DRUGS OF MISUSE

DRUGS OF MISUSE
Cannabis
Cannabis is derived from the dried leaves and flowers of Cannabis sativa. When smoked, the onset of effect occurs within 10-30 minutes; after ingestion the onset is 1-3 hours. The duration of effect is 4-8 hours. Cannabis produces euphoria, perceptual alterations and conjunctival injection, followed by enhanced appetite, relaxation, and occasionally hypertension, tachycardia, slurred speech and ataxia. High doses may produce anxiety, confusion, hallucinations and psychosis. Psychological dependence is common, but tolerance and withdrawal symptoms are unusual. Ingestion or smoking of cannabis rarely results in serious poisoning and supportive treatment is all that is required.
Benzodiazepines
Benzodiazepines may be prescribed or used illicitly. They are of low toxicity when taken alone in overdose, but can enhance CNS depression when taken with other sedative agents, including alcohol. They may also cause significant toxicity in the elderly and those with chronic lung or neuromuscular disease.
Clinical features
Clinical features of toxicity include drowsiness, ataxia and confusion. Respiratory depression and hypotension may occur with severe poisoning in susceptible groups, especially after intravenous administration of short-acting agents.
Management
Activated charcoal may be useful after ingestion in susceptible patients or after mixed overdose, if given within 1 hour. Conscious level and oxygen saturation should be monitored for at least 6 hours after substantial overdose.
The specific benzodiazepine antagonist flumazenil increases conscious level in patients with overdose but carries a risk of seizures, and is contraindicated in patients co-ingesting proconvulsant agents such as TCAs and in those with a history of seizures.
Stimulants
Amphetamines, ecstasy and cocaine are sympathomimetic amines and, as a result, some clinical features of poisoning are similar.
Cocaine
Cocaine is available as a water-soluble hydrochloride salt suitable for nasal inhalation ( snorting ), or as an insoluble free base ( crack cocaine) which, unlike the hydrochloride salt, vaporises at high temperature and can be smoked, giving a more rapid and intense effect.
Clinical features
Cocaine s toxic effects appear rapidly after inhalation and especially after smoking. Sympathomimetic stimulant effects are common. Serious complications usually occur within 3 hours of use, and include coronary artery spasm which may result in myocardial ischaemia or infarction, even in patients with normal coronary arteries. This may lead to hypotension, cyanosis and ventricular arrhythmias. Cocaine toxicity should be considered in young adults who present with ischaemic chest pain. Hyperpyrexia may be associated with rhabdomyolysis, acute renal failure and disseminated intravascular coagulation.
Management
All patients should be observed with ECG monitoring for a minimum of 4 hours. A 12-lead ECG should be performed. Troponin T estimations are the most sensitive and specific markers of myocardial damage. Benzodiazepines and intravenous nitrates are useful for managing patients with chest pain or hypertension, but ?-blockers are best avoided because of the risk of unopposed ?-adrenoceptor stimulation. Coronary angiography should be considered in patients with myocardial infarction or acute coronary syndromes. Acidosis should be corrected. Physical cooling measures may be required for hyperthermia.
Amphetamines and ecstasy
These include amphetamine sulphate, methylamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy ). Tolerance to amphetamines is common, leading regular users to seek progressively higher doses.
Clinical features
Toxic features usually appear within a few minutes of use and last 4-6 hours or substantially longer after a large overdose. Sympathomimetic stimulant effects are common. A proportion of ecstasy users develop hyponatraemia as a result of drinking large amounts of water and inappropriate antidiuretic hormone secretion. Muscle rigidity, pain and trismus (jaw-clenching) may occur. Hyperpyrexia, rhabdomyolysis, metabolic acidosis, acute renal failure, disseminated intravascular coagulation, hepatocellular necrosis, acute respiratory distress syndrome (ARDS) and cardiovascular collapse have all been described following MDMA use but these are rare. Strokes, due to either cerebral infarction or haemorrhage, have been reported, especially after intravenous amphetamine use.
Management
Management is supportive and directed at complications.
Gammahydroxybutyrate (GHB)
GHB is a sedative agent with psychedelic and body-building effects.
Clinical features
Toxic features are those of a sedative hypnotic. Nausea, diarrhoea, vertigo, tremor, myoclonus, extrapyramidal signs, euphoria, bradycardia, convulsions, metabolic acidosis, hypokalaemia and hyperglycaemia may also occur. The sedative effects are potentiated by other CNS depressants, e.g. alcohol, benzodiazepines, opioids and neuroleptic drugs. Coma usually resolves spontaneously and abruptly within a few hours, but may occasionally persist for several days.
Management
Activated charcoal is recommended within 1 hour for ingestion of GHB in amounts greater than 20 mg/kg. Urea, electrolytes and glucose should be measured in all of cases. All patients should be observed for a minimum of 2 hours, with monitoring of blood pressure, heart rate, respiratory rate and oxygenation. Patients require supportive care only.
LSD
d-Lysergic acid diethylamide (LSD) is a synthetic hallucinogen. The drug causes perceptual effects, such as heightened visual awareness of colours, distortion of images, and hallucinations which may be pleasurable or terrifying ( bad trip ) and associated with panic, confusion, agitation or aggression. Dilated pupils, hypertension, pyrexia and metabolic acidosis may occur and psychosis may sometimes last several days.
Patients with psychotic reactions or CNS depression should be observed in hospital. Where sedation is required, diazepam is the drug of choice. Antipsychotics should be avoided if possible, as they may precipitate cardiovascular collapse or convulsions.
Opioids
Toxicity may result from drug misuse (e.g. heroin) or after overdose of medicinal opiates (e.g. dextropropoxyphene). Intravenous use of heroin or morphine gives a rapid, intensely pleasurable experience, often accompanied by heightened sexual arousal. Physical dependence occurs within a few weeks of regular high-dose injection; as a result, the dose is escalated and the user s life becomes increasingly centred on obtaining and taking the drug. Withdrawal, which can start within 12 hours, presents with intense craving, rhinorrhoea, lacrimation, yawning, perspiration, shivering, piloerection, vomiting, diarrhoea and abdominal cramps. Examination reveals tachycardia, hypertension, mydriasis and facial flushing.
Accidental overdose with prescribed strong opioid preparations is common, especially in the elderly.
Clinical features
Reduced respiratory rate and ventilation, Hypotension, relative bradycardia, Confusion, hallucinations, slurred speech Sedation, coma, Ataxia, reduced muscle tone, Hypothermia, Miosis, Ileus, Needle tracks , and Respiratory failure .
Severe poisoning results in respiratory depression, hypotension, non-cardiogenic pulmonary oedema and hypothermia, leading to respiratory arrest or aspiration of gastric contents. Dextropropoxyphene (the opioid component of co-proxamol) may also cause cardiac conduction effects, particularly QRS prolongation, ventricular arrhythmias and heart block. Excess deaths caused by these complications have prompted the withdrawal of co-proxamol (dextropropoxyphene and paracetamol combination) in the UK. Methadone may cause QTc prolongation and torsades de pointes.
Symptoms of opioid poisoning can be prolonged for up to 48 hours after use of long-acting agents (e.g. methadone, dextropropoxyphene and oxycodone).
Management
The airway should be cleared and, if necessary, respiratory support and oxygen given. Oxygen saturation monitoring and measurement of arterial blood gases should be performed. Prompt use of the specific opioid antagonist naloxone (0.8-2 mg i.v., repeated if necessary) may obviate the need for intubation. An infusion may be required in some cases because the half-life of the antidote is short compared to that of most opiates, especially those with prolonged elimination. It is important that patients are monitored for at least 4 hours after the last naloxone dose. Other complications of naloxone therapy include fits and ventricular arrhythmias. coma, fits and hypotension should be managed. Non-cardiogenic pulmonary oedema does not usually respond to diuretic therapy, and continuous positive airways pressure (CPAP) or positive end-expiratory pressure (PEEP) ventilatory support may be required.
CHEMICALS AND PESTICIDES
Carbon monoxide (CO)
CO is a colourless and odourless gas produced by faulty appliances burning organic fuels. It is also present in vehicle exhaust fumes and sometimes in smoke from house fires. It causes toxicity by binding with haemoglobin and cytochrome oxidase, which reduces tissue oxygen delivery and inhibits cellular respiration. It is a common cause of death by poisoning and most patients who die of CO poisoning do so before reaching hospital.
Clinical features
The early clinical features of acute severe carbon monoxide poisoning are headache, nausea, irritability, weakness and tachypnoea. Because these are non-specific, the correct diagnosis will not be obvious if the exposure is occult, e.g. from a faulty domestic appliance. Subsequently, ataxia, nystagmus, drowsiness and hyper-reflexia may develop, progressing to coma, convulsions, hypotension, respiratory depression, cardiovascular collapse and death. Myocardial ischaemia may occur and result in arrhythmias or myocardial infarction. Cerebral oedema is common and rhabdomyolysis may lead to myoglobinuria and renal failure. In those who recover from acute toxicity, longer-term neuropsychiatric effects are common, such as personality change, memory loss and concentration impairment. Extrapyramidal effects, urinary or faecal incontinence, and gait disturbance may also occur. Poisoning during pregnancy may cause fetal hypoxia and intrauterine death.
Management
Patients should be removed from exposure as soon as possible and the patient resuscitated as necessary. Oxygen should be administered in as high a concentration as possible via a tightly fitting facemask, as this reduces the half-life of carboxyhaemoglobin from 4-6 hours to about 40 minutes. Measurement of carboxyhaemoglobin is useful for confirming exposure but results do not correlate well with the severity of poisoning, partly because concentrations fall rapidly after removal of the patient from exposure, especially if supplemental oxygen has been given.
An ECG should be performed in all patients with acute poisoning, especially those with pre-existing heart disease. Arterial blood gas analysis should be checked in those with serious poisoning. Oxygen saturation readings by pulse oximetry are misleading since both carboxyhaemoglobin and oxyhaemoglobin are measured. Excessive intravenous fluid administration should be avoided, particularly in the elderly, because of the risk of pulmonary and cerebral oedema. Convulsions should be controlled with diazepam.
Hyperbaric oxygen therapy is controversial. In theory, at 2.5 atmospheres, it reduces the half-life of carboxyhaemoglobin to 20 minutes and increases the amount of dissolved oxygen by a factor of 10. The logistical difficulties of transporting sick patients to hyperbaric chambers and managing them therein should not be underestimated and recent systematic reviews have shown no improvement in clinical outcomes.