Transcript Management of Alcohol Misuse

Epidemiology & Pharmacological
approaches in Substance Misuse
Dr Shivashankar, ST6
29th October, 2009
Agenda

Epidemiology

Pharmacological approaches

MCQs

CASCs
Alcohol



1 Unit = 10 ml or 8 g of absolute alcohol
Recommended max level= 21 for men & 14
for a women
The permissible limit of alcohol for driving is
80 mg per 100 ml of blood, here in UK.
Epidemiology:




Increase in per capita alcohol consumption in UK by
31% over the last 20 years.
22000 premature deaths per year and costs an
estimated £20 billion (PM’s strategy unit, 2003)
In UK, prevalence of dependence – 5% (Farrell et
al, 2001)
In US, ECA study – 14% lifetime (Reiger et at,
1991)
Epidemiology:




Age- heaviest in late teens & early twenties
- less with advancing age
- peak for dependency b/n 30-44 yrs
Sex - M: F=3:1
More in divorced, separated or never married
In unskilled manual occupations, publicans,
travelling salesmen, journalists, dentists & doctors
Neurobiology:


Agonist at neuroinhibitory GABA
receptors
Antagonist at Neuroexcitatory
glutamate / NMDA
Brain-reward circuit
Alcohol
Functions
• reward (motivation)
• pleasure, euphoria
• motor function
(fine tuning)
• compulsion
• perseveration
Heroine
Amphetamine
Cocaine
Heroin
Nicotine
Goals of treatment:

Physical health

Psychological adjustment ( or Mental health)

Vocational adjustment

Social adjustment

Interpersonal adjustment

Legal status & Criminal activity

Polydrug use & dependence; Blood-borne virus risks,
needle sharing and sexual behaviour
Stages of Change Model:
Pre-contemplation
Contemplation
Relapse
Decision
Maintenance
Action
Prochaska, JO, DiClemente, CC (1992) Stages of change in the modification of problem
behaviors. Prog Behav Modif. 28:183-218.
Abstinence v/s Controlled drinking



Traditionally one of the controversial topic
Controlled drinking may be an option for
young, socially stable drinkers with short,
less severe drinking histories
Abstinence should be the goal for people
with heavy dependence or those with
protracted alcohol problems.
Screening
Questionnaires:





CAGE
AUDIT (Alcohol Use Disorders Identification Test)
FAST (Fast Alcohol Screening Test)
MAST (Michigan Alcoholism Screening Test)
PAT (Paddington Alcohol Test)
Chemical investigations:





AST
ALT
GGT
MCV
CDT
Characteristics of Tests
Sensitivity
Specificity
Duration
AST
30-50%
80-86%
1-2 months
ALT
30-50%
80-86%
1-2 months
GGT
50-70%
75-85%
1-2 months
MCV
25-52%
85-95%
1-3 months
CDT
40-70%
80-98%
1-3 weeks
AUDIT
70-92%
93-98%
Past Year
Alcohol Withdrawal Syndrome:

wide range of severity of withdrawal symptoms and in some cases
withdrawal may be life-threatening

Early withdrawal symptoms
-occur up to 12 hours after the last drink (sometimes within a few
hours if the patient is severely alcohol dependent).
- include restlessness, tremor, sweating, nausea, vomiting, loss of
appetite, and insomnia, with tachycardia and systolic hypertension.
-in moderate withdrawal, the signs are more marked and transient
auditory hallucinations in clear consciousness may also occur.
Alcohol Withdrawal Syndrome:

Withdrawal fits
-can occur at 12 to 48 hours, especially if there is a
previous history of withdrawal fits or epilepsy.
-Fits tend to be generalized and may occur in
bouts.
-30% of cases are followed by DTs.
Alcohol Withdrawal Syndrome:

delirium tremens
-usually develops at 48 to 72 hours
-patients consuming more than 30 units per day (a bottle
of spirits per day or equivalent) are particularly at risk.
-Clinical features include: marked tremor, confusion,
disorientation, agitation, restlessness, fearfulness, visual
and auditory hallucinations, delusions, autonomic
disturbances; tachycardia, sweating, fever and
dehydration
-DTs often present insidiously with night time confusion
and carry a mortality of 1-2%.
Community Vs in-patient detoxification:
Most patients can be managed in the community but in-patient
detoxification is required if a patient:

is severely dependent on alcohol, therefore likely to have severe
withdrawal symptoms;

has a current or past history of severe withdrawal symptoms such
as delirium tremens (DTs) or epileptiform seizures;

suffers with a serious or life threatening medical or psychiatric
condition;

is at risk of self harm or harming others;

is homeless, lacks social support or had previous unsuccessful
community detox attempts
Detoxification




Reducing doses of Benzodiazepines
Commonly used benzo is the Chlordiazepoxide
(diazepam 5mg  chlordiazepoxide 15mg)
Longer acting benzos- risk of accumulation in elderly
and with liver failure
Shorter acting benzos like lorazepam or oxazepam in
patients with alcoholic liver disease
Dose of benzodiazepines


Severity of dependence
-clinical history
-number of units per day
-score of SADQ
Severity of Withdrawals
-CIWA
Severity of Alcohol Dependence Questionnaire
(SADQ)



is a self-administered, reliable questionnaire
The SADQ questions cover the following aspects of
dependence syndrome
-Physical withdrawal symptoms
-Affective withdrawal symptoms
-Relief drinking
-Frequency of alcohol consumption
-Speed of onset of withdrawal symptoms
The degree of severity of alcohol dependence can be
classified as mild (upto 15), moderate (16-29), severe (30-40)
and very severe (up to 40-60).
SEVERITY OF ALCOHOL DEPENDENCE QUESTIONAIRE (SADQ)
Please recall a typical period of heavy drinking in the last 6 months.
When was this? MonthYearPlease answer all the following questions about your drinking by circling your
most appropriate response
During that period of heavy drinking
1. The day after drinking alcohol, I woke up feeling sweaty
ALMOST NEVER
SOMETIMES
OFTEN
NEARLY ALWAYS
2. The day after drinking alcohol, my hands shook first thing in the morning
3. The day after drinking alcohol, my whole body shook violently first thing in
the morning if I didn’t have a drink.
4. The day after drinking alcohol, I woke up absolutely drenched in sweat.
5. The day after drinking alcohol, I dread waking up in the morning
6. The day after drinking alcohol, I was frightened of meeting people first
thing in the morning
7. The day after drinking alcohol, I felt at the edge of despair when I awoke.
8. The day after drinking alcohol, I felt very frightened when I awoke.
9. The day after drinking alcohol, I liked to have an alcoholic drink in the
morning
10. The day after drinking alcohol, I always gulped my first few alcoholic
drinks down as quickly as possible.
SEVERITY OF ALCOHOL DEPENDENCE QUESTIONAIRE (SADQ)
11. The day after drinking alcohol, I drank more alcohol to get rid of the shakes
12. The day after drinking alcohol, I had a very strong craving for a drink when I
awoke.
13. I drank more than a quarter of a bottle of spirits in a day (OR 1 bottle of wine OR
7 beers)
14. I drank more than half a bottle of spirits per day (OR 2 bottles of wine OR 15
beers)
15. I drank more than one bottle of spirits per day (OR 4 bottles of wine OR 30
beers)
16. I drank more than two bottles of spirits per day (OR 8 bottles of wine OR 60
beers)
Imagine the following situation:
1. You have been completely off drink for a few weeks
2. You then drink very heavily for two days
How would you feel the morning after those two days of drinking?
17. I would start to sweat.
18. My hands would shake
19. My body would shake
20. I would be craving for a drink.
Measurement of withdrawals:



can be measured by using Addiction Research
Foundation Clinical Institute Withdrawal
Assessment of Alcohol scale, revised. (CIWA-Ar)
a very sensitive instrument and helps in
adjusting the dose of benzodiazepines
can be mild (<10), moderate (10-20) or severe
(>20).
Clinical Institute Withdrawal Assessment of
Alcohol Scale, Revised, (CIWA-Ar)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Nausea & Vomitting
Tremor
Paroxysmal sweats
Anxiety
Agitation
Tactile disturbances
Auditory disturbances
Visual disturbances
Headache
Orientation
Treatment Regime
Daily Alcohol Consumption
15 – 30 Units
30 - 40 Units
40 - 60 Units
Severity of dependence
Moderate
SADQ Score 15-30
Severe
SADQ Score 30-40
Very Severe
SADQ Score 40-60
Starting doses of Chlordiazepoxide
15 - 30 mg q.d.s.
30 - 40 mg q.d.s.
50 mg q.d.s
Day 1 (starting dose)
15 qds
20 qds
30 qds
40 qds
50qds
Day 2
10 qds
15 qds
25 qds
35 qds
45 qds
Day 3
10 tds
10 qds
20 qds
30 qds
40 qds
Day 4
5 tds
10 tds
15 qds
25 qds
35 qds
Day 5
5 bd
5 tds
10 qds
20 qds
30 qds
Day 6
5 nocte
5 bd
10 tds
15 qds
25 qds
5 nocte
5 tds
10 qds
20 qds
Day 8
5 bd
10 tds
15 qds
Day 9
5 nocte
5 tds
10 qds
Day 10
5 bd
10 tds
Day 11
5 nocte
5 tds
Day 7
Day 12
5 bd
Day 13
5 nocte
A flexible regimen for moderate
dependence:
Day 1
Morning
Lunch
Tea
Bedtime
PRN
20mg
20mg
20mg
20mg
20mg up to x 4 in 24 hours
If 3-4 PRNs used on Day 1 - remain on 20mg QDS for Day 2 with 2 PRN doses of 20mg available
If 1-2 PRNs used on Day 1 - remain on 20mg QDS with no PRN
If no PRNs used on Day 1 – proceed to Day 2 on protocol
Day 2
15mg
15mg
15mg
15mg
Day 3
10mg
10mg
10mg
10mg
Day 4
10mg
-
10mg
10mg
Day 5
5mg
-
5 mg
5mg
Day 6
5mg
-
-
5mg
Day 7
-
-
-
5mg
PRN is not usually required after initial 48 hour
period.
Vitamin Supplementation


Wernicke’s encephalopathy
- due to thiamine deficiency
- triad of nystagmus, ophthalmoplegia & ataxia
- lessions around third ventricle and aqueduct,
including dorsomedial thalamus, the mamillary
bodies & hypothalamus
Korsakoff’s syndrome
- persistent, prominent impairment of recent
memory & hence new learning
- immediate recall & procedural memory may
be intact
- confabulation can occur


About 80% of alcoholic patients recovering from
Wernicke’s encephalopathy develop Korsakoff’s
syndrome.
Victor et al (1971) reported that 25% of patients with
Korsakoff syndrome recovered, 50% showed
improvement over time and 25% unchanged.
While it is unlikely that any established patients
completely recovering, it is probably correct to say that
75% show a variable degree of improvement, while 25%
show no change.
Vitamin Supplements



All heavy drinkers should receive vitamin
supplements.
Severely dependent drinkers and those at a
risk of Wernicke’s Encephalopathy will
require parental preparations (e.g. Pabrinex
High Potency).
Anaphylaxis is a rare but recognised
complication.
Vitamin Supplements

Incipient Wernicke’s encephalopathy : Two pairs high-potency
thiamine injection three times daily for 3 days, followed by one
pair once daily for 3-5 days depending on response.

At-risk (significant weight loss, poor diet, signs of malnutrition) :
One pair high-potency thiamine injection once daily for 3-5 days

Lower risk: Thiamine 100 mg orally, three times daily, plus vitamin
B compound strong two tablets two times daily during detox

Continue Oral Thiamine 50 mg TDS for six months after
detoxification or indefinitely in persons with chronic alcohol
problems or low oral thiamine intake.
Others


Carbamazepine loading in patients
with untreated seizure or those with
more than two seizures during
previous withdrawal episodes
Neuroleptics like Haloperidol in small
doses can be used for severe
behavioural disturbances.
Relapse Prevention
Disulfiram (Antabuse):

Inhibits aldehyde dehydrogenase

Leads accumulation of acetaldehyde, causing
headache, flushing, palpitations, nausea & vomiting

Halitosis is common side effect.

CI – in cardiac failure, coronary artery disease, HT,
liver disease, pregnancy & breastfeeding

Can cause fatal acute hepatotoxicity in about 1 in
25000 patients.
Disulfiram



Hughes & Cook (1997) reviewed 24 outcome
studies for oral disulfiram & 14 for disulfiram
implant
-No good evidence for implant
Others (Fuller et al, 1986; Chick et al, 1992)- no
overall difference in drinking outcome, but
reduction in the number of drinking days
Better outcome if supervised.
Acamprosate

A synthetic taurine analogue, acts on
Glutamate & GABA system

Reduces craving

CI- severe renal & hepatic impairment

Modest treatment effect in a recent metaanalysis (Boothby LA et al, 2005)
Naltrexone



An opioid receptor antagonist
Blocks endogenous opioid pathways
stimulated by alcohol use
Reduces the reinforcing effects
Project COMBINE




Anton et al, 2006; Designed to evaluate the efficacy of two
relapse prevention medications in combinations with
behavioural treatment
1,383 abstinent patients with dependence
Naltrexone, acamprosate, N+A, placebo; all medical treatment
with or without behavioural management. Ninth gp only with
behavioural management.
Naltrexone gp did better than others, no evidence of benefit
from acomprosate
MCQ1: One of your A&E colleague asks for you
to suggest a screening test for problem alcohol
use which can be quick but efficient.
What do you suggest?
A.
B.
C.
D.
E.
AUDIT
MAST
FAST
TWEAT
T-ACE
MCQ1: One of your A&E colleague asks for you
to suggest a screening test for problem alcohol
use which can be quick but efficient.
What do you suggest?
A.
B.
C.
D.
E.
AUDIT
MAST
FAST
TWEAT
T-ACE
Answer: c. FAST
Fast alcohol Screening Test (Hodgson et al.,2002)
MCQ 2: Clinical Institute Withdrawal
Assessment of Alcohol Scale, Revised, (CIWAAr) does not include the following
A.
B.
C.
D.
E.
Tremor
Auditory disturbances
Visual disturbances
Seizure
Orientation
MCQ 3: The chemical composition of
Acomprosate is
A.
B.
C.
D.
E.
Calcium bisacetyl homotaurine
Magnesium bisacetyl homotaurine
Calcium acetyl homotaurine
Magnesium acetyl homotaurine
Calcium tetraacetyl homotaurine
MCQ 4: Project COMBINE (Anton et al, 2006) which was
designed to evaluate the efficacy of two relapse
prevention medications in combinations with behavioural
treatment showed relative superiority with the following
group
A.
B.
C.
D.
E.
Naltrexone
Acomprosate
Naltrexone + Acomprosate
Placebo
Combined behavioural intervention
MCQ 5: Severity of Alcohol Dependence
Questionnaire (SADQ) doesnot include the
following
A.
B.
C.
D.
E.
Physical withdrawal symptoms
Affective withdrawal symptoms
Relief drinking
Use inspite of harmful consequences
Frequency of alcohol consumption
CASC 1
You assessed Mrs Smith, a 38 year old
lady and diagnosed her as suffering
from alcohol dependence. She has
previous history of DTs and altered
LFTs.
Discuss the management options with
her partner, Mr Smith. She has given
consent to speak to him.
Break !
Opioids

Natural (poppy, papaver somniferum extracts) –
morphine, heroin, codeine

Synthetic – pethidine, methadone, buprenorphine,
dipipanone

Endogenous opiates- enkephalins & endorphins

Acts through opioid receptors, morphine & heroin
are quite selective for mu receptors

Smoked (chasing the dragon), snorting or injected
(IV, IM / SC) (Skin popper)
Opioids



Average opiate use in the previous year in
adult population – 1% ( British household
survey, Coulthard et al, 2002)
UK has one of the higher prevalence of
problem opiate use in Europe – 6/1000
(Kraus et al, 2003)
Annual mortality for opiate dependent users
– 1-2%, mostly from overdose
Effects:



Euphoria & analgesia
Sedation, emotional numbing, dream like state
Physiological
- pupillary constriction
- respiratory depression
- decreased sympathetic outflow
- nausea & vomiting
- constipation
- seizures can occur
Withdrawals




Thought to reduce firing at NA neurones in the
locus coeruleus, sudden cessation increased NA
activity.
Appears within 6-12 hrs, peaking at 48-72 hrs and
subsiding by 7-10 days.
Muscle & joint pains, dysphoria, insomnia,
agitation, lacrimation, dilated pupils, yawning,
shivering, diarrhoea, fatigue, sweating and
gooseflesh (cold turkey)
Unpleasant but not life threatening
Pharmacological Treatment


ODs: IV /+ IM naloxone ( opioid antagonist)
Detoxification v/s Maintenance
- Clonidine & Lofexidine: alpha 2 agonists
- Methadone: long acting mu agonist
- Buprenorphine: partial mu agonist
- Suboxone ( buprenorphine+ naloxone 4:1)
-Ultra rapid detoxification: antagonists under GA
-Injectable opioid treatment

Relapse prevention
- Naltrexone: opioid antagonist.
NICE Guidelines, Jan 2007:

Methadone and buprenorphine (oral formulations)
are recommended as options for maintenance
therapy in the management of opioid dependence.

The decision about which drug to use should be
made on a case by case basis. If both drugs are
equally suitable, methadone should be prescribed
as the first choice.

Methadone and buprenorphine should be
administered daily, under supervision, for at least
the first 3 months. Both drugs should be given as
part of a programme of supportive care.
Amphetamine

Powder form, ‘speed’ ‘whizz’

Methamphetamine ‘ice’

Used orally (bombing), IV or snorting


Release of catecholamines, particularly dopamine, from
presynaptic terminals
In UK, 22% of 16-29 yr olds have used at least once
with further 2% in the last yr (Ramsay et al, 2001)
Effects






Elevate mood, induce euphoria and
feeling of wellbeing
Over-talkativeness, overactivity, anorexia
and insomnia
Pupils dilate, pulse & BP increases
Arrhythmia, severe HT, CVA & circulatory
collapse
Seizures & Coma
Sometimes dysphoria, anxiety & panic



Amphetamine induced psychosis and exacerbation of
underlying psychotic illness
Withdrawals
- ‘crash’: anxiety, tremulousness, dysphoric mood,
lethargy, fatigue, nightmares (with rebound REM
sleep), headache, sweating, cramps and insatiable
hunger.
- depression
Treatment is mainly psychosocial, with some
evidence for dexamphetamine substitute
prescription.
Cocaine

‘charlie’, ‘coke,’ ‘snow,’ ‘crack’

In UK, lifetime use – 6% (Ramsay et al, 2001)

Effects & withdrawals similar to speed.


Cardiac arrhythmias, MI, myocarditis ,
cardimyopathy, cerebral infarction & subarachnoid
haemorrhage can occur
Treatment is mainly psychosocial
MDMA (Ecstasy)

3,4 methylenedioxymethamphetamine

Stimulant with mild hallucinogenic properties

Increases release of DA and also 5-HT

Produces positive mood state with euphoria, sociability &
heighted perceptions along with loss of appetite, tachycardia,
bruxism, sweating

Deaths can occur with hyperthermia, cardiac arrhythmias,
hypertensive crises & intracranial haemorrhage

Can cause 5-HT neuronal damage (McCann et al, 1998)
Hallucinogens

Lysergic acid diethylamide (LSD)

Natural: magic mushrooms (psilocybe semilanceata) containing
psilocybin

In UK, 29% aged 16-29 have used atleast once, with 5% in the
previous month (Ramsay et al, 2001)

Act mostly as 5-HT2A partial agonists

‘Trip’: pleasant state of detachment, euphoria with distortions
of perception , synaesthesia

General physiological arousal with increase in pulse, BP, dilated
pupils
Hallucinogens


‘Bad trip’: anxiety, mood disturbances,
hallucinations with alterations in
consciousness
No withdrawal syndrome &
dependence syndrome is uncertain.
Phencyclidine & Ketamine





NMDA antagonists
Produce drunkenness, analgesia of toes &
fingers and anaesthesia
Agitation, altered consciousness, psychotic
like symptoms, nystagmus, inc BP, ataxia,
muscle rigidity, convulsions and absence of
response to environment with eyes open.
Adrenergic crises with heart failure, CVA &
malignant hyperthermia
Tolerance can occur, withdrawals are rare
Cannabis

From cannabis sativa, ‘marijuana’, ‘grass’, ‘hashish’

Psychoactive component: delta-9-tetrahydrocannabinol

In UK, 27% used at least once with 6% current users (Ramsay et al, 2001)

Causes dry mouth, tachycardia, injected conjunctivae, distorted sense of time,
perceptual abnormalities, panic, paranoia, impaired concentration & confusion

Irritate respiratory tract & potentially carcinogenic

No evidence of tolerance or dependence

Arseneault et al (2004) : cannabis use in adolescence increased the risk of
developing schizophrenia about two fold; and removal of cannabis from society
would prevent 8% of schizophrenia cases.
Khat

‘natural amphetamine’, from catha edulis plant

Possession & use are not illegal in UK

Active constituents, cathinone & cathine, are scheduled as
class C drugs

Chewing of leaves, common in countries around red sea and
eastern coast of Africa

Produces sympathomimetic & CNS stimulation similar to
amphetamine

Dependence- debatable, psychological rather than physical.

Short lived psychosis, mania and rarely depression
Nicotine

In UK, 29% of adults smoke tobacco

Around half of all smokers die prematurely

Their overall life expectancy reduced by an average of 8
years.

Single most common preventable cause of death in
Britain, 120,000 death/ year (13 / hour)

1000 admissions/ day with smoking related illnesses,
with estimated cost of £1500 million/ year for NHS;
while UK treasury earns £8 billion in tax on tobacco sold
in the UK.
Nicotine

Each cigarette provides around a mg of nicotine.

Less than 4% of smokers smoke less frequently
than daily

Agonist at nicotinic Ach receptors

Causes dependence, activates reward circuit like
other addictive drugs
Nicotine





Smoking cessation is UK government’s one of
the top 13 priorities
Smoking cessation programmes
Bupropion: inhibits reuptake of DA & NA
Varenicline: partial agonist of nicotinic receptor
Nicotine replacement therapy
MCQ 1:
What is the best time for detoxification in
pregnancy?
Options:
A.
B.
C.
D.
E.
Never in pregnancy.
First trimester
Second trimester
Third trimester
Anytime in pregnancy
MCQ 2:
You want to prescribe an alpha 2 agonist to control opioid
withdrawals for one of your patients attending the drug and
alcohol clinic. He has a tendency to get low blood pressure with
various drugs. Select the most appropriate drug you choose .
Options:
A.
B.
C.
D.
E.
Buprenorphine
Clonidine
Lofexidine
Methadone
Naltrexone
MCQ 3:
What is the recommended minimal period of
supervised consumption for someone starting on
methadone treatment for opiate dependence?
Options:
A.
B.
C.
D.
E.
One month
Two months
Three months
Four months
Six months
MCQ 4:
One of your patients in the ward wants quit smoking and seen a
new drug varenicline in the internet. How does the new drug act?
Options:
A.
B.
C.
D.
E.
Alpha2
Alpha4
Alpha4
Alpha2
Alpha2
beta4
beta2
beta2
beta4
beta4
nicotinic
nicotinic
nicotinic
nicotinic
nicotinic
acetylcholine
acetylcholine
acetylcholine
acetylcholine
acetylcholine
receptor
receptor
receptor
receptor
receptor
partial agonist
partial agonist
antagonist
antagonist
agonist
MCQ 5:
Choose the structure that plays a dominant role in
the reward pathway of the brain facilitating the
reinforcing effects of drugs that cause dependence.
Options:





Amygdala
Frontal operculum
Temporal pole
Superior temporal gyrus
Ventrotegmental area
Thank You!