Opioids

Opioids, Sedative-Hypnotics, and Hallucinogens

Karen Drexler, M.D.

Sedative-hypnotics-anxiolytics

Hallucinogens

Opioids

History and Overview

Epidemiology

Neurobiology

Diagnosis of abuse and dependence

Medical complications

Psychiatric complications

Treatment

Opioids: History and Overview

Ebers Papyri (7000 B.C.):

Opium to treat colic in children

Opiates

Opium is the milky exudate from the capsule of the opium poppy.

Morphine (4 - 21%), codeine (0.7 - 25%), and thebaine

Semisynthetic Opioids:

Hydromorphone (Dilaudid), hydrocodone (Vicodin), oxycodone (Percocet, Tylox),

Synthetic Opioids:

Meperidine (Demerol), Propoxyphene (Darvon), fentanyl (Sublimaze), methadone

Buprenorphine, Pentazocine (Talwin), butorphanol (Stadol), tramodol (Ultram)

Epidemiology

Monitoring the Future (1997)

2.1% of 8th, 10th, and 12th graders report ever using heroin.

National Household Survey on Drug Abuse

1993- 68,000 current users

1996- 216,000 current users

Recent influx of low-cost, high purity heroin especially in the Northeast

Opioids: Epidemiology

Analgesic Pain Medication Addiction:

Of 12,000 patients prescribed opioids for acute pain, 2 became addicted.

Of 38 patients prescribed opioids chronically, 2 became addicted, both had a history of drug abuse.

Opioids: Neurobiology

Opioid binding sites occur in:

Brain: nucleus accumbens, pituitary, hypothalamus, periaqueductal gray, others

Spinal cord

GI tract, Vagus Nerve

Endogenous polypeptides:

Met- and Leu-enkephalin (pentapeptides)

Betaendorphin (30 peptide sequence)

Opioids: Neurobiology

Receptors

Mu: euphoria, analgesia, respiratory depression, miosis, decreased GI motility, prolactin release, hypothermia

Kappa: analgesia

Sigma: psychosis, respiratory depression

Delta: respiratory depression

Opioid Intoxication

Initially:

Warm flushing of skin

Euphoria

Dry mouth

Heavy extremities

Pupillary constriction

Slurred speech

Later:

Poor attention

Sleepiness

Coma (in high doses)

Hypoactive bowels (constipation)

Opioid Withdrawal

Dysphoric mood

Nausea or vomiting

Muscle aches

Lacrimation or rhinorrhea

Pupillary dilation

Piloerection

Sweating

Diarrhea

Yawning

Fever

Insomnia

Opioid Withdrawal

Onset:

2 - 24 hours with heroin
2 - 4 days with LAAM

Peak:

1 - 3 days with heroin
4 - 7 days with LAAM

Duration:

5 - 7 days with heroin
Weeks for LAAM

Chronic:

Anxiety, dysphoria, craving, anhedonia, insomnia
Weeks to months

Opioids: Medical Complications

Coma and death from respiratory depression

Heroin is the second most frequently mentioned drug in overall drug-related deaths.

Infectious diseases

HIV/AIDS

Hepatitis

Sepsis, endocarditis, pericarditis

Pulmonary emboli

Opioids: Medical Complications

Skin absesses

Urinary retension

Spontaneous abortion

Opioids: Psychiatric Complications

Delirium

Psychosis

Depression

Anxiety

Sleep disorder

Opioids: Treatment

Overdose:

Naloxone

Monitoring and respiratory support

Detoxification:

Clonidine (suppresses about 75% of sx)

With NSAIDS, benzodiazepines

Methadone (up to 21 days by Federal Law)

Opioids: Treatment

Abstinence-based:

Naltrexone

12-step

Cognitive-behavioral

Community reinforcement

Opioids: Treatment

Agonist therapy:

Methadone
LAAM
Buprenorphine

Dual diagnosis:

Antidepressants
Antipsychotics
Mood stabilizers
Vocational rehabilitation
Counselling
Non-addicting antianxiety agents

Sedative-hypnotics-anxiolytics

Barbiturates

Benzodiazepines

Flunitrazepam (Rohypnol)

Clonazepam (Klonopin)

Diazepam (Valium), etc.

Others:

Gamma-hydroxybutyrate (GHB)

Neurobiology/ Pharmacology

Benzodiazepines potentiate GABA

Used in treatment of anxiety disorders, muscle spasm, seizures

Barbiturates cause general and reversible CNS depression

Used in treatment of seizures, irritable bowel, headache

Intoxication

Maladaptive behavior or psychological changes

inappropriate aggressive behavior
inappropriate sexual behavior
mood lability
impaired judgement

Slurred speech

Incoordination

Unsteady gait

Nystagmus

Impaired attention or memory

Stupor or coma

Sedative-, hypnotic-, anxiolytic- Withdrawal

Autonomic hyperactivity

hand tremor

insomnia

nausea or vomiting

transient visual, tactile or auditory hallucinations

Psychomotor agitation

Anxiety

Grand mal seizures

Medical Complications

Coma and death from barbiturate or alcohol and benzodiazepine overdose

Seizures from withdrawal

Cardiac arrhythmias from withdrawal

CVA and AMI from withdrawal

Psychiatric complications

Anxiety

Psychosis

Mood swings

Treatment

Overdose:

Flumazenil (Mazicon): benzodiazepine antagonist

Respiratory monitoring

Detoxification:

Pentobarbital challenge test

Substitution of long acting benzodiazepine

Treatment

Rehabilitation

12-step

Cognitive-behavioral

Residential

Dual diagnosis

Antidepressants

Anxiolytics (buspirone, propranolol)

Mood stabilizers

Hallucinogens

Lysergic acid diethylamide (LSD)

Mescaline

Psilocybin

Dimethyltryptamine

Methylenedioxymethamphetamine: MDMA

Methylenedioxyamphetamine: MDA

Scopolamine

Hallucinogens: Neurobiology

Varies

Stimulation of central dopaminergic function

Suppression of serotonin function

Stimulation of NMDA receptors

Stimulation of sigma opioid receptors

LSD Intoxication

Unpredictable

Onset 30 to 90 minutes

Dilated pupils

Increased temperature

Increased heart rate and blood pressure

Sweating

Anorexia

Sleepiness

Dry mouth

Tremors

Hearing colors

Seeing sounds

Clear after 12 hours

Hallucinogens: Epidemiology

NHSDA

1996, 7.7% ever used LSD

1988, 6.0%

Monitoring the Future

1997, 13.6% of 12th graders reported using LSD at least once

Hallucinogen Persisting Disorder

Reexperiencing after cessation of use of a hallucinogen of one or more:

Geometric hallucinations

False perceptions of movement

Flashes of color

Intensified colors

Afterimages, Halos

Macropsia, Micropsia

Hallucinogens: Treatment

12-step

Cognitive-behavioral

No good empiric data specifically on hallucinogens

PCP and other Arulcyclohexylamines

PCP was developed in the 1950s as an intravenous anesthetic

Snorted, smoked or eaten

PCP Intoxication

Low to moderate doses:

Euphoria
Increased BP and P
Shallow respirations
Sweating
Numbness
Incoordination
Vertical nystagmus

High doses:

Nausea
Vomitting
Blurred vision
Dilated pupils
Drooling
Seizures
Coma
Hallucinations

PCP Epidemiology

Monitoring the Future

1979, 12.8% of high school seniors ever used

1997, 3.9% of high school seniors ever used

Lowest rate of 2.4% in 1992.

PCP Pharmacology

Intoxication begins within 5 minutes of smoking and lasts for 4 to 5 hours, may take days to recover

NMDA antagonist

Treatment

Intoxication:

Antipsychotics

Anxiolytics

Monitoring

Rehabilitation:

12-step

Cognitive behavioral

Dual diagnosis