Opioids

1
Opioids
2
Opioids

• Opiate (n)
• an unlocked door in the prison of identity. It
  leads to the jail yard.
• Ambrose, Bierce (1906) The Devils Dictionary

Opioids
3
The GPs Role?

• While most GPs are unlikely to see a large number
  of patients who use opioids illicitly, they will
  encounter some.
• GPs are well placed to intervene effectively and
  offer important harm reduction advice and
  support.
• GPs will also encounter increasing numbers of
  young people injecting various substances (most
  often amphetamines), some of whom will progress
  on to inject opioids.
• What are your ethical and legal obligations in
  regard to meeting the health care needs of
  patients with opioid-related problems?

Opioids
4
Opioid-related Problems

• Most prominent problems are associated with
  heroin dependence
• Not all users of heroin develop dependence.
  Between 14 to 13 regular users develop
  dependence
• Development of heroin dependence usually requires
  regular use over months (or longer where use is
  more irregular).
• There is considerable scope for early
  intervention by GPs if the early stages of use
  are detected.

Opioids
5
GPs Role

• As heroin dependence develops over a period of
  time, there is scope for GP intervention
• Most heroin is injected in Australia, but it is
  not the first drug usually injected.
  Amphetamines usually first injected drug
• Where a GP is aware of amphetamine use,
  intervention is warranted to counsel patients
  against progressing on to other drugs with more
  severe dependence producing properties, such as
  heroin.

Opioids
6

Case Study

• Caitlyn, 19, presents seeking a test for
  hepatitis. During the course of the interview,
  you find out that at a recent party she had her
  first experience of using what she believed to be
  heroin. She stated that she used a clean needle,
  but just wants to be sure she is virus free.
• How would you conduct a brief intervention with
  Caitlyn?

Opioids
7
Development of Dependence

• In Wordsworths poem The Prelude, a group of
  people set out to walk to Italy along a path that
  leads across the Alps. Engrossed in their climb
  and excited by the knowledge that they must soon
  reach the highest point, they meet a traveller
  who explains that they have, in fact, already
  crossed the Alps. The moment that they had
  waited for and toiled towards had passed
  unnoticed.
• For junkies too, the most significant moment of
  their journey often passes unnoticed. They
  travel onwards believing themselves to be still a
  long way from addiction when they are very close.

Stewart (1996)
Opioids
8
Who Uses Heroin

• Estimated to be 80,000100,000 dependent heroin
  users. In 2001, 252,600 persons reported ever
  having used heroin. Recent use reported by
  38,000.
• Approx. 7,000 teenagers reported recent heroin
  use
• 32 ratio malesfemale (increasing trend for F
  use)
• Highest usage amongst 2029 years. About a ¼ of
  recent users are over 40 years.
• Lifetime prevalence 1.6. Around 0.2 prevalence
  of recent use down from 0.8 in 1998.

Opioids
9
Opioids
10
The Revolving Door

• Heroin dependence is a chronic relapsing
  disorder. It is a dependency which is very
  difficult to resolve
• Relapse is extremely common. GPs should not
  despair in the face of relapse. It is part of
  the process of resolving the dependence much
  like giving up tobacco
• A principal health care objective is to get the
  patient into treatment, help keep them in
  treatment and to return them to treatment when
  relapse occurs.

Opioids
11
Polydrug Use Patterns and Risks

• Polydrug use is the norm among drug users
• Most people who use illicit drugs use a variety
  of different drugs
• Heroin users also are heavy users of alcohol and
  benzodiazepines
• As CNS depressants, these combinations are
  especially dangerous and known to be significant
  contributors to overdose
• GPs should advise against the use of these
  combinations and explain the risks involved.

Opioids
12
GPs Role in General Health Care

• Many long-term opioid users often have highly
  compromised health
• Poor dental care, poor nutrition and general
  lifestyle neglect may lead to a range of health
  problems to be addressed by the GP
• Resolution of dependence will be assisted by
  improvements in overall health status.

Opioids
13
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
14
Detecting Opioid Dependence

• Look for a pattern (not an isolated event)
• with patients who frequently run out of scripts
  for a prescribed opioid
• where patient is on a high and increases the dose
  of prescribed opioids
• where a patient injects oral medications
• of observed intoxication or in withdrawal
• which presents plausible conditions that warrant
  prescribed opioids, but with specific requests
  for medication type and amount
• that threatens or harasses staff for a fit-in
  appointment
• where a patient alters, steals or sells scripts
• where a patient is addicted to alcohol or other
  drugs.

Opioids
15
Classification of Opioids
Pure Opioid Agonists
Semi-synthetic
opium papaverine morphine codeine
heroin home-bake buprenorphine hydromorphone oxyco
done
Synthetic
LAAM fentanyl meperidine dextromoramide dextroprop
oxyphene hydrocodone methadone pentazocine pethid
ine
Partial Agonists/Antagonists
naltrexone buprenorphine LAAM
Opioids
16
Opioids Pharmacology (1)

• PET scan of µ opioid receptors

Opioids
17
Opioids Pharmacology (2)

• 3 main families of opioid receptors (µ, ? and s)
• Opioid receptors and peptides are located in the
  CNS, PNS and GI tract
• Opioid receptors are inhibitory
• inhibit release of some neurotransmitters (e.g.
  5-HT, GABA, glutamate, acetylcholine)
• enable the release dopamine (considered to
  contribute to the dependence potential of
  opiates)
• Effects on the limbic system produce changes in
  emotion.

Opioids
18
Opioids Pharmacology (3)

• Heroin
• Morphine is produced through heroin hydrolysis
• heroin ? monoacetylmorphine (MAM) ? morphine
• Heroin and MAM are lipophilic, hence more rapid
  action
• Heroin excreted in urine as free and conjugated
  morphine
• Heroin metabolites are present in urine for
  approximately 48 hours following use.

Opioids
19
Morphine Immediate Effects (1)

• Perception altered, possible delirium
• Analgesia, to some degree
• Impaired cognition, though consciousness may be
  preserved
• Autonomic nervous system affected
• Suppression of cough reflex
• GI system affected
• Hypothermia.

Opioids
20
Morphine Immediate Effects (2)

• Miosis
• Urinary retention
• Reduced GI motility
• Endocrine
• Non-cardiogenic pulmonary oedema
• Coma or death (from respiratory depression)
• Other
• pruritis, flushed skin, dry mouth, skin and eyes.

Opioids
21
Opioids Long-term Effects (1)

• Little evidence of long-term direct toxic effects
  on the CNS from opioid use
• Long-term health-related complications may result
  from
• dependence
• antisocial behaviour
• poor general self-care
• imprisonment
• drug impurities or contaminants, BBV.

Opioids
22
Opioids Long-term Effects (2)

• Possible
• Constipation / narcotic bowel syndrome
• Cognitive impairment from hypoxia as a result of
  repeated non-fatal overdose
• Reproduction and endocrine irregularity
• Medication-induced headaches
• Intense sadness (depression, dysthymia).

Opioids
23
Injecting Drug Use and AIDS
Opioids
24
By 2010, AIDS will have caused more deaths than
any disease outbreak in history.Injecting drug
use is an important contributor to the spread of
HIV.
The Threat From HIV / AIDS
Opioids
25
Opioids
26
Opioids Drug Interactions
Opioids
27
Opioids Considerations for Assessment

• Pregnancy
• BBV
• Polydrug dependence
• Opioid related overdose
• Major or pre-existing medical conditions (e.g.
  liver, cardiac)
• Major psychiatric/mental health issues (e.g.
  psychosis, depression, suicide).

Opioids
28
Physical Exam

• Signs of opioid dependence
• needle marks on wrists, antecubital fossa, legs
  (inner thighs), feet, hands, neck
• intoxication pinpoint pupils, nodding off,
  drowsiness, sweating
• withdrawal restlessness, goosebumps, sweating,
  increased bowel sounds, lacrimation, sniffles,
  dilated pupils, muscle tenderness, tachycardia,
  hypertension.

Opioids
29
Complications From Use

• The following slides depict complications from
  use, dependence and overdose.

Opioids
30
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
31
Opioids
32
Opioids
33
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
34
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
35
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
36
Opioids
37
Opioids
38
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
39
Opioids
40
Opioids
41
Opioids
42
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
43
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
44
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
45
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
46
Opioid Withdrawal

• Signs
• Yawning
• Lacrimation, mydriasis
• Diaphoresis
• Rhinorrhoea, sneezing
• Tremor
• Piloerection
• Diarrhoea and vomiting.

• Symptoms
• Anorexia and nausea
• Abdominal pain or cramps
• Hot and cold flushes
• Joint and muscle pain or twitching
• Insomnia
• Drug cravings
• Restlessness/anxiety.

Opioids
47
Opioids
Courtesy of Dr. John Sherman, St. Kilda Medical
Centre
48
Progress of the Acute Phase of Opioid Withdrawal
Since Last Dose
Withdrawal from heroin Onset 624 hrs Duration
410 days
Withdrawal from methadone Onset 2448 hrs,
sometimes more Duration 1020 days, sometimes
more
Severity of signs and symptoms
0 10 20
Days
deCrespigny Cusack (2003)Adapted from NSW
Health Detoxification Clinical Practice
Guidelines (2000-2003)
Opioids
49
Predictors of Withdrawal Severity

• Main predictors
• Greater regular dose
• Rapidity with which drug is withdrawn.
• Also consider
• Type of opioid used, dose, pattern and duration
  of use
• Prior withdrawal experience, expectancy, settings
  for withdrawal
• Physical condition (poor self-care, poor
  nutritional status, track marks)
• Intense sadness (dysthymia, depression)
• Constipation or Narcotic Bowel Syndrome
• Impotence (M) or menstrual irregularities (F).

Greater withdrawal severity
Opioids
50
Opioid Withdrawal Scales

• Withdrawal scales
• guide treatment
• monitor progress of withdrawal (subjective and
  objective signs)
• do not diagnose withdrawal but describe severity
• guide ongoing assessment.
• If the withdrawal pattern is unusual, or the
  patient is not responding, suspect other
  conditions.

Opioids
51
Opioid Withdrawal Management

• Withdrawal management aims to
• reverse neuroadaptation by managing tolerance and
  withdrawal
• promote the uptake of post-withdrawal treatment
  options.
• Withdrawal management may occur
• in the home
• as an outpatient
• in a residential/treatment setting.

Opioids
52
Opioid Withdrawal Treatment

• Involves
• reassurance and supportive care
• information
• hydration and nutrition
• medications to reduce severity of somatic
  complaints (analgesics, antiemetics, clonidine,
  benzodiazepines, antispasmodics)
• opioid pharmacotherapies (e.g. methadone,
  buprenorphine, naltrexone).

Opioids
53
Opioid Withdrawal Complications

• Anxiety and agitation
• Low tolerance to discomfort and dysphoria
• Drug-seeking behaviour (requesting or seeking
  medication to reduce symptom severity)
• Muscle cramps
• Abdominal cramps
• Insomnia.

Opioids
54
Heroin Withdrawal

• Non-life threatening
• Commences 624 hours after last use
• Peaks at around 2448 hours after use
• Resolves after 57 days.
• Increasing recognition of the existence of a
  protracted phase of withdrawal lasting some weeks
  or months, characterised by reduced feelings of
  wellbeing, insomnia, dysthymia, and cravings.

Opioids
55
Dependent Opioid Use and Treatment Pathways
Abstinence

• Relapse Prevention
• Residential (drug-free)
• Outpatient (drug-free)
• Psychological counselling
• Support group
• Antagonist (e.g. naltrexone)

? Relapse

• Substitution Treatment
• Buprenorphine
• Methadone
• (LAAM)
• SR morphine

• Withdrawal Management
• Setting
• Medication
• Speed

Cessation ?

• Harm Reduction
• Education about overdose
• BBV risk reduction info

Dependence
Heroin use
Opioids
56
DSM IV Criteria for Opioid Dependence

• Tolerance
• Withdrawal symptoms on cessation of drug use
• Increasing quantity or frequency of use
• Persistent desire for the drug or unsuccessful
  attempts to cut down
• Salience of drug use over other responsibilities
  (most time involves taking, recovering from, or
  obtaining drugs)
• Continued use despite evidence of psychological
  or social problems.

Opioids
57
General Principles of PharmacotherapiesPharmacody
namics

• Agonists
• directly activate opioid receptors (e.g.
  morphine, methadone)
• Partial agonists
• unable to fully activate opioid receptors even
  with very large doses (e.g. buprenorphine)
• Antagonists
• occupy but do not activate receptors, hence
  blocking agonist effects (e.g. naloxone).

Opioids
58
Maintenance Pharmacotherapies

• Methadone
• Buprenorphine
• Naltrexone
• LAAM
• Slow-release morphine.

Opioids
59
Key Outcomes of Maintenance Pharmacotherapy
Programs

• ?Retention in treatment
• Facilitates reduction/cessation of opioid use
• Reduces risky behaviours associated with opioid
  use
• Enables opportunity to engage in harm reduction
  measures
• ? Mortality and morbidity
• ? Psychological, emotional and physical wellbeing
  of patients
• ? Social costs associated with illicit drug use
• ? Crime.

Opioids
60
Methadone Clinical Properties

• The Gold Standard Treatment
• Synthetic opioid with a long half-life
• µ agonist with morphine-like properties and
  actions
• Action CNS depressant
• Effects usually last about 24 hours
• Daily dosing (same time, daily) maintains
  constant blood levels and facilitates normal
  everyday activity
• Adequate dosage prevents opioid withdrawal
  (without intoxication).

Opioids
61
Methadone Advantages of Treatment

• Suppresses opioid withdrawal
• Pure no cutting agents present
• Oral administration (syrup or tablet forms used)
• Once daily doses enable lifestyle changes
• Slow reduction and withdrawal can be negotiated
  with minimal discomfort
• Counselling and support assists long-term
  lifestyle changes
• Legal and affordable reduced participation in
  crime
• Free in public methadone programs
• Few long-term side-effects.

Opioids
62
Methadone Disadvantages of Treatment

• Initial discomfort to be expected during
  stabilisation phase
• Opioid dependence is maintained
• Slow withdrawal (preferably) negotiated with
  GP/counsellor/ treatment agency and undertaken
  over a period of months
• Protracted withdrawal symptoms
• Can overdose, particularly with polydrug use
• Daily travel and time commitment
• Can be expensive.

Opioids
63
Methadone Initial Effects and Side-effects
Polydrug use may cause overdose.
Opioids
64
Methadone Inappropriate Dosing

• Dose too low Withdrawal
• Flu-like symptoms
• Runny nose, sneezing
• Abdominal cramps, diarrhoea
• Tremor, muscle spasm, ache and cramping
• Yawning, teary eyes
• Hot and cold sweats
• Irritability, anxiety, aggression
• Aching bones
• Craving.

• Dose too high Intoxicated
• Drowsy, nodding off
• Nausea vomiting
• Shallow breathing
• Pinned (pinpoint) pupils
• Drop in body temperature
• Slow pulse, low BP, palpitations
• Dizziness.

Opioids
65
Methadone Drug Interactions

• Methadone reacts with many prescribed
  medications, leading to
• increased risk of overdose with other CNS
  depressants
• disruption of methadone metabolism
• destabilisation of responses to treatment
• competition for liver enzymes
• Contraindicated drugs include
• alcohol, benzodiazepines, phenothiazines, other
  opioids, barbiturates
• MAOIs, tricyclic antidepressants
• anticoagulants
• carbamazepine, phenytoin etc.

Opioids
66
Buprenorphine

• Derived from the morphine alkaloid thebaine
• Partial opioid agonist at µ opioid receptors
• Blocks opioid receptors, diminishes cravings,
  prevents opioid withdrawal.

Opioids
67
Buprenorphine

• Subutex (SL tablets) is the form registered in
  Australia for treating opioid dependence, and for
  managing short-term moderate to severe pain
• PPC reached in 12 hours (half-life 25 hours)
• Peak clinical effects at 14 hours, lasting 812
  hours at a low dose (lt4 mg) or lt2472 hours at
  higher doses (gt16 mg)
• High margin of safety
• Trial outcomes indicate it is at least as
  effective and acceptable to patients and
  clinicians as methadone.

Opioids
68
Buprenorphine vs. Methadone

• Buprenorphine
• Advantages
• Milder withdrawal
• Convenient (dose every 2/7)
• Better receptor blocker
• Relative ease of use i.e. ready transmission
  from heroin withdrawal state or methadone
• Easier to taper than methadone
• Wider safety margin.

• Buprenorphine
• Disadvantages
• SL route results in reduced bio-availability
  compared with IV preparations
• Easier to divert
• Difficult to reverse respiratory depression if it
  does occur
• Increased time required for supervised dosage
  (to get dissolution).

Opioids
69
Buprenorphine Drug Interactions

• Other CNS depressants
• e.g. alcohol, benzodiazepines have additive CNS
  depressant effect
• Opioid antagonists
• naltrexone can precipitate withdrawal
• high doses of naloxone needed to reverse
  buprenorphine effects
• Opioid agonists
• as a partial agonist has a blockade effect on
  opioid analgesics
• initial dose may precipitate withdrawal (e.g.
  recent, heavy heroin use, methadone transfer).

Opioids
70
Naltrexone

• Morphine antagonist, true blockade
• No psychoactive effect
• Prevents euphoria from opioid use therefore
• drug money spent money wasted
• Prevents reinstatement of opioid dependence,
  although does not reinforce compliance
• No withdrawal experienced upon cessation
• Reported to reduce cravings in some people.

Opioids
71
Naltrexone Indications for Use

• Prescribed for the management of opioid
  dependence by registered prescribers
• Primary role relapse prevention
• Abstinence-based treatment option
• Non-dependence inducing
• Commenced at least a week after cessation of
  heroin use.

Opioids
72
Naltrexone

• Side effects
• Acute opioid withdrawal precipitated (e.g.
  lethargy, aches, cramps, low energy)
• Depression, irritability
• Anxiety, nervousness
• Sleeping difficulties
• Skin rash
• Poor appetite
• Dizziness.

• Precautions
• If naltrexone ceased and opioid use reinstated,
  reduced tolerance to opioids increases risk of
  overdose and death
• Precipitates withdrawals in opioid-dependent
  patients.

Opioids
73
Naltrexone

• Effectiveness tends to be dependent on
• situation, circumstances, support, commitment of
  patient
• inclusion as part of comprehensive treatment
  program (including counselling)
• Long-term treatment efficacy still under
  investigation
• While effective for some, inappropriate for
  others.

Naltrexone is not a miracle cure for opioid
dependence.
Opioids
74
LAAM (Levo-a-acetylmethadol)

• Long-acting analogue of morphine
• Maintenance agent after stabilized on methadone
• Given every 4872 hours
• Due to long half-life, more difficult (c.f.
  methadone) to induct and maintain
• Not available in Australia.

Opioids
75
Slow Release Oral Morphine

• Opioid agonists (e.g. Kapanol, MS Contin)
• Duration of action 1224 hours
• Although indicated for use as a maintenance
  treatment is not registered for treatment of
  heroin dependence
• Current trials under way in Australia
• Similar in terms of effects, outcome and
  disadvantages to methadone. May be useful if a
  full agonist is required and methadone cant be
  tolerated.

Opioids