review for final Flashcards
molecular target for Cocaine
DAT- dopamine plasma membrane transporter
reuptake blockade of dopamine by cocaine correlates with
the ability of the drug to mediate behavioral reward
lesions of DAT expressing dopamine neurons in the midbrain leads to
reduction of cocaine reward
cocaine reward in transgenic DAT vs DAT knockouts
- in transgenic mice the reward is altered
- in knockout the reward is intact due to reuptake of dopamine at the NEPI and 5-HT plasma membrane transporters
target for amphetamine
targets vesicular monoamine storage
neuronal vesicular monoamine transporter is a
ATP- dependent and linked to a vesicular proton pump
amphetamine competes with who for binding free protons in the vesicle?
amphetamine
displaced catecholamines in cytosol leak out via
reverse DAT transport
partially blocks DAT reuptake?
amphetamine
target for opioid
mu opioid receptor
mu receptor is a
seven-transmembrane spanning G protein linked receptor
what happens to mu-receptor knockouts
lose the rewarding actions of morphine
mu receptor activates Gi, Go and Gq proteins, which then activate ___ and ___ channels, adenylyl cyclase in distinct cell types
K and Ca
acute morphine reward, morphine tolerance and morphine dependence are mediated through the same receptors?
Yes
methadone and heroine act on what type of receptors?
Mu opioid receptor
cannabinoids active ingredient?what is it?
receptor primarily in CNS? PNS?
endogenous ligand
- delta-9-tetrahydrocannabinol
- G protein linked
- CB1- CNS
- CB2- PNS
- endogenous ligand: anandamide
target of ehtanol
positive modulator? negative?
withdrawal? what is increased during acute withdrawal
disinhibits dopamine neurons in VTA (euphoric effect)
- positive modulator of GABA receptors
- negative modulators of NMDA receptors
withdrawal upregulates NMDA receptors and in acute there is increased neuronal excitability
SMART
- disruptive thinking about the misused substance is the problem
- I can solve the problem
- tools are learned to deal with situations
- power through knowledge of techniques
12-step program
- misused substancce is a symptom
- I am the problem
- there is a spiritual solution
- power through surrender
4th step inventory
resentment- kills more alcoholics than anything else
- part of the 12 step program
DSM 5
criteria for substance use disorders
Role of the primary provider preventions
- discussion about risk factors
- assessment of pt. begun with use
- prevention/reduction of substance use
screening as a primary provider
avoid sterotypes
- single alcohol screening Q- how many times in the past year have you had 5/4 more drinks in a day
preliminary tx. plan
presentation to pt/family
- determination to change
Treatment/ referral
Level 1, 2, 3 and 4
Level 1. outpatient tx.
Level 2. intensive outpatient program
Level 3. medically monitored program
Level 4. medically managed program
lifetime prevalence of abuse in males vs females?
males: 15%
females: 5%
incidence of abuse in males vs females s
males: 6-8%
females: 2-3%
what is up with the elderly and substance abuse?
prevalence of use decreases but a greater proportion not recognized
what is up with the women and substance abuse?
greater social stigma, poverty, parenting issues may prevent DX/RX
special problems in female alcoholics
- BAC 50% higher compared to men
- greater incidence of hepatic dx.
- greater cerebral atrophy
substance abuse diagnosed in what % in primary care clinic
- hospital estimates
2-4; at least 94% are misdiagnosed
- hospital estimates 30-70%
ABC’ of poisoned pt.
- Airway- most common cause of death
- Breathing
- Circulation/Cessation/C-spine
- Decontamination
- Diagnostics
- Enhanced elimination
- Specific antidotes
decontamination and types
reduce absorption from body surface
- dermal
- gastric
- cathartics
- whole bowl irrigation
is lab evaluation more important than history and toxidrome?
NOOOOOO
chem 7, CBC, APAP, ASA
suicide panel
opioids, benzo, cocaine, amphetamine, THC, PCP, +/- TCA
urine tox screen– not very helpful
APAP, theophylline, CO, ASA, DIG, PHenobarb, ETOH, Phenytoin, Iron, Lithium
quantitative levels limited
symptoms of opiate/narcotic toxidrome
coma, respiratory depression
signs of an opioid overdose and what to do
signs: miosis, respiratory depression and coma
supportive tx.: ventilations, fluids and Naloxone
symptoms of sympathomimetic toxidrome
hypertension tachycardia increased temp dilated pupils anxiety
blood alcohol concentration
- 20-50
- 50-100
- 100-150
- 150- 250
- 300
- 400
- 600
- 20-50: exhilaration, loss of inhibition
- 50-100: impaired judment/coordination
- 100-150: difficulty with gait/balance
- 150- 250: lethargy and difficulty sitting upright
- 300: coma
- 400: respiratory depression
- 600: death
alcoholism type I
late onset
- male/female
- after 25
- abstain is infrequent
- personality is anxious, depressed and passive-depend
- 2/3: functional/intermediate
alcoholism type II
early onset
- males
- before 25
- abstain frequent
- personality: antisocial, conduct dis., impulsive
- 4/5: anti-social, severe/chronic
neurobiological susceptibility to alcoholism:
- temperamental deviations
- pre-existing ____ deficits in type II alcoholics
- _____ receptor gene mutation
- ________ plasma Beta-endorphines
- temperamental deviations: prefrontal-midbrain neuroaxis
- pre-existing serotonin deficits in type II alcoholics
- D2-dopamine receptor gene mutation
- lower baseline plasma Beta-endorph
CDT is a diagnostic test that is
most sensitive indicator of relapse
stages of change
- pre-contemplation
- contemplation
- preparation
- action
- maintenance
pre-contemplation
feedback
contemplation
ambivalence
preparation
menu
action
choose
maintenance
relapse prevention
drug of choice for treating withdrawal
Benzo
Benzo
GABA receptor
long actin benzo
clordiazepoxide
diazepam
short acting benzo
lorazepam
meds in long tx. of managment of alcoholism
- disulfram
- naltrexone
benzo have a role in the primary tx. of alcoholism
nope
pyrazole inhibits
alcohol DH
disulfram inhibits
aldehyde DH
cigarette smoking among adults
people with less education, lower income, psych illness or other substance abuse are more likely to smoke
are there withdrawal symptoms for nicotine?
yep
craving, impatience, insomnia, anxiety, increased appetite
tx. with evidence of efficacy for smoking
- behavioral counseling
- pharmacotherapy
- combination
pharm tx. for smoking
- nicotine replacement
- bupropion
- varenicline
- each at least doubles quit rate vs placebo
addictive nature of a drug is in part a function of how fast it works and how fast it wears off
yep
physician intervention for smoking
routine advice very effective
brief counseling is more effect
- ask
- advise
- assess
- assist
- arrange
positive effects of cocaine
- euphoria
- decreased sleep
- decreased appetite
- sexual stimulation
- garrulousness
negative effects of cocaine
- irritability
- anxiety
- restlessness
- paranoia
cocain-induced paranoia
- occurs in about 2/3 of heavy users
- not necessarily dose-related, but there may be kindling effect
time course of cocaine effects
smoking has the fastest onset while intranasal takes the most
local complications of cocaine
- irritation/ulcers of nasal mucosa
- rhinorrhea
- nasal septal perforation
cardiovascular complications of cocaine
- MI
- ventricular dysrhythmias
- cardiomyopathy
- endocarditis
neurological complications of cocaine
- hemorrhagic stroke
- ischemic stroke
- grand mal seizures s
gender difference in intranasal cocaine response
males:
- higher peak plasma cocaine levels
- detected cocaine effects faster
- experienced more episodes of euphoria
- hear rate paralleled plasma levels
females:
- earlier onset
- more rapid development of dependence
- slower recovery
cocaine metabolism:
metabolized by?
metabolite?
present in urine for _____ hr and half-life of cocaine is ________ minutes
metabolized by plasma cholinesterases
metabolite is benzoylecgonine which is inactive
present in urine for 48 hr and half-life of cocaine is 40-60 minutes
tx. for cocaine dependce
- behavioral tx.
- cognitive-behavioral relapse prevention
- disease model 12 step counseling
anti-drug abuse act of 1986
- 5 yrs w/out parole for 5gm of crack/500 gms powder cocaine
- racial disparity
fair sentencing act of 2010
- 28gm crack
Gateway theory
age of initiation:
- early: tobacco
- middle: marijuana
- late: narcotics
- non-sepcific: cocaine
marijuana 4 basic clinical effects
- stimulation: increases BP, P, RR, appetite
- sedation
- anesthesia
- Hallucinogen
amphetamine is a
hallucinogen
methamphetamine leads to ____ discharge which leads to hyperthermia, sweating, tachycardia and hypertension. it also releases _____ leading to euphoria
sympathetic
- releases serotonin
methamphetamine effect leads to
- meth mouth
- crank bugs
- burns
opium is derived from _____. natural alkaloids include
derived from poppy flower
- natural alk.- morphine and codeine
semi-synthetics are derivatives of
morphine
synthetics include
methadone
pharm. management of withdrawal:
- full agonist
- partial agonist/antagonist
- suppress nE release
- antagonist precip. of withdrawal
= additional agents of Symptom relief
- full agonist: methadone
- partial agonist/antagonist: naloxene
- suppress nE release: clonidine
- antagonist precip. of withdrawal: naltrexone
- additional agents of Symptom relief : Benzo
iatrogenic misinterpretation of relief-seeking behaviors caused by undertreatment of pain that is identified by the clinician as inappropriate drug-seeking behavior
pseudoaddiction
less predictive drug-related behavior
Rx from multiple MDs
stimulants like amphetamine block
transporters
physical exam:
- vital signs have added one new criteria
determining pain
stages of change:
feedback
pre-contemplation
stages of change:
psychotherapy to deal with ambivalence
contemplation
stages of change:
menu of treatment options
preparation
stages of change:
let patient choose
action
stages of change:
relapse prevention
maintenance
number one drug involved in U.S. overdose death
fentanyl
controlled use of opioids should lie between sedation and pain
analgesia
informed consent is needed in ongoing persistent pain treatment
yep
