FINAL PSYCH 345A Flashcards
SEDATIVE-HYPNOTICS
General Description
- Drugs which slow/reduce/depress nervous system
activity and behavior - Collectively, most widely used class of psychoactive
drugs - Arbitrarily classified into four groups
- barbituate
- benzodiazapines
- non-barbituate …
- misc compounds (includes alcohol)
similarities w hypnotics
- similar uses (to tread anxiety)
- benzodiazapine to tread anxiety
- Similarities:
– Uses
– Sites of action
– Ability to induce various levels of behavioral
depression - Differences
– Individual potency
– Chemical structures which affect ADME
anxiolytic = tranquilizer ) - used to treat agittion and anxiety disorders
sedative hypnotic used to sadate and air sleep
meprobamate - Miltown
mathaqualone - Quaaludes (widely used in 60s)
z drugs - widely used for insomnia
*** PRIMARY MECAHNISM IS MODULATION OF THE GABAA RECEPTOR - BUT HAVE DIFFERENT BINDING AFFINITIES
fast acting short duration - as sedative hypnotic
longer acting barbituate as anxiolytics
Z drugs can target specific symptoms
have been perscribed for bed wetting, arthritis, anxiety, … by the 90s, benzodiazepines have mostly replaced the barbituates. benzodiasapines are safer
- benzodiazepine - diazapam - Valium
phenobarbital is still prescribed for epileptic seisures - used to antagonize stimulant effects of other drugs given
illicit barbituates - “downers”
SEDATIVE-HYPNOTICS
Sites and Mechanisms of Action
effects of these drugs: Their effects are
mediated primarily by their ability to modify transmission
of the inhibitory transmitter GABA, specifically at
the GABAA receptor
(1) Ascending Reticular Activating System - Messaging becomes depressed (role of neurological arousal), causes fogginess and sedation
(2) Diffuse Thalamic Projection System - Role in alertness and responsiveness, so sedatives depress this
(3) GABA Receptor Complex System - Receptors(GABA, benzo, or barb) connected to Cl- ion channel, when Cl- enters produces IPSP, induces behavioral depression and neural activity
(3) GABA Receptor Complex System
- see textbook for GABA receptor, slowing activity .. how this works.
- barbituate can open receptor on its own
- overdose on barbituate is more common than on benzodiazapines
The barbiturates, benzodiazepines, and nonbenzodiazepines
do not modify GABAA receptor activity by
altering levels of GABA or by interacting directly with
GABA’s receptor binding site. Instead, these drugs are
positive allosteric modulators—they have their own
binding sites on the GABAA receptor complex that,
when occupied, enhances the effects of GABA binding.
(4) Cells - Reduce cellular metabolism
(5) Norepinephrine synapses - Decrease activity at NE receptors
SEDATIVE-HYPNOTICS - effects, tolerance, depenencey
SEDATIVE-HYPNOTICS
* Effects are additive
* Potentiation can occur
* Inhibitory synapses are depressed slightly before
excitatory synapses
* Dependency can develop
* Tolerance can develop
More severe dependency seen when people have been taking high doses for about 6 months
- Causes extreme withdrawal symptoms
Acute tolerance - very rapidly developing, single dose of benzodiazepines
Chronic tolerance - anticonvulsant and drowsiness effects of benzos or barbs
Cross-tolerance - b/w barbs, benzos, and alcohol
Sedative-hypnotic withdrawal
more severe, tremors, delirium, confusion, hallucination, cramps, convulsions - seen at very high doses for a month, but mostly within 6 months
Low-dose withdrawal
seen w benzos taking a therapeutic dose taken for longer than 6 months - symptoms emerge more slowly and never become as severe - no consistent data showing when withdrawals stop - symptom re-emergence of anxiety or sleep that were present before starting drug - irregular HR, increased BP, sensitivity to light, poor attention, perceptual problems
- initially, only barbituates were used as sedatives and tranqs
- brandy used before this
*** respiratory depression seen with barbituates is similar to depression causes by alchohol.
Similarities w different setadive hypnotics:
- Similarities: - Uses - Sites of action - Ability to induce various levels of behavioral depression
- Differences - Individual potency - Chemical structures which affect ADME
- barbituates can open the Cl- ion channel themselves, without GABA binding co-presence.
- high levels can depress breathing and autonomic centres in brainstem
- benzodiazapine in contrast, can cause extreme sedation and grogginess but not life threatening
barbituates have much higher portntial for lethal overdose
ALCOHOL
Absorption
Alcohol is completely and rapidly absorbed when
taken orally
- some absorption in stomach, but majority in
intestines - Rate of absorption modified by a # of factors
Volume of fluid (higher concentrated alcohol more quickly absorbed)
Time it takes for stomach to empty
Amount of food in stomach
ALCOHOL
Distribution
- Alcohol fully and evenly distributed through all body
fluids and tissues - BBB is 90% permeable to alcohol
- Dissolves more readily in water than in fat, thus:
- Readily crosses placental
Fetal Alcohol Spectrum Disorders
- Prenatal exposure to alcohol is associated with a
range of congenital physical and behavioral
abnormalities categorized under the umbrella
term of Fetal Alcohol Spectrum Disorders - likely underestimated idea of how many ppl have FAS due to underreporting
5 drinks for a setting will increase risk
** third leading cause of birth defects - this is the only preventable one
- Distinction between conditions is the number
and/or severity of the symptoms - Symptoms include:
– Facial abnormalities
** check in on FAS facial characteristics - Lip-philtrum guide
FASD video - about child CJ
child CJ born w FAS (low birth weight) - very thin upper lip, sometime you dont see this in older age.
- often smaller eyes, flatter nose
- a reason that FASD must be diagnosed at birth (problem is that mothers might not be honest about alcohol use during pregnancy)
- diagnosis before 8yo gives kids better chance
- gangrene in intestines, multiple severe medical disability)
- adopted kids
- ppl see her as a totally normal kid and expect things of her.. however she feels more gullible (easily manipulated)
- she finds it hard to adapt to new situations
- come challenges w common sense
- alcohol effects fetus more than cocaine or heroin
- biggest impact is on brain, can cause severe cognitive impairments
- causes improper development of brain cells
FAE - older umbrella term for some effects, but not a lightswitch diagnosis (now we call it FASD because its on a spectrum)
- as CJ gets older, look for signs of depression. ppl get really stressed and worries.
FASD video - about mother Janet
- mother was addicted to alcohol since 13, drink during pregnancy
- mother drank during pregnancy to relieve nausea
- child in school was easily distracted, disruptive, lacked work ethic…child had challenges
- recovered from alcohol, around grade 10 worries about FASD
- her doctor doubted that she would be one of the parents that who would drink during pregnancy … she reached out to FAS advocacy group and spoke with Jan
- more difficult to diagnose FAS in adults - we usually stop looking in adults
- for adults, if their IQ is too high, they dont qualify for any support like $, meals, support homes … etc.
- trying to keep kid alive and out of jail …
FASD video mark
- adopted son
- as adult, lots of criminal activity
- big challenges, Mark is super easily influenced
- had 24hr house arrest supervision for 2 years
- 25 yo, but “maturity of 13yo boy”
- has a daughter and is always supervised when theyre together
- emotional plea from Marks dad about disabled people in prison and corrections officers
FASD video - genesis house
- support service, programming for adults with FASD
Burns Lake - FASD video
- fas prevention programming, support for women thru pregnancy
- healthier babies program
- FOCUS program - for adults with FASD to gain job skills, life skills, work on challenges theyve dealt with
- people reflect that FOCUS teachers see potential in them
- *** importance of proactive services - severity of impacts, knowledge that prevention and proactive services are more important
Fetal Alcohol Spectrum Disorders
Symptoms include:
– Facial abnormalities
– Heart defects
– Low intellectual functioning
– Growth retardation
– Learning disabilities
* CDN Prevalence Estimates
– 9 /1000 births FASD
– 1-3/1000 births FAS
FASD Cont’d
* Risk and extent of abnormalities believed to be doserelated
* Type of abnormality believed to be related to timing
of alcohol use
– Feldman et at (2012)
ALCOHOL
Metabolization & Elimination
- 90-98% of alcohol ingested is metabolized is stomach (
and liver (80-85%) before excreted - Excretion can occur thru breath, sweat, tears, urine,
and feces - Metabolization in liver occurs in two steps
- 1
st step: slow step, determined by amount of alcohol
dehydrogenase
process of alcohol elimination
ethanol –> alcohol dehydrogenaze->, 1. acetaldehyde –> (antabuse) aldehyde dehydrogenase
2. acetyl coenzyme a –> energy, citric acid cycle, carbon dioxide, water
** the first step (w/ aldehyde dehydrogenase) is rate limiting, changes how fast alcohol is metabolized
aldehyde dehydrogenase causes hangover nausea
antabuse - trade name for a medication that prevents abuse of substance (can stop ppl w substance use disorder from drinking be interfering w enzymes) - ppl get very sick from drinking when n this med
nutrition on alcohol?
alcohol does NOT have nutritional value, but it does have caloric value
ALCOHOL
Metabolization & Elimination rates of metabolization
ALCOHOL
Metabolization & Elimination
* Rate of metabolization is linear with time (10-20
mg/100 ml of blood per hour)
– 1 to 1.5 hours for
* 30 ml of whiskey (40%)
* 120 ml of wine (11%)
* 360 ml of beer (5%)
* Considerable variability between individuals in
elimination rates
- Non-drinkers metabolize alcohol at slightly lower
rates than light to moderate drinkers
(12-15 mg/100mL)
steady metabolism of alcohol - one drink per hour normally keeps u safe w this
*** only slight increases in likelhood of being intoxicated
Alcohol - MEOS
Metabolization & Elimination
* Microsomal Ethanol Oxidizing System (MEOS)
– Handles approximately 5 to 10% of alcohol
metabolization, but activity will increase with
higher BALs (blood alc levels)
- this system substantially increases action when drinking
- Operation of this system believed to be
responsible for tolerance seen with heavy
drinking
*** can have 30-50% increases - Operation of this system believed to be
responsible for cross tolerance to barbiturates
and benzodiazepines
ALCOHOL
Mechanisms of Action
ALCOHOL
Mechanisms of Action
* Facilitates action at the GABAA
receptor chloride
ionphore complex system
– Binds to an allosteric site
– This affects binding at GABA receptor; opens up Cl- ion channel
*** binds to receptor inside the Cl ion channel
- At high levels, alcohol can directly open up Cl- channel (same as barbiturates)
- Antagonist of glutamate at NMDA receptors
- Impacts production and release of endorphins and
dynorphins; increases release of DA in nucleus
accumbens - Increase activity in mesolimbic dopamine
system/levels of DA in nucleus accumbens thru release
of inhibition
*peripheral vision depressed … due to depression of thalamus, brain step …
action of alcohol on GABAergic neurons (Alpha and Beta)
GABAergic neurons (ALPHA) coming from
Nucleus Accumbens ACTIVATE GABAergic
Interneurons (BETA)
GABAergic Interneurons (BETA) INHIBIT dopaminergic neurons in VTA: This is the normal state
INTRODUCE ALCOHOL
GABAergic neurons coming from Nucleus Accumbens (the ALPHAs) increase release of GABA onto the Inhibitory GABAergic interneurons (BETAs) - which decrease the
BETAs activity
Decreased BETA activity, less inhibition of dopaminergic neurons, more DA released in nucleus accumbens
receptor site activiation determines effects
ALCOHOL
Physiological Effects
- Sleep disturbances
- fall asleep faster, sleep longer
– Induces SWS and depressed REM - effects on RED varies with dosage (REM reduced in first sleep cycle)
- v high doses, theres no REM sleep at all
- Affect on REM varies with dose
- we can dev tolerance to sleep effects
- Depressed Respiration
- w very high doses - bc it effects the pons
- Prevents Seizures
- Vasodilation
- causes flushed faces
- can actually cause loss of body heat and freezing
- Diuretic effect on kidney (decreases vasopressin and antidiuretic hormones)
- has nothing to do with breaking the seal, but when the blood levels start to fall, causes constant urination
- vision / balance problems
- Immunosuppression -
- relief from anxiety
- disinibition
Euphoria
** these 3 are unpredictable!
disrupted memory function - disrupts long term potentiation
- causes issues w attention (then wouldnt remember)
alcohol - blackout
unable to remember effects of being under effects of alcohol
- couldnt remember things youve said or done
- laurie couldnt remember handing out flowers at a party
** does not always mean you LOC
Alcohol Effects and BAL
.01-.02 - Slight changes in feeling
.03-.05 - Overt feelings of relaxation,
happiness, skin may flush
- may have tingling
.05-.06 - More noticeable changes in
emotion, slight increase in RT (respond slower)
- noticeable tingling
- cortex effected first
.08-.09 - Moderate increase in RT, possible
numbness in cheeks, lips,
extremities, impaired judgment
.10 Coordination/balance impaired
- cerebellum effects
.20 - approx 14 drinks - Difficulty staying awake, standing,
walking without assistance; sensory
functions impaired
- usually LOC
.30 Confusion and stupor
.40 Typically unconscious, threshold of
coma
.45-60 Typically deep coma, LD50 in humans
due to circulatory and respiratory
depression
Toxic Effects with Chronic Alcohol Use - Liver
breaks down rather than fat, liver gets compromised
* Liver Disease
– Fatty Liver
– Alcoholic Hepatitis
– Alcoholic Cirrhosis
if stop drinking, fatty liver can be reversed
** BUT alcoholic hepatitis and alcoholic cirrhosis can be permanently broken down and scarred
progression of scar tissues chokes off blood vessels in liver
- not reverible - only treatment is liver transplant
- high death rate
- most deaths in 40-60 yo men
seen w 5 drinks per day / 5 years
do most alcoholics get liver cirrosis?
false, usually get help first
highest rates of heavy drinking age group?
young men 20-24
toxic effects chronic alcohol - cancer and heart probs
- Cardiovascular Problems
– Inflammation of Heart Muscle
– Irregular Heart Contractions
– Fatty accumulation in heart and arteries
– High Blood Pressure - Cancer
– Esophagus, Pharynx, Larynx, Breast - breast cancer, 41% of women who had 2-5 drinks/day
- cancer may be due to immunosuppression effects and carcinogenic effects
- Wernicke-Korsakoff Syndrome
- Wernicke-Korsakoff Syndrome
– Permanent diffuse damage to hippocampus and
cerebral cortex
– Memory problems
– Primarily due to malnutrition, but other factors
may play a role
wernickies encephalopathy - due to efficiency in vitamin B (thiamin)
- can be reveresed w vit therapy
- neuronal death due to vit B deficiency, inability to synthesize glucose. interferes with absorption of vitamin
alcohol will kill off brain cells - can cause irreversible brain damage
Alcohol Tolerance
- Can develop with heavy use re: effects of mood
and behavior - Minimal tolerance re: depressant actions of
respiration - Mechanisms responsible:
– Increased # of Cytochrome P450 enzymes
– Increased activity of alcohol dehydrogenase in
liver and stomach
– Increased activity of MEOS
– Down regulation of GABA receptors
– Upregulation of NMDA receptors
– Behavioral compensation - move more slowly to compensate for loss of coordination
acute tolerance can develop - more pronounced effects when blood alcohol levels are rising
Alcohol dependence
- Psychological and physiological dependency can develop (need to consume lots for months to get physiological dependence)
“hair of the dog” kind of like secondary psychological dependencey
- Withdrawal can be life-threatening
- can have heart failure occur
low depressed mood with withdrawal can cause suicide - hallucinations can cause suicides
- Withdrawal symptoms begin in 6-48 hours
- after stopping consumption
- Two clusters of symptoms
person she worked with - head injury, withdrawal, hallucinations … (due to opiates after injury?)
first cluster - alcohol withdrawal syndrome
- More common cluster
- significant rem sleep
(rem-rebound, agressive sleep_ - Characterized by:
– Insomnia, vivid dreaming
– Tremors, sweating, agitation, n/v, increased hr and bp
could have sroke due to increased BP
- Peak in 24-36 hours, typically over in 48
second withdrawal cluster - delirium tremens
Delirium Tremens
* less common cluster
* More dangerous
- Characterized by:
– Extreme disorientation
– Fever, profuse sweating
– Periods of hallucinations - see small animals, insects
- antipsychotics might be given to deal with
- Fever, sweating can lead to heart failure and
dehydration - Suicide sometimes seen
- agitation and tenseness remains. loss of pleasure
- dsyphoria, low mood
excessive consumption of ancohol can cause death by overstimulation of nerve cells?
FALSE
- nerve cells die by vitamin deficienceies
it is difficult to consume a lethal dose of alcohol
FALSE - its easy ish to do this (17 shots in a row …)
new canadian drinking guidelines?
2 drinks per week
alcohol has no medicinal value?
- some (less that 3) reduces risk of diabetes t2
- prevents blood clotting, prevents stroke
The opiates
THE OPIATES
Definitional Issues
▪ Naturally occurring, derived, and synthetic
compunds with analagesic properites
▪ Often referred to as “narcotic analgesics”
Naturally Occuring Opiates
▪ Morphine, codeine, and
thebaine found in opium
▪ Opium is the sap from
seedpods of opium poppy
(white milky oooze)
▪ Morphine – 10%
▪ Codeine - .75 to 2.5 %
▪ Thebaine - <1%
Opiate Derivatives/Semi-Synthetics
Heroin
- derived from **
▪ Other examples
▪ Hydromorphone (derived from morphine),
Oxycodone (derived from _thebane___,
Oxymorphone (can be derived from codnine)
Hydrocodone can be derived from thebaine
adding acetyle groups makes heroin more lipid soluble and more potent than morphine
