MANAGEMENT OF DRUG ADDICTION / SUBSTANCE

ABUSEDr 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

• Opiods; Heroin• Alcohol• Benzodiazepines & Barbiturates• Stimulants: Cocaine & Amphetamines• Cannabinoids• Hallucinogens; LSD, Mescaline• Solvents• Nicotine

Patterns of Drug Use

• Experimental

• Recreational

• Habitual

• Dependant

• Other: - Polysubstance use

- Dual diagnosis use

Clinical situations

• Harmful use

• Dependence syndrome

• Withdrawal state +/- delirium; “DT’s”

• Drug induced Psychosis

• Cognitive impairment syndromes

• Acute intoxification

• Residual disorders

ICD-10 Criteria

• 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 GABA- inhibitory 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 diseasesHIV

• 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

• 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

• 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

• 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

• 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 programmes- minnisota 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 issuesAnd 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