6/17- Substance-Related and Addictive Disorders II Flashcards
Sedatives, hypnotics, and anxiolytics include what?
- Barbiturates
- Benzodiazepines
- Prescription sleep meds
How is intoxication with sedative, hypnotic, or anxiolytic defined?
- Recent use of sedative, hypnotic, or anxiolytic
- Maladaptive behavioral or pscyhological changes 1 or more:
- slurred speech
- incoordination
- unsteady gait
- nystagmus
- impaired attn/memory
- stupor/coma
How is withrdrawal from sedative, hypnotic, or anxiolytic defined?
- Cessation (or reduction in) prolonged use of a sedative, hypnotic, or anxiolytic 2 or more (developing in hours-few days):
- autonomic hyperactivity (diaphoresis, HR > 100)
- hand tremor
- nausea/vomiting
- anxiety
- insomnia
- hallucinations (A/V, tactile)
- pscyhomotor agitation
- grand mal seizures
List of some Barbiturates?
- Phenobarbital (Luminal)
- Butalbital (Fiorinal)
- Secobarbital (Seconal)
- Amobarbital (Amytal)
- Phentobarbital (Nembutal)
Characteristics of Barbiturates?
- Uses
- Result from long-term use
Uses:
- Sedatives/anxiolytics
- Anticonvulsants
May have:
- Tolerance
- Dependence/withdrawal
- Lethal in overdose
What has largely replaced the use of barbiturates?
Benzodiazepines (think: similar to transition of TCA -> SSRIs)
List of Benzodiazepines
- Alprazolam (Xanax)
- Lorazepam (Ativan)
- Oxazepam (Serax)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Temazepam
- Triazolam
Indications for Benzodiazepines?
- Highly effective anxiolytics and sedatives
- Muscle relaxants, anticonvulsants, amnestics
- GAD, Panic Disorder
- Insomnia
- Increase affinity of GABAA receptor for endogenous GABA, bind to BZD binding site
May see,cross-tolerance with alcohol and barbiturates (alcohol-like effects; treat withdrawal symptoms)
Risks of Benzodiazepines?
- Tolerance -> dose escalation
- Abrupt discontinuation -> withdrawal
- Requires gradual tapering of dose
- Abuse potential
- Low lethality in overdose, unless combined with other sedatives, then lethal !!!
- Intoxication, confusion, falls: esp. in elderly
- Paradoxical agitation - Disinhibition
What are some hypnotics? Used for?
Prescription sleeping medications
- Zolpidem (Ambien)
- Zaleplon (Sonata)
- Eszopiclone (Lunesta)
- Remelteon (Rozerem)
- Chloral hydrate (Noctec)
- Meprobamate (Miltown
What are opiates? What are opioids?
Opiates- opium and naturally-occurring derived drugs (morphine and codeine)
Opioid- class of substances that acts on opioid receptors, includes synthetic drugs that bear little resemblance to opium
What are some natural opiates?
- Opium
- Morphine
- Codeine
What are some semi-synthetic derivatives of opioids?
- Heroin
- Hydrocodone
- Hydromorphone
- Meperidine - Oxycodone
What are some synthetic opioids?
- Fentanyl
- Meperidine
- Methadone
- Propoxyphene
3 phenomena seen in the neurobiology of opiods?
- Euphorigenicity of the drugs
- Capacity to positively reinforce drug seeking
- Avoidance of aversive feelings (including withrawal)
What are the different opioid receptors?
Responsible for?
Mu
- Opioid drugs (morphine is prototypic agonist)
- Analgesia, respiratory depression, mood elevation, constipation, immuno-suppression, physical dependence
Delta
- similar to mu
Kappa
- Dysphoria (endogenous dynorphins)
OFQ/N
- Analgesic or pro-nociceptive ffects
Which receptor do opioid drugs bind?
Mu opioid R
What is opioid intoxication?
Recent use of an opioid
Problematic behavior or psychological changes:
- Initial euphoria followed by apathy, dysphoria
- Psychomotor agitation or retardation
- Impaired judgment & social/occupational fxn
Pupillary constriction and 1 or more:
- Drowsiness/coma
- Slurred speech
- Impaired attention/meory
What is opioid withdrawal?
- Cessation of or reduction in prolonged opioid use (or administration of an antagonist)
3 or more:
- Dysphoric mood
- Nausea/vomiting
- Muscle aches
- Lacrimation/rhinorrhea
- Diarrhea
- Pupillary dilation/piloerection/diaphoresis
- Yawning
- Fever
- Insomnia (everything runs)
Opioid Intoxication vs. Withdrawal?
Treatment of opioid intoxication?
Naloxone (Narcan): IV, IM, SC, ET
- Treatment of acute opioid overdose (0.4-2.0 mg Q 2-3 min prn)
- Diagnosis of physical dependence via relief upon reception
- Poor PO absorption (wouldn’t be able to take it by mouth at this point anyway)
- Rapid parenteral metabolism
Treatment of opioid withdrawal: detoxification?
Often done inpatient b/c so distressing
- Clonidine (Catapres)
- Methadone
Characteristics of opioid withdrawal treatment with Clonidine
Clonidine (Catapres)
- Alpha 2 adrenergic agonist and anti-HTN
- Suppresses autonomic Sx of opiate wd
- Allows for more rapid etox
- Monitor for hypotension
- SE: hypotension, sedation, limits outpt use
- Lethargy, restlessness, anxiety, insomnia, cravings, not well relieved
Benzodiazepines for anxiety
Low-dose propranolol for restlessness
Characteristics of opioid withdrawal treatment with Methadone
Methadone
- Mu receptor agonist
- Commonly used drug to treat withdrawal Sx
- Detox over several days inpatient
- 6 mo outpatient
- Morphine: methadone equivalency varies widely (2.5:1 to 14:1)
- Careful not to overdose
- More rapid with clonidine
- Outpatient taper very gradual
Characteristics of opioid withdrawal treatment with Buprenorphine?
Buprenorphine
- Partial agonist at mu receptors
- Becoming more widely used for detox
Characteristics of opioid withdrawal treatment with Ultrarapid detoxification?
- General anesthesia, antagonist therapy
- Efficacy and safety being studied
Treatment of opioid use disorder?
Agonist replacement:
- Methadone maintenance
- Buprenorphine maintenance
Opioid antagonists:
- Naltrexone- only antagonist currently used
Characteristics of opioid use disorder with Buprenorphine?
- Mu-receptor agonist
- Decreased acute euphoric effects
- Readily absorbed orally
- 4 hrs to peak concentration
- Large extravascular reserve (not much withdrawal if weaned off)
- T1/2 of 1-2 days
- Cytochrome P450 CYP3A4
Characteristics of opioid use disorder with methadone maintenance therapy?
- High doses alleviate craving, induce cross tolerance, blocks heroin-induced euphoria
- Theory: no need for heroin or associated maladaptive behaviors with obtaining the drug
- Proven efficacy in reducing: heroin use, other drug use, health problems, crime
- Controversy: primary purpose crime reduction? trading one addiction for another?
Characteristics of opioid use disorder with Buprenorphine?
Partial agonist at mu opioid recpetors (kappa antagonist)
- High affinity for mu receptors (can precipitate w/d)
- Dissociates very slowly from receptors (long duration of action: 24-48 hrs, reduced capacity to produce withdrawal Sx)
- Ceiling effect, low risk of overdose, no respiratory depression Less effective for those with larger opioid habits
Formulations of Buprenorphine?
Subutex: SL buprenorphine tabs
- Office based treatment of opiate dependence
Suboxone: SL buprenorphine/naloxone tabs (naloxone there to prevent abuse; for safety)
- Okay for take home dosing
- Naloxone has no activity PO; full antagonist if injected
- Minimizes risk of diversion Buprenex: IM buprenorphine
- FDA approved for pain
- Inpatient detox protocols exist
Characteristics of opioid use disorder with Naltrexone (ReVia)?
- Opioid antagonist
- Treatment of opioid addiction
- Orally effective and long acting
- Initiate after drug free (7 days heroin, 10 days methadone)
- Better in populations with established careers, family support, high motivation
- SE: decreased energy, hepatotoxicity
What are some common stimulants?
- Amphetamine-type substances
- Cocaine
- Other stimulants
How is stimulant intoxication defined?
- Recent use of a stimulant
- Maladaptive behavioral or psychological changes: euphoria or affective blunting, changes in sociability, hypervigilance, interpersonal sensitivity, anxiety, tension, anger, sterotyped behaviors, impaired judgment
2 or more:
- Pupillary dilation
- Tachy/bradycardia
- BP changes
- Diaphoresis/chills
- Confusion, seizures, dyskinesias, dystonias, coma
- N/V
- Psychomotor agitation, retardation
- Weight loss
- Muscle weakness, respiratory depression
- Chest pain, cardiac arrhythmia
+/- Psychosis
How is stimulant withdrawal defined?
- Cessation of or reduction in prolonged stimulant use
- Dysphoric mood
- Withdrawal dysphoria- often severe (psychiatric emergency!)
2 or more:
- Fatigue
- Vivid, unpleasant dreams
- insomnia or hypersomnia
- Increased appetite
- Psychomotor retardation or agitation
What are some amphetamine substances/medications?
- Methamphetamine
- Amphetamine
- Dextroamphetamine
- Methylphenidate
- Adderall
- Dexedrine
- Ritalin
- Concerta
Mechanisms of amphetamine activity?
- Inhibits DA reuptake
- Promotes DA release via DA transporter
- Slow metabolism, effects last several hours longer than cocaine
What is the natural source of cocaine?
Erythroxylon coca plant
Characteristics (broad) of cocaine?
- Indigenous to S. America
- First used 2000 years ago
- Chemically isolated in 1880s
- Sigmund Freud impressed with “mood and work”
- Involved in original Coca-Cola formula
Forms and delivery of cocaine? Times of action
Snorting powdered cocaine (intranasal)
- 2-3 min
Injecting dissolved cocaine (intravenous)
- 15-30 sec
Smoking “crack” cocaine (inhalational)
- 6-8 sec
What are some of the reinforcing effects of cocaine?
- Extreme euphoria in pure form
- Hyperalertness
- Grandiosity
- Hypersexuality
- Hypertalkativeness
- Rapid onset of action
- Rapid extinction of euphoria
- Rapid tolerance
Mechanisms of cocaine activity?
Immediate mechanism of action:
- Increased NT levels (DA, NE, 5-HT)
- Inhibition of reuptake
Mesolimbic dopamine system
What is the natural origin of cannabis/marijuana?
Cannabis sativa plant
Characteristics (broad) of cannabis?
- Indigenous to Central Asia and China
- Used by humans for > 4000 years-
- “Gateway” or entry drug for many addicts
- Most commonly abused illicit drug
- “marijuana”, “hashish”, “kush”
Cannabis has been legalized for medical use in treating what conditions?
- Cancer
- HIV
- Glaucoma
How is cannabis intoxication defined?
- Recent use of cannabis
- Problematic behavioral or psychological changes: impaired coordination, euphoria, ANXIETY, sensation of slowed time, impaired judgment, social withdrawal
2 or more:
- Conjunctival injection - Increased appetite
- Dry mouth
- Tachycardia
How is cannabis withdrawal defined?
- Cessation or reduction in heavy and prolonged cannabis use (daily or almost daily/at least a few months)
3 or more (generally mild, flu-like Sx):
- Irritability, anger, or aggression
- Nervousness/anxiety
- Sleep difficulty
- Abdominal pain, tremors, sweats, fever, chills, headache
- Restlessness
- Depressed mood
- Decreased appetite/wt loss
- NAUSEA, vomiting
Chronic adverse effects of cannabis?
- Cognitive difficulties (concentration, memory)
- Impaired motor function
- Depression
- Paranoia
- Psychosis
- Amotivational Syndrome
What are some common hallucinogens?
- Phenycyclidine (PCP)
- Ergot
- LSD
- Mescaline
- Psilocybin
- MDMA (ecstasy)
Characteristics (broad) of Phencyclidine (PCP)?
- “Dissociative anesthetic”
- 1960s: street use
- “Angel dust”
- PCP lace marijuana cigarettes
- Surreptitiously mixed with other illicit drugs- economics
- Inhalational, intranasal, IV
- PCP binding site on NMDA receptors
Characteristics of Ketamine?
- Veterinary anesthetic
- Club drug
- “Special K”
- PCP-like pharmacology
- Inhalational, intranasal, IV, tablets
How is Phencyclidine intoxication characterized?
- Recent use of phenycyclidine (or pharmacologically-similar substance)
- Problematic behavioral changes: belligerence, assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment
2 or more:
- Nystagmus (vert or hor)
- HTN or tachycardia
- Numbness/decreased pain
- Ataxia
- Dysarthria
- Muscle rigidity
- Seizures or coma
- Hyperacusis
How is intoxication with other (non-PCP) hallucinogens characterized?
- Recent use of a hallucinogen (other than PCP)
- Problematic behavioral or psychological changes: anxiety/depression, IOR, fear of losing one’s mind, paranoia, impaired judgment
- Perceptual changes in full wakefulness and alertness: intensification of perceptions, depersonalization, derealization, illusions, hallucinations, synesthesias (hearing colors, seeing sounds)
2 or more:
- Pupillary dialtion
- Tachycardia
- Sweating
- Palpitations
- blurred vision
- Tremore
- Incoordination
What is Hallucinogen Persisting Perception Disorder?
(Flashbacks)
Following cessation of use: re-experiencing of perceptual symptoms experienced while intoxicated with the hallucinogen
- Geometric hallucinations
- False perceptions of mvt in peripheral vision
- Flashes of color
- Intensified colors
- Trails of images of moving objects
- Positive afterimages
- Halos around objects
- Macropsia, micropsia (things appearing larger/smaller than they really are)
What are some common inhalants?
Aliphatic and aromatic hydrocarbons
- Gasoline, glue, paint thinner, spray paint
Halogenated hydrocarbons
- Cleaners, typewriter correction fluid, spray can propellants
Toluene, benzene, acetone, methanol, others
“Huffing” and “Bagging”
How is inhalant intoxication characterized?
- Recent short-term, high-dose exposure to inhalants
- Problematic behavioral or psychological changes: belligerance, assaultiveness, apathy, impaired judgment or function
2 or more:
- Dizziness
- Nystagmus
- Incoordination
- Slurred speech
- Unsteady gait
- Lethargy
- Depressed reflexes
- Psychomotor retardation
- Tremor
- Muscle weakness
- Blurred vision/diplopia
- Stupor or coma
- Euphoria
What are bath salts?
- Synthetic cathinones (Catha edulis- “Khat”)
- Mephedrone
- Originally sold as “bath salts”
- Labeled “not for human consumption”
- No relation to Epsom salts
- Amphetamine-like: DA, NE, 5-HT release
- Psychosis and agitation
What are characteristics of synthetic Cannabinoids?
- Research compounds: designer drugs
- Mixed with leaves from traditional herbs
- Spice, K2, incense
- Very little structural similarity to cannabis
- Psychosis and agitation
General Take Home Points:
- Abuse:
- Dependence:
- New in DSM 5: Substance ______
- Intoxication states are the opposite of withdrawal states
- Common neurobiological addiction process across substances
General Take Home Points:
- Abuse: maladaptive pattern of substance use
- Dependence: behavioral (drug seeking and drug taking) and physiological (tolerance and withdrawal)
- New in DSM 5: Substance Use Disorder (spectrum)
- Intoxication states are the opposite of withdrawal states
- Common neurobiological addiction process across substances
