Addiction Medicine - BMed Exam 2

Addiction

chronic disease of the brain's reward system characterized by drug-seeking behavior despite its negative consequences

Dependence

inability to function normally without a drug

Tolerance

reduced response to a drug with repeated use

cross-tolerance

-occurs when there is a reduced response to a similar drug with repeated use

-ex: alcohol and benzos

Intoxication

temporary physical and mental changes caused by drug use

withdrawal

temporary physical and mental changes caused by reduced drug use

Substance Use Disorder

defined by DSM as 2 or more of the following 10 criteria

-tolerance (discludes prescribed)

-withdrawal (discludes prescribed

-use of more or for a longer period than intended

-unable to cut back

-forced to give up activities

-craving

-unfulfilled obligations

-unable to complete activities

-dangerous situations

-medical problems

Neurotransmitters

-chemical messengers made by neurons that transmit signals from one neuron to the next

-located in the CNS and PNS

CNS

NT activity in the ________ is largely responsible for the addictive qualities of these substances

PNS

NT activity in the ________ is largely responsible for many of the side effects associated with these substances

CNS depression NT

-adenosine

-GABA

-Mu

CNS Stimulation NT

-glutamate

-acetylcholine

-norepinephrine

-dopamine

adenosine

Caffeine NT, works in antagonism

GABA

-Alcohol, benzo NT

Mu

opioids CNS depression NT

Glutamate

-PCP (antagonism)

-ketamine (antagonism)

acetylcholine

-nicotine NT

NE and dopamine

NTs that works with caffeine, nicotine, cocaine, methamphetamines

Dopamine

-the reward center of the brain is the nucleus accumbens

-dopamine is the NT involved in stimulation of the reward center

-almost all drugs that cause physical addiction affect the brain's reward center

ventral tegmental area

dopamine is produced by the ______________, a cluster of neurons in the midbrain

mesolimbic pathway

the VTA is connected to a pathway of neurons called the what?

nucleus accumbens

the mesolimbic pathway connects to neurons in the what?

reward center

CNS depression and stimulation NT are involved in the stimulation of what?

alcohol, opioids, benzos

what are examples of CNS depressants?

Alcohol

-broad class of chemicals

-1 standard drink is = 0.6 oz

-percentage of alcohol is typically listed on beer and wine containers

-percentage is listed as "proof" on various spirits

Alcohol MOA

-GABA agonist --> CNS depression

-ADH inhibition --> increased urination, dry mouth

liver

alcohol is mostly metabolized where?

blood, breath, sweat, and urine

what body secretions are used to test for alcohol?

zero-order

alcohol is a ___________ metabolizer, meaning a constant amount is eliminated per unit of time independent of BAC

0.03%

roughly _________ BAC is metabolized per hour

Alcohol Intox S/S

-common amongst CNS depressants: slurred speech, disinhibition, poor coordination, memory impairment, irregular breathing, bradycardia, pupil constriction

-unique to alcohol: dehydration (ADH inhibition)

Alcohol Withdrawal Timing

-rapid onset (within hours)

-peaks around days 2-4

-resolves around days 5-7

Alcohol Withdrawal Sx

-common amongst CNS depressants: irritability, diaphoresis, tachycardia, HTN, pupil dilation

-Unique to alcohol: seizure, death, delirium tremens

seizure and death

abrupt cessation of alcohol can result in what?

delerium tremens

-occurs around days 2-3

-lasts around 3-5 days

-consists of confusion, hallucinations (visual and tactile), and marked tremor

Alcohol Intox Tx

-IV fluids for dehydration

-ventilation if respiratory compromise

Alcohol Withdrawal Tx

-long-acting benzo and vit B supplementation

-thiamine (B1) prevents Wernicke's Encephalopathy

-Folate (B6) helps resolve blood cell ANL

Alcohol remission tx

-naltrexone and/or acamprosate and vitamin B supplementation

Naltrexone

-mu antagonist, may alter reward associated w/ drinking

-pros: most effective agent, available as once monthly injection

-cons: CI w/ comorbid opioid use and comorbid liver dysfunction

Acamprosate

-may restore GABA-glutamate imbalance

-pros: may use in patients who use opioids and in patients w/ liver dysfunction

-cons: less effective agent, TID dosing, CI w/ comorbid kidney dysfunction

Alcohol Scales

-CAGE screening

-MAST screening

-CIWA withdrawal screening

Alcohol Labs

-any LFT elevation

-AST to ALT ratio of greater than 2:1

-GGT elevation

-MCV greater than 100 (macrocytosis)

Blood Alcohol Content

-most commonly measured via blood or breath

-illegal to drive w/ BAC >0.08% or higher

-a BAC of 0.4% or higher may cause CNS depression, coma, and/or death

-tolerance does not affect BAC

one

CDC recommends no more than ______ drink daily for women

two

CDC recommends no more than ______ drinks daily for men

codeine, morphine

what are examples of natural opiates?

semi-synthetic opioids

-hydrocodone

-oxycodone

-hydromorphone

-heroin

-buprenoprhine

fully synthetic opioids

-tramadol

-fentanyl

-methadone

Opioids

-Mu receptor antagonism

-CNS depression, analgesia, decreased GI motility

-metabolized by the liver, remainder is excreted in urine

opioid intox s/s

-common amongst CNS depressants: euphoria, slurred speech, poor coordination, memory impairment, irregular breathing, bradycardia, pupil constriction

-unique to opioids: rapid-onset overdose

Opioids Withdrawal - Timing

-begins around 1-2 days after discontinuation

-peaks around 3-5 days after discontinuation

-resolves around 1-2 weeks after discontinuation

Opioids Withdrawal - Sx

-common amongst CNS depressants: irritability, diaphoresis, tachycardia, HTN, pupil dilation

-unique to opioids: yawning, rhinorrhea, piloerection, upset GI, bone/muscle aches

Opioids Intox - Tx

-supportive care

-overdose --> naloxone nasal spray

Opioid withdrawal - tx

-clonidine for HTN and tachycardia

-ondansetron for nausea

-loperamide for diarrhea

-hydroxyzine for anxiety

-ibuprofen for pain

Opioid Remission - Tx

-naltrexone

-buprenorphine

-methadone

Naltrexone - Opioids

-mu antagonist

-Pros: non-scheduled non-opioid, no risk of physical dependence, qm available, office use

-Cons: may precipitate withdrawal (must wait 7 days), less effective than opioid options

Buprenorphine

-mu partial agonist

-Pros: more effective than non-opioid options, no significant risk of respiratory depression, analgesia, office use

-Cons: scheduled opioid, physical dependence, may precipitate withdrawal (wait 1 day)

Methadone

-mu agonist

-pros: more effective than non-opioid options, analgesia, will not precipitate withdrawal

-cons: scheduled opioid, physical dependence, significant risk of respiratory depression, monitoring (LFTs, QTc)

alprazolam

what is the most commonly misused benzo?

Benzodiazepines

-GABA agonism --> CNS depression

-metabolized by the liver

-metabolism rate varies significantly between specific drugs

Benzo Intox

-euphoria, slurred speech, disinhibition, memory impairment, irregular breathing, bradycardia, pupil constriction

-amnesia

-overdose (lethal is rare)

Flunitrazepam

-the date rape drug brand named Rohypnol and commonly referred to as "roofies"

-causes amnesia

Benzo Withdrawal Timing

-varies significantly based upon dose, duration of use, and drug

-withdrawal onset and resolution may be significantly prolonged with long-acting benzos

Benzo Withdrawal Sx

-irritability, diaphoresis, tachycardia, HTN, pupil dilation, upset GI, insomnia

-abrupt cessation may result in seizure and death (can occur at any time during withdrawal)

-psychosis (can occur at any time during withdrawal)

Benzo Intox Tx

-supportive care

-overdose: IV flumazenil

IV flumazenil

-GABA antagonist with onset of less than 5 minutes and duration of around 1 hour

-benzo overdose tx

IV benzos

what do you treat benzo withdrawals with?

Benzo Remission Tx

-oral benzos

-slow titration with a long-acting benzo (decreasing by 10% each month)

Caffeine

-adenosine antagonist --> CNS and PNS stimulation

-tachycardia and vasoconstriction

-onset within 1 hr, peaks around 1-2 hr, half-life around 4-6 hr

Caffeine Intox S/S

-irritability, diaphoresis, tachycardia, HTN, pupil dilation, upset GI (n/v)

-unique to caffeine: seizure and death only w/ excessive intake (around 10 g)

CNS stimulants

-caffeine

-nicotine

-cocaine

-amphetamines

-ecstasy

Caffeine Withdrawal - Timing

-begins around 1-2 days after discontinuation

-peaks around 3-5 days after discontinuation

-resolves around 1-2 weeks after discontinuation

Caffeine withdrawal sx

-irritability, headache, fatigue, depression, poor mental clarity

-not really any specific for caffeine

self-guided taper

what is the treatment for caffeine overuse?

caffeine dosages

400 mg daily appears to be safe

Caffeine - Potential Benefits

-associated w/ lower risk of Alzheimer disease, Parkinson disease, diabetes, cirrhosis, and strokes

-FDA approved tx for headaches

Caffeine Misinformation

-no significant effect of moderate intake on CV system

-no significant association w/ cancer risk

-does not cause dehydration; mild diuretic

Nicotine

-central: nicotinic acetylcholine receptor agonism --> CNS stimulation

-PNS: adrenal medulla stimulation --> secretion of epi and NE --> tachycardia, vasoconstriction

Nicotine intox Sx

-irritability, diaphoresis, tachycardia, HTN, pupil dilation, upset GI

-unique: pallor, dizziness, muscle fasciculations, cholinergic toxicity

Cholinergic Toxicity

-SLUDGE: salivation, lacrimation, urination, dehydration, GI upset, emesis

Nicotine Withdrawal Timing

-rapid onset (within hrs)

-delayed resolution (1-2 months)

Nicotine withdrawal sx

irritability, HA, fatigue, depression, poor mental clarity

Nicotine Intox Tx

-supportive care, anticholinergic meds

IV atropine, inhaled ipratropium

what are the two anticholinergic meds used in treatment of nicotine intoxication?

nicotine replacement therapy

what is the treatment for nicotine withdrawal?

Nicotine Remission Tx

-nicotine replacement therapy

-varenicline

-bupropion

Nicotine gum, lozenges, patches

-nicotine agonist

-pros: various forms, well-tolerated

-cons: risk of dependence

varenicline

-nicotinic partial agonist

-pros: most effective option, no risk of dependence

-cons: side effects relatively common

Bupropion

-NE and dopamine reuptake inhibition

-Pros: no risk of dependence

-Cons: less effective than varenicline

Vaping

-components: battery, atomizer, cartridge, liquid, coil, cotton

-EVALI --> contamination w/ vitamin E acetate

-Risks: heavy metal exposure, potential association w/ COPD, limited data

-Benefits: harm reduction --> not approved for smoking cessation in US

Cocaine

-white powdered form is referred to as cocaine or "coke" --> typically snorted but can be injected or swallowed

-solid form is often referred to as crack --> typically smoked

Cocaine

-potent monoamine reuptake inhibition --> CNS stimulation

-half-life is around 1 hr

Cocaine Intox Sx

-irritability, diaphoresis, tachycardia, HTN, pupil dilation, GI upset

-unique: psych effects (paranoia, panic, grandiosity), potent vasoconstriction (resultant hyperthermia, MI, CVA)

Cocaine Withdrawal - Timing

-onset around 1-2 days after discontinuation

-peak around 3-5 days after discontinuation

-resolution around 1-2 weeks after discontinuation

Cocaine Withdrawal - Sx

-fatigue, depression, poor mental clarity, insomnia

-unique: crash around days 1-3 --> hypersomnia, agitation, depression, and psychomotor retardation

Cocaine Intox and withdrawal Tx

-medical sedation --> benzo, antipsychotics

-external cooling

Cocaine Remission Tx

-there is no FDA approved medication for cocaine use disorder

-Mirtazapine, bupropion and naltrexone (IM)

Methamphetamine

-white, powderized form --> meth

-swallowed, snorted, smoked, or injected

-solid form --> crystal, glass

-usually smoked or injected

Meth MOA

-potent monoamine reuptake inhibition, potent monoamine agonism, inhibition of enzymes involved in monoamine breakdown, and activation of enzymes involved in monoamine synthesis

-CNS stimulation

Meth DOA

usually around 6-12 hr