Drug therapy, poisoning, and alcohol misuse

DRUG PRESCRIBING

Medicines should be prescribed only when they are necessary; and in all cases the expected benefit of administering the medicine should be consid-ered in relation to the risk of causing adverse effects. During pregnancy and breast feeding the risk of medicines to the fetus or baby must be considered in addition to the mother. Titles of drugs and preparations should be written in full. Where non-proprietary (‘generic') drugs are available they should be used in prescribing other than rare exceptions where stated, e.g. modified release theophylline to avoid variable drug pharmacokinetics. Names followed by the symbol® are or have been used as proprietary names in the UK.

Concordance with medication

It is estimated that about one third of medicines that are prescribed for long-term conditions are not used as recommended. Concordance aims to ensure a more effective use of medicines. A concordant consultation describes a consultation process between a healthcare professional and a patient in which the decision-making process regarding management takes into account the views of both the patient and the professional. The previous terms of non-compliance or non-adherence implied a paternalistic and dog-matic approach to drug prescription with little engagement of the patient in the decision-making process. Simplifying a drug regimen may help to improve concordance. Once-daily and twice-daily administration is better than three- or four-times daily. Combination products reduce the number of drugs taken but at the expense of inability to titrate individual drug doses. Using a multi-compartment medicines system is often helpful particularly in the elderly.

A discussion with the patient about prescription medication should include:

■ What the medicine is and how and when to take it

■ Likely benefits of treatment

■ Likely or serious adverse effects and what to do if they think they are experiencing an adverse effect

■ What will happen if they do not take the medicine

■ Instructions for stopping the medicine or reducing the dose if necessary

■ Choosing between medicines and also non-pharmacological alternatives.

Adverse drug reactions

Any drug or vaccine may produce unwanted or unexpected adverse reactions. Health professionals (doctors, dentists, coroners, pharmacists and nurses) and, in some countries patients and carers, are encouraged to report sus-pected adverse drug reactions (even if in doubt about causality) to the rele-vant regulatory agency. In the UK this is via the Yellow Card Scheme to the Medicines and Healthcare products Regulatory Agency (MHRA). Reports should be submitted for adverse reactions occurring with new drugs or vac-cines on the market and established drugs causing a serious or unlisted reaction. Reporting acts as an early warning system for the identification of previously unrecognized reactions. The elderly are more susceptible to adverse drug reactions and drug interactions because of co-morbidity, poly-pharmacy and changes in drug distribution associated with a reduction in body mass and relatively more of the stroke volume reaching the brain (which explains why the elderly are more vulnerable to the effects of drugs acting centrally). Impairment of renal and liver function may necessitate a reduction in drug dosage or contraindicate prescribing of some drugs.

Writing a prescription

All prescriptions should be written legibly in ink or otherwise so as to be indelible and should be dated with the drug written in full or using only approved abbreviations, usually listed in the National Formulary. The pre-scription should include the full name of the prescriber (and address for outpatient prescriptions), and the name, address and date of birth or age of the patient. Inpatient prescription drug charts should also have the patient's hospital identification number and list of drug allergies. The prescriber should sign each prescription. Many hospitals and local authorities will have local guidelines and policies, particularly, for antibiotic prescribing which should be referred to. Prescribing errors are amongst the most common medical errors. They include the wrong drug or dose being administered due to poor handwriting, drugs administered via the wrong route, and drugs prescribed for a patient who is clearly documented to be allergic to that drug.

Best practice for drug prescribing

■ Write clearly in legible handwriting

■ Include details of the dose, frequency, route of administration and the start date for each drug. Duration of treatment e.g. antibiotics, should also be stated.

■ Intravenous drugs should give the name and volume of diluent or infusion fluid or both

■ The actual total dose should be specified when drugs are prescribed based on body weight, e.g. mg/kg

■ State maximum dose and maximum frequency for ‘as required' drugs

■ Existing prescriptions should not be alerted. The prescription should be rewritten if a change is made

■ Abbreviations are a major cause of clinical incidents and should be avoided: use microgram not μg, nanogram and not ng, units and not U or u

■ Unnecessary use of decimal points should be avoided, e.g. use 125 microgram not .125 mg.

Specific drugs

Each chapter has listed some of the drugs commonly prescribed, particularly by junior doctors. The doses given are for adults. A full list of drug interactions and dosage adjustment in renal and liver failure is beyond the scope of this book and readers should refer to the National Formulary. Similarly reference should be made for guidance during pregnancy and breast feeding.

DRUG POISONING

In many hospitals in the developed world, acute poisoning is one of the most common reasons for acute admission to a medical ward. Poisoning may be:

■ Deliberate

♦ Self harm or suicide

♦ Child abuse or Mũnchausen's syndrome by proxy

♦ Third party, e.g homicide or illicit drugs.

■ Accidental

♦ In children

♦ Dosage error by patient or doctor

♦ Recreational use, e.g. heroin, methadone and cocaine.

■ Occupational exposure

■ Environmental

♦ Plants, foods, stings and bites.

Self-poisoning is the most common way by which people attempt suicide (deliberate self-harm, DSH) and those who succeed (suicides). Other means of DSH and suicide are usually by violent methods, e.g. hanging, shooting or drowning. In adults with self-poisoning admitted to hospital in the UK the most common drugs taken are paracetamol, benzodiazepines, antidepres-sants, non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. In many cases more than one substance is taken; alcohol is frequently a secondary poison. Outside hospital, where most deaths occur, the commonest cause is deliberate carbon monoxide poisoning from inhalation of vehicle exhaust fumes. This is also seen in cases of accidental poisoning with faulty appli-ances using natural gas. In the developing world ingestion of pesticides, heating fuels, antimalarials and traditional medicines is more common.

The majority of cases (80%) of self-poisoning do not require intensive medical management, but all require a sympathetic and caring approach to their problems. Both the patient and the family may require psychiatric help (see p. 595) and the social services should be contacted to help with social and domestic problems.

Clinical features

Eighty per cent of adults are conscious on arrival at hospital and the diagnosis of self-poisoning is usually made from the history. In the unconscious patient a history from friends or relatives is helpful, and the diagnosis can often be inferred from tablet bottles or a suicide note brought by the ambulance attendants. Tablet identification may be helped by the use of TICTAC, a visual drug identification database with information and high-quality images on thousands of tablets, capsules and related products (http://www.tictac.org.uk). In any patient with an altered conscious level drug overdose must always be considered in the differential diagnosis.

On arrival at hospital the patient must be assessed urgently (Airway, Breathing, Circulation) and Glascow Coma Score recorded (p. 739).

The physical signs that may aid identification of the agents responsible for poisoning are shown in Table 13.1.

Investigations

A blood sample should be taken at an appropriate time post drug overdose if the following drugs are likely to have been taken: aspirin, digoxin, ethylene glycol, iron, lithium (do not use a lithium heparin tube for blood sampling), methanol, paracetamol or theophylline. The determination of the concentra-tion of these drugs will be valuable in management. Drug screens of blood and urine are also occasionally helpful in the seriously ill unconscious patient in whom the cause of coma is unknown. Further investigations depend on the drugs ingested and knowledge of their likely impact on metabolic and cardiorespiratory function and the clinical assessment of the patient, e.g. arterial blood gases in the comatose patient.

Table 13.1 Some physical signs of poisoning

Features

Likely poisons

Constricted pupils

Opioids

Organophosphorus insecticides

Nerve agents

Dilated pupils

Tricyclic antidepressants

Amfetamines

Cocaine

Antimuscarinic drugs

Divergent strabismus

Tricyclic antidepressants

Nystagmus

Phenytoin

Carbamazepine

Loss of Vision

Methanol

Quinine

Papilloedema

Carbon monoxide

Methanol

Convulsions

Tricyclic antidepressants

Theophylline

Opioids

Mefanamic acid

Isoniazid

Amfetamines

Dystonic reactions

Metoclopramide

Phenothiazines

Delirium and hallucinations

Antimuscarinic drugs

Amfetamines

Cannabis

Recovery from tricyclic antidepressant overdose

Hypertonia and hyperreflexia Tricyclic antidepressants
  Antimuscarinic drugs

Tinnitus and deafness

Salicylates

  Quinine

Hyperventilation

Salicylates

Phenoxyacetate herbicides

Theophylline

Hyperthermia

MDMA (Ecstasy)

Blisters

Usually occur in comatose patients

Lips and skin ‘cherry red’

Carbon monoxide poisoning

MDMA: 3,4-methyỉenedioxymethamfetamine

Management

Most patients with self-poisoning require only general care and support of the vital systems. However, for a few drugs, additional therapy is required. The online TOXBASE® database (http://www.spib.axl.co.uk) provides up-to-date information about the diagnosis, management and treatment of patients suffering from exposure to a wide range of substances and Products. It should be the first point of reference in all cases of poisoning. The management of a patient with overdose is summarized in Table 13.2.

Emergency resuscitation (ABCDE, p. 740)

■ Nurse the patient in the left lateral position to reduce the risk of aspiration.

■ Clear the airway and intubate if the gag reflex is absent.

■ Administer 60% oxygen by face mask in patients not intubated.

■ Artificial ventilation is sometimes necessary if ventilation is inadequate (p. 582).

■ Treat hypotension (p. 578), arrhythmias (p. 420) and convulsions (p. 756).

■ Respiratory function (arterial blood gas analysis or pulse oximetry) and ECG monitoring in selected patients.

■ Measure temperature with a low-reading thermometer and treat hypo-thermia (p. 659).

Prevention of further drug absorption These measures are reserved for those who have taken a potentially serious (life-threatening) overdose by mouth:

■ Gastric lavage is rarely used due to the risk of complications and only if the procedure can be undertaken within 1 hour of ingestion. 200-300 mL of warm water or 0.9% saline are repeatedly instilled and aspirated from the stomach via a large-bore orogastric tube with the patient in the left lateral decubitus position. It is contraindicated if the airway is not pro-tected or overdose of corrosives, petrol or paraffin taken. Complications include pulmonary aspiration and oesophageal perforation.

■ Activated charcoal (50 g orally) adsorbs unabsorbed poison still present in the gut. It is given if the patient has ingested a drug absorbed by charcoal (e.g. aspirin, digoxin, paracetamol, barbiturates) up to 1 hour previously.

Table 13.2 Principles of management of patients with self-poisoning

1. Emergency resuscitation

2. Prevent further drug absorption

3. Increase drug elimination

4. Administration of speciíic drug antidotes

5. Psychiatric assessment

■ Whole bowel irrigation is only given for potentially toxic ingestions of iron, lithium, sustained-release or enteric-coated drugs and ingested drug packets. Polyethylene glycol electrolyte solution, e.g. Klean-prep, is infused via a nasogastric tube (1-2 L/h) until the rectal effluent is clear (usually 3-6 hours).

Increasing drug elimination

■ Multiple-dose activated charcoal (50 g 4-hourly until charcoal appears in the faeces or recovery occurs) interrupts the enterohepatic or entero-enteric recirculation. It is only used in patients who have ingested a life-threatening amount of carbamazepine, phenobarbital, dapsone, quinine or theophylline.

■ Urinary alkalinization increases the urine pH and enhances the elimination of salicylates. It is rarely used now.

■ Haemodialysis is used with severe lithium, ethanol, methanol, ethylene glycol and salicylate poisoning (see below).

Antagonizing the effects of poisons Specific antidotes are available for a small number of drugs and discussed under the individual drugs.

Psychiatric assessment All patients with DSH must be taken seriously and an assessment made of suicidal intent (Table 13.3). In some patients, often young females, the act was not premeditated, they have no wish to die and the tablets were taken in response to an acute situation, e.g. an argument with the boyfriend. The risk of suicide is low and formal psychiatric assess-ment is not always necessary. In the absence of potential medical problems these patients may not necessarily need to be admitted to hospital, provided there is the necessary social and emotional backup at home. In other patients there is clear suicidal intent: the act was planned, a suicide note was written and efforts were made not to be discovered. These patients must be assessed by a psychiatrist before they leave hospital.

SPECIFIC DRUG PROBLEMS

In this section only specific treatment regimens will be discussed. The general principles of management of self-poisoning should always be applied.

Aspirin

Overdosage of aspirin (salicylate) stimulates the respiratory centre, directly increasing the depth and rate of respiration and thereby producing a respira-tory alkalosis. Compensatory mechanisms include renal excretion of bicar-bonate and potassium, which results in a metabolic acidosis, and a fall in arterial pH indicates serious poisoning. Salicylates also interfere with carbo-hydrate, fat and protein metabolism, as well as with oxidative phosphoryla-tion. This gives rise to increased lactate, pyruvate and ketone bodies, all of which contribute to the acidosis.

Table 13.3 Guidelines for the assessment of patients who harm themselves

Questions to ask: be concerned if positive answer

■ Was there a clear precipitant/cause for the attempt?

■ Was the act premeditated or impulsive?

■ Did the patient leave a suicide note?

■ Had the patient taken pains not to be discovered?

■ Did the patient make the attempt in strange surroundings?

■ Would the patient do it again?

Other relevant factors

■ Has the precipitant or crisis resolved?

■ Is there continuing suicide intent?

■ Does the patient have any psychiatric symptoms?

■ What is the patient’s social support system?

■ Has the patient inílicted self-harm before?

■ Has anyone in their family ever taken their life?

■ Does the patient have a physical illness?

Indications for referral to a psychiatrist

Absolute indications include:

■ Clinical depression

■ Psychotic illness of any kind

■ Clearly preplanned suicide attempt which was not intended to be discovered

■ Persistent suicidal intent

■ A violent method used

Other common indications include:

■ Alcohol and drug abuse

■ Patients over 45 years, especially if male, and young adolescents

■ Those with a family history of suicide in first-degree relatives

■ Those with serious physical disease

■ Those living alone or otherwise unsupported

■ Those in whom there is a major unresolved crisis

■ Persistent suicide attempts

■ Any patients who give you cause for concern

Clinical features

These include tinnitus, nausea and vomiting, overbreathing, hyperpyrexia and sweating with a tachycardia. Alternatively, the patient may appear completely well, even with high plasma concentrations of salicylate. Ingestion of 10-20 g of aspirin by an adult (or one-tenth of this amount for a child) is likely to cause moderate or severe toxicity.

In severe poisoning (plasma salicylate concentration >700 mg/L; 5.07 mmol/L) there may be cerebral and pulmonary oedema resulting from increased capillary permeability. Coma and respiratory depression may be seen with severe poisoning, but more frequently are due to the ingestion of a second drug or alcohol.

Investigations

■ Plasma salicylate concentration. Peak concentrations are usually reached 2-4 hours after ingestion but can be delayed till 24 hours. Rising con-centrations are detected by measuring levels on admission and repeating after 2-4 hours

■ Serum urea and electrolytes and blood glucose (hypoglycaemia may occur)

■ Prothrombin time (may be prolonged)

■ Chest X-ray and arterial blood gases.

Management

■ Correct dehydration and hypokalaemia with intravenous fluids

■ Intravenous vitamin K (10 mg) to correct hypoprothrombinaemia

■ Activated charcoal if appropriate (p. 594)

■ Urine alkalinization if plasma salicylate >500 mg/L (>3.62 mmol/L). Infuse 225 mL of 8.4% sodium bicarbonate intravenously over 1 hour to ensure a urinary pH (measured by narrow-range indicator paper or pH meter) of more than 7.5 and preferably close to 8.5. Increasing urine pH from 5 to 8 increases urine salicylate excretion by 10-20 fold

■ Haemodialysis if plasma salicylate >700 mg/L (5.07 mmol/L).

Paracetamol (acetaminophen)

Paracetamol in overdose may cause fatal hepatic necrosis and is the com-monest form of poisoning encountered in the UK today. Paracetamol is converted to a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), which is normally inactivated by conjugation with reduced glutathione. After overdose, glutathione is depleted and NAPQI binds covalently with sulphydryl groups on liver cell membranes, causing necrosis. Marked liver cell necrosis can occur with as little as 7.5 g (15 tablets) and death with 15 g. The pro-thrombin time or international normalized ratio (INR) is the best guide to the severity of the liver damage.

Clinical features

The main danger is liver failure, which usually becomes apparent in 72-96 hours after drug ingestion. Initial symptoms include malaise, nausea and vomiting, with preserved consciousness unless another drug has also been taken. Acute tubular necrosis may occur in the absence of severe liver failure.

Management

Treatment depends on the interval between overdose and presentation and on the plasma concentrations of paracetamol (Emergency Box 13.1 and Figure 13.1). Levels are unreliable in a staggered overdose. W-acetylcysteine (NAC) is the treatment of choice and increases the availability of glutathione. Anaphylactoid reactions (urticarial rash, angio-oedema, bronchospasm, hypotension) occasionally occur with NAC and are treated by stopping the infusion, giving an antihistamine (e.g. chlorpheniramine 10-20 mg i.v.) and usually restarting the infusion once the reaction has settled. Patients who develop liver damage with a raised INR should remain in hospital until the values are returning to normal. Fresh frozen plasma should not normally be given to patients with a raised INR, as the trend in the INR is helpful in assessing prognosis and in determining the need for possible transplantation. Advice should be sought from a specialist liver unit at an early stage and usual transfer criteria are INR >3, hypotension after resuscitation with fluid,

Emergency Box 13.1
Management of paracetamol poisoning
• Take blood for paracetamol levels (at or after 4 h since ingestion), full blood count, INR, ALT activity, plasma creatinine and glucose
• Gastric lavage or single-dose activated charcoal if appropriate (p. 594)
• Give intravenous NAC in 5% dextrose immediately, without waiting for paracetamol levels, if potentially serious overdose (>150 mg/kg):
♦ 150 mg/kg in 200 mL over 15 min, then
♦ 50 mg/kg in 500 mL over 4 h, then
♦ 100 mg/kg in 1 litre over 16 h.
• Decision to continue treatment based on paracetamol levels and nomogram (Fig. 13.1). Discontinue treatment if plasma paracetamol concentration is below relevant treatment line and there is no abnormality of INR, plasma creatinine or ALT.
• In patients presenting more than 24 hours after ingestion, NAC should not be started until results of investigations are available and toxicological advice has been sought.
• Repeat blood investigations (except paracetamol) at the end of NAC treatment. If the patient is asymptomatic and the investigations are normal, there is little risk of serious complications and the patient can be discharged.
NAC, N-acetylcysteine

Fig. 13.1 Nomogram for treatment of paracetamol poisoning. Patients whose plasma paracetamol concentrations are above the normal treatment line should be treated with acetylcysteine. The high-risk (lower) treatment line should be used in patients with:

■ Regular alcohol excess

■ Poor nutrition

■ Anorexia nervosa

■ HIV infection

■ Pre-existing liver disease

■ Recent ingestion of enzyme-inducing drugs (carbamazepine, phenobarbital, phenytoin, rifampicin, St John’s wort).

The prognostic accuracy after 15 hours is uncertain but a plasma-paracetamol concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage and treated with NAC.

metabolic acidosis and prothrombin time (seconds) > interval (hours) from paracetamol overdose. Patients with severe hepatic damage may require liver transplantation.

Other drugs

Table 13.4 outlines the clinical features and management of other drugs that are commonly taken in cases of overdose. Initial management also includes gastric lavage and activated charcoal if indicated (p. 594).

Table 13.4 Clinical features and specific management for certain drugs taken in overdose

Drug

Clinical features

Management

Tricyclic

antidepressants

(TCA)

Tachycardia, hypotension, fixed dilated pupils, convulsions, urinary retention, arrhythmias, decreased conscious level

Treat convulsions with diazepam

Treat supraventricular and ventricular tachycardia with 8.4% sodium bicarbonate 50 mmol i.v. over 20 min, even in the absence of acidosis

Benzodiazepines

Drowsiness, ataxia, dysarthria, respiratory depression and coma. Potentiate the effects of other CNS depressants taken concomitantly

Give flumazenil (0.5-1.0 mg i.v. and repeated if necessary), a benzodiazepine antagonist, if respiratory depression. C/I if TCA also taken or history of epilepsy

Phenothiazines

Hypotension,

hypothermia, arrhythmias. Respiratory depression and coma. Convulsion and dystonic reactions

Symptomatic treatment of complications, e.g. diazepam for convulsions. Dystonic reactions treated with i.v. benzatropine

NSAIDs

Coma, convulsions, metabolic acidosis and renal failure

Treatment is symptomatic and supportive

β-Blockers

Bradycardia and hypotension. Coma, convulsions and hypoglycaemia with severe overdose

Glucagon 50-150 |xg/kg i.v. followed by an infusion of 1-5 mg/h has a positive inotropic action on the heart Atropine 0.6-1.2 mg i.v. is less effective

Carbon monoxide

Carbon monoxide (CO) poisoning is usually the result of inhalation of smoke, car exhaust or fumes from improperly maintained and ventilated heating systems. Methylene chloride, a component of paint remover, is readily absorbed and metabolized to CO by the liver and may lead to poisoning. CO combines with haemoglobin to form carboxyhaemoglobin, thus preventing the formation of oxyhaemoglobin. Clinical features are non-specific and include headache, mental impairment and, in severe cases, convulsions, coma and cardiac arrest. In spite of hypoxaemia the skin is pink. A venous carboxyhaemoglobin (COHb) level >3% in non-smokers and >10% in smokers confirms exposure to carbon monoxide by levels correlate poorly with symptoms. Treatment consists of removing the patient from the CO source and giving 100% oxygen via a face mask (do not use a rebreath reservoir). Hyperbaric oxygen treatment hastens CO elimination and is indi-cated if the victim has been unconscious, has cardiovascular dysnfunction, or has a blood carboxyhaemoglobin concentration of more than 25%.

Alcohol

Acute intoxication with alcohol produces severe depression of consciousness and hypoglycaemia, particularly in children. Treatment is supportive. Blood glucose is measured and glucose given if indicated.

DRUG USE

Drugs with a high abuse potential, drugs of addiction and other drugs with non-therapeutic psychotropic activity are categorized as controlled drugs. In the UK, The Misuse of Drugs Act categorizes controlled drugs as class A, B and C. Class A drugs (ecstasy, LSD, heroin, cocaine, crack, magic mush-rooms and injected amphetamines) are those considered to be the most harmful. In the UK, possession of a controlled drug is an offence. Any patient who is believed to be dependent on or addicted to controlled drugs must, by law, be notified to the Home Office.

Opioids

Opioid drugs, e.g. diamorphine (heroin), codeine and buprenorphine, produce physical dependency, such that an acute withdrawal syndrome develops (‘cold turkey') if the drugs are stopped. These severe withdrawal symptoms - profuse sweating, tachycardia, dilated pupils, leg cramps, diarrhoea and vomiting - may be reduced by giving methadone, a pharmaceutical prepara-tion of an opioid.

Drug addicts frequently overdose themselves, causing varying degrees of coma, respiratory depression and pinpoint pupils. Treatment is with

intravenous naloxone (opiate antagonist) 0.4-2 mg repeated at intervals of 2-3 minutes until breathing is adequate, up to a maximum of 10 mg. If respiratory function does not improve an additional or alternative cause must be considered particularly poly-drug use - death associated with opiate overdose is often associated by concurrent misuse of benzodiazepines (p. 600). Intramuscular naloxone is given if intravenous access cannot be obtained. Naloxone is short acting and repeated doses or an infusion is necessary, with the rate titrated according to the clinical response.

Cannabis

Cannabis (grass, pot, skunk, spliff, reefer) is a class B drug. It is usually smoked and is often taken casually. It is a mild hallucinogen and also increases the preexisting mood, e.g. depression, euphoria. Withdrawal symp-toms are uncommon. Long-term use is associated with memory problems, apathy, manic-like psychoses and an increased risk of schizophrenia.

Lysergide

Lysergic acid diethylamine (LSD) is a much more potent hallucinogen; its use can lead to severe psychotic states in which life may be at risk. Even in overdose, severe physiological reactions do not seem to occur. Adverse reactions are treated with repeated reassurance; a sedative, e.g. diazepam, is sometimes necessary. Phenothiazines may be necessary in severe cases.

Cocaine

Cocaine can be taken by injection, inhalation (‘crack’) or ingestion. It stimu-lates the central nervous system, producing euphoria, agitation, hypertension and tachycardia. Convulsions, pyrexia and cardiorespiratory depression may occur in severe cases of overdose and management is supportive with diazepam (10 mg i.v.) for agitation and active external cooling for hyperther-mia. It is a powerful vasoconstrictor and cocaine overdose should always be considered in a young person presenting with angina, myocardial infarction or stroke. P-Adrenoreceptor blockers are contraindicated as they may worsen hypertension; phentolamine 2-5 mg i.v. can be used for hypertension and nitrates for angina.

Amfetamines

Amfetamines are taken for their stimulatory effect. In overdose there is confu-sion, delirium, hallucinations and violent behaviour. Cardiac arrhythmias can be a major problem. Treatment is with sedatives, such as diazepam. Forced acid diuresis may be used but is rarely required.

Ecstasy (MDMA, 3,4-methylenedioxy-methamfetamine) is a synthetic amfetamine derivative taken orally as tablets or capsules. The adverse effects of the drug are the result of the drug's pharmacological properties com-pounded by physical exertion, e.g. at a ‘rave'. Serious acute complications are convulsions, hyperpyrexia, coagulopathy rhabdomyolysis, renal and liver failure and death. Treatment is rehydration, diazepam 10-20 mg i.v. for severe agitation, p-adrenoreceptor blockers for hypertension, and dantrolene (1 mg/kg bodyweight i.v.) for hyperthermia.

Solvents

The inhalation of organic solvents is a common problem, particularly in teenagers. The patient presents either in the acute intoxicated state (with euphoria and excitement) or as a chronic user with excoriation and rashes over the face and a peripheral neuropathy. Sudden death can occur and is probably the result of cardiac arrhythmias.

Management of body packers

Body packers or ‘mules' are persons who attempt to smuggle drugs by swal-lowing drug-filled packets often containing cocaine or heroin. The packet may rupture in the gut resulting in massive intoxication or cause gastrointestinal obstruction or perforation. Suspected body packers should have a plain abdominal X-ray and a urine drug screen. Contrast-enhanced CT scan is performed if the plain film is negative and there is a high index of suspicion. Asymptomatic carriers are treated with an oral polyethylene glycol/electrolyte lavage solution at a rate of 2 L per hour to speed passage of packets, with follow-up imaging to document clearance of packets. Packets in the vagina can be removed manually. Immediate surgery is indicated if there is evidence of intestinal obstruction, perforation or systemic toxicity, particularly if the drug involved is cocaine for which there is no antidote.

ALCOHOL USE

Drinking-related problems have increased in recent years. In the UK approxi-mately one in five male admissions to acute medical wards is directly or indirectly the result of alcohol. Over the past 20 years admissions to psychi-atric hospitals for the treatment of alcohol-related problems has increased 25-fold. Excessive alcohol use is the leading cause of preventable hyperten-sion and increases the risk of myocardial infarction and stroke. There is a steady rise in recorded alcohol consumption in developing countries but these data are also likely to conceal heavy drinking in some localities and popula-tions. Associated with this is an increase in alcohol-related problems includ-ing trauma, violence, various cancers and alcohol-associated organ damage.

Alcohol dependence is defined by a physical dependence on or addiction to alcohol. The key feature of alcohol dependence is a lack of control over alcohol use, indicated by a compulsive need to drink and the inability to cut down or stop drinking. Guidelines for safe drinking limits are 21 units weekly for males and 14 units weekly for females. A slightly higher intake is probably unlikely to lead to harm, but more than 36 units per week in men and 24 units in women increases the risk to health. Units of alcohol in a drink are calculated by a simple equation:

Units of alcohol in a drink = volume (1) X % alcohol by volume (ABV)

e.g. a 3/4 L bottle of whisky which is 40% ABV contains 30 units of alcohol.

In general, 1 unit = a measure of spirits, a glass of wine or half a pint of standard-strength beer.

Screening for problem drinking

An elevated serum Y-GT (y-glutamyl transpeptidase) (p. 141) and raised red cell mean corpuscular volume (MCV) are useful screening tests for excess alcohol use and are helpful in monitoring progress. Blood and urine alcohol levels are sometimes measured to demonstrate high intake.

Consequences of alcohol use and dependence

Physical complications

These usually occur after a long period of heavy drinking, e.g. 10 years. Problems are generally seen earlier in women than in men. Damage is the result of direct tissue toxicity and the effects of malnutrition and vitamin deficiency which often accompany excess alcohol use:

■ Cardiovascular: a direct toxic effect in the heart leads to a cardio-myopathy and arrhythmias

■ Neurological: acute intoxication leads to ataxia, falls and head injury with intracranial bleeds. Long-term complications include polyneuropathy (p. 787), myopathy, cerebellar degeneration (p. 724), dementia (p. 784) and epilepsy.

Wernicke's encephalopathy (WE) is the result of vitamin B1 deficiency (thiamin) and also occurs in severe starvation and prolonged vomiting. The classic triad of WE (confusion, ataxia and ophthalmoplegia) occurs in a minor-ity of patients. Mental changes are the most common (acute confusion, drowsiness, pre-coma and coma) whereas ataxia and ophthalmoplegia occur in less than one-third of patients. The diagnosis is clinical. A high index of suspicion and a low threshold for making a presumptive diagnosis is neces-sary. Treatment is urgent and is with an intravenous complex of B vitamins (e.g. two pairs of ampoules of high potency vitamins three times daily for 3 days followed by one pair of ampoules daily for 5 days), which may reverse some of the early changes. Inappropriately managed, WE is fatal in 20% of patients. Of survivors, many will develop long-term brain damage (Korsakoff’s syndrome) with a gross defect of short-term memory, associated with con-fabulation. Patients at risk of WE (significant weight loss, signs of undernutri-tion, alcohol withdrawal symptoms requiring hospital admission) should be treated prophylactically with one pair of ampoules of high potency B vitamins daily for 3-5 days followed with oral B vitamins on discharge. Administration of glucose may exacerbate the acute loss of thiamine and it is essential that thiamine is given before glucose:

■ Gastrointestinal: liver damage (p. 174), acute and chronic pancreatitis (p. 189), oesophagitis and an increased incidence of oesophageal carcinoma

■ Haematological: thrombocytopenia (alcohol inhibits platelet maturation and release from bone marrow), a raised MCV and anaemia caused by dietary folate deficiency

■ Psychiatric complications: there is an increased incidence of depression and deliberate self-harm among patients with alcohol dependence. Attempted suicide must always be taken seriously and a psychiatric referral made (p. 596)

■ Social complications: marital and sexual difficulties, employment prob-lems, financial difficulties and homelessness.

Alcohol withdrawal

Most heavy drinkers will experience some form of withdrawal symptoms if they attempt to reduce or stop drinking. No patient should ever be advised to stop drinking immediately due to the potentially life-threatening complica-tions of alcohol withdrawal without appropriate detoxification:

■ Early mild features occur within 6-12 hours and include tremor, nausea and sweating. Treatment is with a reducing dose of chlordiazepoxide (see Emergency Box 13.2).

■ Late major features usually occur within 2-3 days, but may take up to 2 weeks:

■ Generalized tonic-clonic seizures (p. 753)

■ Delirium tremens is a potentially fatal severe alcohol withdrawal syndrome. There is fever, marked tremor, tachycardia, agitation and visual hallucinations (‘pink elephants’). Treatment must be given urgently (see Emergency Box 13.2).

Alcohol detoxification is sometimes carried out in the community under the care of a specialist team. The patient attends daily for medication and moni-toring. Exclusion criteria for community detoxification are inadequate social support, severe liver disease, concurrent medical or psychiatric illness or a previous history of delirium tremens or alcohol withdrawal fits.

Emergency Box 13.2

Management of alcohol withdrawal in hospital

• Prevent or treat established Wernicke’s encephalopathy by administration of intravenous B vitamin complex (see p. 605). Give before administration of glucose-containing i.v. fluids.

• Correct dehydration and electrolyte imbalance. Hypophosphataemia and hypomagnesaemia is common.

• Chlordiazepoxide 30 mg four times daily decreasing to zero over 7 days. With very heavy alcohol intake and severe withdrawal symptoms the dose is increased up to 60 mg four times a day decreasing to zero over 10 days.

• Oxazepam is the drug of choice for alcohol detoxiíication in patients with severe liver disease as it is not metabolized by the liver.

After alcohol withdrawal it is essential that relapse is prevented. This involves local alcohol services, specialist psychiatry and the alcohol nurse specialist. ‘Brief interventions' refers to 10-15 minutes of counselling, with feedback about drinking, advice and goal setting, and follow-up contact (one or more discussions lasting 10-15 minutes with a clinician or specialist nurse). Oral acamprosate, a GABA analogue, reduces relapses by 50%. Naltrexone is a pure opioid receptor antagonist that modifies the effects of alcohol by blunting its pleasurable effects and by reducing the craving. It reduces relapse rate

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology



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