Tox Flashcards
Poisoning can be ?
- acute (ie a one time thing ) or chronic (where exposure over time leads to poisoning)
- Accidental or intentional
What are toxidromes?
A cluster of clinical features that are often the effect of an overdose of a toxic agent. They can be used to aide diagnosis
What are the 5 main toxidromes?
- opioid
- serotenergic
- anticholinergic
- cholinergic
- sympathomimetic
Describe the opioid toxidromes?
- pinpoint pupils
- clammy / cold skin
- reduced consciousness
- reduced respiratory rate
- blue lips/ skin
- shallow and slowed or stopped breathing
Describe the serotenergic toxidrome.
(Think of SSRI overdose)
This is XS serotonin (5HT)
- ie agitation and delirium
- fever
- tremor
Sweating
- hypertnonia
Describe the anticholinergic toxidrome.
(Think xs anticholinergic drugs)
- urine retention
Tachycardia
Warm dry skin
Confusion, restlessness and hallucinations
What are some anticholinergic drug examples?
- antimuscarnics (ie atropine and scopolamine)
- anti - nicotinic drugs (ie bupropion ipatroprium)
Describe the cholinergic toxidrome
Mitosis (ie small pupils)
Bradycardia
Sweating and excessive secretions such as diarrhoea, rhinorrhoea, bronchorrhoea, hypersalivation and lacrimation
What are some sympathomimetic drugs?
- amphetamines
- ecstasy
Describe the sympathomimetic toxidrome?
- psychosis
- hypertension
- dilated pupils of the eye
- sweating
- agitation
- paranoid
If someone has been admitted to the hospital for poisoning, we’ll need to do some labs. What are the things we need to assess for in the blood tests?
- routine bloods
- ABGs (ie CO and MetHB)
- anion gap and osmolol gap
- analytical toxicity —-> so that we can get the emergency meaurements of some substances
- screening for drugs in the blood (ie paracetamol, will indicate if there has been an overdose).
What information does the anion gap tell you?
The anion gap compares the (n) of anions and cations int he bold and will indicate what kind of poisoning has occurred.
What are the causes of a raised anion gap?
- Ketoacidosis
- lactic acidosis
- xs alcohols
- salicylate overdose
What is the osmolality gap?
Is the difference between the measured osmolality and the calculated osmolality.
What are some causes of an increases osmolol gap?
- alcohol overdoses (ie ethanol, methanol , ethylene glycol).
What should we offer int he general management of poisoning in secondary care?
- supportive care (ie fluids , oxygen, raising the patients blood pressure).
- prevention of absorption of the drug (ie via emesis, gastric lovage, activated charcoal).
- use of antidotes
- enhancing elimination of drugs
What are the different ways we can try to prevent absorption of xs drugs / poisoning?
- emetics (not recommended)
- gastric lovage
- activated charcoal :)
- whole bowel irrigation
How can we enhance the elimination of ingested poisons?
- urine alkalisation (ie IV sodium bicarbonate)
- multiple doses of activated charcoal.
- extracorporeal methods (ie haemofiltration, haemodialysis).
What is an antidote? (Def)
A therapeutic substance administered to counteract the adverse effects of a poison
What is the pharmacist role in antidotes?
- they need to know the stock levels, what is in stock, how much and where to source them from if there is a shortage or if a particular type is not available (ie snake venom).
What are some examples of drugs that should be available immediately in A and E?
(Ie as antidotes)
- flumenazil for resp depression in BZD OD
- acetylcystein for paracetamol poisoning
- intralipid for anaesthetic overdose.
- activated charcoal for many oral poisons.
What are some examples of some drugs that should be available within 1hr (antidotes)?
- desferrioxamine for iron toxicity.
- fomepizole for ethylene glycol and methanol toxicity.
- folinic acid for methotrexate toxicity.
What are the 6 main mechanisms of actions for antidotes?
- Block the receptor targeted by the poison.
- Chelate or form a complex with the poison inactivating it.
- Accelerate the process of deactivation
- Compete with the poison for the receptor it targets
- Reduce the rate at which its converted to an active poisonous metabolite.
- Bypass the action of the poison
Give examples of drugs that form complexes with the poison and the poison they target.
Desferrioxamine —> binds to Fe
Dicobalt edentate —> binds to cyanide
Protamine —> heparin
Digoxin specific antibody —> digoxin
Idarucizumab —-> dabigatran, an anticoagulant.
Give 2 examples of antidotes that accelerate the detoxification of the poison, and the poison.
- Acetylcystein —> targets paracetamol
- Methylene blue —> methaemoglobinaemia.
How does methylene blue work against methaemoaglobinaemia?
MetHB is when the blood contains xs ferric blood (ie Hb has Fe3+).
Methylene blue acts as an electron donor and will reduce Fe3+ —-> Fe2+ in the blood to form the ferrous Hb that we need
Give an example of a drug that will reduce the rate at which the poison converts to a more toxic compound?
- Fomepizole —-> prevents the conversion of ethylene glycol and methanol by alcohol dehydrogenase to a more harmful substance.
Give an example 3 antidotes that competewith the toxic substances for essential receptor sites?
- flumenazil competes with BZDP in resp depression
- naloxone completes with opioids for mu receptor
- vitamin K and warfarin
Why do we need to be careful with Naloxone administration?
- it has a short half life and so if the px returns to a OD state we may need to administer a 2nd dose.
Give an example of a drug that is used to block the essential receptor needed by the toxic substances and eg of the toxic substance.
Atropine and nerve agents
Give some an example of an antidote that bypass the effect of the poison?
-
Glucagon and Beta blockers
Glucagon used in beta blocker over dose.
Beta blockers inhibit beta 1 receptors in the heart resulting in a reduced heart rate. Xs can lead to bradycardia —> glucagon will increase formation of cAMP in cells —> increased ca2+ release and muscle contractility of the heart. -
Intralipid and local anaesthetic*
- intralipid will act like a skin and will suck the lipophilic drugs into it.
What is ethylene glycol?
Anti freeze.
What is ethylene glycol metabolised by and into what?
- metabolised by alcohol dehydrogenase
- metabolised into toxic metabolites ie oxalic acid
What is a lethal dose of ethylene glycol?
- 100mL
How does ethylene glycol lead to toxicity?
❌ metabolic acidosis
❌ inhibition of OXPHOS and protein synthesis
❌ oxalic acid precipitates with calcium to cause end - organ damage.
Symptoms of ethylene glycol toxicity.
❌ MUSCLE WEAKNESS
❌ PERIPHERAL NEUROPATHY (ie paraesthesia shooting or stabbing pains, muscle weakness) 💫
headache 🤕
Dizziness 😵💫
Vomiting 🤮
Diarrhoea 💩
Fatigue 😴
3 methods of treating ethylene glycol poisoning ?
- haemodialysis (best option).
- fomepizole —> inhibits alcohol dehydrogenase (however its £££ and not readily available :( )
- ethanol (ie alcohol) —> ADH has a greater affinity for alcohol and thus will reduce the formation of toxic metabolites via metabolising ethylene glycol.
What is cyanide?
The product of burning lots of substances — often found in fire smoke and thus ppl who inhale fire smoke are liable to cyanide poisoning.
Where can cyanide be found in ?
- natural substances such as wool, silk, cotton
- synthetic substances such as plastic, nylon, polyurethane foam.
Symptoms of cyanide poisoning.
😃 euphoria/ excitement
🫁 chest pain and tightness
🫤 Confusion
😵💫 dizziness
👁️ eye pain and tearing
🗣️ difficulty breathing
❌ ** COMA, RESP ARREST and CV COLLAPSE *
What is the mechanism of cyanide poisoning?
It interferes with cytochrome oxidase and inhibits respiration, killing cells at the point of cellular respiration.
What are the 4 main cyanide antidotes?
- oxygen
- dicobalt edentate
- cyanokit (ie hydroxycobalamin)
- sodium nitrate
How do we administer dicobalt edentate in cyanide poisoning?
IV injection - rapidly effective
We need to ensure that the persons we administer the dicobalt edentate is definitely suffering from cyanide poisoning. Otherwise if we administer in Px lacking cyanide —> liable to COBALT TOXICITY.
What are the ADRs/ effects associated with COBALT TOXICITY.
- facial and laryngeal oedema
- vomiting
- urticaria
- anaphylactic shock
- hypotension
- cardiac arrhythmias
- convulsions
We can also use hydroxycobalamin in the treatment of cyanide poisoning. How must this be administered?
CYANOKIT (IV infusion)
HYDROXYCOBALAMIN (IM infusion
Given as a LARGE DOSE
Moa of hydroxycobalamin?
It bonds tightly to cyanide to form a non toxic cyanocobalamin, which is then excreted in the urine.
What is a side effect of hydroxycobalamin you need to be aware of?
- it may make the patient turn bright RED and the urine very PINK
What are the main sources of lead poisoning in the UK?
- occupational —> ie inhalation via mining, use of lead in battery making, recycling, manufacturing industry.
- non occupational —> house renovation, imported toys and cookware, use of old lead pipes, or contaminated, traditional remedies and cosmetics
What are the symptoms of lead poisoning.
- some patients may present as asymptomatic.
- some may have non - specific symptoms, ie abdominal pains, headache, anaemia, constipation.
** ENCEPHALOPATHY ie swollenness brain 🧠 💧 **
- however this tends to occur more in children than adults.
** 🫘 PROXIMAL TUBE DYSFUNCTION, PROGRESSIVE RENAL INSUFFICIENCY ***
Why is it difficult to detect lead poisoning?
It can occur slowly and is chronic and thus can take a while to pick up.
What is the mainstay treatment of lead poisoning?
Chelation therapy.
What are the 2 main treatment options used to chelate lead in lead poisoning?
Oral DMSA
IV sodium calcium edentate
Why do patients who have lead poisoning need to have multiple courses of chelation therapy?
- the 1st course pulls the lead out of the blood mainly but less so from the bone
- repeated courses will help to pull out lead from the bone.
Antidotes can be very _______________ and need to be used appropriately?
- expensive
What is the use of recognising toxidromes?
- can help in diagnosing what type of poisoning has occurred.
