C20 Substance Use and Addictive Disorders

C20.1 Introduction and Overview

Intoxication	Impairment due to drug use
Abuse	??? ??? or ??? ?? ??
Dependence	??, ??, ??????
Withdrawal	?? ?? ??? ??
Tolerance	Hepatic enz. Induction, Neuronal adaptation
Tachyphylaxis	LSD, MDMA

Substance	Signs & Sx of Intoxication	Treatment of Intoxication	Signs & Sx of Withdrawal	Treatment of Withdrawal	Location/Effect of Drug Action
Mind expander	Hallucinogen
Cannabis	Impaired motor coordination, slowed sense of time, social withdrawal, increased appetite, conjunctival injection, psychosis	Antipsychotics if needed	Irritability, anxiety, insomnia, decreased apetite	N/A	Inhibitory G protein, GABA, increased serotonin
K2/spice *synthetic marijuana	Perceptual disturbances, agitation, seizures	Antipsychotics and/or benzodi- azepines	Not yet known	N/A	Not yet known
Hallucinogens *LSD	Ideas of reference, perceptual disturbances, impaired judgment, dissociative symptoms.	Place in quiet room, Antipsychotics, BZD	N/A	N/A	Stimulate glutamate and serotonin
Phencyclidine (PCP) “Angel dust”	Belligerence, psychomotor agitation, violence, nystagmus, loss of coordination, hyper- tension, seizures	Place in quiet room, Anti-hypertensives, Antipsychotics(항콜린 s/e), BZD (대사↓), 위세척 (흡인↑)	• Elevated body temperature, seizures, and muscle breakdown • Muscle twitching, agitation, and hallucinations may also occur	Benzodiazepines, antipsychotics	Antagonist of NMDA glutamate receptors
Inhalants	• Belligerence, apathy, aggression, impaired judgment, stupor or coma • Nasal crusting, rash, drunken appearance, dilated pupils • Use can be fatal (BM suppression, multiple organ failure) • Parkinsonism has been associated with huffing	Antipsychotics	Nausea, exces- sive sweating, muscle cramps, headaches, chills, agitation, shaking, and hallucinations	Benzodiazepines, antipsychotics	GABA, cerebellum
Dreamer
Opiates	Apathy, dysphoria, pinpoint pupils, drowsiness, slurred speech, coma, death	Naloxone	Fever, chills, cholinergic Sx. (runny nose, diarrhea), muscle spasms, cramps	Clonidine, methadone, buprenorphine	• Mu, kappa, and delta receptors • Nucleus accumbens
Krokodil (desomorphine) *synthetic opiate	Skin, blood vessel, bone, and muscle damage leading to gangrene, phlebitis, sepsis	Symptomatic	Not yet known	N/A	Not yet known
Upper	CNS stimmulants
Amphetamine *cocaine	Euphoria, hypervigilance, autonomic hyperactivity, weight loss, pupillary dilatation, perceptual disturbances. Meth mouth (amphetamine), 비중격 천공(cocaine)	Antipsychotics and BZD, anti-hypertensives	Anxiety, tremors, headaches, increased appetite, depression, risk of suicide	If suicidal, consider antidepressants	Mesolimbic pathway, nucleus accumbens
Bath salts *synthetic cocaine, cathinones, flakka	Severe agitation, combativeness, myoclonus. Delirium, psychosis can last up to 1 week	Antipsychotics and/or benzodiazepines	Anxiety and depression	If suicidal: consider SSRIs	Not yet known
Ecstasy (MDMA, Molly, E, X)	Euphoria, mild hallucinations, visual distortions, enhanced sensa- tions, hyperthermia, bruxism, autonomic hyperactivity, seizures, dry mouth	Dantrolene, benzodiazepines Hydration	Depression, anxiety, and panic attacks	SSRIs	• Increases serotonin and dopamine • Affects hypothalamus (drinking behavior/body temp); motor neurons of spinal cord (muscle spasms and jaw clenching)
Downer	BZD, sedatives, hypnotics 등은 오래 쓰면 영구적인 CSF enlargement 유발.
Alcohol	Talkative, gregarious, moody, disinhibited	If severe, consider mechanical ventilation	Tremors, hallucinations, seizures, DTs	Thiamine, MVI, folic acid, BZD	Decreases glutamate and increases GABA
Benzodiazepine	• Slurred speech, confusion, memory deficits, falls • Respiratory depression (rare)	Supportive flumazenil or mechanical ventilation if needed	• Increased anxiety, tremors • Insomnia • Seizures	반감기가 긴 BZD	GABA
Barbiturates	• Restlessness, agitation, insomnia, N/V, anxiety • Tremors, seizures, hallucination, increased heart rate • Respiratory depression	Supportive mechanical ventilation if needed	• Anxiety, depression • Cognitive impairments • Memory deficits, lack of attention • Seizures, delirium	Phenobarbitol	GABA
Others
Anabolic steroids	Irritability, aggression, mood instability, psychosis	Antipsychotics	Depression, headaches, anxiety	If depressed, consider SSRIs	May activate dopamine and serotonin release

Standard drug screening

Usually performed by immunoassay

False positives

? Gas chromatography/mass spectrometry technique.

Drug	False positives
Amphetamine	Atenolol, propranolol Bupropion Nasal congestants
Cocaine	(high specificity)
Cannabis	Hemp-containing foods
Opioids	Poppy seeds
Phencyclidine	Dextromethorphan Diphenhydramine, doxylamine Ketamine Tramadol Venlafaxine

False negatives

Semi-synthetic (eg, oxycodone, hydrocodone, hydromorphone) & synthetic opioids (phentanyl, meperidine, methadone, tramadol) typically do not trigger positive UDS.

C20.2 Alcohol-Related Disorders

Etiology

??????: ??? ??, guilt, self-medication
????: ??? ? ?, TIQ

Physiology

Nucleus accumbens, OFC, Ant.Cingulate? craving? ???

Pregnancy

Drinking between weeks 6-9 is most likely to lead to facial abnormalities associated with fetal alcohol syndrome (FAS).

Diagnosis and management

Self-awareness
??? ????? (CAGE) ? 2? ??

Cut down	?? ??? ??? ??? ?? ??
Annoying	?? ??? ?? ?? ???? ???? ?? ?? ??
Guilt	?? ?? ??? ?? ??? ???? ?? ?? ??
Eye-opener	??? ???? ???

Intoxication, withdrawal, substance use disorders

Treatment

Alcohol withdrawal, seizure

????; Long acting BZ (e.g. Diazepam, Chlordiazepoxide)
? ??? ??? ????? ???? lorazepam, oxazepam
?? tapering?? ??, 10? ?? X

Drugs for alcoholism

Mechanism of action	Example	Application	Liver disease	Renal disease
Aldehyde DH ??	Disulfiram, Calcium carbamide	?? ??? (2nd-line)
Anti-? receptor	Naltrexone, Nalmefene	? ?? ? ?? ?? ? (1st-line)	X
Glutamate modulator GABA?NMDA?	Acamprosate	? ??? ? ?? ??? (1st-line)	OK	? Dosage
Serotonergic	Ondansetron	Early onset? ??
	??? (SSRI, etc.)	Depression? ??
Dopaminergic		?? ?? x

NIAAA? Project MATCH

3? ? ??? ??? ??. ????!

CBT (cognitive)	Relapse – craving? ??
MET	???? ??.. ??? ??
TSF (12 steps)	Self help group – AA, Alanon, Alateen
CBT (community)	Brief intervention

Behavior modification techniques

e.g., aversive conditioning

When the physician should take into account that the patient does not recognize his/her drinking as being problematic (stage of precontemplation) -> Motivational interviewing

Typology

Type I	Late onset	?? ??? ??, guilt
Type II	Early onset	Antisocial, ???

Withdrawal

??/?? (6-8hr) ? psychotic Sx (8-12hr) ? seizure (12-24hr, “rum fits”, 2~5%)

Chlordiazepoxide? diazepam? PO? ?????
??, ??? ?? haloperidol, ~~chlorpromazine(?? ???)~~

Alcohol withdrawal syndrome is divided into 4 categories:

Manifestations	Onset (hr)	Symptoms/signs
Minor withdrawal (withdrawal tremulousness)	6-24	Tremor, anxiety, nausea, vomiting, and insomnia.
Major withdrawal (alcoholic hallucinosis)	12-48	Visual/auditory hallucinations, whole body tremor, vomiting, diaphoresis, and high BP ?? ??? ?? ??? ???? ?? 1?? ??? ??.
Seizures (rum fits)	12-48	Single or multiple GTC
Delirium tremens	48-96	Confusion, agitation, fever, tachycardia, hypertension, diaphoresis, hallucinations

Wernicke: ????/????/????
Korsakoff: ?? ????, ???

? ? ??? thiamine ??! But irreversible.

C20.3 Caffeine-Related Disorders

C20.4 Cannabis-Related Disorders

The primary psychoactive chemical in cannabis is delta-9-tetrahydrocannabinol(THC)

Intoxication

Physiologic
- Conjunctival injection (red eyes), dry mouth, tachycardia, ?appetite
Cognitive
- Slow reaction time, incoordination, impaired short-term memory, and poor concentration
- Some may experience dysphoria, social withdrawal, anxiety, and paranoia when exposed to higher doses of THC
- Psychomotor impairment lasts beyond the timeframe of euphoria and can persist for up to a day.

Withdrawal
Insomnia, decreased appetite

C20.5 Hallucinogen-Related Disorders

Preparations

Epidemiology

Phencyclidine

Neuropharmacology

Phencyclidine

NMDA receptors, particularly in the hippocampus and limbic system (causing excitatory and psychotic effects)
Dopamine, norepinephrine, and serotonin receptors (causing adrenergic and dopaminergic effects)
The sigma receptor complex (causing psychotic and anticholinergic effects)

Diagnosis

Hallucinogen use disorder
Hallucinogen intoxication
Hallucinogen persisting perception disorder
Hallucinogen intoxication delirium
Hallucinogen-induced psychotic disorders
Hallucinogen-induced mood disorder
Hallucinogen-induced anxiety disorder
Unspecified hallucinogen-related disorder

Clinical features

Lsysergic acid diethylamide (LSD)

Phenethylamines

Severe agitation, delusions of enhanced strength, psychosis (eg, paranoia, hallucinations), analgesia, and aggression
P/E: multidirectional nystagmus, hypertension, tachycardia, and disorientation
Severe: hyperthermia, ataxia, muscle rigidity, seizures, and coma

Mescaline

Psilocybin analogs

Phencyclidine

Ketamine

Additional hallucinogens

Canthinones
Ibogaine
Ayahuasca
Salvia divinorum

Treatment

Hallucinogen intoxication
Hallucinogen persisting perception disorder
Hallucinogen-induced psychosis
Pencyclidine
- Supportive management.
- BZDs are preferred for PCP-associated agitation.

C20.6 Inhalant-Related Disorders

Physiology

Toluene, the main component of volatile glues, lacquer thinners and aerosol paints is the chemical responsible for most clinical toxicity.

Inhalants cause an initial excitatory response through the release of epinephrine and activation of the dopamine system, followed by central nervous system depression mediated by the use of GABA pathway

Clinical presentation

Immediate effects
- As they are highly lipid soluble and act as CNS depressants
- Sense of euphoria, excitation, dizziness, disinhibited behaviour and exhilaration similar to alcohol intoxication, thus resulting in psychological dependence.
- Effects typically last 15-45 minutes.
Repeated inhalations
- Headache, slurred speech, diplopia, gait abnormality, delusions, visual hallucinations and disorientation.
- Behavioral changes and characteristic odor on breath or clothing.
- Suspected users may also complain of cough, stuffy nose, sneezing, flushing, salivation, nausea, vomiting and photophobia.
Other signs and symptoms of inhalant abuse include �
- Spots or sores in or around the mouth, injected sclera, nystagmus, irritability or excitability, anxiety and sleep disturbances.
- Paint or other stains on the face, hands, or clothes are other indicators of abuse.
- Severe dryness of facial skin and mucus membranes can also be a feature of repeated, prolonged use of volatile substances .
- Bacterial infection of the dry and cracked skin may result in perioral and perinasal pyodermas, sometimes referred to as �Huffer�s rash�
Complications
- Cardiac dysrhythmias, dangerous behavior, seizures, and death.

Diagnosis

Presence of maladaptive behavioral changes and at least two physical symptoms.

The intoxicated state is often characterized by apathy, diminished social and occupational functioning, impaired judgment, and impulsive or aggressive behavior, and it can be accompanied by nausea, anorexia, nystagmus, depressed reflexes, and diplopia.

Clinicians can sometimes identify a recent user of inhalants by rashes around the patient’s nose and mouth; unusual breath odors; the residue of the inhalant substances on the patient’s face, hands, or clothing; and irritation of the patient’s eyes, throat, lungs, and nose.

C20.7 Opioid-Related Disorders

Epidemiology

Neuropharmacology

Tolerance and dependence

Comorbidity

Etiology

Psychosocial factors

Biologic and genetic factors

Psychodynamic theory

Diagnosis

Opioid use disorder

Risk factors associated with increased risk for prescription drug misuse:

Age<45, psychiatric disorder, personal or family history of substance use disorder, or a legal history.

Review of the state’s prescription drug-monitoring program data

Random urine drug screening (UDS)
Frequent follow-up visits
Patients prescribed long-term opioids should be seen at least once every 3 months throughout the course of treatment and even more frequently in high-risk situations.

Opioid intoxication

Miosis
- But normal pupil size does not r/o intoxication d/t possible coingestants(eg, sympathomimetics)
Decreased bowel signs
Hypotension
- D/t opioid-induced histamine release from mast cells.
Reduced respiratory rate
- <12/min is the best predictor of opioid toxicity
Prolonged QTc with methadone overdose
- Consider continuous cardiac monitoring if QTc >500 msec.

Opioid withdrawal

Begins approximately 12 hours after last use.
Gastrointestinal distress (eg, nausea, diarrhea, abdominal cramping)
Myalgias, mydriasis, pilorerection, and lacrimation
Buprenorphine(sublingual) for symptomatic treatment

Opioid intoxication delirium

Can cause rhabdomyolysis

Opioid-induced psychotic disorder

Opioid-induced mood disorder

Opioid-induced sleep disorder and opioid-induced sexual dysfunction

Unspecified opioid-related disorder

Clinical features

Adverse effects

Opioid overdose

MPTP-induced Parkinsonism

Treatment and rehabilitation

Overdose treatment

Medically supervised withdrawal and detoxification

Methadone
- Long-acting oral opiate used for heroin detoxification or long-term maintenance therapy
Buprenorphine + naloxone
- Buprenorphine: partial agonist, sublingual
- Naloxone is added to lower IV abuse potential (not orally bioavailable)
Naltrexone
- Long-acting opioid given IM or as nasal spray.

Pregnant women with opioid dependence

Neonatal abstinence syndrome
- At-risk newborns
  - Born to mothers with poor mental health, no prenatal care, HCV
- Complex disorder involving CNS, ANS, and GI systems.
  - Uncoordinated sucking reflexes, irritability, high-pitched crying
  - Tremors, tachypnea, sneezing, diarrhea, and possible seizures.
- Treatment: opiate replacement
Fetal AIDS transmission

Psychotherapy

Therapeutic communities

Narcotic anonymous

C20.8 Sedative-, Hypnotic-, or Anxiolytic-Related Disorders

Benzodiazepine

Intoxication

Depress central respiratory drive
Treatment
- Flumazenil
  - Nonspecific competitive antagonist
  - It does not consistently reverse respiratory depression and can potentiate seizures in patients who have developed a tolerance to BZDs.

Dependence

Rebound phenomenon: reemergence of symptoms (e.g., depression, insomnia, and anxiety) that were previously absent or controlled by benzodiazepine therapy when the medication is discontinued for a few days
Withdrawal symptoms
- Autonomic nervous system
  - Sweating
  - Nausea, vomiting, and anorexia
  - Hypertension
- Neurological
  - Seizure
  - Tremors
  - Memory impairment
- Psychiatric
  - Withdrawal psychosis with optic and auditory hallucinations
  - Depressive moods
Treatment
- Nonpharmacological measures: psychotherapy, inpatient care
- Pharmacological measures
  - Dose tapering
  - Seizure prophylaxis (e.g., carbamazepine)
  - Catatonic excitement: antipsychotics (e.g., haloperidol)

C20.9 Stimulant-Related Disorders

Amphetamines

Intoxication

Sympathetic stimulation
- ?BP & pulse, hyperthermia
- Sweating, pupillary dilation
Marked weight loss
Psychotic symptoms
- Paranoid delusions
- Auditory, visual, and tactile hallucinations (eg, bugs crawling under the skin)
Excoriations d/t chronic skin picking.
Severe dental problems (“meth mouth”)
- Brown discoloration, tooth decay, and cracked teeth d/t severe bruxism and dry mouth.
Mood disturbances, anxiety, irritability, confusion, violent behavior

Diagnosis by urine toxicology testing

False positives
- Decongestant pseudoephedrine
- Antidepressants bupropion and selegiline

Cocaine

Intoxication

Sympathetic stimulation (? & ?)
- Diaphoresis, tremulousness, tachycardia, hypertension, mydriasis
- Coronary vasoconstriction & ?HR
  - Chest pain, ST-depressiono
- Enhances thrombus formation by promoting platelet activation and aggregation.
Intranasal abuse
- By local vasoconstriction and impaired cell-mediated immunity and reduced mucociliary clearance, as would the effects of any impurities in the inhaled substance.
- Chronic nasal discharge, atrophic nasal mucosa, thinning of the nasal septum leading to perforation, oropharyngeal ulcers, and osteolytic sinusitis
Psychologic effects
- Elevated or irritable mood, hyperactivity, agitation, and pressured speech
- Delusions, paranoia, hallucinations (auditory, visual, tactile), grandiosity
Treatment of acute intoxication
- Benzodiazepines
  - By reducing sympathetic outflow, reduce anxiety and agitation, improve BP and HR, and alleviate cardiovascular symptoms.
- Aspirin
  - To retard thrombus formation
- Nitrates, CCB
  - Vasodilation
- ~~Beta blocker~~
  - Contraindication d/t unopposed ? adrenergic stimulation and worsen coronary vasoconstriction.
Psychotherapy
12-step groups
- eg, Cocaine anonymous, Narcotics anonymous

Exposure in utero

Hypertonia, tremors in neonates and impairments in attention, language development, and behavioral regulation in school-aged children.

C20.10 Tobacco-Related Disorders

Nicotine? ??

Dopamine reinforcement ? ?? ???? ?
??? 2hr, ??? 90???, 24~48hr? ???
???? ??? ??? ??? ? ?? ?? ???.

Pharmacological strategies

Nicotine replacement therapy
- First-line approach.
- Nicotine patch
- Nicotine gum
- Nicotine lozenges
- Headaches and insomnia
Varenicline
- ?4?2 nicotinic acetylcholine receptor – partial agonist/antagonist, ????? D???
- First-line drug. ????, ???? ??? ???. ???? ?? ?????
- Begin at least one week prior to smoking cessation and continue for a maintenance period of 12 weeks once smoking cessation is achieved.
- Patients with pre-existing psychiatric conditions should be stable and suicidal ideation should be ruled out prior to initiating treatment.
- Used with caution in patients with seizure disorders
Bupropion HCI SR
- ??? ??? ???
- Contraindicated in patients who have predisposing conditions that increase the risk of seizures (e.g., seizure disorders, anorexia or bulimia nervosa, alcohol withdrawal, abrupt discontinuation of benzodiazepines) because it reduces the seizure threshold.

Pharmacologic management combined with behavioral interventions are more effective than pharmacologic management alone.

C20.11 Anabolic-Androgenic Steroid Abuse

Compounds usually administered orally
Fluoxymesterone (Halotestin, Android-F, Ultandren)
Methandienone (formerly called methandrostenolone; Dianabol)
Methyltestosterone (Android, Testred, Virilon)
Mibolerone (Cheque Dropsa)
Oxandrolone (Anavar)
Oxymetholone (Anadrol, Hemogenin)
Mesterolone (Mestoranum, Proviron)
Stanozolol (Winstrol)
Compounds usually administered intramuscularly
Nandrolone decanoate (Deca-Durabolin)
Nandrolone phenpropionate (Durabolin)
Methenolone enanthate (Primobolan Depot)
Boldenone undecylenate (Equipoisea)
Stanozolol (Winstrol-Va)
Testosterone esters blends (Sustanon, Sten)
Testosterone cypionate
Testosterone enanthate (Delatestryl)
Testosterone propionate (Testoviron, Androlan)
Testosterone undecanoate (Andriol, Restandol)
Trenbolone acetate (Finajet, Finaplixa)
Trenbolone hexahydrobencylcarbonate (Parabolan)

Epidemiology

Pharmacology

Therapeutic indications

Adverse reactions

Etiology

Diagnosis and clinical features

Reproductive
- Men: ?testicular function & sperm production, gynecomastia
- Women: acne, hirsutism, voice deepening, menstrual irregularities
Cardiovascular
- LVH, possible ?HDL & ?LDL
Psychiatric
- Aggressive behavior (men), mood disturbances
Hematologic
- Polycythemia, possible hypercoagulability

Medical Archive

Leave a Reply Cancel reply

Your cart (items: 0)