Addiction Issues in Critical Care

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Addiction Issues in Critical Care

• Kevin Kunz, M.D., M.P.H., FASAM

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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

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The United States of Drugs
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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

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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.

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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

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Addictions 5 Cs

• Control is Lost
• Consequences of Use
• Continued Use Despite Consequences
• Craving
• Compulsive Use

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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

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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.

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Neurobiology of Addictive Drugs

• All Addictive Drugs Stimulate Dopamine Release
  in Brain Reward Pathways

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Mesolimbic pathway
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Why Do People Use Drugs?
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Once A Person Has Used Dependence Producing Drugs
For Awhile..Why Cant They Just Stop?
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Prolonged Drug Use Changes The Brain In
Fundamental and Long-Lasting Ways
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Sedative-Hypnotics
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Sedative-Hypnotics

• Alcohol (ethanol)
• Benzodiazepines
• Barbiturates
• GHB

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Alcohol
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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

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Treatment of EtOh OD

• ABCs
• Thiamine
• Usually supportive only, dont discharge until
  BAL lt.1
• Fructose, hemodialysis rarely used

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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

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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

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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.

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Arnold Alcohol Overdose

• At what mg/dl was Arnold overdosed?

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Goals Principles of Detox
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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

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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

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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

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Clinical Expression of the Alcohol Withdrawal
Syndrome
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AWS SubTypes
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Receptor Directed Treatment
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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

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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

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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

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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

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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 ?

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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)

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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

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Example 1Mixed AWS SubType Treatment
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Example 2- DeliriumAWS Subtype Treatment
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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.

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Example 3 Delirium Tremens
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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

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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.

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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

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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

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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

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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

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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

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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)

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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

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Other EtOh Related Neurologic Disorders

• Intermediate Brain Syndrome
• Wernickes Encephalopathy
• Korsakoffs Psychosis
• Alcoholic Dementia
• Alcoholic Cerebellar Degeneration
• Alcoholic Polyneuropathy
• Central Pontine Myelinolysis

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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

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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

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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

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GHB
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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

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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

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GHB Effects

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

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GHB - Pharmacodynamics

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

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GHB- Toxicity, Adverse Effects

• Drowsiness, confusion, delirium
• Antegrade amnesia
• Respiratory depression/arrest, aspiration
• Hypotension, hypothermia
• Hallucinations
• Crisis Triad bradycardia, myoclonus, coma

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GHB Overdose - Treatment

• ABCs, Supportive Care
• No antagonist

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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.

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GHB Withdrawal
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GHB Withdrawal Treatment

• Benzodiazepines
• Barbiturates
• Propofol
• Gabapentin
• Neuroleptics ( questionable value)

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Stimulants
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Stimulants

• Ephedra and Pseudoephedrine
• Cocaine
• Methamphetamine
• Ecstasy

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All Stimulants Can Cause
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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

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Cocaine
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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

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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

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Why Smoke Drugs?
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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

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Cocaine Toxicity/Overdose

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

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Cocaine Critical Care Treatment

• ABCs
• Benzodiazepines
• Neuroleptics (Haldol, droperidol)

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Cocaine Withdrawal

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

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ICE
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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

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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.

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Medical Methamphetamine

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

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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

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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

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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.

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Dangerous Tweakers

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

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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

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Ice Toxicity and Overdose

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

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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

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CVA
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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

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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.

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Ecstasy
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Ecstasy

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

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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)

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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

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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

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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

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Ecstasy Critical Care Treatment

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

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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

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Opioids
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Heroin ad
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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

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.morphine molecule
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.opioid receptor model

• .
• .

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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

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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

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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)

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Opioid Overdose

• Pinpoint pupils (later dilated)
• Respiratory depression
• Coma

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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

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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

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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

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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

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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