Pharm Substance Abuse

Front 1

Among which group is use of Rx drugs increasing?

Back 1

increasing rates among drinkers and recreational drug users

Front 2

What are the most commonly used Rx psychoactive drugs?

Back 2

opioids, tranquilizers, stimulants

Front 3

What's the definition of physiological dependence?

Back 3

evidence of tolerance or withdrawal

Front 4

what's the definition of psychological dependence?

Back 4

evidence of a persistent or repeated compulsion to use despite seemingly adverse consequences

Front 5

what's substance abuse?

Back 5

maladaptive pattern of substance use that causes significant impairment (social or occupational) or physical hazard (driving while intoxicated

Front 6

what's substance dependence?

Back 6

same as abuse plus uncontrolled use and tolerance and/or withdrawal Sx.

Front 7

What's sensitization?

Back 7

some substances (psychostimulants) may produce a progressive enhancement of motor or other responses

Front 8

what's the evidence that substance abuse causes persistent changes in brain structure and fxn?

Back 8

enduring nature of Sx
vulnerabilitity of repeated relapse, even in the absence of continued use
these changes give rise to maladaptive behavior patterns

Front 9

what's the criteria for substance abuse?

Back 9

w/o dependence (or history of) and includes one or more:
failure to fulfill major oblig
use in hazardous situations
legal problems
use despite problems

Front 10

criteria for substance dependence?

Back 10

maladaptive pattern, includes 3 or more in same 12 month period:
tolerance/withdrawal
more use than intended
unsuccessful attempt to cut down
reduced other activities
great deal of time spent on drug use
cont'd use despite adverse consequences

Front 11

What does NAc stimulation cause?

Back 11

induces craving (wanting or seeking) rather than "rush" or euphoria

Front 12

Is DA the only trigger for drug related behaviors?

Back 12

No, activation of Glu pathways and NAc AMPA receptors also may trigger

Front 13

Which areas of the brain do conditioned drug cues stimulate?

Back 13

amygdala
prefrontal limbic cortical regions

Front 14

What provides glut input to NAc?

Back 14

amygdala
prefrontal limbic cortical regions

Front 15

A lesion in the amygdala prevents what?

Back 15

association of stimuli w/ reinforcement value.

Front 16

what does the orbital and medial prefrontal cortex have to do with drug behavior?

Back 16

they recieve mesocortical DA input and process motivational cues (determine goal directed behavior) in response to food or addictive stimuli too.

Front 17

What does the NAc integrate?

Back 17

emotional nature and the intended direction with the contextual condition (via glu input)
amplified by appropriate motivation (via DA) to act on different specific NAc pathways

Front 18

What does the hippocampus and ventral subiculum do?

Back 18

provide contextual background which conditioned reinforcement depends on

Front 19

what do DAergic pathways encode?

Back 19

motivational value or "incentive salience"

Front 20

what is the reverberatory circuit that can be considered the neuroadaptive core of dependence?

Where is the integration center?

Back 20

the cortico-striato-pallido-thalamo-cortical loop.

The NAc may be the integration center in this forebrain addiction circuit?

Front 21

What biological factors influence whether addiction will develop w/ the 1st exposure?

Back 21

1) intrinsic state and effect of the substance
2) magnitude of reward circuit response
3) degree of neural adaptation as consequence

Front 22

what is acamprosate?

Back 22

a taurine derivative
modulates glu hyperactivity and drug craving during alcohol abstinence (b/c of NMDA R sensitivity during withdrawal)

may inhibit neural plasticity necess for the learning of new behaviors and appropriate responses

Front 23

what's the main mechanism of action for the following:
1. opiates
2. cocaine
3. amphetamine
4. alcohol
5. marijuana
6. nicotine
7. hallucinogens
8 PCP

Back 23

Action:
1. agonist at mu opiod R's
2. inhibit MA, DA, 5-HT reuptake
3. stim MA, 5-HT trans and blk reuptake
4. activate GABAa and mu R inhibit NMDA R's
5. agonist at cannaboid GB4 R
6. agonist ACh nicotinic R
7. partial agon at cortical 5-HT2a R's
8. antag at cortical glu NMDA

Front 24

how much does genetics contribute to addiction?

Back 24

30-60% of variablility of expression of addiction

multiple genetic variants work in concert to affect vulnerability and severity of addiction

Front 25

What % of the population drinks?

How many are alcoholics?

Back 25

50% over 18 consume alcohol but 5-10% account for 1/2 the consumption

12-18 million alcoholics and problem drinkers in the US

Front 26

How many people smoke in the US?

How many use Cocaine?

Opiates?

Back 26

60 million smokers in US (29%)

2-3.5 million americans dependent on cocaine

~1 million heroin dependent and 2-4 mill depend on Rx opoids

Front 27

what are the health effects of drug addiction?

Back 27

infections (hepatitis/HIV for heroin, cocaine, etc)

GI pain/bleeding, ulcers (EtOH)

brain, periph neural damage, dementia (alcohol, stim)

CV, stroke, MI (stim)

Front 28

what are the annual death rates for tobacco, alcohol and drugs/AIDS?

Back 28

tobacco - 400,000
alcohol - 100,000
drugs/AIDS - 25,000

Front 29

What are some 6 treatment models?

Back 29

1. advice model and Brief intervention
2. Self-help model
3. cognitive-behavioral-motivation
4. biolog-pharmacol model
5. social models
6. dual-diag interventions

Front 30

what's detox?

Back 30

short term, pharmacol tx for substance dependence

goal=prevent rebound fx of withdrawal (can be fatal)

Front 31

what are the tx outcomes for substance abuse disorders?

Back 31

variable depending on the population

dual dx pts worse prognosis than psychiatric condition

physician monitoring shown to be very effective (e.g CAGE)

Front 32

what's a rational-empirical approach to prevention?

Back 32

disseminate facts and people will do what's in their own best interest (e.g. surgeon general's warning on smoking)

Front 33

what's normative reductive strategy for demand reduction?

Back 33

promote social norms around abstinence or responsible use (peer counseling, media)

Front 34

what's the power coercive approach to demand reduction

Back 34

enact laws to prohibit/limit certain drug use (limit distribution, increase taxes)

Front 35

How does acamprosate help prevent alcohol relapse?

Back 35

alcohol inhibits glutamate transmission leading to upregulation of the NMDA receptor. Acamprosate might work by maintaining the NMDA inhibition during periods when the subject is not intoxicated.

Front 36

what are the average blood concentrations of alcohol after a drink?

Back 36

One drink is about 14-16 g of alcohol: gives a concentration of 30 mg/dl (30 mg%)

This corresponds to about 6.5 mM.

Legal intoxication is set at 17 mM which is 80 mg/dl.

Front 37

what's the lifetime prevalence of addiction? Is it common?

Back 37

lifetime prevalence nearly 15%

Front 38

What are some general concepts about addiction?

Back 38

common
chronic and relapsing condition
complex w/ multiple causes (psycho/bio/genetic contributors)
Addiction is treatable

Front 39

what's the continuum of drug use?

Back 39

initiation/intoxication
harmful use/abuse
dependence/withdrawal
relapse/craving
recovery, persisting deficits

Front 40

what's substance intoxication?

Back 40

reversible substance-specific syndrome due to recent substance exposure/ingestion

clinical changes due to the effect of the substance on the CNS during/shortly after use

Front 41

what's tolerance?

Back 41

either:
a. need for markedly increased amounts to achieve same effect

b. markedly diminished effect w/ cont'd use of same amount

Front 42

what's withdrawal?

Back 42

either:
a. develop specific syndrome due to cessation or reduction after prolonged heavy use

b. syndrome causes clinical distress or impairment

Front 43

where are the DA pathways in addiction?

Back 43

from substantia nigra and ventral tegmental area to

NAc, prefrontal cx, cingulate gyrus, and striatum

Front 44

how much do natural rewards like food and sex elevate DA levels in the NAc?

How about drugs?

Back 44

food--150% baseline levels
sex--200%

Amphetamine=1050%
Cocaine=340%
Nicotine=225%
Morphine=200% Sustained

Front 45

1. With addiction, what brain area causes goal directed activity/ insight?

2. Cue and contextual conditioning?

3. Reward/reinforcement/ relapse

Back 45

1. Prefrontal Cx

2. Hippocampus

3. NAc

Front 46

1. Which brain area is most responsible for Action?

2. Motivation/salience of drugs

3. emotional and stress fx

Back 46

1. VP--input from NAc, projects to MD thalamus

2. VTA

3. amygdala - input from VTA, projects to NAc (w/ Glu)

Front 47

what are the factors predisposing to relapse?

Back 47

physiological withdrawal > cue reactivity

time of abstinence is directly proportional to decreased risk of relapse

Front 48

what's the major cell type of both NAc and dorsal striatum?

Back 48

the medium spiny neuron

Front 49

what does the medium spiny neuron do?

Back 49

DA-glutamate interxns in the striatum

it is characterized by dendritic spines which serve its fxn of integration:
glu afferents from cerebral cx
DA afferents from VTA and SN

these come together at spines in NAc and dorsal striatum to integrate motivational info

Front 50

what drugs cause an increase of AMPA/NMDA ratio compared with baseline?

Back 50

all drugs of abuse

reflects an increase in basal excitatory synaptic strength

Front 51

how is delta-FosB (a transcription factor) implicated in long term drug abuse?

How does it act?

Back 51

it's selectively induced.

delta-FosB binds regulatory regions (AP-1 sites) in target genes

the AMPA R (GluR2) is an example of a gene regulated by its overexpression

Front 52

what are the principles of detox?

Back 52

medical discontinuation of use of addictive substance and physio/mental readjustment
-oral medication
-long duration of action
-clear target Sx/signs

Front 53

how can you maximize motivation for abstinence?

Back 53

-psychoeducation w/ pt and fam

-motivational enhancement therapy

-Cog behavior Tx

-Self Help groups (AA, NA)

Front 54

How is relapse prevented?

Back 54

avoid high risk situation
anticipate minor relapse
recover from relapses
id triggers
alternative coping strategies

Front 55

What are some drugs to reverse OD?

Back 55

flumazenil

naloxone

Front 56

What are some drugs for detox?

Back 56

chlordiazepoxide

methadone

Front 57

What are some pharmacological ways to prevent relapse?

Back 57

substitution (methadone)

blockade (naltrexone for opioid)

aversion (disulfiram)

anti-craving (naltrexone/acamprosate)

Front 58

how are benzos used for EtOH detox?

Back 58

titrate dose to Sx (chlordiazepoxide)

peak Sx at day 3 (last 7 d)

oxazepam in older or liver impaired alcoholics

can supplement w/ adrenergic blockers

Front 59

How does methadone maintenance for opioids work?

Back 59

mu opioid agonist

significantly improves tx retention and decreased relapse

x-tolerance to opioids

start at 30 mg, increase to over 70 mg po q 1/day

duration: 1-20 years

Front 60

How is buprenorphine used to prevent opioid relapse?

Back 60

partial opioid agonist, x-tolerance

can be combined w/ naloxone

comparable to methadone tx

lower OD potential and liability

less severe withdrawal than methadone

can be prescribed in office

Front 61

What is used for nicotine detox and relapse prevention?

Back 61

nicotine gum/patch/aerosol

bupropion

varenicline

Front 62

Risks of naltrexone in alcoholism

Back 62

6-10% initial dropout due to S/E (vomiting, nausea, anxiety)

lack of efficacy in severe alcohol dependence

Front 63

benefits of naltrexone in alcoholism?

Back 63

~50% reduction in relapse risk

improved rating of employment problems

relapse prevention > than 6 mo after discontinuation

more abstinence at end-point and follow up

Front 64

How is acamprosate useful in EtOH relapse prevention?

Back 64

helps maintain abstinence after detox

blocks craving

modulates Glu NT system

well tolerated, few S/E's

Front 65

24 yo college student smokes a drug. feels euphoria and power
collapses several mins later and has grand mal seizure
at ED: pulseless and apneic, v fib.

Back 65

most likely crack or meth (free base)

blk reuptake of MA (DA, NE, 5-HT)

severe S/Es: arrhyth, myo ischemia (stim β noradrenergicin heart and α in vasc)

Front 66

what system plays a crucial role in reinforcing the effects of psychostimulants?

Back 66

mesolimbic DA systerm (project from VTA to NAc)

X-dependence w/ psychostims (amphetamines, morphine, heroin,opioids, cocaine)

Front 67

what's the withdrawal to psychostimulants?

Back 67

relatively mild (vs opiate):
dysphoria
fatigue
unpleasant dreams
insomnia
incr apetite
psychomotor agitation
bradycardia
DRUG CRAVING (most salient feauture)

Front 68

who uses psychostimulants?

Back 68

all social classes
(similar rate among physicians as general pop)
cocaine use 2:1 (m:f) (1:1 for crack)

Front 69

relapse rate among detoxed psychostim users?

Back 69

HIGH,no effective pharmacological tx

current tx's:
antidepressants (desipramine, fluoxetine)
DA agonists, reuptake blkers (bromocriptine, mazindol)
mixed opioid ag-antag (buprenorphine)
anticonvulsant (carbamazepine)
AA for alcoholics

Front 70

29 yo medical resident w/ access to drugs. began injecting w/ incr freq to relax (self medicate for problems w/ sleeplessness and anxiety)
fxned well at work, sometimes sluggish/inappropriate
drank some EtOH-marked intox
withdrawal: marked insomnia, anxiety, fatigue

Back 70

Benzo (vallium, librium)
tx for anxiety
sedation at higher dose
act at GABAa (but not GABAb) R's-bind directly to specific site on GABAa R/ion ch complex distinct from GABA binding site
incr GABAa mediated Cl- conductance
x-depend w/ benzos, barbs, EtOH

Front 71

benzo OD

Back 71

very safe drugs but OD can be lethal w/ EtOH

Front 72

side effects w/ benzos?

Back 72

initial drowsiness but tolerance w/ use

Front 73

benzo withdrawal

Back 73

anxiety, agitation, paresthesias, muscle cramps, myoclonic jerks, sleep disturbance and dizziness
long-term use - more severe sx: seizures and delirium.

Front 74

who uses benzos

Back 74

roughly the same among physicians (most common type of drug abuse) and gen pop

abuse usually starts w/ a physician's prescription

Front 75

how should a pt be detoxed from benzo?

Back 75

slow withdrawal effective (may take months depending on length of use)
can use non-benzo anxiolyitic (buspirone) or long acting benzo (diazepam)

many pts on low dose for yrs have few/no withdrawal sx

Front 76

opiate withdrawal

Back 76

heroine/morphine:
protracted withdrawal (5-10 d), intense

Sx: intense craving, restlessness, irritability, sens to pain, nausea, cramps, muscle aches, dysphoria, insom, anxiety, pupil dilation, sweating, piloerection, tachycardia, vomit, diarr, incr BP, yawn, fever.
Methadone-slower onset and lasts longer.

Front 77

how do morphine and heroin work?

Back 77

µ opioid R agonists

heroin: prodrug (conv to morph), rapid onset, more lipid sol (x's BBB faster), deacetylated in brain to morph
stim VTA µ R's--euphoria, causes DA firing in NAc (reinforcing fx's)

Front 78

S/E's of opiates

Back 78

miosis (excite Para nerve of pupil)
resp depression (direct fx on the BS resp centers--death from OD nearly always due to resp arrest)
nausea,vomit-stim of area postrema-medulla, CTZ for emesis;
release pit H's inhib in response to the stimulation of opiate R's in hypothal
constipation-decr peristalsis
at high doses-convulsions from inhib of GABAergic neur of CNS
depress cough reflex

Front 79

sx of alcohol withdrawal

Back 79

delirium tremens
impaired liver fxn (chronic alcoholism)

Front 80

mech of alcohol intox?

Back 80

enhance transm through GABAa R's
excit and inhib Nic R's
inhib NMDA and kainate R's

ataxia, sedation by incr inhib trans (GABA) and decr excit trans (N ACh, NMDA, kainate glu R's)

x toler to other sedatives (benzos)

Front 81

toxicity of EtOH

Back 81

many organs:
liver dz
CV dz
endocrine/GI fx
CNS dysfxn (depression, cognitive decline, memory impair)
X's placenta (FAS--MR)

Front 82

EtOH withdrawal

Back 82

craving, tremor, irritable, nausea, insomnia, tachycard, hypertxn, sweating, perceptual distortions, seizures and DTs.

Sx of DT's: agitation, confusion, hallucinations, fever, sweating, tachycardia, nausea, diarrhea, dilated pupils.
DT's rare w/o other complications like infection, trauma, malnut or electrolyte imbal

Front 83

who uses alcohol

Back 83

70% of American adults occasionally consume
lifetime prevalence of alcoholism is 5-10% for men and 3-5% for women
among physicians is similar to the general public

Front 84

what should be done for EtOH withdrawal?

Back 84

hydration, electrolytes and vitamins (especially thiamine).
Short-acting benzos to diminish EtOH withdrawal sx
Long-acting benzos: use cautiously b/c of potential liver dz

Front 85

what can be done to treat alcoholism after detox?

Back 85

AA for motivated alcoholics
disulfiram (if pt willing)
naltrexone (blks reinforcing fx, lower relapse)
acamprosate (lower relapse)

Front 86

MDMA intoxication sx

Back 86

altered mental status, tachycardia, tachypnea, sweating, dry mouth, clench jaw, hypertherm

severe: rhabdomyolysis, acute renal fail, card collapse, malig hypertherm, hepatic fail, water tox

Front 87

pharmacology of MDMA

Back 87

similar to other psychostims but greater affin for 5-HT and DA transporters

incr extracell DA in NAc

x-depend w/ psychostims and opiates

Front 88

S/Es of MDMA

Back 88

due to NE release in PNS:
tachycard, incr BP, mydriasis, tremor, palpitation, diaphoresis
salivation, bruxism(teeth grind), trismus (lock jaw) (latter 2 fx due to 5-HT on CNV)

Front 89

effect of MDMA on the liver?

Back 89

toxic: metab by CYP2D6 (approx 5% of pop deficient--predispose to hypertherm and liver tox)

Front 90

fx of MDMA:

Back 90

elevates mood, positive view of self, decr sleep, "love drug"
visual perceptual distortions

Front 91

withdrawal of MDMA?

Back 91

unknown,
long actin--hangover effect (fatigue, drowsy, musc ache, difficulty conc, irritable)

Front 92

effects of MDMA on Serotonergic neurons in animals?

Back 92

degeneration of serotonergic neurons after repeat exposure

still debated fx of neurotoxicity in humans.