, aid sleep, act as anticonvulsants and as anaesthetics

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2
Q

the three classes of drugs to achieve these effects

A
  • benzodiazepines
  • barbiturates
  • other
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3
Q

illicit use of BDZs

A
  • misused by those with drug addictions and used in ways that are not consistent with optimal therapeutic goals
  • combined with other drugs (opiates & alcohol)
  • controlled substances according to WHO standards
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4
Q

modern BDZs without active metabolites

A
  • ozazepam
  • temazepam
  • lorazepam
  • clonazepam
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5
Q

modern BDZs with active metabolites

A
  • diazepam
  • chlordiazepoxide
  • nitrazepam
  • alprazolam
  • flurazepam
  • bromazepam
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6
Q

examples of BBTs

A
  • secobarbital
  • phenobarbital
  • amobarbital
  • mephobarbital
  • secobarbital
  • aprobarbital
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7
Q

administration

A
  • orally, parenaterally (i.v., i.m.) absorption from digestive system better than i.m. absorption bc of biochemical properties
  • BBTs & BDZs readily absorbed after oral and parenteral routes
  • choice of route of admin depends on reason for use
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8
Q

Absorption - barbituates

A
  • weak acid
  • pKa near 8.0 - almost entirely nonionized at pH of digestive system - readily absorbed
  • variability in lipid solubility
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9
Q

absorption - benzodiazepines

A
  • weak acid
  • pKa of 3.5 to 5.0 readily absorbed from digestive dystem
  • range of lipid solubility
  • absorption may be increased by alcohol
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9
Q

distribution

A
  • determined by lipid solubility
  • cross placental barrier and present in break milk
  • highly lipid soluble will cross BBB, effects seen quickly but dissipate quickly
  • drug released slowly from fat deposits - metabolised by liver
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9
Q

2-phase excretion: BDZs

A

phase 1: rapid drop in blood level due to redistribution in fat deposits (half life ~2-10 hours)
phase 2: metabolism liver, CYP450 enzyme (half-life ~27-48 hours)

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10
Q

excretion - BDZs

A
  • older BDZs almost fully metabolized - active metabolites of these drugs = duration of effect not determind by half-life
  • metabolism increased by repeated administration; slowed by alcohol
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10
Q

excretion - BBTs

A
  • most fully metabolized by liver enzymes before excretion
  • repeated admin = increase metabolism
  • metab also increased by anti-psychotics, anesthetics, chronic alcohol use, antihistamines, nicotine
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11
Q

excretion - BBTs (other drugs)

A
  • BBTs stimulate enzymes that metabolize other drugs (chlorpromazine, morphine, caffeine, general and local anesthetics)
  • ODs can be treated by making urine more alkaline
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12
Q

how do they affect GABA receptors

A
  • ionotropic, mainly postsynaptic, quick response, couple to Cl- channels
  • own receptor sites on GABA-Chloride Ionophore Complex
  • make GABA NT more effective at these sites: increases ability to open channel
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13
Q

BBT vs BDZ mode of action

A

BBTs: increase time channel is open creates larger increases of Cl-
BDZs: increases frequency of channel opening & increases affinity of GABA for receptor

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14
Q

neurophysiology

A
  • some act as negative GABA modulators
  • interact with their own receptor sites
  • BDZs affect adenosine by blocking re-uptake
  • increases dopamine in nacc via GABA
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15
Q

BDZ effects on the body

A
  • relatively mild decrease in respiration
  • mild decrease in blood pressure
  • increase appetite/ weight gain
  • increase muscle relaxation
  • anticonvulsant - petit mal seizures & infantile spasms
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15
Q

BDZs effect on sleep

A
  • widely used for sedative-hypnotic properties
  • effective as short-term intervention
  • decreases time to fall asleep; decreases awakening and REM & stage 3 & 4 sleep, increase total sleep time - withdrawal rebound effect
  • tolerance to effects does not develop
  • eliminate withdrawal rebound by re-administer drug
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15
Q

BDZs subjective effects

A
  • sedation/fatigue/confusion
  • euphoria & ‘liking’
  • anxiolytics
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16
Q

BDZs effects on performance

A
  • decreased visual & auditory acuity
  • decreased simple RT (at high doses)
  • explicit memory - anterograde amnesia, not implicit memory
  • if clinicallty anxious, BDZs may improve performance
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17
Q

BDZs hangover effects

A
  • disruption in mood and performance 12 hrs after admin
  • amplifies effects of alcohol
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18
Q

BDZs effects of driving

A
  • increases collisions
  • increased by alcohol
  • increased risk in first time users who report feeling fine
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19
Q

BBTs effects on the body

A
  • significant decrease in respiration
  • heart rate
  • blood pressure
  • anticonvulsants
20
BBTs effects on sleep
- sleeping pills - decreased sleep onset latency; increased total sleep time - decrease REM sleep - tolerance after 1 week - withdrawal rebound up to 40% of sleep time for several weeks
21
BBTs subjective effects
similar to benzodiazepines
22
BBTs effects on performance
- decreased visual acuity - overestimate time - decreased steadiness - decreased visual tracking - decreased divided attention - decreased athletic performance
23
BBTs hangover effects
- simple RT deficits detcted the next day - decreased pursuit tasks - decreased body steadiness after 18 hours
24
BBTs effects on driving
equivalent to BAL of .15
25
unconditioned behaviour
- taming seen in lab animals first - restricted to decreased defensive aggression
26
conditioned behaviour
- increased responding to punished stimuli - decreased avoidance behaviour
27
discrimination - barbituates
- not able to discriminate different types of BBTs - generalized to other BBTs, BDZs - not to amphetamines or LSD - can discriminate alcohol
28
discrimination - benzodiazepines
- animals readily discriminate BDZs from saline - generalize to other BDZs & BBTs but not antipsychotics - discrim effects can be blocked by drugs that block BDZ receptor
29
Chronic tolerance- barbituates
develop at different rates for different effects examples: - antiepileptic effects = no tolerance - RT/coordination ~ 1 week - total sleep time ~ 70 days
30
acute tolerance - benzodiazepines
- can develop during single administration - behaviour and motor-imparing effects
31
chronic tolerance - benzodiazepines
- depressant effects develop tolerance 1st - locomotor, ataxic, muscle relaxant & anticonvulsant effects - anti-anxiety: variable in humans - drowsiness - sleep: after ~ 4wks - short-acting drugs avoid residual effects but progess to tolerance quicker - REM suppression does not develop tolerance
32
cross-tolerance - barbituates
- cross tolerant with each other, alcohol & BDZs - considerable cross-tolerance with other depressants - cross-tolerance with metabolizing enzymes induce by BBTs
33
cross-tolerance - benzodiazepines
- other depressant drugs - alcohol & BBTs
34
BBT withdrawal
low doses - REM rebound high doses - can precipitate medical emergency - symptoms commence 12-24 hrs (or 48-72 hrs for long acting) after final dose and may last up to 2 wks
35
symptoms of BBT withdrawal
- tremors - anxiety - insomnia - nausea - delirium - seizures - death - hallucinations - disorientation - confusion - fear - agitation - REM rebound most symptoms gone in 2 wks similar to high-dose BDZ withdrawal
36
2 types of BDZ withdrawal
- sedative-hypnotic withdrawal - low-dose withdrawal
37
Sedative-hypnotic withdrawal
- occur with high doses > ~ 1month - usually seen in benzodiazepines with short half-lives - usually gone <10 days - sensitive to resuming treatment - notable symptoms: tremors, cramps, delirium, convulsions
38
low-dose withdrawal
- occur when low doses taken for extended periods (>6mnths) - duration 2 weeks or up to a year - usually come in waves - sensitive to resuming treatment - notable symptoms: anxiety, panic, irregular HB, decreased memory and concentration, increased BP, sensory sensitivity, distortion of reality
39
BBT self-administration in animals
- reinforcing properties using various reinforcement schedules - reinforcement properties of short vs long-acting barbituates - monkeys increase consumption until stable, then constant level of admin
40
BDZ self-administration in animals
- IV and oral - short & long acting - not as reinforcing as BBTs - reinforcing properties can be enhanced by priming with the drug, BBTs or other BDZs - longer acting BDZs, past use determines how reinforcing they are
41
BBT experimental self-administration in humans
- not chosen more often than placebo in lab studies - reinforcing for those with a history of use
42
BBT non-experimental self-administration in humans
1. street use - usually in high-dose binges combined with other drugs - injected with heroin or amphetamines 2. Iatrogenic use - initially prescribed for variety of symptoms - reinforcing properties lead to abuse & doctor shopping
43
BDZ experimental self-administration in humans
not chosen more often than placebo in lab studies even by those with high anxiety
44
BDZ non-experimental self-administration in humans
1. street use - usually combined with another drug (alcohol/methadone) - rohypnol 2. Iatrogenic use - prescribed for anxiety
45
BBTs effects on reproduction
- baby goes through withdrawal when born - onset 7 days - birth defects - cleft lip & palate - abnormalities of heart, skeleton & CNS - brain weight - neurological development - decreased later male sexual behaviour (decreased testosterone) - learning disabilities, decreased IQ and psychosocial problems
46
BBTs overdose
- low TI - additive effect with alcohol - BAL .1 + .5mg secobarbital = lethal - poisoning causes unconsciousness, decrease HR & BP, blisters, decreased urine flow, decrease temperature regulation, respiratory depression
47
BDZs on reproduction
- suggestion that BDZ cause birth defects (fetal benzodiazepine syndrome similar to FAS) - withdrawal in infants similar to opiate withdrawal, start <2.5-6hrs after delivery - floppy baby syndrome after BDZ delivery process
48
BDZ overdose
- not as dangerous as BBT OD; seldom fatal on its own - sleep/drowsiness, no coma or severe respiratory depression - intensify depressant effects of alcohol and BBTs - combo of these in OD usually fatal - can be treated with BDZ receptor antagonist
49
BDZ use as anxiolytic or s-h
- symptomatic - underlying cause of anxiety/insomnia remains untreated - rebound insomnia/ rebound anxiety
50
BDZ on sleep
disruption to sleep architecture may have harmful effects (re chronic REM sleep deprivation)
51
BDZ over sedation
2 mechanisms 1. risk increase with BDZ with active metabolite (when used for anxiolytic or s-h purposes) 2. when use is combined with additional CNS depressants
52
BDZ on memory
- appears to impair memory - nature of impairment: intentional retrieval; explicit memory - significant drug related impairtment on average 82% of the times tested
53
BDZ effects on older people
- older people sensitive to CNS depressant effects - may cause confusion, amnesia, ataxia & pseudodementia - recommendations to minimise harm ( 1/2 regular adult dose, short term use, use without active metabolites)
54
BDZ dependency
- dependency leads to chronic use - withdrawal should be done under medical supervision to avoid convulsions, respiratory failure - involves gradual reduction of dose over 8-12 weeks - alternative coping strategies are essential - longer term management may be needed to avoid relapse