general addiction Flashcards
Basal Ganglia
striatum (putamen, caudate and nucleus accumbens)- movement/reward
substantia nigra (dopaminergic neurons)-movement
globus pallidus (movement)
sub thalamic nucleus (receives input from striatum-movement)
reward system: which are the main pathways
mesolimbic dopamine pathway:
VTA (midbrain structure rich in dopaminergic neurones) and Nucleus nucleus accumbens.
mesocortical dopamine pathway: connects the VTA with the cortex, many connection with frontal cortex
Cannabis (11-hydroxy-delta9THC) receptors
CB1: responsible of psychoactive effects. Are central (striatum, hippocampus and cerebellum, less cortex)
CB2: periferic
cannabis intox:
poor coordination, euphoria, anxiety, slowing of time, social isolation, judgment affected.
red conjunctiva, more appetite, dry mouth, tachycardia.
can also give hypertension, constipation, mydriasis, low libido.
medical indications for cannabis:
chronic pain
anti nausea in chemotherapy
for spasticity in MS
which enzymes are involved in ROH metabolism?
which order of elimination?
ADH: alcool deshydrogenase
ALDH: aldeide desydrogenase (blocked by Disulfiram)
Zero order of elimination
marker for ROH use
most sensitive: CDT (used in research)
GGT (most clinical sensitive)
VGM, uric acid, AST, ALT, LDL, TG, alcool level,
LDH is not a marker.
ROH
which neurotransmitters are involved in ROH intox
which are involved in ROH wd
ROH intox: GABA agonist, NMDA antagonist
ROH wd: glutamate.
criteria for hospital admission ROH detox
Hx of delirium tremens or seizure Hospital: moderate-severe wd Sx comorbid psychiatric Dx or comorbid medical condition pregnant more than 60 yo dangerosity for self others heavy use failure of previous outpatient detox Residential: living conditions focused on substance poor support system poor social skills
what is ROH hallucinosis?
develops during or after ROH intox. not disconnected from reality mainly visual hall, also auditory and tactile paranoid delusions can respond to antipsychotic depression and anxiety (no OCD)
Wernicke encephalopathy triad
ataxia, confusion, ophthalmoplegia
WACO acronym
Wernicke prevention vs treatment
prevention: thiamine B1 100 mg IV/IM for 3 days, then P
treatment: thiamine IM-IV 500 mg TID for 3-5 days
replete thiamine before glucose (thiamine is required for glucose metabolism)
complications of Wernicke
mortality if not treated 15-20%
complete remission 40%
80% develop Korsakoff
Korsakoff syndrome
caused by thiamine depletion
mammillary body affected
it’s a permanent condition in more than 50%
20% remission
symptoms: anterograde amnesia, retrograde amnesia, poor rappel, preserved working memory, confabulation, poor insight, possible hallucinations. ataxia, aphasia, agnosia and impaired executive functioning.
which are the stages on ROH wd
6-8 hrs: tremors, anxiety increased HR, HTN, diaphoresis.
8-12 hrs: visual hallucinations (5X auditory hallucinations). can last 1-3 days
12-24 hrs: seizures usually generalized, no aura, tonic clonic and short post ictal.
24-96 hrs delirium tremens: usually starts 5-14 days after the last drink. Can last up to 5 days. confusion, tremors, agitation, anxiety, hallucinations, delirium, diaphoresis, low grade fever, dehydration, autonomic lability.
complication of ROH DT
20% death is not treated
mortality linked to arhytmia and respiratory failure. other exacerbation are cardiac failure, liver insufficiency
almost impossible before are 19 or in patient without long history of use. Most common age 30-40, after 5-15 years of use.
don’t use antipsychotics, more hyperthermia.
ROH intoxication = sedative intox
stammering speech ataxia, poor coordination can't walk straight nystagmus impaired attention and memory stupor or coma change in behaviour
MDMA intoxication
MDMA (serotoninerigic effect): effects amphetamine and hallucinogen like
high mood, more self confidence, more empathy, increased senses, less appetite, closer to others.
arrhythmia, HTA, lethal hyperthermia, bruxisme.
PCP intoxication
PCP (NMDA antagonist, anti glutamatergic and pro dopaminergic effect). extremely aggressive (don't talk down), hypersensitive to stimuli ataxia nystagmus vertical and horizontal HTN and increased HR muscular rigidity hyperacousis seizure and coma parenthesis and decreased pain
opioids intoxication criteria
myosis, mydriasis in super severe cases secondary to prolonged anoxia
somnolence or coma
stammering speech
impaired attention and memory
opioids withdrawal
3/9 criteria. very uncomfortable but not dangerous. dysphoric mood nausea and vomiting myalgia tearing and rhinorrea diarrhea yawning hypertermia insomnia mydriasis, piloerection /transpiration
opioid withdrawal Sx tx
1st line Suboxone.
2nd line Methadone (first line for pregnancy)
3rd line slow release morphine (Kadian) and naltrexone
full agonist: morphine, other short acting, methadone
partial agonist: buprenorphine/naloxone (Suboxone) partial mu receptor agonist
kappa receptor weak antagonist
full delta receptor agonist
full antagonist: naltrexone
symptomatic Tx includes: clonidine, BZD, Bentyol, Imodium, naproxen, Tylenol, Seroquel etc.
methadone dosing
60 mg DIE usually able to cover for WD Sx however higher dose needed to control cravings.
pregnancy and opioids
avoid withdrawal++
methadone is first line
metabolism is faster in 3rd trimester, requires higher doses
BB will have WD Sx, NICU admission
hallucinogens (LSD and MDMA)
mechanism of actions and intox Sx
effect pro-serotoninergic
mydriasis, tachycardia, transpiration, palpitations, blurry vision, tremors, ataxia, synesthesia and hyperesthesia
can have a long term effect of perceptual disturbances and hallucinations (up to years, not related to number of intox)
cocaine mechanism of action
blocks dopamine recapture from its transporter
stimulant intoxication (cocaine, amphetamines) which are the symptoms
myosis tachycardia or bradicardia HTN or hypotension sweating or shivering nausea vomiting weight loss agitation or psychomotor slowing muscle weakness, respiratory depression arrhythmia, chest pain seizure confusion , dyskinesia, dystonia coma
Classic: persecutory delusions and auditory hallucinations
cocaine medical complications
arrhythmia,
coronary spasm, MI, myocarditis
ischemic CVA, nasal septum ulcers, seizures, respiratory depression.
less dangerous inhaled
more dangerous IV, includes possible Hep C HIV
stimulant withdrawal
9hrs to 4 days: crash (no cravings)
withdrawal: 1-10 weeks cravings
extinction: cravings on and off
dysphoric mood change in psychomotor status insomnia or hypersomnia nightmares increased appetite
caffeine general info
most used substance
substrate of CYP1A2 (same as clozapine, can increase clozapine level)
can decrease Li level bu increasing excretion.
antagonist of adenosine receptors, increases dopaminergic activity
generate cerebral vasoconstriction
1 cup of coffee 95-170 mg caffeine
1 cup of tea= 1/3 of 1 cup of coffee
recommended/safe : max 400 mg DIE for an healthy adult.
caffeine intoxication: criteria
Dose more than 250mg DIE, and 5+ of criteria:
febrile, nervous, excitation, insomnia,incresed HR
nicotine general info
smoking is the first cause of premature death and disability
majority of SUD die of smoking related illness
action via nicotinic ACh receptors widely spread in the brain.
1A2
most smokers are motivated to quit but have trouble going through it.
nicotine withdrawal
irritability restlessness craving
increased appetite
low concentration
vivid dreams
approved nicotine cessation Tx
NRT (patch, lozenges, etc)
Champix (Varenicline 1 mg BID, start with 0.5 DIE) partial agonist of a specific NACh receptor
Bupropion 150 mg BID mechanism unclear (probably related to dopamine), less cravings, cigarette tastes bad. maybe better for pt with depression Hx. CI: eating DO, seizure. Monitor: SI
most effective for smoking cessation
Varenicline Champix > Bupropion=NRT
warning about Varenicline?
Depression and suicidality increase, however not really clear data.
