Substance-Related Addictive Disorders Part 2 (Psych) - CAM III

What medications potentiate GABA inhibitory actions?

1. Benzodiazepines

2. Barbituates

3. Z- drugs

4. Gamma-hydroxybutyrate (GHB)

What are Gamma-hydroxybutyrate (GHB)?

CNS depressants that produce dizziness, confusion, drowsiness, memory loss, respiratory distress, and coma at excessive doses when combined with other CNS drugs

What is the illicit use of gamma-hydroxybutyrate (GHB)?

"date-rape drug"

What medication is similar to gamma-hydroxybutyrate (GHB)?

Sodium oxybate (xyrem) for narcolepsy

CNS depressants Key Facts

1. drugs with rapid onset are more likely to cause intoxication, ↑ risk of abuse

2. May be misused to alleviate unwanted effects from others

3. More euphoria combined with opioids, synergistic with alcohol/CNS depressants

4. Extensive use may cause severe depression - suicide

Benzodiazepines (BZD) Use

1. Anxiety

2. Midazolam (Versed) - sedation

3. Anxiety and amnesia in critical care settings before anesthesia

4. Some used for muscle spams and seizure tx

Common Age of Misuse of Benzos

18-25 y/o

Important Fact with Benzos

1. Taken every day for 6 weeks - likely dependence

2. 2% of people get addicted to them

Beers Criteria

1. Increased risk of falls and fractures in elderly, cognitive impair

2. Can be lethal in overdose

Withdrawal from Benzos

Fatal withdrawal - same sxs as alcohol withdrawal

Barbituates

1. Tx of epilepsy and as anesthetics

2. Potentiate the effects of GABA

Barbituates Intoxication/Withdrawal

1. Intoxication can be lethal - respiratory depression

2. Withdrawal - anxiety, insomnia

3. Fatal Withdrawal - seizures (1-3 weeks later), delirium, life-threatening CV collapse

Urine Direct Testing for Sedative-Hypnotics

1. Variable sensitivity for specific benzodiazepines

2. Z drugs and barbituates are not typically screened for

If a benzo does not metabolize to oxazepam, are they detected on POC tests?

1. No

2. Alprazolam, clonazepam, lorazepam, midazolam, and triazolam

What is the metabolite of benzos that can be tested on screening assays?

Oxazepam

Sedative, Hypnotic, or Anxiolytic Intoxication - DSM-5

Same as alcohol intoxication

Treatment of Sedative, Hypnotic, or Anxiolytic Overdose

1. ABCs/monitor VS supportive care: resp/hypotension

2. Monitor for respiratory depression

3. Benzos - flumazenil (cause seizures)

4. Barbituates - sodium bicarb to alkalinize urine

Sedative, Hypnotic, or Anxiolytic Related Disorders Withdrawal - DSM-5

Similar to EtOH withdrawals

Sedative, Hypnotic, or Anxiolytic Withdrawal

1. Within hours for short-acting agents

2. 1-2 days longer for long-acting metabolite drugs

Sedative, Hypnotic, or Anxiolytic Withdrawal Treatment

1. Occur when tapering drug

2. Can be protracted, PAWS for over a year

3. Taper gradually as outpatient , consider long acting

4. For acute withdrawal use CIWA Ar protocol inpatient tx

DSM-5 Sedative, Hypnotic, or Anxiolytic Use Disorder

1. Criteria Similar to AUD criteria

2. Mild - presence of 2-3 symptoms

3. Moderate - presence of 4-5 symptoms

4. Severe - presence of 6 or more symptoms

Sedative, Hypnotic, or Anxiolytic Related Disorders Treatment

1. Same as SUD

2. No FDA approved medications

3. Treat underlying anxiety with medications that are not controlled substances

Opioids

Natural or derived from a lab

Opiates

Refers specifically to natural compounds derived from the poppy plant (heroin and morphine)

Opioids/Opiates Use

1. Prescription - analgesia, antidiarrheal, anesthetics, cough suppressants

2. Non-medically - misuse, illicit use

Natural opioids

1. Morphine

2. Codeine

Semisynthetic Opiods

1. Oxycodone

2. Hydrocodone

3. Hydromorphone

4. Oxymorphone

Synthetics with Morphine-Like Action

1. Methadone

2. Meperidine

3. Tramadol

4. Tapentadol

5. Fentanyl

Buprenorphine

Opiate agonist and antagonist effects

What should we check before prescribing opioids?

Drug Prescription Monitoring Program (PDMP)

Opioid-Related Disorders Epidemiology

1. In teens or early 20s

2. Decrease risk by prescribing lowest dose and few days supply

3. Highest rate of death than any other drug

4. Some can contain fentanyl

Complications of Opioid-Related Disorders

1. Cardiovascular - endocarditis, QT prolongation, hypotension, bradycardia

2. ID - bacterial infections, HIV, hep C, tetanus

3. Respiratory - pulmonary edema

4. GI - ileus, constipation

5. Neuro - cognitive impairment

6. Withdrawal symptoms

7. Endocrine/Metabolic - menstrual irreg., hypogonadism

8. Derm - skin infections

Dermatologic Opioid Complications

1. Hep C/HIV

2. Rare tetanus, clostridium botulinum

3. Sclerosed veins - peripheral edeam

4. Skin popping d/t bad veins -> causing cellulitis, abscesses, circular-appearing scares from healed lesions

Kratom

1. Used as a opioid-substitute analgesic & drug

2. Mitragynine and 7-hydroxymytragynine

3. Available OTC

4. Not approved for any medical use

What are the effects associated with kratom?

1. N/V/pruritis

2. Sweating, dry mouth

3. Constipation/increased urination

4. Tachycardia

5. Drowsiness/insomnia

6. Loss of appetite/anorexia/WL

7. Seizure/hepatotoxicity

Kratom and dosing

1. Low dose - stimulant effect

2. High dose - sedative effects, can lead to psychotic sxs (hallucinations, delusions, confusion)

How do we treat withdrawal of Kratom?

Similar to opioid w/d

Medical Complications A/w Opioid Usage

1. Dry mouth/nose; irritation of nasal mucosa, perforation of septum

2. TB

3. Slow GI activity

4. Visual impairment d/t pupil constriction

5. Sexual dysfunction

What does opioid usage do to pain tolerance?

Causes opioid-induced hyperalgesia

Opioid Intoxication DSM-5 Criteria

1. Recent use of opioid

2. Problematic behavioral or psychological changes

3. Pupillary constriction and drowsiness or slurred speech or Impairment in attention or memory

4. Not attributable to another medical conditions

What needs to be specified in Opioid Intoxication criteria?

1. With perceptual disturbances

2. Rare instance in which hallucinations with intact reality testing or auditory, visual, or tactile illusions occur in absence of delirium

What makes up the classic triad of OD from opioids?

1. Respiratory depression

2. AMS

3. Miosis (pupil constriction)

What does an OD on meperidine have that is different from typical OD symptoms?

Dilation of pupils (mydriasis)

What are other symptoms of opioid intoxication?

N/V/constipation

What are opioid overdose reversal medications (OORMs)?

1. Naloxone

2. Nalmefene

Which OORM has a longer half life?

Nalmefene

How do OORMs work?

Rapidly reverse opioid overdose and opioid receptor antagonist

Opioid Withdrawal Symptoms

1. myalgias / arthralgia

2. muscle cramps

3. diarrhea, N, V

4. abdominal cramps

5. insomnia

6. anxiety

How long does withdrawal begin in short acting opioids?

6-12 hours of last dose

How long does withdrawal begin in long acting opioids?

2-4 days

What can be used for withdrawal of opioids?

1. Methadone

2. Buprenorphine

Clinical Opiate Withdrawal Scale (COWS)

1. 5-12 -mild

2. 13-24 -moderate

3. 25-36 moderately severe

4. >36 severe

What must be specified on Opioid Use Disorder DSM-5-TR Criteria?

1. In early remission, for at least 3 mo but less than 12 mo

2. In sustained remission, period of 12 mo or longer

3. On maintenance therapy like methadone or buprenorphine

4. In a controlled environment

What are FDA approved medications for Opioid Use Disorder?

1. Methadone

2. Buprenorphine

3. Naltrexone

4. Naloxone - used ONLY in tx of OD

Methadone

1. Full agonist at mu-opioid receptor

2. Schedule II

3. Pt can take other opioids with methadone

4. QT prolongation/constipation/sedation

Burprenorphine

1. Partial opioid receptor agonist; antagonism at kappa and agonist at opioid receptor/like 1

2. Safer than methadone

Buprenorphine-Naloxone (Suboxone)

Safer option as it prevents intoxication from IV or intranasal use

How do we start buprenorphine induction?

1. Start and dose depends on severity of withdrawal symptoms and hx of last use

2. COWS >12

3. Short acting requires 12 hrs since last use

4. Long acting requires 48-72 hours since last use

Emergency Medicine Buprenorphine

1. Microdosing (repeated doses of 4-8mg to saturate MORs and reverse w/d sxs

2. Safe if recent use of opioids

Naltrexone (ReVia or Vivitrol)

1. Competitive opioid antagonist

2. Precipitates w/d if used within 7 days of heroin use

3. Also used for AUD tx

4. Monitor LFTs

5. Maintain abstinence after withdrawal tx

What medication for opioid use disorder is DOC for pregnant patients?

Methadone

Cannabis

1. DEA Schedule 1

2. State laws differ

3. No approved medications for cannabis use disorder Tx

Cannabidiol (CBD)

1. one of the two main cannabinoids

2. In its pure form has no psychoactive effect

What two cannabinoids produce psychoactive effects?

1. Delta-8-THC

2. Delta-9-THC (more potent)

FDA Approved CBD product (Schedule V)

Epidiolex - treatment of rare, severe forms of seizure disorders

Psychiatric Effects fo Cannabis Use

1. INCR. risk of psychosis or schizophrenia

2. assoc. w/ social anxiety & depression

K2

Illicit synthetic cannabinoids compounds-plant material sprayed with cannabinoid - designed to mimic cannabis effects

Complications of Cannabinoids

1. CV - tachy, HTN, arrhythmias, MI, stroke

2. Pulm - chronic bronchitis, inflammation, lung cancer

3. Psych - psychosis, acute catatonia, A/D, cognitive impairement

4. Neuro - thunderclap HA and seizures

5. GI - canabinoid hyperemesis syndrome

6. Developement - LBW, SGA

Cannabinoid Hyperemesis Sydndrome

Cyclic vomiting with severe abdominal pain; relieved by hot showers

Synthetic Cannbinoids

200-fold higher incidence of acute psychosis relative to natural marijuana

EVALI

1. Dx of exclusion

2. Resp symptoms

3. Gi symptoms

4. Non-specific systemic

5. Decrease blood O2, elevated WBC

EVALI and Cannabis

MC THC with Vitamin E acetate

Cannabis Intoxication

1. 2 or more symptoms within 2 hours

2. Conjunctival injection

3. Increased appetite

4. Dry mouth

5. Tachycardia

6. Note visual perceptual disturbances

Cannabis Withdrawal

1. 3 more more within a week after cessation of heavy use

2. Irritability, anger, aggression

3. Nervousness or anxiety

4. Sleep difficulty

5. Decreased appetite or WL

6. Restlessness

7. Depressed mood

8. Physical symptom (at least 1)

Hallucinogens

1. MC in 18-25 yo men

2. Does not cause physical dependence or withdrawal

3. No FDA treatment

Mescaline (Peyote)

1. DEA Schedule I

2. Dish shaped "buttons" in the crown of several cacti; swallowed

Psilocybin (magic mushrooms)

1. DEA Schedule I

2. Mushroom; swallowed

3. Researched as therapy for tx resistant depression

Salvia

1. Not DEA scheduled

2. Herb in mint family native to Mexico

3. Intoxication only a few minutes; smoked, chewed, or brewed

Ayahuasca

1. Schedule I

2. Tea made in amazon from Psychotria vriridis containing hallucinogen DMT along with Banisteriopsis caapi that contains an MAOI preventing the natural breakfown of DMT

Phencyclidine (PCP)

1. DEA Schedule I and II

2. Synthetic; injected, snorted, swallowed, smoked

3,4 Methylenedioxymethamphetamine-MDMA (Ecstasy)

1. DEA Schedule I

2. Synthetic similar to amphetamine and mescaline

3. Researched for use in PTSD under supervision

4. Swallowed or snorted

5. Long-term neurotoxic effects

Lysergic acid diethylamide (LSD)

1. DEA Schedule I

2. Synthetic

3. Intoxication can last for hours

4. Hallucinogen Persisting Perception Disorder - frightening flashbacks, ongoing visual disturbances, disorganized thinking, paranoia, and mood swings

Ketamine

1. Schedule III

2. Anesthetic and resistant depression tx under medical supervision

3. Used as date rape drug

Dextromethorphan

1. Opioid common in OTC cough syrup/pills

2. Causes depressant effect and hallucinogenic effect

3. Contain other ingredients that can be harmful

Effects of Dextromethorphan at Higher Doses

1. 100-200 - mild stimulation

2. 200-400 - euphoria, visual and auditory hallucinations

3. 300-1500 - distorted visual perceptions, loss of motor coordination, out of body sensation

What symptoms are associated with dextromethrophan?

1. Slurred speech

2. Increased HR and BP, dyspnea

3. Dizziness, seizures

4. N/V

PCP Intoxication Sxs

1. Violence aggression

2. Hyperthermia

3. Cardiac tachyarrhythmias, HTN

4. Pneumothorax

5. Hypernatremia

6. motor incoordination

7. Torsional nystagmus, mydriasis

8. Restlessness/hallucinations/delusions

How long can intoxication of hallucinogens last and how do we manage agitation?

1. 6-12 hrs to several days

2. Benzos PRN

3. Antipsychotics PRN

PCP Effect on Labs

1. Elevated Creatinine Phosphokinase

2. Elevated Aspartate Aminotransferase

Complications of PCP

Neurotoxic - seizures, dystonia, dyskinesias, catalepsy, hypothermia or hyperthermia

PCP Intoxication Criteria DSM-5

1. Clinically significant problematic behavior

2. Within 1 hr, two or more sxs (from MC Clinical Presentation)

Most Common Clinical Presentation of PCP Intoxication

1. Disorientation, confusion w/o hallucinations

2. Nystagmus

3. Numbness or diminished response to pain

4. Ataxia, dysarthria, muscle rigidity

5. Hyperacusis

6. Coma

Other Hallucinogen Intoxication DSM 5

1. Clinically significant problematic behavior

2. Perceptual changes occurring in a state of full wakefulness and alertness

3. Two or more of:

4. Pupillary dilation

5. Tachycardia

6. Sweating, palpitations

7. Blurring of vision

8. Tremors, incoordination

Hallucinogen Persisting Perception Disorder DMS5

Re-experiencing of one or more of the perceptual symptoms that were experienced while intoxicated

Inhalant-Related Disorders (Epidemiology)

1. 13 yo - mean age of first use

2. Higher prevalence in those that drop out of school, involved in juvenile and criminal justice system, poor, mentally ill

3. Higher rates in Latinx and white than in black

Inhalant Intoxication DSM5

1. sig. problematic behavioral or psychological changes (e.g., belligerence, assaultiveness, apathy, impaired judgement)

2. Two or more of:

3. Dizziness/nystagmus

4. Incoordination, unsteady gait

5. Slurred speech, lethargy

6. Depressed reflexes/psychomotor retardation

7. Tremor/generalized muscle weakness

8. Blurred vision/diplopia

9. Stupor/coma/euphoria

How long can intoxication last with inhalant related disorders?

15-30 minutes by may be sustained with repeated use

Why would overdose be fatal with inhalant related disorders?

Respiratory depression or cardiac arrhythmias

Direct Drug Testing for inhalant related disorders

Blood containing ethylenediaminetetraacetic acid or heparin

Other Effects from Inhalant related disorders

1. HF

2. Death from asphyxiation, suffocation

3. Seizures/coma

4. Choking