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Addiction Issues in Critical Care

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Title: Addiction Issues in Critical Care


1
Addiction Issues in Critical Care
  • Kevin Kunz, M.D., M.P.H., FASAM

2
Overview of Todays Talk
  • Addiction What is It?
  • Complications of Addiction
  • Central Nervous System
  • Toxicity and Overdose,Withdrawal
  • Other Brain Syndromes
  • Other Organ Systems
  • Virtually all systems can be effected
  • Liver hepatitis Cardiovascular MI, DCM,CVA
    Pulmonary COPD, Crack Lung Etc., Etc.
  • Sedative-Hypnotics, Stimulants, Opioids

3
The United States of Drugs
4
Drug Dependence or Addiction?
  • Physical Dependence
  • A normal physiologic response to the medical
    use of certain drugs
  • Addiction
  • Involves the non-medical use of drugs

5
Physical Dependence
  • A state of neuroadaption manifested by a drug
    class-specific withdrawal syndrome
  • Produced by abrupt cessation, rapid dose
    reduction, decreasing bioavailability, or use of
    antagonist.
  • An expected occurrence in all individuals in the
    presence of continuous use of opioids for days
    or weeks.

6
Addiction
  • A Primary Disease
  • A Neurobiological Disease
  • It Has A Genetic Component/Vulnerability
  • Psychosocial, Environmental Component
  • Its Development and Manifestations are Influenced
    by the Interplay of Biology and Environment

7
Addictions 5 Cs
  • Control is Lost
  • Consequences of Use
  • Continued Use Despite Consequences
  • Craving
  • Compulsive Use

8
What Does Addiction Look Like?
  • Non-medical use of drugs
  • 10-15 of U.S. population (excluding nicotine)
  • Patients often unable to discern negative impact
    on quality of life
  • Denial, minimalization, rationalization, other
    defense mechanisms prominent
  • Affective Component
  • Set, Setting, Substance

9
Based on 25 Years of Research
  • Drug addiction is a brain disease. A disease
    that disrupts the mechanisms responsible for
    generating, modulating, and controlling our
    cognitive, emotional, and social behavior.
  • Due to stigma, ignorance and mis-conceptions,
    there is a disconnect between the scientific
    data and the public and sometimes professional
    view of the nature of addiction and its
    appropriate treatment.

10
Neurobiology of Addictive Drugs
  • All Addictive Drugs Stimulate Dopamine Release
    in Brain Reward Pathways

11
Mesolimbic pathway
12
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13
.
14
.
15
.
16
.
17
Why Do People Use Drugs?
18
.
19
Once A Person Has Used Dependence Producing Drugs
For Awhile..Why Cant They Just Stop?
20
Prolonged Drug Use Changes The Brain In
Fundamental and Long-Lasting Ways
21
.
22
.
23
.
24
Sedative-Hypnotics
25
Sedative-Hypnotics
  • Alcohol (ethanol)
  • Benzodiazepines
  • Barbiturates
  • GHB

26
Alcohol
27
Alcohol Toxicity/Overdose
  • Mg/dl
  • .03
  • .05
  • .100
  • .200
  • .300
  • .400
  • .500
  • Typical Symptoms
  • Mild euphoria
  • Mild incoordination
  • Ataxia
  • Confusion, somulence
  • Stupor
  • Deep anesthesia
  • Lethal dose in 50 of patients

28
Treatment of EtOh OD
  • ABCs
  • Thiamine
  • Usually supportive only, dont discharge until
    BAL lt.1
  • Fructose, hemodialysis rarely used

29
Other Alcohols
  • Isopropyl Alcohol (rubbing alcohol)
  • Rx same as for ethanol
  • Methanol (wood alcohol)
  • Common industrial solvent
  • Snowstorm vision, blurred vision, blindness
  • Headache, abdominal pain, seizures
  • Rx Gastric lavage, ethanol, thiamine,
    pyridoxine, dialysis
  • Ethylene Glycol (antifreeze)
  • narcosis, seizures, renal failure, coma,
    CaOxylate Xtals
  • RX Respiratory support, ethanol drip/fomepizole,
    thiamine, pyrodixine, hemodialysis

30
Arnold Alcohol Overdose
  • Arnold is a 20 year-old student who
  • was partying with friends. They decided to see
  • who could best handle their liquor, and
  • began downing shots of vodka.
  • After 22 shots, Arnold stood up, vomited and
  • collapsed. In the ED, he was unconscious with
  • decreased reflexes. RR 10, BP 70/40, BAL .624

31
Arnold Alcohol Overdose
  • He received supportive care (ABC), was
  • intubated, given thiamine stat, aspiration
  • precautions. 11 monitoring with soft
    restraints.
  • Drug screen THC. He awoke 16 h later, and
  • was oriented. Extubated, observed and
  • discharged to his sisters care. He pledged to
  • quit alcohol, join the gym, and enlist in the
  • Marines. He was given the toll-free number for
  • a Behavioral Health referral line.

32
Arnold Alcohol Overdose
  • At what mg/dl was Arnold overdosed?

33
Goals Principles of Detox
34
Goals of Detoxification
  • To provide a safe withdrawal.
  • To provide a withdrawal that is humane and
    protects the patients dignity.
  • To prepare the patient for ongoing treatment of
    his/her primary addictive disease

35
Principles of Detoxification
  • Detox does not constitute treatment
  • Use protocols of established safety/efficacy
  • Control patients access to medication, and use
    lowest effective doses
  • Initiation of withdrawal should be individualized
  • When possible, substitute long-acting meds for
    short acting drugs of addiction
  • The intensity and course of withdrawal is
    variable and not always predictable
  • Patients should begin participating ASAP in
    recovery treatment programs

36
Alcohol Withdrawal Syndrome
  • EtOh is a CNS depressant
  • Enhances GABA effect
  • Inhibits autonomic adrenergic systems
  • modulates dopamine in the mesolimbic system
  • Abstinence or Decrease causes rebound
  • Relative GABA deficiency leads to anxiety,
    increased psychomotor activity, seizure kindling
  • Rebound sympathetic adrenergic activity leads to
    tachycardia, HBP, tremor, diaphoresis

37
Clinical Expression of the Alcohol Withdrawal
Syndrome
38
AWS SubTypes
39
Receptor Directed Treatment
40
Receptor Directed Treatment
  • Each AWS SubType may present alone, or with one
    or both other Subtypes
  • Each type can be variable in intensity
  • Titrate the specific antidote for each Subtype
    to its clinical intensity
  • Presence and Intensity can be scored for each
    subtype, and score can direct treatment

41
Standard AWS Protocol
  • CMP, CBC, PT/PTT/INR, UA, B12, Urine Drug Screen.
    EKG.
  • Monitor and correct minerals, lytes, NH3
  • Screen for Hep A,B,C, HIV, TB
  • Thiamine, Multivits
  • IV access
  • AWS Type Score q 2-4 hr and prn Titrate Rx to
    Type Scores

42
AWS Type A Treatment (CNS Excitation)
  • Score
  • 1 Anxious/Nervous?
  • 1 Restless?
  • 1 Bothered by Bright Light?
  • 1 Bothered by Loud Sounds?
  • Treat to Attenuate
  • Score 2 or more?, then
  • diazepam
  • lorazepam
  • gabapentin
  • other sedative/hypnotic

43
Type A Treatment Caveats(CNS Excitation)
  • Tendency to use benzodiazepines (BNZ) in too low,
    or too high a dose
  • Librium and Valium contraindicated in liver
    disease use Ativan. Valium ½ life extended.
  • Potential adverse effects may complicate and
    prolong withdrawal
  • BNZ and barbiturates may cause ataxia,
    over-sedation, respiratory depression,
    dis-inhibition, cognitive disruption

44
AWS Type B Treatment(hyperadrenergic)
  • Treat to Attenuate
  • Score 2 or more?, then
  • Inderal
  • Atenolol
  • Clonidine
  • Tizanidine
  • Score
  • 1 Nausea/Vomiting?
  • 1 Any Tremor?
  • 1 Any Sweat?, SBP gt 140 ?
  • 1 Diastolic BP gt 90 ?
  • 1 Heart Rate gt 100?
  • 1 Extra/Skipped Beats ?

45
Type B Treatment Caveats(hyperadrenergic)
  • Beta Blockers
  • Contraindications
  • Volume depletion, asthma/COPD, CHF, sick sinus
    syndrome, high-grade conduction blocks
  • Potential Adverse Effects
  • Hypotension, bradycardia, bronchospasm
  • Alpha Agents
  • Contraindications
  • As above except asthma/COPD
  • Potential Adverse Effects
  • Hypotension, bradycardia, confusion (rare)

46
AWS Type C Treatment(dopaminergic)
  • Score
  • 1 Inappropriate responses?
  • 1 Hearing voices, seeing something that is not
    there?
  • 1 Knows Name? Location?
  • 1 Days in Hospital?
  • 1 Year, Month, Day of Week
  • Treat to Attenuate
  • Haldol 2.5 IV/PO q 4 hours prn
  • Droperidol 1.25 IV q 4 hours prn
  • add antiEPS med to above meds
  • Zyprexa Melt

47
Example 1Mixed AWS SubType Treatment
48
Example 2- DeliriumAWS Subtype Treatment
49
Heres Arnold.
  • Arnold kept his word until the Marine recruiter
    told
  • him that he could drink alcohol, but would have
    to
  • discontinue marijuana. So he began drinking
  • again. After Gulf War I, he began drinking large
  • daily amounts. He was fired from his hotel job,
  • went broke and stopped drinking. Three days
    later
  • his sister found him urinating on her new rug.
    He
  • had a seizure in the ambulance, was stabilized in
  • The ED, sent to the Critical Care Unit.

50
Example 3 Delirium Tremens
51
Classic Alcoholic Delirium
  • Tom Sawyer described it in his alcoholic father
  • Incidence of 5 in hospitalized AWS pts
  • Abrupt onset is usual
  • Global confusion and disorientation
  • Patient in a separate psychic reality
  • Auditory and visual hallucinations
  • No insight to condition, can be frightening
  • Agitation, increased psychomotor activity common
  • Disturbed sleep cycle

52
Risk Factors for Delirium, DTs
  • Often no identifiable risk factor other than
    decrease/abstinence of alcohol
  • Poor Correlation Duration of heavy drinking and
    amount of daily intake
  • High blood alcohol on admission (greater than
    300mg/dl)
  • Age
  • Co-morbidity
  • GI Bleed,trauma,Hx of past AWS,malnutrition,
    concurrent drug use, etc.

53
Delirium and Delirium Tremens
  • delirium can occur with or without the tremens
  • tremens refers to the extreme Type B
    withdrawal signs and symptoms
  • appears 3-4 days after the last drink
  • continues an average of 2-3 days, with a range
    from a few hours to over 30 days
  • Cannot always be predicted nor prevented

54
Initial Treatment ofDelirium and DTs
  • ABCs
  • Routine laboratory panels. Rx Thiamine, Folate,
    Mg
  • Diazepam 5-10 mg IV bolus q 5-15 minutes until
    sedated ( lorazepam if diazepam contraindicated)
  • If diazepam not working, may use pentobarbital,
    initially 50 mg IV over several minutes, then q
    5-15 minutes until sedated
  • Neuroleptics, after acute treatment/stabilization

55
Delirium Rx in Kona
  • Haldol 2.5 5mg IV q 4H prn
  • Benadryl 25-50mg/d to prevent dystonia
  • Ativan (Valium if liver OK), IV q 2-4 hours prn
  • Pentobarbital protocol if Haldol fails
  • Sublinqual atypical neuroleptics now being used
    in some settings
  • Hydration, monitoring and correction of
    lytes/minerals, restraints when needed
  • Minimize dose of all meds, make patient
    comfortable, conscious sedation not necessary

56
Type C Treatment Caveats(dopaminergic)
  • Haldol, Droperidol
  • Contraindications
  • Prolonged QT interval, Parkinsons, hypotension
  • Potential Adverse Effects
  • Heavy sedation, dystonic reactions, Parkinsonian
    crisis, neuroleptic malignant syndrome,
    pro-convulsant
  • Risperdal, Zyprexa
  • Relative Contraindication cost
  • Potential Adverse Effects
  • Pro-convulsant, at high dose may exacerbate
    pre-existing psychotic disorder

57
Delirium Differential Diagnosis
  • D
  • E
  • L
  • I
  • R
  • I
  • U
  • M
  • (S)
  • Drugs, Drugs, Drugs
  • Eyes, ears
  • Low O2 states
  • Infection
  • Retention (urine,stool),Restraints
  • Ictal
  • Underhydration/nutrition
  • Metabolic
  • Subdural, Sleep Deprivation

58
Delirium I Watch Death
  • Infection
  • Withdrawal (drugs)
  • Acute Metabolic
  • Trauma
  • CNS Pathology
  • Hypoxia
  • Deficiencies ( B12, folate, niacin, thiamine)
  • Endocrinopathies
  • Acute Vascular
  • Toxins or drugs
  • Heavy Metals (lead, Manganese, mercury)

59
Seizures
  • Seizures reported in 11-35 of patients
    withdrawing from alcohol in the hospital setting
  • Usually grand mal and single, or a burst of
    several over 1-6 hours
  • Always rule-out other causes subdural,
    stimulant (and tramadol) induced not uncommon
  • Phenytoin is not prophylactic, and not indicated
    for Rx - use BNZ
  • Seizures can occur without any other
    manifestations of AWS
  • Seizure Protocol

60
Other EtOh Related Neurologic Disorders
  • Intermediate Brain Syndrome
  • Wernickes Encephalopathy
  • Korsakoffs Psychosis
  • Alcoholic Dementia
  • Alcoholic Cerebellar Degeneration
  • Alcoholic Polyneuropathy
  • Central Pontine Myelinolysis

61
Wernicke Korsakoff
  • Wernickes Disease
  • Caused by thiamine deficiency
  • Diagnostic triad mental disturbance (apathy,
    confusion, etc), sixth nerve palsy (and
    nystagmus), ataxia
  • Delay in treatment risks permanent damage
  • Korsakoffs Psychosis
  • Profound deficit in retentive memory, learning
  • Intelligence and verbal abilities preserved
  • Confabulation
  • Often follows Wernickes Disease

62
Thiamine and Wernicke-Korsakoff
  • Thiamine 100mg IV to every EtOhic ASAP
  • Give thiamine before glucose solution
  • Then give thiamine 100 mg daily IV or PO
  • Thiamine is used to prevent Wernickes disease,
    and to treat Korsakoffs psychosis

63
Central Pontine Myelinolysis
  • Dysarthria
  • Dysphagia
  • Flaccid paralysis
  • Edema of the pons, caused by sudden/quick
    correction of hyponatremia (confirm w CT/MRI)
  • Increased Riskhypokalemia, malnutrition,
    alcoholism

64
GHB
65
GHB
  • G, Scoop, Grievous Bodily Harm, Easy Lay,
  • Blue Nitro, Pro-G, Thunder, Georgia Home
  • Boy, Great Hormones at Bedtime, Remedy,
  • Gamma G, Serenity II, Zen, Weight Belt
  • Cleaner, Liquid Ecstasy, Somatomax

66
GHB
  • The industrial solvent 1,4-butanediol is
    converted to gamma-aminobutyric acid(GHB) when
    ingested.
  • GHB is a natural brain metabolite of GABA
  • GHB synthesized in 1960 as anesthetic agent
  • 1970 sleep aid 1980 growth hormone
    stimulator for body builders
  • 1991 banned by FDA after deaths
  • 1,4-butanediol, GABA and GHB are all found
    endogenously in non-abusing humans

67
GHB Effects
  • Sedation and Euphoria
  • Relaxation, disinhibition, tranquility
  • Sexual enhancement, sensual drug
  • No appreciable hangover
  • Synergistic effects with alcohol

68
GHB - Pharmacodynamics
  • Steep dose response curve
  • Peak plasma levels at 20-60 minutes
  • Effects last 1-3 hours
  • Not detected in routine drug screens

69
GHB- Toxicity, Adverse Effects
  • Drowsiness, confusion, delirium
  • Antegrade amnesia
  • Respiratory depression/arrest, aspiration
  • Hypotension, hypothermia
  • Hallucinations
  • Crisis Triad bradycardia, myoclonus, coma

70
GHB Overdose - Treatment
  • ABCs, Supportive Care
  • No antagonist

71
Arnold and Amy
  • Arnold met Amy at a drug treatment program. Love
  • at first sight. They had some Thunder Nectar
    that
  • a friend got from the Internet. He ingested
    200ml,
  • she 120ml. Her last memory was 15 m. after the
  • drink, she awoke 7 hours later, on the floor with
  • Arnold, both with fecal incontinence and covered
  • with vomitus. Arnold was dead. Autopsy
  • pulmonary edema, no aspiration. BAL was zero,
  • drug screen negative. Amy moved in with her
  • Mother.

72
GHB Withdrawal
73
GHB Withdrawal Treatment
  • Benzodiazepines
  • Barbiturates
  • Propofol
  • Gabapentin
  • Neuroleptics ( questionable value)

74
Stimulants
75
Stimulants
  • Ephedra and Pseudoephedrine
  • Cocaine
  • Methamphetamine
  • Ecstasy

76
All Stimulants Can Cause
77
Ephedra, Pseudoephedrine, Etc.
  • Naturally occurring alkaloids
  • Regulations and restrictions increasing secondary
    to morbidity/mortality of herbal, natural
    energy/weight loss formulations
  • Same range of physiological and psychological
    effects as cocaine, ice
  • Associated with severe CV and CNS effects
  • Can cause false methamphetamine urine screen
  • Phenylpropanolamine outlawed in 2002

78
Cocaine
79
Cocaine
  • Occurs naturally in coca leaves. Must grow it,
    cant cook it.
  • Coca chewers like coffee drinkers, but 5 of
    snorters become addicted, risk is very high for
    smokers, injectors
  • Street cocaine 10-50 pure may contain
    talc,flour, sugars, procaine, cafffeine,
    amphetamine, theophylloine, bacteria,fungi,
    viruses

80
Cocaine
  • Inhibits reuptake of dopamine, norepinephrine,
    serotonin at pre-synaptic neuronal terminal
  • Euphoria, increased energy and libido, decreased
    appetite, increased self-confidence, etc.
  • Smoked Freebase or Crack (Rock)
  • Freebase lipid soluble, similar or faster than
    IV
  • Crack preprepared, inexpensive, impurities

81
Why Smoke Drugs?
82
Cocaethylene(Ethyl Cocaine)
  • Psychoactive Substrate from EtOhCocaine
  • Drink alcohol first, inhibiting cocaine
    metabolism, produces cocaethylene
  • Prolongs duration of high, brain effects
  • 60-90 of cocaine abusers, abuse EtOh
  • Higher seizure risk
  • Greater cardiac toxicity, hepatic damage

83
Cocaine Toxicity/Overdose
  • Anxiety, agitation, confusion, anger
  • Tactile hallucinations
  • Paranoid ideation
  • Muscle twitching, rhabdomyolysis, seizures
  • Cardiac ischemia and arrythmias
  • Cerebral infarct and hemorrhage

84
Cocaine Critical Care Treatment
  • ABCs
  • Benzodiazepines
  • Neuroleptics (Haldol, droperidol)

85
Cocaine Withdrawal
  • Rarely a Critical Care Issue
  • Dysphoria, Depression, Suicidality
  • Insomnia and hypersomnia
  • Increased appetite, fatigue
  • Unpleasant dreams
  • Agitation
  • Anhedonia ( lack of pleasure, joy)

86
ICE
87
ICE
  • Synthesized in Japan, 1919, as a decongestant and
    bronchodilator
  • Hawaii has replaced San Diego as the ice capital
    of America
  • In Hawaii, 99 smoked, lt1 injected. Can be
    snorted or ingested
  • After marijuana, ice is the most widely used
    illicit drug in the world

88
ICE Easy to Cook, and Cheap
  • Over 100 recipes available for cooks
  • Ingredients still available despite sale
    restrictions
  • 1 gram provides about 30 doses, cost is about 5
    a dose.

89
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90
Medical Methamphetamine
  • Schedule II Psychostimulant (Desoxyn)
  • Medical use for narcolepsy, ADD, obesity
  • Pharmaceutical companies were the first dealers,
    pushers

91
ICE
  • Causes release of dopamine, norepinephrine
  • Metabolized to amphetamine, renal excretion.
    Urine for meth and amph
  • Subjective effects similar to cocaine the poor
    mans cocaine
  • Fat Soluble, liver degrades it, kidneys excrete
    it

92
ICE Use and Effects
  • Smoking
  • Instantaneous
  • Rush, flash
  • High lasts only minutes, other effects lasts
    hours
  • Tolerance occurs within minutes
  • Binge and crash pattern
  • Euphoria, alertness, vigilance, anxiety, paranoia

93
Tweaking
  • During the tweaking stage, the user has often
  • not slept for days and is extremely irritable.
  • The tweaker craves more ice, which results in
  • frustration and contributes to anxiety and
  • restlessness. At this stage the user may
  • become violent without provocation, anything
  • can antagonize him/her. The urine screen can be
  • negative.

94
Dangerous Tweakers
  • Keep your distance
  • Dont shine bright lights
  • Move, speak slowly
  • Keep the tweaker talking

95
Users Self-Reported Problems
  • Previous Psych Rx 14
  • Depressed a lot 19
  • Suicidal thoughts 7
  • Hallucinations 35
  • Paranoid thoughts 29
  • Chest pain 30
  • Headaches 43
  • Seizures 2
  • LOC 8
  • Need Rx 11

96
Ice Toxicity and Overdose
  • Typical catecholamine excess presentation
  • Elevated BP, P, mydriasis
  • Malignant Hyperthermia
  • Vasoconstriction
  • Muscle rigidity
  • Severe Agitaton
  • Acute Psychosis/Protracted Psychosis

97
Ice Critical Care Diagnoses
  • Cardiotoxicity (vasospasm, CAD, CHF, DCM)
  • Acute Aortic Dissections, Ruptured Berry
    aneurysms
  • Acute Pulmonary Edema
  • Pulmonary Hypertension
  • Rhabdomyolysis
  • Intracranial Hemorrhage, Seizures
  • Psychosis
  • Homocidal/Suicidal

98
CVA
99
ICE CCU Treatment Issues
  • ABCs, Control of BP, Rx of Med Complications
  • Minimize sensory stimulation
  • Haloperidol for agitation, psychosis
  • Benzodiazepines for anxiety, agitation, seizures
  • External cooling, Dantrolene, hydration important
  • Acidify the urine

100
Amy was in trouble.
  • Amy deteriorated after Arnolds death. She was
    severely depressed, and when a friend offered her
    a hit on an ice pipe, she tried it. After the
    second use, she was hooked. A year later she was
    arrested, and went to drug court. She thrived in
    the treatment program although she didnt
    continue in any community 12-step program. After
    one year, with all negative urine tests, her
    arrest record was cleared, and she returned to
    school. Seven years later she was still clean,
    and working as a nurse in a CCU.

101
Ecstasy
102
Ecstasy
  • 3,4 methylenedioxymethamphetamine MDMA
  • XTC, X, Adam, Clarity, Lovers Special
  • Orally ingested as pill or powder

103
Ecstasy
  • Being seen more frequently in Hawaii
  • Popular Club Drug 11 high school seniors
  • Patented by Pfizer in 1914
  • Appetite suppressor, psychotherapy enhancer
  • 1985, classified as Schedule I
  • Chemically Similar to
  • Amphetamine (stimulant)
  • Mescaline (hallucinogen)

104
Ecstasy Use and Effects
  • Onset 20-40 minutes
  • Sudden amphetamine-like rush
  • Plateau lasts 3-4 hours
  • Feeling of relatedness to the world
  • Wellbeing and openness, Sensual not sexual
  • Repetitive and trance-like movements
  • Serotonin
  • Induces release of serotonin stores
  • Blocks reuptake of serotonin

105
Ecstasy Toxicity
  • Hyperthermia
  • Acute Hepatic Toxicity
  • Depletion of glutathione leads to cell death
  • Acute Cardiovascular Toxicity
  • Acute Neurologic Toxicity
  • Antidiuretic effect of MDMA
  • Water intoxication
  • Hyponatremia leads to seizures
  • Serotonin Syndrtome

106
Serotonin Syndrome
  • Diagnostic Triad
  • Cognitive and Behavioral Changes
  • Confusion, agitation, delirium
  • Autonomic Instability
  • Tachycardia, HBP, fever, nausea/vomiting
  • Neuromuscular Changes
  • Myoclonus, hyperreflexia, rigidity
  • Differential Diagnosis
  • Neuroleptic Malignant Syndrome, sepsis, DTs, heat
    stroke, opioid withdrawal

107
Ecstasy Critical Care Treatment
  • Rx of hyperthermia and its complications
  • Rapid cooling is essential
  • Dantrolene (skeletal muscle relaxant) may be
    life-saving
  • Benzodiazepines
  • Anticonvulsants

108
Ecstasy Crash and Chronic Use
  • Crash, Aftereffects
  • Lasts 24 hours
  • Negative emotions, severe anhedonia
  • hangover effect
  • Decreased motivation
  • Chronic use is rare
  • Decreases serotonergic neurons
  • Inhibits synthesis of new serotonin
  • Serotonin Depletion Syndrome
  • Confusion, depression, anxiety
  • Insomnia, paranoia
  • Cognitive impairment

109
Opioids
110
Heroin ad
111
Prescribed Opioids In Hawaii(Source K. Kamita,
Chief, NED, State of Hawaii. 11/7/03)
  • Drug
  • APAP/hydrocodone
  • Tussionex
  • Endocet
  • OxyContin
  • Morphine sulfate
  • Methadone
  • Dosage Units
  • 2,310,398
  • 564,258
  • 561,658
  • 506,408
  • 335,502
  • 326,446

112
.morphine molecule
113
.opioid receptor model
  • .
  • .

114
Receptor Mediated Actions
  • Mu
  • Supraspinal analgesia
  • Euphoria
  • Respiratory depression
  • GI stasis, Pruritis
  • Urinary retention, Bradycardia
  • Physical dependence
  • Kappa
  • Analgesia, sedation, miosis,
    hyperalgesia
  • Sigma
  • Dysphoria, hallucinations, hypertonia,
    tachycardia,
  • tachypnea

115
Opioid Drug Classes
  • Agonist
  • Relieve pain and alter mood. Morphine,
    hydrocodone, fentanyl, tramadol, propoxyphene,
    codeine, etc.
  • Antagonist
  • Displace or block opioids from receptors, no mood
    altering effect. Naloxone, Naltrexone
  • Mixed agonist/antagonist
  • Have both agonist and antagonist actions.
    Buprenorphine (Suboxone), Stadol, Talwin

116
Opioid Adverse Effects
  • Sedation, Respiratory depression
  • Nausea, vomiting, sweating
  • Constipation (no tolerance)
  • Miosis (no tolerance), Truncal rigidity
  • Hypotension, Histamine release
  • GI effects decreases HCl, secretions, propulsive
    waves sphincter of Oddi
  • Inhibition of urinary voiding reflex
  • Tolerance,dependence,addiction (rare)

117
Opioid Overdose
  • Pinpoint pupils (later dilated)
  • Respiratory depression
  • Coma

118
Rx for Opioid Overdose
  • Airway and ventilation
  • Opioid antagonist (Narcan)
  • Dilute .4 mg in 10cc saline, titrate to effect
  • Be alert to rebound sympathetic response
    arrhythmias, pulm. Edema
  • Can precipitate major withdrawal syndrome

119
Opioid Withdrawal
  • Acute
  • Autonomic
  • Rebound increased NE activity from locus
    coeruleus
  • Increase BP, HR, peristalsis, diaphoresis, CNS
    irritability, etc.
  • Affective
  • Suppressed in the dopaminergic reward pathways
  • Depression, anxiety, anhedonia, craving, anergia
  • Protracted
  • 3-6 months or longer
  • Anxiety, insomnia, craving, cyclic changes in
    wgt, pupil size

120
Opioid Withdrawal Rx in the CCU
  • Administer opioids to extinquish withdrawal
  • Morphine is first choice
  • Buprenorphine
  • If agonist or agonist/antagonist contraindicated,
    move to other options

121
Buprenorphine(Subutex, Suboxone)
  • Opioid agonist/antagonist. Low diversion risk.
  • Replacing methadone in France, ? US
  • Excellent safety profile, decades of experience
    as IM-IV-SL analgesic. MDs now Rx for pain.
  • FDA approved for opioid detox or maintenance
  • Formulated as Subutex, and Suboxone -naloxone
    added to deter IV use, diversion
  • Being used in addiction and dependence
  • MDs can acquire DEA Detox OK CME required

122
Amy and Dr. Kunz
  • Amy was taking care of her mother, who was dying
    of
  • lung cancer. Amy, who had intermittent back pain
    and
  • was very stressed, tried some of her mothers
    liquid
  • MS. She eventually began diverting fentanyl from
    the
  • CCU for her own, IV use. Her co-workers caught
    on,
  • and sent her to Dr. Kunz. He admitted her to the
  • hospital, waited for her to go in withdrawal,
    then began
  • Suboxone, which she took for 4 days. She had no
  • significant withdrawal, and entered a residential
    drug
  • treatment program. She entered a monitoring
    contract
  • with a Hawaii professional organization.

123
Medical Withdrawal vs. Medical Detoxification
  • Withdrawal the process of safely and
    comfortably discontinuing opioids from a patient
    who is physically dependent
  • Detoxification the process of safely and
    comfortably discontinuing opioids from a person
    who is opioid addicted

124
Medical Withdrawal Options
  • Taper by 50 every several days (weaning),
    without signs/symptoms of withdrawal
  • Goodman Gilmans The Pharmacologic Basis of
    Therapeutics, Ninth Edition. McGraw-Hill 1996.
    P. 533
  • Transition to longer acting analgesic
    (propoxyphene, methadone if experienced) and
    taper
  • Symptomatic Rx clonidine, NSAID,
    anti-anxiety/sleeper, muscle relaxant, etc.
  • Suboxone safe, easy, effective
  • Always educate patient on withdrawal and WD Rx

125
Detoxification Options
  • Detoxification the treatment that is not a
    treatment provides a drug free person with an
    addictive disease, not a disease free person!
  • Ultra-Rapid Detox (with general anesthesia)
  • Naltrexone induced, hospital setting
  • Licensed methadone clinic (detox or maintenance)
  • Symptomatic medications
  • Clonidine, NSAID, Vistaril, Robaxin etc. high
    fail rate
  • Subutex/Suboxone (detox or maintenance)
  • Still need Rx for primary disease of addiction

126
References
  • Principles of Addiction Medicine 3rd Ed
  • American Society of Addiction Medicine, 2001,
    www.asam.org
  • Alcohol Withdrawal Manuel. P.B. DePetrello, M.K.
    McDonough. 1999. www.sagetalk.com
  • GHB NEJM, Vol.344, No.2, Jan. 11, 2001 Annals
    Emergency Medicine, eVersion, February 2001, Vol.
    37, No.2
  • National Institute of Drug Abuse.
    www.nida.nih.gov
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