MANAGEMENT OF DRUG
ADDICTION / SUBSTANCE
ABUSE
Dr Jacinta O’Shea
Research Registrar ERHA
DRUG ADDICTION
• Chronic relapsing disorder
• Compulsive drug seeking & drug taking
behaviour, despite serious negative consequences
• ICD 10 Criteria
• Induce pleasant states (positive reinforcer) or
relieve distress (negative reinforcer)
• Continued use induces adaptive changes in the
CNS, leading to the development of tolerance,
dependence, sensitization, craving & relapse
Substances of abuse
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Opiods; Heroin
Alcohol
Benzodiazepines & Barbiturates
Stimulants: Cocaine & Amphetamines
Cannabinoids
Hallucinogens; LSD, Mescaline
Solvents
Nicotine
Patterns of Drug Use
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Experimental
Recreational
Habitual
Dependant
Other: - Polysubstance use
- Dual diagnosis use
Clinical situations
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Harmful use
Dependence syndrome
Withdrawal state +/- delirium; “DT’s”
Drug induced Psychosis
Cognitive impairment syndromes
Acute intoxification
Residual disorders
ICD-10 Criteria
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A strong desire/compulsion to take the substance
Difficulties in controlling substance-taking
A physiological withdrawal state
Evidence of tolerance
Progressive neglect of alternative pleasures
Persisting with substance use despite clear
evidence of OVERTLY harmful consequences
Epidemiology
• British Psychiatric Morbidity study 1993/2000
“ neurosis”- 160/1000
Probable psychosis – 5/1000
Personality disorder- 44/1000
Alcohol dependant- 70/1000
Drug dependant- 40/1000
UK Community surveys
• 3o% have tried illegal drugs; 10% in last year.
• <25y.o – 50% lifetime; 33% in last year.
• At all ages, males have higher rates of drug use
than females; M:F 3-4:1
• Use of illegal drugs commoner in:
- young adults especially males,
- Lower socioeconomic groups
- Those with psychiatric illness
- Urban areas
Drug use prevalence Ireland 2002/03
Factors influencing drug abuse
and dependence
• Pharmacological & physiochemical properties
of drugs
• Personality & Psychiatric disorder - increased
risk associated with schizophrenia, BPAD,
depression, ADHD.
• Genetic factors (that influence metabolism
and the effects of drugs)
Pharmacologic and
physiochemical properties
• Liposolubility increases the passage through the
blood-brain barrier
• Water solubility facilitates injection
• Volatility favours inhalation in vapour form e.g
aerosols / solvents
• Heat resistance favours smoking e.g. cannabis
• Rapid onset and intensity of effect increase the
potential for abuse
• A short half-life produces abrupt & intense
syndromes of withdrawal
OPIATES
• Strong narcotic analgesics
• Derived from the ripe seed capsule of the
poppy
• Crude opium contains morphine, codeine,
other alkaloids
• Diamorphine (heroin) made by acetylation
• Eaten, sniffed, smoked, injected
OPIATES
• Short term effects – Euphoria, analgesia,
sedation & a feeling of tranquillity
• Long term effects / Repeated use – Rapid
tolerance & physical dependence
• Over dose – Lethal respiratory depression
Opiate Receptors
• 3 Major opiate receptors - µ, δ, and к
• 3 Endogenous opiate peptides –
Encephalins, beta-endorphin, dynoorphin
• Agonist action at μ and к receptors causes
tolerance and dependence
• Opiates activate these receptors which then
couple G proteins
Opiates &The dopamine pathway
• Natural rewards and addictive drugs stimulate the
release of dopamine from neurones of the
presynaptic ventral tegmental area into the nucleus
accumbens, causing euphoria & reinforcement of
the behaviour
• Habituation ( rapid adaptive changes ) occur with
natural rewards but not with addictive drugs &
each dose stimulates the release of dopamine
• Dopamine binds to a G-protein coupled receptor
with two subtypes, D1 like, and D2 like.
Opiates Cont…
• Most drugs that produce elevations in mood or
euphoria, release dopamine in either the nucleus
accumbens or the prefrontal cortex
• Opiods release dopamine mainly by an indirect
mechanism that decreases the activity of GABAinhibitory neurones in the ventral tegmental area
• Stimulation of κ receptors decreases dopamine
levels in the nucleus accumbens and produces
aversive responses
• Reward & physical dependence are mediated by
the activation of μ receptors
Opiate tolerance
• Tolerance leads to increasing doses, or
reduction between intervals, or both
• Short term administration of opiates
activates the μ-opiod Gαi/o- coupled
receptor, this leads to a decrease in the
number of opiod receptors and to the
development of tolerance
Opiate withdrawal
• Withdrawal causes reinstatement of drug use to prevent
or decrease physical symptoms and dysphoria
• Inhibition of neurones in the locus ceruleus by opiate is
a key mechanism in withdrawal
• When opiate levels fall the unopposed neurones lead to
adrenergic over activity
• Activation of к receptors in the ventral tegmental area
decreases dopamine in the nucleus acumbens, leading
to dysphoria and anhedonia
Opiate withdrawal
• Grade 0 – drug craving, anxiety, drug seeking
• Grade 1 – yawning, sweating, runny nose, restless
sleep
• Grade 2 – dilated pupils, hot and cold flushes,
goose flesh (“cold turkey”), aches and pains
• Grade 3 – insomnia, restlessness and agitation,
abdominal cramps, N+V, diarrhoea, increased
pulse , BP and RR
Hazards
• Sterility – abscesses,
septicaemia
endocarditis
• Adulterants – gangrene
DVT and pulmonary emboli
• Sharing – blood borne diseases
HIV, Hepatitis B and C
Blood borne diseases
HIV
• Currently IVDU’s account for 37% (1048)
• Though the numbers of IVDU’s with HIV increased
between 1998-2001, it was followed by a reduction of
almost 50% during 2001-2002. This may reflect service
expansion or the delay between infection and diagnosis
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EMCDDA(2002) record a prevalence rate of 3.3-8.7% of
HIV infection among IVDU’s between 1996-2001
Hepatitis C
• HCV prevalence is very high in all countries and
settings in Europe, with infection rates of between
40-90% among different IDU subgroups
• Prevalence rates 72-73% 1996-2001 (EMCDDA)
• No routine data collection in Ireland
• 1st study 1995 HCV prevalence 84% <2 years injecting 70% +ve
>2 years injecting 95% +ve
Methadone
• Synthetic opiate
• Administered orally
• Half-life 24-36 hrs (10-90) ; once daily
dosage
• Steady state 4-5 days
• Dosage 30-60mg
• Harm reduction approach
• Maintenance / Detoxification
Methadone Maintenance
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Used in the USA since 1960’s
Stabilises lifestyle
Harm reduction benefits 75-90% of patients
Reduces HIV, Hepatitis
Reduces crime
Aim for a dose of 60mg and over
Harm reduction
• As opposed to Abstinence / “curing”
• WHO defines Harm reduction as a concept to
prevent or reduce negative health consequences
associated with certain behaviours
• Concerns about transmission of HIV; epidemics in
>110 countries; relapsing nature of Addiction
• Focuses on minimising health, personal and social
harms associated with drug use - the spread of
blood-borne diseases, overdoses etc
• Ongoing interventions, not short term, as a way to
improve health of drug users, their families and
society
• Marginalised groups
Interventions include
• Information, education, communication
• Education about STD’s +safer sex, family
planning ; injection techniques
• Health care in relation to infectious diseases;
screening, immunisation
• Substitution with oral drugs
• Needle exchange programmes
• Linking with other services – e.g. medical,
psychiatric, obstetric, dental ; social and forensic
• other
Benefits of methadone
• “safe” substitution drug
• Effective in engaging and retaining people in
treatment
• Reduces risk, reduced levels of injection
• A factor in improving physical/Mental health and
quality of life of patients and their families
• Reduces criminal activity and demands on the
criminal justice system
Lofexidine
• Alpha-2 adrenergic agonist inhibiting
noradrenaline release
• Useful in short term users
• Detoxify over 2-3 weeks using up to 2mg daily
• Daily BP monitoring is essential
• Mainly used in in-patient units
Naltrexone
• Narcotic antagonist
• Half-life 96 hours
• Dose 50mg daily
• Used after detoxification
• Best when supervised by family
• Breaks the cycle of craving
Alcohol
• 1 unit = 10ml / 8g absolute alcohol ( ½ pint lager,
glass wine, 25ml spirits)
• Hydrophilic, with rapid absorption through the gut
• Peak plasma levels reached 30-60 mins post
ingestion
• Metabolized by hepatic oxidation (ADH)
Neurobiology of alcohol
• Stimulant at low doses, sedative at higher
concentrations
• Anxiolytic effects mediated by potentiation of
inhibitory effects GABA at GABA-A receptors
• Disturbs glutamate transmission by inhibiting
NMDA receptors,- related to withdrawal seizures,
DT’s etc
• Unopposed action of GABA and NMDA,
increasing neuronal excitability
Alcohol related physical problems
• GIT – oesophagitis, gastritis, reflux, m-w tears, varices,
pancreatitis, portal HT, ca’s
• Liver – hepatitis, fatty liver, cirrhosis, haemochr, hepatic Ca,
hepatic encephalopathy
• Cardiovascular – arrythmias, cardiomyopathy,
coronary/cerebrovascular disease, hypertension
• Metabolic
• Endocrine e.g. pseudocushings, hypogonadism, infertility, low
libido/impotence
• Musculoskeletal e.g. gout, fractures, osteoporosis
• Haematological e.g. anaemia, thrombocytopaenia
• Respiratory
• Dermatological e.g. spider naevi, palmar erythema, eczema,
worsening psoriasis
Alcohol – Neurological problems
• Acute intoxication
• Mania a potu – pathological drunkenness with
minute amounts of alcohol (not in ICD-10)
• Methanol poisoning
• Amnesic (Korsakoff’s) syndrome & Wernicke’s
encephalopathy
• Cerebellar degeneration
• Ambylyopia- retrobulbar neuritis; may be
associated with peripheral neuropathy
• Central pontine myelinosis
• Dementia, amnesia/blackouts etc
• Fetal alcohol syndrome
Psychological related disorders
• Alcoholic Hallucinosis- 10-20% > 6/12
-5-20%...schizoph
• Psychiatric comorbidity ECA study
-psychiatric dx x3 risk of lifetime alc disor
- 13% alcoholics 2nd mood disorder
- 22% mood disorder also alcohol disorder
• Suicide – approx 25% attempt; male, divorced, personality
disorder, older, unemployed, medical issues, hx of DSH
• Pathological jealousy- “Othello syndrome”
• Anxiety states- panic, OCD, phobias
• PTSD - alcohol dampens hyperarousal
• Eating disorders – bulemia
• Other drug use
Alcohol withdrawal
• Important to recognise – 25% of male medical
patients are problem drinkers
• Occurs from 6-24 hours after cessation, peaking at
day 2-3, highest risk in first 24-48hrs
• Range of features – sweating, tremor, nausea,
anorexia, vomiting, anxiety, insomnia,
restlessness, hallucinations, seizures, nightmare,
confusion, hallucinosis
Delirium tremens
• Toxic confusional state with somatic
disturbance, occurring in < 5%
• Mortality rate of approx 10%( -20%)
• Symptoms peak at 3-4 days of withdrawal
• Triad of clouding of consciousness, sensory
distortion and tremor
• Agitation, fear and insomnia, worse at night
Features of DT’s
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Confusion and disorientation.
Clouding of consciousness.
Delusions and hallucinations.
Psychomotor agitation and automatic dysfx.
Perceptual disturbance and fear.
Insomnia and truncal ataxia.
Electrolyte disturbance and dehydration .
Leukocytosis and disordered LFT’s.
EEG shows an increase in fast activity.
Treatment
• Acute withdrawal – Short acting benzodiazepines;
chlordiazepoxide, diazepam – minimise the risk of
seizures
• 40mg clordiazepoxide, 6hourly, (Max 300mg in
24hrs)
• Reducing doses over 5-10 days
• Consider anticonvulsants (carbamezepine)
• Multivitamin preparations- Thiamine / B vitamin
- Wernicke-Korsakoff psychosis
• Treat infection, dehydration, suicidal ideation etc
In Patient Treatment
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Past History of seizures or epilepsy
Comorbid severe mental illness
Intercurrent acute illness
Previous failed OPD attempts
Elderly patients
Post-detoxification
• Disulfuram (Antabuse) – Inhibitor of aldehyde
dehydrogenase. Blocks ethanol metabolism at the
acetaldehyde level. ‘Flushing reaction’
• Loading dose 600-800mg per day for 3-4 days
• Maintenance 200mg daily
• Hypotension and MI with heavy alcohol
consumption, potentially fatal
• Useful in highly motivated groups and where
assisted by family or friends
Post Detoxification
• Naltrexone- Opiate receptor antagonist,
thought to negate the euphoria associated
with alcohol
• DOSE
• Acamprosate (Calcium bisacetyl
homotaurine)- Synthetic GABA analogue
• DOSE
• SSRI’s
Post Detoxification
• Psychological interventions; Relapse
prevention, MET, cue exposure with response
prevention, social skills, relaxation techniques,
CBT, Family therapy etc
• Alcoholics anonymous – 12 step programme
• Residential rehabilitation programmesminnisota model- social skills, relaxation,
structured relapse prevention
Cognitive & behavioural strategies
• By identifying triggers for relapse
– neg/pos mood states
- poor coping skills
- social isolation
- craving
- family issues
And developing global self management strategies in
areas of cognitive restructuring, skills training,
lifestyle changes
Brief intervention
• Assessmint of intake
• Information on harmful drinking, advice
Decrease by 50%, as effective as more
expensive specialist tx.
Motivational interviewing
• Addressing ambivalence, moving through a
cycle of change
• 5 tenets - express empathy
-help see discrepancies
-avoid argument
- roll with resistance
- support sense of self efficacy
Prognosis
• Poor – alcoholic brain damage, comorbidity, divorced,
criminal record, low IQ, poor support and motivation
• Valient 2003 – 60 yr follow up
-25% dependant
-Death rate x 2-3, rare after 70; predictors of positive
outcome
“the most and least severe alcoholics appeared to enjoy
the best longterm chance of remission”
Cocaine
• Substantial increases in drug treatment population
• Increasingly reported as 2nd problem drug –
50%IV ( < benzodiazepines )
• Anecdotal reports- across general population
• No substitute drug available
• Some combined pharmacotherapy's; counselling,
CBT, Motivational interviewing
• 3% general population report lifetime use;
increasing
Effects and risks of cocaine
• Perceived as safe
• Increased energy, alertness, talkative, sex drive
• Combined with alcohol more toxic than either
alone
• Severe psychological dependence, cravings
• Tolerance develops
• unpleasant side effects – dry mouth, sweating,
palpitations, anorexia, headaches, abd pain,
irritability, paranoia, hallucinations, MI
• Fatigue and depression; “crash”; mental problems;
nasal / breathing problems
• Increased sexual risk behaviour; association with
prostitution
Benzodiazepines