Society tends to ostracize the addict - this further aggravates feelings of inadequacy, isolation and general resentment.

Parenteral administration of any drug may cause hepatitis B due to sharing needles, abscesses (heroin, barbiturates), septicaemia , endocarditis and AIDS .

DRUG ABUSER DEATHS

Overdoses (by mistake/deliberate) of various drugs are the main cause of death in 'known' addict group (about 60% of the deaths). Large number of what seems to be 'natural causes' like renal failure, septicaemia, malnutrition, are possibly all drug related. Likewise, those due to accidents (fire, drowning) in drug addicts are related to the drug misuse.

Death may occur due to an overdose of opioids and in the past Barbiturates.

Lysergic acid Diethylamide (LSD) is psychotomometic. It produce symptoms similar to mental illness and therefore has to be considered in the differential diagnosis of any psychosis.

Hoffman, manufactured it by chance in his laboratory. He experienced marked perceptual changes after accidentally inhaling the dust.

All Ergot compound contain LYSERGIC ACID AMIDE and some natural compounds has similar pharmacological effects. Morning Glory has some of the potency of L.S.D - Lysergic Acid diethyl amide.

The dose to produce subjective effects in human is as low as 1 microgram.

(i) rapidly absorbed

(ii) distributed throughout tissues

(iii) concentration highest in (a) gut (b) liver lower in brain

(i) Constricts peripheral blood vessels

(ii) Potentiates the PRESSOR (BP) response to adrenaline

(iii) Increases temperature

(iv) Dilates the pupil - in the human (the degree of pupillary dilation correlates with the degree of psychological arousal)

(v) EEG and other studies suggest it increases SENSORY input to the RECTICULAR formation

(vi) Psychological Effects

(b) hallucinations : LSD antagonises 5-HT (serotonin) both centrally and peripherally. Gaddum suggested that this could cause hallucinations. However, )several other 5-HT antagonists do not cause hallucinations, also we may find hallucinogenic action of a compound not dependent on 5-HT antagonism. It can only regarded that the mental state effects of L.S.D. as due to complex biochemical and physiological effects.

(vii) 'Flash backs' - recurrence of psychotic episodes may persist for several months following L.S.D.

(viii) It can be detected in urine by immunoassay.

(i) Pulse rate increased.

(ii) Electrical functions of heart changed.

(iii) Carbon monoxide decreases oxygen carrying capacity of the blood (as with tobacco smoking).

(iv) BP lowered (a) standing (b) in hypertension, but not of therapeutic significance.

(v) Dilation of conjunction of blood vessels - red eye.

Acute:- inhalation constrict bronchi.

No convincing evidence of short and medium term harm.

Animal tissue: similar effects from tobacco and cannabis, but extrapolation to man difficult.

Animal studies:- inadequate in methodological control procedures. However, evidence of adverse effects.

(i) Cerebral atrophy not confirmed.

(ii) Localised disturbance of electricity activity (man and experimental animals).

In animals:- ultramicroscopic changes in the brain were reported.

(1) Dependence - use can cause tolerance and withdrawal symptoms. Evidence vague, Dependence syndrome may exist

(2) Cannabis Psychosis

(i) Acute short lived psychoses reported with moderate dosage

(ii) Chronic continuous cannabis use causes psychotic illness.

(3) Prolonged depersonalisation following Cannabis use

(i) Experimental studies in normal volunteers and from clinical studies show acute cannabis intoxication causes depersonalization and derealization.

(ii) Prolonged depersonalization also reported with preservation of insight. Symptoms have temporal relationship to cannabis in absence of other psychiatric illness/drug abuse.

'Flashbacks':- Cannabis excreted over several weeks but that alone cannot explain persistence of flashbacks for over 1 year. Hence, we have to consider residual neurotoxic effects.

Psychiatric sequelae following cannabis so far remain under-recognised.

Rarely used nowadays. They cause

(i) Dependence - physical and psychic

(ii)

(a) Tolerance - due to enzyme induction (increases rate of metabolism)

(b) Cross tolerance - described with alcohol

Anxiety, irritability, agitation

Tremor

Twitching

Convulsions (in the absence of any underlying epilepsy)

Delirium

Vomiting, nausea

BP reduced (slight orthostatic)

P increased rate

Sweating

(iv) Prolonged heavy dosage

- personality changes

- persistent intoxication

- labile effect

- poor concentration

- impaired judgement

- motor incoordination

Overdose - dangerous. Addicts attempt to prepare oral preparations for IV use (as with amphetamines)

(vii) Acute intoxication

Consciuosness - drowsy to coma (often taken + alcohol)

Temp./Pulse/Heart Rate are all decreased

Muscle flaccidity

Nystagmus

Ataxia

Incoordination

Dysarthria..

(viii) Chronic Intoxication (as with Alcohol)

Mood - variable

grasp impaired

irritability

impaired judgment

Treatment of Barbiturate Addiction:-

(a) Slow reduction of dosage to prevent fits

(b) Epanutin 100 mg. t.d.s.

(c) Valium

In order to withdraw an addict effectively from barbiturates, in-patient programme required.

Drugs (Prevention of Misuse) Act 1964 Possession unlawful without prescription. Now Class B (Schedule 2).

(1) Tolerance and psychic dependence

(2) No physical dependence - can withdraw from large IV dosage of methylamphetamine (Methedrine)

(3) Stimulant activity on reticular activating system causes arousal. When fatigued, performance may be improved.

(4) Mood

(5) Interactions:

(i) Tricyclic and MAOI's potentiate amphetamines

(ii) Barbiturates are nullified as regard hypnotic effects.

(6) Indications: (Many authorities consider NONE)

The following are the only ones ever to be considered:

(i) Narcolepsy

(ii) Hyperkinetic hyperactive child (paradoxically, and again there is real risk of promoting adolescent dependence)

(iii) Nocturnal enuresis

Dangers of

(i) Drug dependence

(ii) Amphetamine paranoid psychosis (consider this along with LSD as possible causes of organic psychosis). Amphetamine psychosis remits when drug withdrawn.

-Apart from Indications (above), there is NO place for amphetamine prescription as 'pick-me-up'. GP¹s are sometimes coaxed to prescribe for obesity, but this is contra-indicated.

AMPHETAMINE DEPENDENCE

1. Taken with barbiturates to produce euphoria + alcohol

Pre-morbid personality of user

(i) unstable

(ii) psychopathic

3. However, Dependence may follow prescription for depression or obesity

4. Overdose: Restlessness to Delirium

Differential diagnosis: (i) Mania (ii) Hypomania

5. Dependence may result in organic psychosis with

(i) paranoid delusions

(ii) auditory hallucination

Differential diagnosis: paranoid schizophrenia

Irresponsible and aggressive behaviour may occur.

Withdrawal may aggravate the paranoid features, or the depression.

(1) Fresh leaves of khat bush have stimulating effect.

(2) Grown in East Africa and Arabian peninsula.

(3) Chewed habitually, may be compulsiaddictive.

(4) Health is impaired plus some economic aspects for countries concerned.

(5) Due to rapid air travel, now in UK while leaves still fresh.

 (6) CNS stimulation due mainly to the alkaloid cathinone, a 'natural amphetamine', effects resembling those caused by amphetamines:-

Compulsive use lead to

Constipation (tannin effect)

Anorexia

Insomnia

Excess energy

Excitation

Euphoria

Hyperthermia

Increased respiration

Cathinone is pharmalogically and chemically like amphetamine of which it is an analogue but more difficult to synthesise because it is a labile substance. Animal experiments (in vitro) shows that it has the same mechanism as amphetamine action. It is the dependence producing constituent of khat leaves. Monkey experiments show that its reinforcing effects equate with those of cocaine. Currently, UK use including trading is not illegal.

Caffeine along with alcohol and nicotine are the 3 most widely used psychoactive substances. Caffeine use may occur from childhood onwards. 80-200 mg may produce pharmacological effects

(i) mood elevation

(ii) alertness and clarity of thought

(iii) increased productivity and intellectual effort

(a) In coffee and Tea, Caffeine/average cup is 80-150 mg varying with brewing

(b) Caffeine - significant amounts in cocoa, chocolate, soft drinks, over counter analgesics, common cold remedies, diuretics and patent stimulants. Caffeine content of analgesics and cold remedies - equivalent to that of patent stimulants

Caffeine is absorbed from gastrointestinal tract and is rapidly distributed throughout tissues. Peak blood level is reached in 15-45 minutes. The plasma half-life varies between 3-10 hours and is reduced by smoking and increased by oral contraceptives and pregnancy up to twice the normal. In the Neonate - the half-life is up to 80 hours as it has no enzymes responsible for metabolism.

(i) intoxication may occur from 250 mg (DSM III, 1980). The picture simulates acute anxiety and is characterised by nausea, agitation and restlessness.

2. euphoria replaced by dysphoria when intake exceeds 600-700 mg per 24 hours (wide individual variation) features include:-

Anxiety and mood disturbance

Sleep impairment

(a) restless, irritability, dizziness

(b) diuresis, gastro-intestinal disturbance

(c) headache, insomnia

(d) arrhythmias, flushing

(e) anxiety state cannot be differentiated and may co-exist

Identification of Caffeine abuse - essential for accurate diagnosis of anxiety states, depressive illness, sleep disorder, anorexia and even psychotic disorder.

(i) caffeine antagonises diazepam at electrophysiological and behavioural levels

(a) diazepam induced performance impairment antagonised by caffeine 250 mg

(b) anxiolytic effect of diazepam 10 mg counteracted by 500 mg caffeine

(c) benzodiazepine sedative hypnotic effects antagonised by caffeine

(1) Excessive amounts of caffeine produce unpleasant symptoms, over 600 mg daily when suddenly stopped produces withdrawal .

(2) Sources to be considered include coffee, tea, soft drinks and over counter medication for pain/headaches.

(3) Caffeine withdrawal (from 600-1000 mg/more) causes severe headache, rhinorrhoea, irritability, nervousness, drowsiness, depression, poor work performance. It is counterproductive to use caffeine containing analgesics for withdrawal headaches.

(4) Consider in the differential diagnosis with anxiety, atypical depression, sleep disturbance, headache, poor response to minor tranquilisers and hypnotics. Diagnosis confirmed by significant reduction of intake and return when challenged with caffeine.

(1) A stimulating drug with sympathomimetic activity.

2. Morphine and heroin addicts use it as an adjuvant.

(3) Administration:

sniffed (hence nasal ulceration associated with peripheral vasoconstriction)

self-injected. Free basing

(4) Effects on mental state:

Energy increased

Excitement + Hallucinations (formication)

Restlessness

(5) Withdrawal effects: Mild.

Following the introduction of 1968 legislation cocaine was very much less used. Recently, there is evidence for increase in its use, particularly in upper social classes and business world. 'Yuppies¹.

1. Include here

(i) Heroin (diacetylmorphine)

(ii) Morphine

(iii) Synthetic agents, eg methadone

2. At risk:

(ii) psychopathic, unstable personalities

(3) Administration: IV. IM (skin popping) much less popular.

(4) Analgesic and euphoriant properties predispose.

(5) Tolerance, physical and psychological dependence.

(i) Onset, within a few hours of last dose.

(ii) Peak, 24-48 hours.

(iii) Subsiding, 7-10 days.

(iv) Clinical features: Anxiety, Yawning, Dilated pupil, Restlessness, Sweating, Gooseflesh, Tension, Lacrimation, Abdominal cramps, Rhinorrhoea

Abstinence symptoms increase in degree over first 18-26 hours, during which time:

Sleeplessness, Vomiting, Respiratory rate increases, Twitching of muscles, Anorexia

These effects are due to continued sympathetic and parasympathetic over-activity (release phenomenon). There is cross-tolerance within the opiate group.

Chronic malaise, Constipation, Tremors, Weakness, Small pupils, Impotence

Often associated with amphetamine misuse, occasionally with cocaine nowadays

Depends on motivation

(a) (i) After hospitalisation - allows assessment of true degree of

dependence - promethazine useful if withdrawing

(ii) Intensive support - group work

(b) Maintenance Methadone

NB: The interest and support of caring person - family -accommodation and rehabilitation is most important.

1.25 million of UK population use benzodiazepines for more than 1 year. There is no evidence for long term effectiveness and they lead to psychological impairment and neurological changes.

Normal doses:- (30-45 mg max/24 hrs)

A specific physical withdrawal syndrome following withdrawal of a normal therapeutic dose.

e.g. Chlordiazepoxide 45 mg/24 hours (in divided doses) for 20 weeks. Sudden withdrawal produces feelings of anxiety, tension, trembling, decreased appetite, faintness and dizziness.

Withdrawal syndrome after cessation of normal dosage had the same clinical features as that following high dosage cessation. 15-45% long term benzodiazepine users experience syndrome.

Withdrawal features:-

increased sensory perception:- hyperacusis, photophobia, paraesthesiae, hyperosmia. Hypersensitive to touch and pain.

Sleep disturbance, headache, pain, muscle spasm and gastro intestinal symptoms.

Anxiety symptoms including choking sensation, dry mouth, hot and cold flushes, irritability, depersonalisation and derealisation.

Insomnia (less than 3 hrs sleep) for up to 4 days (sleep rhythm normal after 2 weeks).

Less common features:- Hand tremor, profuse perspiration, and headaches.

Depression - if it occurs, not prolonged.

Psychological performance

Motor co-ordination, impaired before withdrawal with later improvement.

(a) Dependence

This is uncertain. Some 12-20% of those commenced on benzodiazepines remain on them for some 6 months.

Withdrawal symptoms appear : -

After 1 year in 25-40%

After 7 years: the majority are physically dependent

(b) Tolerance - uncommon. Steady maintenance dose. Special stress may cause increase which is not reduced. Any signs of development of tolerance or increased dosage indicate dependence.

Withdrawal can be done on an outpatient or in-patient basis. Better to try as Drug Detox Unit or out-patient or by GP. There is inadequate research to say which withdrawal procedure is optimal.

High dosage and long term dependence may necessitate hospitalisation to cope with seizures or psychotic features. Basic, how well does the individual cope with distress? e.g. alcohol, self medication, sedatives. Social support, family and motivation from GP are all important.

Out-patient detoxification is safe for most even long-standing normal-dose patients provided adequate medical supervision. The dose is reduced over 4 weeks. Relaxation and anxiety management, cognitive therapy and self help groups are useful, provided anticipation of problems is not augmented.

Pharmacology :- withdrawal symptoms related to rate at which circulating benzodiazepines and active metabolites are metabolised and excreted. Gradual withdrawal reduces the severity of withdrawal symptoms.

One third well. No problems since completing withdrawal.

One third some anxiety and depression. Respond to anti-depressent. Overall relieved.

One third chronically anxious and use alternative anxiolytics return to benzediazipine.

Abrupt withdrawal - higher dropout rate.

Rate of withdrawal - abrupt cessation more likely to cause severe symptoms, including fits and confusional states. Tapering is more effective (Diazepam 0.5-2.5 mg). Opinions vary as to size of dosage decrement and duration of each stage. 4-16 week programmes described. Ideally, titrate dose against withdrawal symptoms. Weekly reduction until first withdrawal signs, then delay rate. Next decrement when withdrawal signs abated. Psychological aspects of dependence may respond in final stages to a placebo or taking final miniscular dose on alternate days/even less frequently. Sometimes withdrawal features do not occur until the final withdrawal.

(i)Other medication substituted. As long acting bdz associated with less marked withdrawal features, substitute for short acting before starting withdrawal. Onset of withdrawal features delayed by 2-5 days. However, incomplete cross tolerance by substitute can itself cause withdrawal signs.

(ii)Clonidine (alpha 2 adrenoceptor agonist);

(iii) Propranolol may reduce somatic symptoms, not psychological ones.

(iv) Antidepressant because of severe depressive episodes and sedative effect are helpful.

1. Careful prescribing: Lorazepam is responsible for 3 times the problems due to all other bdzs combined, based on recent GP survey of 1500 NHS GPs.

(2) Duration of bdz prescription to be shortest possible.

(3) Lowest possible dose and intermittent use.

(4) Brief counselling by GP for minor affective problems is preferable.

(5) Do not use bdz for acute stress associated with traumatic life events, e.g. death, bereavement, marital breakdown.

Surveys in Australia and Western Scotland show that (1) the majority of those taking analgesics infrequently use single drugs, e.g. aspirin or paracetemol. These are taken appropriately for pain or colds. (ii) Some 60-70% taking daily analgesics use compound powders containing caffeine or tablets containing codeine. These compound preparations are frequently taken inappropriately for insomnia, agitation and depression.

Pathology: Papillary necrosis and chronic interstitial nephritis.

Associated with the use of :- phenacetin, phenazone, caffeine and aspirin.

It is controversial whether phenacetin or aspirin is most toxic in this respect. Both are potentially dangerous and nephrotoxicity is increased by their combination.

More than 90% of those with analgesic nephropathy have used compound preparations.

Self medicators always under estimate their intake.

Analgesic nephropathy is a feature of dependence as is alcoholic cirrhosis.

Dependence aspect supported by:-

(a) continued consumption despite known medical risks and warnings.

(b) use of caffeine and codeine containing preparations.

Caffeine, codeine and phenacetin all have psychotropic effects potentiated in mixture or powder form.

Development and Course - gradually over several years in association with analgesic effect, invigorating, stimulating and enhanced performance effects ensued. These secondary effects become obligatory.

Attempts to stop may cause caffeine withdrawal headaches.

Progressive anaemia and uraemia make the psychotropic effects more necessary in the abusers coping efforts.

Those with analgesic nephropathy:-

(i) have disturbed families;

(ii) smoke excessively;

(iii) abuse alcohol;

(iv) abuse other psychotropic drugs;

(v) high psychiatric morbidity;

(vi) personality - passive, neurotic and introvert traits higher than controls;

(vii) Female psychiatric patients with chronic neurotic disorders, reactive depression and inadequate personality are prone to abuse analgesics.

Phenacetin is the common constituent of most nephrotoxic analgesic mixtures.

Withdrawal of phenacetin led to an apparent decline of analgesic nephropathy.

But, renal function continued to deteriorate from non phenacetin containing analgesics.

Explanation: -

(i) Paracetomol was substituted for phanacetin. Although paracetemol is the major metabolite of phanacetin;

(ii) Other manufacturers increased the dose of aspirin. Both paracetemol and aspirin are nephrotoxic in very large quantities. In animals, they potentiate each other's toxicity;

(iii) The increased caffeine/codeine content stimulated the users's desire for continued and increased use.

(a) asphyxiation (b) inhaled vomit

(ii) Many substances are taken in solvent abuse such as dry cleaning fluids, petrol, aerosols

(iii) Sniffing is not a criminal offence

(iv) 1980 Scotland : 1,300 new cases were reported out of 420,000 secondary school population.

(1) Children and adolescents (8-17)

(2) Males : females 10:1

(3) Group activity - truancy - rebellious behaviour

(1) Polystyrene plastic glue vapours

(2) Inhaled in sufficient quantities to intoxicate

(3) Vapours affect CNS causing

(a) dizziness

(b) euphoria, grandiosity, recklessness

(c) impaired consciousness

 1. Assessment

2. Prescribes if thought appropriate. Notify.

3. Support - rehabilitation - CPN, social worker, key caring person.

4. Treatment programmes vary and include detoxification, methadone maintenance, drug free regimes and Narcotics Anonymous.

Remember, the overall problem of Drug Dependence must be considered in the context of general psychiatry and medicine and not regarded as being dealt with exclusively in Drug Dependence Clinics. Primary care must be closely involved together with statutory and voluntary community agencies.

1. Usually, those too severely dependent for out-patient care

2. One indication of severity is re-admissions. Ghodse showed that more than a third of all admissions in 1984 were re-admissions.

3. Purpose of admission

(i) treatment of opiate dependence. Ghodse showed that 74% of opiate detoxification programmes were completed. This finding is similar to that of Gossop.

4. The Pattern of addiction has altered.

(i) Benzodiazepine abuse replaced barbiturates e.g. benzodiazepines identified in urine of 60% of Drug dependence clinic 0-P's and 76% of these illegally obtained.

(ii) A very high proportion of those admitted for sedative detoxification (benzodiazepines and a barbiturates) were dependent on opiates.

(iii)

(a) proportion of patients giving history of barbiturate usage corresponds roughly with those addicted

(b) only some 25% of those describing regular benzodiazepine usage showed physical dependence.

5. Some units insist on completion of sedative withdrawal programme, once common, because of risk of fits.

Poly drug abuse includes

(i) alcohol to level of dependence

(ii) cocaine

6. In-patient programme - 2 phases usrecognised

(i) Drug withdrawal - mainly dealing with symptoms and physical illness.

(ii) Recovery, rehabilitation and future planning including community links and back-up.

(a) due to inadequate facilities, self discharges occur during this phase due to resentment of restrictions such as being nursed on original closed ward.

(b) high proportion successfully stabilised/withdrawn. However, this is only very much first step as with alcohol detoxification from alcohol.

(iii) While community projects require support, so do I-P programmes for the severely disturbed and physically ill. Their remaining in treatment is essential.

1. programmes require a stated objective.

2. Realistically it has to be accepted that eradication through primary prevention is impossible to achieve.

3. Therefore minimization of harm is sensible goal i.e. modify styles of drug use.

4. While recognising ethical and valid objections, by clarifying ^treasonable use' the programme may be more effective by avoiding blanket rejection.

5. Reduction of harm by

(i) reducing frequency

(ii) changing to 'safer' substances

(iii) change of route to intake, now highly relevant because of AIDS and prevalence among drug users sharing same syringes and needles.

6. Essential to assist people to develop the attitude necessary to handle 'factual information. That is to tackle:

(a) deficiencies within the individual which predispose to drug abuse such as:

(i) low self esteem

(ii) lack of personal skills

(iii) interpersonal problems predisposing to peer group pressure

(b) development of drug free environment.

Rapid increase in

(i) IV drug abusers

(ii) cases infected with HTL V - III virus

Abusers

(i) Those who are not concerned regarding risk of infection are very few

(ii) some request screening despite fairly comprehensive self-acquired knowledge and some have avoided sharing needles

(iii) others have changed to smoking or 'chasing'.

3. The provision of disposable syringes is important.

4. Drug abusers (IV) are second highest risk group.

5. Four strategies were suggested:-

(a) avoid starting - Is it realistic?

(b) counseling/screening of existing addicts

(c) free disposable syringes

(d) treatment.

6. Apparently, being sero-positive does not dissuade continuing IV abuse. Life style is not changed only by counselling.

7. At a drug advisory and treatment centre where seeing a doctor is not mandatory, the fear of contracting AIDS not motivating factor in seeking rehabilitation help.

8. Addicts denial of seriousness of situation is reflected by a series reported by O'Connor with 43% sero-positive patients attending a special programme for pregnant addicts becoming pregnant again despite counselling regarding dangers to health of further conception.