Pharmacology & Poisoning
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Question 129 of 180
A 71 year old man, with a history of alcohol misuse, presents to ED with abdominal pain, nausea and vomiting, and blurred vision. He is being loud and disruptive in the waiting room. His ABG shows a raised anion gap metabolic acidosis. What is the most appropriate management?
Answer:
The patient has most likely ingested methanol. Initial symptoms generally occur 12-24 hours after ingestion. Initially, the symptoms of methanol intoxication are similar to those of ethanol intoxication, often with disinhibition and ataxia. Following a latent period, patients may develop headache, nausea, vomiting, or epigastric pain. In later stages, drowsiness may rapidly progress to obtundation and coma. Seizures may occur, generally as a complication of the metabolic derangement or as a result of damage to the brain parenchyma. Blindness from methanol inhalation is well described. Formic acid accumulates within the optic nerve, which results in the classic visual symptoms of flashes of light and blurring. Patients initially may present with diminished visual acuity, which can progress to scotomata and scintillations. The frank blindness that develops sometimes responds to immediate therapy; however, complete loss of vision is a common sequela.Poisoning and Overdose
Pharmacology & Poisoning
Last Updated: 17th October 2023
Poisoning is the administration of a substance, taken internally or externally, that is injurious to health or dangerous to life. A poison may be a drug, household product, industrial chemical, or plant or animal derivative. The most common route of poisoning is by ingestion, but poisoning by inhalation, injection, skin/eye contamination, or bites may also occur. Poisoning may be accidental or intentional.
Definitions
- Accidental poisoning is where someone is exposed to a poison by an accidental action and develops symptoms. Poisoning is usually accidental in children under 5, and most commonly due to the exploratory ingestion of a substance found at home. Accidental poisoning can happen to adults in the home or at work or due to fire or a transport accident.
- Deliberate poisoning is part of the spectrum of deliberate self-harm. This encompasses both deliberate self-poisoning and deliberate self-injury. Deliberate self-poisoning is the deliberate ingestion of more than the prescribed amount of a medical substance, or of a substance not meant for human consumption or of an illicit drug, irrespective of the motive for the episode.
- Overdose is a term used to describe the use of a quantity of drug in excess of its intended or prescribed dose, and is a major cause of poisoning. It may be accidental or deliberate, and involve the use of prescribed or illicit drugs.
Symptoms and signs of drugs that are commonly involved in poisoning or overdose
| Drug | Symptoms and signs |
|---|---|
| Paracetamol | Frequently asymptomatic, nausea and vomiting (usually settle within 24 hours, if these continue, often with the development of right subcostal pain, this suggests the development of hepatic necrosis which may lead to encephalopathy, hypoglycaemia, haemorrhage, cerebral oedema and death) |
| Aspirin | Hyperventilation, tinnitus, deafness, vasodilatation, sweating, coma |
| Tricyclic and related antidepressants | Dry mouth, seizures, coma, cardiac conduction defects, arrhythmias, hypothermia, hypotension, hyperreflexia, respiratory failure, dilated pupils, urinary retention |
| Selective serotonin reuptake inhibitors (SSRIs) | Nausea, vomiting, agitation, tremor, nystagmus, drowsiness, sinus tachycardia, seizures, serotonin syndrome (marked neuropsychiatric effects, autonomic instability and neuromuscular hyperactivity with hyperthermia, rhabdomyolysis, renal failure, coagulation deficiencies) |
| Beta-blockers | Lightheadedness or syncope due to bradycardia and hypotension; heart failure can be exacerbated or precipitated; sotalol can cause ventricular tachycardia; propranolol can cause coma and convulsions |
| Calcium-channel blockers | Nausea, vomiting, agitation, confusion, dizziness, coma, hyperglycaemia; dihydropyridine calcium-channel blockers cause profound peripheral vasodilatation and severe hypotension; verapamil and diltiazem can cause arrhythmias including complete heart block and asystole |
| Iron salts | Nausea, vomiting, diarrhoea, abdominal pain, haematemesis, rectal bleeding, hypotension, hepatocellular necrosis, coma, shock |
| Lithium | Initially apathy and restlessness followed by vomiting, diarrhoea, ataxia, tremor, weakness, dysarthria, muscle twitching; in severe poisoning: electrolyte imbalance, dehydration, convulsions, renal failure, hypotension, coma |
| Theophylline | Severe vomiting, restlessness, agitation, dilated pupils, hyperglycaemia, tachycardia, hypokalaemia; more serious effects: haematemesis, seizures, arrhythmias (supraventricular and ventricular) |
| Benzodiazepines | Drowsiness, dysarthria, ataxia, nystagmus, respiratory depression, coma |
| Antimalarials - quinine, chloroquine, hydroxychloroquine | Rapid onset of life-threatening arrhythmias and intractable convulsions |
| Phenothiazines and related drugs | Sinus tachycardia, arrhythmias, hypotension, reduced consciousness, respiratory depression, dystonic reactions (may be seen with therapeutic doses), seizures |
| Second-generation antipsychotic drugs | Drowsiness, hypotension, extrapyramidal symptoms, convulsions, ECG abnormalities such as QT prolongation |
| Amphetamines | Initially: excessive activity, wakefulness, hallucinations, paranoia and hypertension; later: convulsions, hyperthermia, exhaustion, coma |
| Cocaine | Agitation, hypertension, tachycardia, dilated pupils, hallucinations, hyperthermia, hypertonia and hyperreflexia, cardiac effects such as chest pain, arrhythmias, myocardial infarction |
| Opioids | Drowsiness, coma, respiratory depression, pinpoint pupils |
| Methylenedioxymethamphetamine (MDMA) | Delirium, coma, hyperthermia, rhabdomyolysis, acute renal failure, acute hepatitis, disseminated intravascular coagulation, adult respiratory distress syndrome, hyperreflexia, hypotension, intracerebral haemorrhage, hyponatraemia, convulsions, ventricular arrhythmias |
Toxidromes
| Toxidrome | Common Agents | Signs and symptoms |
|---|---|---|
| Anticholinergic | Antihistamines, tricyclic antidepressants, carbamazepine, phenothiazines | Tachycardia, hyperthermia, dilated pupils, warm and dry skin, urinary retention, agitation |
| Cholinergic | Carbamates, organophosphates insecticides, some mushrooms | Salivation, lacrimation, urination, diarrhoea, bronchorrhoea, bronchospasm, bradycardia, vomiting |
| Hallucinogenic | LSD, PCP, Magic Mushrooms | Hallucinations, panic, seizures, hypertension, tachycardia, tachypnoea |
| Opiate | Morphine, codeine, methadone | Hypoventilation, hypotension, pinpoint pupils, sedation, bradycardia |
| Sedative/hypnotic | Anticonvulsants, benzodiazepines, ethanol | Ataxia, blurred vision, sedation, hallucinations, slurred speech, nystagmus |
| Sympathomimetic | Amphetamines, cocaine, MDMA | Tachycardia, hypertension, dilated pupils, agitation, seizures, hyperthermia, sweating |
Principles of management
- ABCDE assessment and supportive management
- Maintain a clear airway and ensure adequate ventilation.
- In all patients monitor pulse, blood pressure, temperature, level of consciousness and cardiac rhythm.
- Perform a 12-lead ECG in all patients who require assessment. Repeat 12-lead ECGs are recommended, especially in symptomatic patients or in those who have ingested sustained release preparations.
- Check blood gases, FBC, U&Es, glucose, LFTs, calcium, magnesium and CK.
- Decontamination for external contamination
- Disrobe
- The single most important step is the prompt removal of clothing (down to underwear if possible). Disrobe procedures should be, where possible, conducted by the casualty themselves. This should be as quick as possible and ideally within 15-20 minutes following exposure. While clinically there may be little benefit to the patient after one hour, disrobing is still recommended to reduce the risk to hospital staff. All contaminated waste materials, clothing and personal items should be double bagged, labelled and stored for further evaluation and disposal.
- Dry decontamination
- Evidence suggests that for non-caustic chemicals immediate disrobing followed by dry decontamination is a safer, quicker and more effective option. This also reduces or eliminates the risk associated with the wash-in effect, where the dermal absorption of certain chemicals may be significantly enhanced by the presence of water, particularly organophosphorus compounds and sulfur mustard. Thus the default process for non-caustic chemicals is to disrobe followed by dry decontamination.
- Dry decontamination should be undertaken using dry absorptive materials such as paper tissue (e.g. blue roll, paper towel, toilet paper), surgical dressings, cloths etc. to gently blot or rub any exposed skin surfaces, starting at the face/head/neck and moving down and away from the body. If contaminated patients are able to self-dry decontaminate then this is the best option and should be under the supervision of hospital staff. Where hair is contaminated wet decontamination of hair is recommended but this should follow the disrobe and dry decontamination process.
- Wet decontamination
- Wet decontamination using water should be used for decontamination where the chemical(s) is confirmed as being caustic or corrosive or if the patient is displaying signs and symptoms consistent with exposure to caustic substances (pain, redness, burning, irritation of eyes/nose/throat). Wet decontamination also remains the default decontamination process for biological or radiological contaminants.
- Wet decontamination should be undertaken using warm water, ideally made up with detergent to a 0.5% solution. Any available equipment should be used e.g. portable/fixed decontamination units or showers, buckets etc.. Showers should be limited to a 45-90 second duration and a washing aid such as a cloth or flannel used.
- Disrobe
- Prevention of absorption
- Single dose activated charcoal is used if the person presents within an hour of ingestion. It works by adsorbing substances onto its surface by weak electrostatic forces thereby preventing further absorption of the ingested drug into the blood. The dose is 50 g orally in adults, and it should be given within 1 hour of overdose. Conscious patients should be able to drink the charcoal. However, if they find it impossible to do so, or if vomiting is a problem, it may be given down a nasogastric tube (as in unconscious patients): ensure the airway is adequately protected. Consider an antiemetic e.g. cyclizine (50 mg intravenously) or ondansetron (4 - 8 mg slowly intravenously). Activated charcoal is contraindicated if the patient’s airway is not intact or protected, and in intestinal obstruction.
- Active elimination
- Repeated doses of activated charcoal enhances the elimination of some drugs even after they have been absorbed such as carbamazepine, phenobarbital, quinine, theophylline and dapsone.
- Alkalinisation of the urine for salicylate poisoning.
- Haemodialysis for ethylene glycol, lithium, methanol, phenobarbital, salicylates, and sodium valproate.
- Removal from the gastrointestinal tract
- Gastric lavage is rarely performed. It is indicated only if a life-threatening amount has been ingested within the previous hour, and the poison cannot be removed using other methods. It may be useful for drugs such as lithium and iron that are not absorbed by charcoal.
- Whole bowel irrigation using an enteral administration of a polyethylene glycol solution may be a management option for children who have taken potentially toxic amounts of iron or of sustained release or enterically coated medicines, especially if the child presents more than 2 hours after ingesting these. In adults, this should only be performed following discussion with the NPIS. Consider also for the removal of ingested packets of illicit drugs.
- Specific antidotes
- Psychiatric assessment in cases of deliberate poisoning
Specific antidotes
| Antidote | Poisoning |
|---|---|
| Acetylcysteine | Paracetamol |
| Atropine | Organophosphate insecticides, nerve gases |
| Calcium chloride/gluconate | Calcium channel blockers |
| Calcium disodium EDTA | Lead |
| Cyproheptadine (Periactin®) | Serotonin syndrome |
| Dantrolene | Neuroleptic malignant syndrome |
| Deferoxamine mesylate (Desferal®) | Iron |
| Digoxin Immune FAB (Digibind®, DigiFab®) | Digoxin |
| Flumazenil (Romazicon®) | Benzodiazepines |
| Fomepizole (Antizol®) | Ethylene glycol & methanol |
| Glucagon | Beta blockers, calcium channel blockers, insulin |
| Hydroxocobalamin (Cyanokit®) | Cyanide |
| Intravenous Lipid Emulsion (Intralipid™) | Local anaesthetics |
| Idarucizumab (Praxbind®) | Dabigatran |
| Methylene Blue | Methaemoglobinaemia |
| Naloxone | Opioids |
| Octreotide (Sandostatin®) | Sulfonylureas |
| Physostigmine | Anticholinergic syndrome |
| Phytonadione (Vitamin K1) | Warfarin |
| Pralidoxime (2-PAM, Protopam®) | Organophosphate insecticides, nerve gases |
| Protamine sulfate | Heparin |
| Sodium Bicarbonate | Salicylates, tricyclic antidepressants |
Sources of further information
- TOXBASE in the first instance for general information (see www.toxbase.org).
- TOXBASE is a clinically-based toxicology database and the first-line source of information for health care professionals. It is regularly updated by the National Poisons Information Service (NPIS). It gives information about the diagnosis, treatment and management of patients exposed to drugs, household products, and industrial and agricultural chemicals. It is available through its online database, TOXBASE and the TOXBASE app for iOS and Android mobile devices. These are free to all UK NHS healthcare units and health care professionals. A back-up site is available at www.toxbasebackup.org if the main site cannot be accessed.
- The National Poisons Information Service (NPIS)
- For if there are any uncertainties regarding the person's management after accessing TOXBASE, and for:
- Severe or complex cases, including multiple ingestions
- People with significant comorbidity
- Cases where the poison is unknown
- The NPIS advice line gives information and advice to NHS staff to assist them in deciding whether a person needs admission or can be managed at home. It also provides advice on the hospital management of people requiring admission.
- The NPIS is a network of units commissioned by Public Health England for the UK health departments
- The service is available 24 hours a day via the central UK number 0344 892 0111. Advice is provided by information scientists. Consultant clinical toxicologists provide advice regarding more serious or complex cases of poisoning.
- The service allows unnecessary hospital attendances for people at low risk of harm to be reduced, and improved quality of care for those who require hospital treatment.
- For if there are any uncertainties regarding the person's management after accessing TOXBASE, and for:
Cardiac arrest associated with poisoning
- Ensure your personal safety and wear appropriate personal protective equipment
- Avoid mouth-to-mouth breathing in the presence of chemicals such as cyanide, hydrogen sulphide, corrosives and organophosphates
- Treat life-threatening tachyarrhythmias with cardioversion, according to the peri-arrest arrhythmia guidelines; this includes correction of electrolyte, glucose and acid-base abnormalities
- Once resuscitation has started, try to identify the poison; relatives, friends and ambulance crews may provide useful information; examination of the patient may reveal diagnostic clues e.g. odours, needle marks, pupil size, signs of mouth corrosion
- Measure the patient's temperature because hypo- or hyperthermia may occur in drug overdose
- Provide standard basic and advanced life support if cardiac arrest occurs
- Be prepared to continue resuscitation for a prolonged period of time, particularly in young patients, as the poison may be metabolised or excreted during prolonged attempts; consider extracorporeal life support (ECLS)
- Seek local expert advice and consult a regional or national poisons centre for information on treatment of the poisoned patient
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
