Substance Use Disorder Flashcards
Heroin
Class: synthetic opioid, opiate prodrug
PK: diacetylated morphine, short-acting, lipid soluble, straight to BBB, 2x potency of morphine, half-life 3min IV, first-pass metabolism, po not bioavailable
PD: warm skin rush, pruritis, pleasure, relaxation, satisfaction for -45sec, miosis, “nodding off”, hypotension, depressed respiration, bradycardia, euphoria, floating feeling
OD: classic triad (miosis, coma, depressed respiration), pulmonary edema, seizure, treat with naloxone (narcan)
Withdrawal: begins after 8-12h after last dose, peaks at 3-4d, lasts about 3-5d, lacrimation, yawning, rhinorrhea, sweating, sense of anxiety and doom->restless sleep, mydriasis, anorexia, gooseflesh, irritability, tremor-> increased BP, HR, n/v/d, abdominal cramps, depression, muscle cramps, weakness, bone painu
Affecting 900,000 addicts, account for 14-15% admission for substance abuse program, steady increase in use recently
Morphine, Codeine
Class: synthetic opioid, prototypic mu opioid receptor agonist
Indication: analgesic
Interaction: MAOI can cause severe or fatal rxn
PK: po (~35% bioavailable), iv, im for morphine, po only for codeine (~90% bioavailable), half life 2.5-3h, duration 4-6h, hepatic metabolism, 10% codeine demethylated to morphine by CYP2D6.
C.f. Semi-synthetic opioids: oxycodon (percocet)–now only available in abuse deterrent formulation OxyContin, hydrocodon (vicodin)–high abuse potential
C.f. Fentanyl: opioid analgesic, 80x as strong as morphine
C.f. Tapentadol, Tramadol: opioid analgesic, ADR is same as morphine plus inhibits reuptake of NE and to lesser degree serotonin
C.f. Poppy seed can present false positive in urine toxicology
Methadone
Class: fully synthetic, full mu agonist
MOA: works in modulation phase of nociception, has NMDA antagonist properties, can inhibit reuptake of serotonin
Indication: opioid addiction tx
PK: high bioavailability po (>90%), long half-life 24h, delayed onset of action with long duration 24h, highly protein-bound, slow release to blood, hepatic metabolism, excreted in urine/feces
ADR: same as morphine plus, can prolong QTc, pro-arrhythmic
Special: slow development of opioid tolerance, with chronic use, stored and accumulated in liver tissue
Buprenorphine
Class: partial opioid agonist with “ceiling effect” and higher affinity
Indication: opioid addiction tx, low abuse potential, lower level of physical dependence, less opioid effects than methadone, safety in od quantities
PK: poor oral bioavailability and first-pass metabolism, if swallowed, given sublingual, slow dissociation rate up to 72h
C.f. Suboxone (bupreorphine/naloxone in 4:1 ratio), naloxone blunts high and blocks mu receptors initially, blocking is done by buprenorphine, abuse issue present, crushed and snorted, popular among teens
Cocaine
Class: crystalline, free base or crack smoked (denatured with strong alkali, yielding low temp 98C for vaporization
MOA: blocks dopamine reuptake transporter, increasing dopamine in synapse
PK: IV/smoke- peak 4-7min, diminished by half 17-30min
IN- peak 30min, weaker high, longer duration
Hepatic metabolism, excreted in urine
PD: short-lasting intense euphoria, increased alertness, energy, motor, sense of well being, confidence, sexuality, minor withdrawal
Side effects: anxiety, restlessness, paranoia, frank delusions, hallucination, seizure, hyperpyrexia, increased BP, HR, tremor, heart attack, stroke
Special: expensive, used in binge, used with other drugs, with prolonged use, expect tolerance (low dopamine receptors), and withdrawal (ahedonia, low energy), pulmonary effects from smoking include asthma, bronchitis, alveolar infiltrates, pulmonary eosinophilia, hemoptysis, dyspnea
Methampetamine
Class: schedule II, stimulant, approved for ADHD, obesity
PK: iv, po, im, in
PD: increased sexual confidence, euphoria, sense of well being, alertness, hyperactivity, increased BP, HR, body temp, tremor
Side effects: rhabdomyolysis, cardiovascular events, including MI and stroke, significant bruxism, periodontal disease
Psychiatric effects: at high doses, hypomania, grandiosity, extreme insomnia, irritability, appetite suppression, weight loss, skin picking, ~10%: frank psychosis, similar in presentation to paranoid schizophrenia, violent behavior
Withdrawal: “Terrible Tuesday” depression, irritability, suicidal ideation, carb craving
Special: manufactured in clandestine labs with household chemicals, large profit of margin, aka meth, crystal, ice, speed, crank, glass, fire, chronic use leads to neurotoxicity and depletion of presynaptic dopamine level
C.f. Other stimulants include: dextroamphetamine, amphetamine, bath salt, methylphenidate
Cannabis
Class: cannabinoid agonist
PK: 20-70% delivered in the smoke, 2-3mg can produce brief high, lipid soluble and deposited in fat, hepatic metabolism, eliminated in feces, 33% in urine
PD: sense of well being, relaxation, euphoria, modified level of consciousness, altered perception, time sense, intensified sensory experience, sexual disinhibition, self-medication for anxiety, insomnia, pain, HIV waisting syndrome, MS spasticity
Adverse psychiatric effects: transient panic and anxiety, depersonalization, delusions/paranoia, hallucinations, acute mania, depression (possibly), aggression, impaired short term memory, decreased executive functioning
Withdrawal: irritability, decreased appetite, anxiety, physical discomfort, low mood, increased aggression/anger, insomnia, restlessness
Alcohol
Class: GABA agonist, NMDA antagonist
PK: food delays absorption by slowing gastric emptying, etoh diffusion in all body compartments including placenta and breast milk, except skin and bladder, small amounts 2-10% excreted in urine, rest oxidized in GI and liver via ADH and ALDH, men have higher levels of ADH in stomach, plasma disappearance follow zero order kinetics once ADH is saturated at rate of .015 in BAC
PD: GABA-impaired motor, slurred speech, reduced coordination, NMDA-cognitive impairment, memory deficit, indirect MOA-opioid, dopamine effect, euphoria, positive reinforcement, reward pursuit
Chronic Effects: impaired executive function and social abilities, generalized symmetric peripheral neuropathy, wernicke-korsakoff syndrome due to thiamine deficiency (opthalmoplegia, nystagmus, ataxia, confusion for encephalopathy, amnesia, apathy, lack of insight for korsakoff psychosis), fatty liver-hepatitis-cirrhosis-liver failure (most common medical problem among heavy drinkers), arrhythmia, cardiomyopathy, CHF, HTN, anemia, GI and HEENT cancer, FAS
Tolerance and Withdrawal: hepatic enzymes increase with metabolism, neuroadaptation- glutamate up, GABA and dopamine down in NT and receptor density, as a result with abrupt cessation cause “glutamate storm”->tremor, seizure, anhedonia, dysphoria, lack of motivation, treat with banana bag (thiamine, glucose, folate, potassium, etc) and benzodiazepine.
Thiamine
Class: vitamin
Action: used by the body to breakdown sugars in the diet
Indication: helps correct nerve problems due to lack of thiamine in wernicke-korsakoff syndrome
PK: absorbed from GI tract, metabolized by the liver, renal elimination, the majority being metabolites
ADR: not assoc with toxicity, but hypersensitivity rxn may occur after injection, some soreness and tenderness may occur after im
Interaction: thiamine may enhance the activity of neuromuscular blocking agents, clinical significance unknown
Lorazepam (Ativan)
Class: bzd, GABA modulator, anti-anxiety agent
MOA: “binds to central bzd receptors” which allosterically interact with GABA receptors, potentiating the effect of GABA
PK: absorbed rapidly (90%) and metabolized by liver, excreted in urine, peak onset 1-2h, half life 10-20h, po, iv, im
Advantage: short duration of action, shorter acting than diazepem, lack of metabolites make it attractive for elderly and pts with liver disease
Disadvantage: short-acting means more frequent dose, every hr initially, possibility of bzd-withdrawal seizure
Dose in Alcohol Withdrawal Syndrome (AWS): fixed dosing 1-4mg q1-4h, depending on severity of withdrawal
Chlordiazepoxide (Librium)
Class: bzd, GABA modulator, anti-anxiety agent
MOA: same as lorazepam
PK: high bioavailability >90%, extensive hepatic metabolism to active desmethyldiazepam, peak onset 1.5-4h, half life 5-30h, but active metabolites 36-200h
Advantage: original bzd, side effects and interactions well known, auto-taper, physicians familiar with drug
Disadvantage: build-up of metabolites makes it less attractive for elderly: cognitively and neuromuscularly impairing, not suitable for pts with liver disease, numerous drug interactions
Gabapentin (Neurontin)
Class: GABA analogue, anti-convulsant
Action: mechanism unclear, involves voltage gated calcium channel
PK: absorbed rapidly, 27-60% bioavailability, peak 2h, increased rate and extent with food
Advantage: non-addictive, less sedating and cognitively impairing, less relapse to alcohol, effective in tx of protracted withdrawal
Disadvantage: “off-label”, not reliable for preventing complications (DTs and seizures) of severe withdrawal in high risk pts, used for outpatient tx
Dosing for AWS: 300-400mg po tid qid for outpatients only
Naltrexone
Class: opioid antagonist
MOA: long acting and high affinity for the u receptor
Indication: anti-craving, prevention of relapse
PK: metabolized by liver, excreted in urine, po, im
ADR: nausea common, others include h/a, constipation, dizziness, nervousness, insomnia, drowsiness, anxiety, should be used in hepatic disease with caution bc it can cause hepatotoxicity
Interaction: negates effects of opiates
Advantage: dosing simplicity, FDA-approved, monthly injection improves compliance
Disadvantages: can’t use with pts on opiates, non-compliance, possible interference with endogenous opioid system?
Acamprosate
Class: GABA analogue
MOA: NMDA antagonist + GABAa activator, acts in serotonergic, nonadernergic, dopaminegic receptors, may restore neuronal excitation and inhibition balance
Indication: anti-craving, relapse prevention
PK: not metabolized, renal excretion
ADR: caution in depressed pts, pts with renal impairment
Advantage: well-tolerated with few ADR, no significant drug interactions, may be shown to be effective in comb with Naltrexone and Disulfiram
Disadvantage: studies in US have not consistently shown positive effect
Disulfiram (Antabuse)
Class: alcohol dependence deterrent
MOA: inhibits metabolism of etoh by irreversibly binding to ALDH, resulting in a build-up of acetaldehyde, with development of instant hangover, such as facial flushing, h/a, dizziness, n/v, rapid HR, hypotension, confusion
PK: high oral bioavailability, the onset 5-30 min, half-life 7h, duration of effect up to 2 weeks, which is time to resynthesize ALDH
ADR: rare fulminant hepatitis, use with caution in liver disease, peripheral neuropathy including optic, neuropsych changes, caution >60 known or suspected CAD or cerebrovascular disease
Advantage: helpful in couples behavioral counseling for etoh dependence, abstinence rates of 50% or more in controlled settingky/observed administration
Disadvantage: at one year, no more effective than placebo as sole-treatment, self-administered
