Detoxification Pharmacology

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Detoxification Pharmacology

• Rochelle Head-Dunham, M.D., FAPA
• Medical Director,
• Louisiana Office for Addictive Disorders

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Goals Objectives

• Discuss general guidelines and considerations for
  withdrawal and detoxification
• Discuss detoxification protocols
• for three major classes of substances of
  dependence

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Withdrawal Syndrome

• The characteristic group of signs and symptoms
  that typically develop after a rapid, marked
  decrease or discontinuation of a substance of
  dependence,
• which may or may not be clinically significantly
  of life threatening.

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Withdrawal Syndrome

• Withdrawal severity and duration depend on
  several factors
• Nature of substance
• Half-life and duration of action
• Length of time substance used
• Amount used
• Use of other substances
• Presence of other medical and psychiatric
  conditions
• Individual biopsychosocial variables

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The Clinical Assessment

• The diagnosis of dependence is made through a
  careful patient history and physical examination,
  focusing on the following information
• Drug type, route and duration of use, symptoms
  with cessation and last use
• Risk factors, symptoms and previous testing for
  blood-bourn pathogens
• Past Medical History and review of symptoms of
  chronic use such as malnutrition, tuberculosis
  infection, trauma, endocarditis, and sexually
  transmitted diseases
• Physical Examination to include vital signs, and
  cardiac status for evidence of fever, heart
  murmur, or hemodynamic instability exam should
  focus on skin areas for scarring, atrophy,
  infection
• Laboratory Evaluation should include a complete
  blood count, comprehensive chemistry panel, HIV
  testing, EKG, Chest x-ray, screening for STDs
• Urine Drug Screens and Breath Analysis (Alcohol)

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Detoxification

• The physiological process of withdrawal
• from a substance of dependence
• which requires medication management, careful
  monitoring, and
• the availability of lifesaving emergency
  interventions.

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Detoxification Levels of Care

• Severity of Withdrawal dictates appropriate level
  of care
• Medical Detoxification (24-hour care, hospital
  setting)
• Medically Supported Detoxification (24 hour care,
  non-hospital/residential setting with profession
  medical staff)
• Social Detoxification (24 hour care,
  non-hospital/residential setting without
  professional medical staff)
• May occur in outpatient setting with skilled
  clinician.

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DetoxificationGeneral Consideration

• High index of suspicion, non-judgmental
  questions, careful screening and assessment
• Anticipate inaccurate/minimized reports of use
• Psychological withdrawal for all, physiological
  for some
• All withdrawal syndromes not clinically
  significant
• Dangerous syndromes Alcohol, Sedative/hypnotic
  and Anxiolytic Withdrawal Opiate withdrawal is
  extremely uncomfortable

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DetoxificationGeneral Consideration (cond)

• Rule of thumb Substitute long acting,
  cross-tolerant substance with gradual tapering by
  10-20 per day
• Use adequate dosages for comfort
• Limit access to controlled substances
• Detox alone is rarely adequate treatment
• Management of co-morbid medical and psychiatric
  conditions

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Role of Medication in Detoxification

• Stabilization of psychological or physiological
  withdrawal symptoms
• Medical emergencies Alcohol, Sedative-hypnotics,
  Benzodiazepines,
• Remediation of non-life threatening,
  relapse-triggering symptoms
• Stabilization of co-morbid conditions

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ALCOHOL
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Detoxification

• Alcohol Withdrawal
• Autonomic dysfunction-Insomnia-Anxiety
• Onset 8 hrs, Peak 48hrs, Diminished 5dys,
  Duration 3-6 months
• Withdrawal Syndromes
• Mild, moderate or life-threatening severity
  (increased severity with BAL100mg/dl)
• 3 Withdrawal Seizures (w/in 48hrs of abstinence)
• Delirium Tremens (DTs) Medical Emergency!
• (w/in 48-72hrs of abstinence)
• (4-5 Prev., MM

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Withdrawal Assessment Clinical Institute
Withdrawal Assessment-Alcohol, revised (CIWA-Ar)

• Nausea
• Tremor
• Diaphoresis
• Anxiety
• Auditory disturbances
• Orientation
• Agitation
• Tactile disturbances
• Visual disturbances
• Headaches

• Withdrawal Severity 0 (not present) to 67
  (extreme) Higher risk
• 8-10 Mild Supportive, no Meds
• (i.e. Social Detox)
• 10-15 Moderate - Some meds (BZP)
• (i.e. Medically Supported Detox)
• 15/ Severe - DT Risk
• (i.e.. Hospitalization)
• N.B. May also be used to monitor recovery and
  medication management

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Sample Medication Protocol

• Days 1-2 Lorezepan 1-2 mg three times a day
• Days 3-4 Lorezepam 1-2 mg twice daily
• Day 5 Lorezepam 1-2mg, daily
• Adjust dosage and duration for intoxication
  or prolonged withdrawal
• Adjunctive treatments
• Seizure history Tegretol 200mg/Neurontin 400mg
  (5dy taper)
• Sympathetic activity Clonidine 0.1-0.2q8hrs
  (3-5dys)
• Fluids, MVI, Thiamine
• Manage co-morbid conditions

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BENZODIAZEPINES
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General Consideration

• Sedative-hypnotic (Benzodiazepine) Detoxification
• Symptoms similar to alcohol but no objective
  measure/scoring system
• High risk of delirium, seizures and death
  requires treatment
• Sub-clinical symptoms may persist for months
• Tolerance develops within 3-4 weeks of regular
  use
• Onset of withdrawal symptoms determined by
  half-life of compound

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Benzodiazepine

• Detoxification guidelines
• Slow-tapering of the compound or use of a longer
  acting benzodiazepine recommended
• (i.e., Clonazepam TID with 10 tapering daily)
• Sedatives for insomnia (i.e. antidepressants)
• Avoid beta blockers (mask symptoms)
• Anti-seizure medications adjusted and monitored

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OPIATES
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Opiate Indications for Use

• 1. Addiction Maintenance Therapy
• Methadone (Pure Mu Opioid Agonist)
• Naltrexone (Opioid Antagonist)
• Buprenorphine (Opioid Agonist- Antagonist)
• (N.B. LAMM now Minimally Available)
• 2. Pain Management

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Opiate Detoxification

• Key Considerations
• Medical Detoxification Standard of Care
• Methadone short-term substitution therapy the
  preferred method of detoxification, but
• Goal of treatment reducing withdrawal
  discomforts, with or without Methadone or
  Narcotic Substitution

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Opiate Detoxification

• Key Considerations (cond)
• Comprehensive, long-term treatment is equally
  important as alleviating acute symptoms
• Fear and Anticipatory Anxiety predominate
  emotional responses to detoxification
• Counseling prior to detoxification is necessary
  (i.e. expectations of withdrawal, treatment
  planning, patient responsibilities)
• Treatment should be individualized, reviewed and
  approved by a physician

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Opiate Detoxification andPregnant Women

• CONTRAINDICATED!
• Methadone maintenance is the recognized standard
  of care for decreased risk of miscarriage and
  premature labor.

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Opiate Withdrawal Syndrome

• 1. Not life threatening, Extremely uncomfortable
• 2. Symptom onset and duration, half-life
  dependent
• 3. Common Sns Sxs
• Yawning
• Sweating
• Tearing
• Abdominal Cramps

• Nausea and/vomiting
• Diarrhea
• Weakness
• Dilated Pupils
• Goose bumps
• Muscle twitching aches and pain
• Anxiety
• Insomnia
• Increased pulse
• Increased Resp rate
• Elevated Blood pressure

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Opiate DetoxificationPharmacological Guidelines
(cont.)

• Naltrexone
• Only opioid antagonist approved in the United
  States
• Used for rapid detoxification due to accelerated
  binding and blocking of mu receptors,
  precipitating a profound withdrawal
• Limitation must be administered in hospital or
  supervised environment when prescribed for rapid
  detoxification

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Opiate Detoxification

• Advantages of Methadone
• Daily dosing due to 24 hour half-life, requiring
  slower tapering schedule
• Long half-life safe for all opiates
• Safe in pregnancy
• May be used in combination with other medications
  for co-occurring disorders or mild withdrawal
  symptoms
• Decreases morbidity and mortality, hepatic
  damage, and HIV
• Exception licensing requirements, very addictive

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Opiate Detoxification

• Methadone Guidelines
• Stabilize Withdrawal 5-10 mg prn every 4-6 hours
  to control objective signs of withdrawal
• Monitor respiratory depression and excessive
  sedation until stabilized
• Detoxification Reduce by 10/day after
  stabilized for 2-3 days
• Clonidine 0.1-0.2mg/day for duration

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Opiate DetoxificationLevels of Care

• Inpatient Setting
• Duration 4-7 days
• Usual dose to suppress symptoms 30-40mg/day
  Methadone
• Immediate Referral to drug-free treatment setting
• Clonidine (Catapres) can be considered an
  effective alternative treatment for inpatient
  opioid detoxification but not outpatient

• Outpatient Setting
• 21 day protocol sufficient for most stable,
  motivated patients
• 180 day protocol, done within an opioid agonist
  therapy program, should be considered to work on
  patients early recovery problems, while
  stabilized on relatively low dose (50-60mg)
  Methadone

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Opiate Detoxification

• Buprenorphine
• History October 2000amended Control Substance
  Act 30 patient/MD max for opioid dependence
  treatment, with DEA waiver Goal accessibility,
  expanded treatment capacity
• Partial mu agonist antagonist ceiling effect
  (safer), sublingual absorption, Suboxone
  preferred
• Dosing instructions dependent on half-life of
  substituted opiate
• Average tolerable maintenance dose is 4-32 mg
  SL/day to every 3rd day
• Detox at 10/day as tolerated

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Opiate DetoxificationPharmacological Guidelines
(cont.)

• Adjunctive Treatments
• Nonsteroidal Anti-inflammatory Agents for pain
  and fever (i.e. Tylenol, Aleve)
• Alpha-adrenergic blocker for sympathetic
  hyperactivity such blood pressure, nausea,
  vomiting, diarrhea, cramps and sweating
• (i.e. Clonidine/Catapres)
• Antidiarreals and anti-emetics to control
  gastrointestinal symptoms (i.e. Bentyl,
  Phenergan)
• Antidepressants/Antipsychotic for dysphoria,
  anxiety and insomnia (i.e. Trazedone/Elavil/Seroqu
  el with/without Lexapro)
• Psychotropics for co-morbid psychiatric
  conditions along with medications for medical
  conditions

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Concluding Comments

• All withdrawal syndromes are not clinically
  significant
• Dangerous syndromes Alcohol, Sedative/hypnotic
  and Anxiolytic withdrawal Opiates withdrawal,
  extremely uncomfortable
• Substitute long acting, cross-tolerant substance
  with gradual tapering by 10-20 per day
• Detox alone is rarely adequate treatment
• Management of co-morbid medical and psychiatric
  conditions