Posisoning - specific drugs Flashcards
Epidemiology of paracetamol poisonning
50% overdoses include paracetamol
Leading cause of mortality from overdose
1<% mortality
What are the metabolites of paracetemol
Para-glucorinide
Para-sulphate
N-acetyl-p-benzoquinone-imine
How is paracetemol turned into NAPQI
Oxidation via CYP450 eg CYP2E1/3A4
How is NAPQI detoxified in the liver
Glutathione
How does NAPQI cause hepatocellular injury
glutathione absent or depleted
Early clinical symptoms from paracetemol poisoning
May be none
V non specific symptoms
N+V+ abdominal pain
delayed clinical features of paracetemol overdose
Hepatic necrosis
2-3 days: LIVER FAILUREN
Jaundice
Liver pain
Encephalopathy
Coagulopathy
Fulminant hepatic failure
Death - 3-6 days post overdose
Rare delayed features of paracetemol overdose
Renal failure (acute tubular necrosis)
Hypoglycaemia
Metabolic acidosis
Renal failure in paracetamol overdose
acute tubular necorsis
2-7 days after poisoning
Oliguria
Loin pain
investigations for paracetemol overdose
Paracetamol level
Clotting - PT, INR (baseline then monitor)
U+Es, creatinine at baseline then monitor
Blood gases
LFTs
What does paracetamol level tell you in overdose
- best early predictor of prognosis
Need for antidotes
Why may urea remain low in paracetamol overdose
Even if decreased from kidneys - Hepatic urea production
When is paracetamol treatment a gray area
0-4 hours - best to wait til after when can be interpreted
What paracetemol level treat at 4 hours
100mg
What see in heaptic injury in bloods in paracetamol overdose
Prolonged PT/INR
Elevated transaminases (bad prognostic)
Elevated bilirubin (hepatic necrosis)
Poor prognostic features in paracetamol overdose
PT/INR rising after day 3 or
PT>100s at any time - liver transplant
Bilirubin >70micromol/l
Metabolic acidosis
Encephalopathy - III or IV
AKI:
Raised lactate
Creatinine >300 micromol/l
What are the options for paracetamol overdose treatment
Prevent absorption - activated charcoal large dose within 1 hour
IV acetylcysteine
What is important with paracetamol overdose treatment
Timing is vital - effectiveness declines over time of antidote
How is acetylcysteine delivered
IV over 21 hours
How long is acetyl cysteine effective for
8 hours
decreases gradually afterwards
Still treat after 24 hours as still beneficial even in fulminant hepatic failure
When else is acetylcysteine used except acutely
For people with fulminant hepatic failure from paracetamol awaiting transplantation
Is there a time limit to when you use acetyl cysteine
No - use any time after severe poisoning even if less effective
Complications of acetylcysteine
Anaphylactoid reaction - urticaria, wheeze, hypotension
Dose related histamine release
Treating anaphylactoid reaction to acetylcysteine
Reduce infusion rate
Give antihistamiens
No steroids - not true anaphylaxis
Supportive therapy for paracetamol overdose and hepatic dysfunction
Vit K
FFP if active bleeding
Hepatic intensive care - fluid balance, BP support, IC pressure monitoring if HE
Dialysis for renal failure
Liver transplantation orthotopic
Clinical features of aspirin overdose
Dizzy
Sweat
Tinnitus
vommiting
Vasodilation, hyperventilation, agitation, delirium, coma (esp children)
Metabolic abnormalities in aspirin poisoning
Initially Respiratory alkalosis - direct CNS resp centre stim
Over time -> Metabolic acidosis (salicyclic acid - inhibits aerobic metabolism)
Electrolye abnormalities in aspirin poisoning
Hypoglycaemia
Hypokalaemia
Investigations in aspirin overdose
Plasma salicyclate concentration
Urea, electrolytes, bicarbonate
Blood glucose
ABG
Treatment options aspirin
Gastric deconotamination
Sodium bicarbonate
Enhance elimination - MDAC
Haemodialysis
What does sodium bicarbonate do in aspirin overdose
Prevents CNS penetration
Enhances renal eliminateion - urinary alkalinisation
Treatment of severe aspirin poisoning
Haemodialysis - removes salicyclate v effectively and corrects metabolic abnormalities
What criteria for haemodialysis in aspirin overdose
pH<7.3
Salicyclate level >700mg/l (600 inc hildren)
Renal failure
Supportive treatment in aspirin poisoning
AW
IV fluids
Ventilation
GLucose for hypoglycaemia
KCl for hypokalaemia
Opiate vs opioid
Opiate - natural derivative on opioid receptor
Opioid - synthetic does same - methadone, methidine, tramadol
Presenting features of opiate overdose
CNS and resp depression
Pin point pupils
Hypotension, tachycardia
Hallucinations
Rhabdomyolysis
Non cardiac pulmonary oedema
Managemnet opioid overdose
A=E
AW support
Naloxone and ventilation
C
D- reduced GCS - naloxone if not already
Hep B, C and HIC precautions
When is naloxone used
Suspected opiate intoxication
RR <10/min
Reduced GCS <10/15
Doses of naloxone used
Adult - 400microgram up to 2mg or more
Children - titrate up from 0.1mg/kg
How tackle nalaoxone short half life
Repeat as necessary
Give as IV infusion if large overdose or opiate of long half life
2/3 initial dose required to rouse patient IV per hour
Symptoms of acute withdrawal from naloxone
Muscle aches, diarrhoea, palpitations, rhinorrhea, yawning, irritability, nausea, fever, tremor, cramps
Risks with naloxone treatmnet
Acute withdrawal
Short halflife - wear off
Self discharge during alert phase -> coma/death after
Unmasking of pain
HPTN
behavioural disturbances - high doses
Rare - fits, arrhythmias, pulmonary oedema
Why dont make patient fully wake up with nalaxone dose (lower dose to keep sleep)
Behavioural issues
If self discharge die in community
Pharmacological effects of benzodiazapines
Sedation
Hypnotic
Muscle relaxant
CNS depressant
Anaesthetic
Amnesia
Anxiolytic - anti-anxiety
Mechanism of benzodiazapines
Enhance GABA - inhibits CNS
Benzodiazapine features of overdose
Drowsiness
Ataxia
Dysarthria
Hypotension
Bradycardia
Resp depression
Coma
NO CHANGE TO PUPILS
Benzodiazapine overdose management
Supportive mostly - ABC support
Oral activated charcoal (1 hr)
Obs monitoring
ECG
FLUMAZENIL
Deaths are rare - supportive alone mostly
Flumexanil affect on the patient and administration
Reverse sedative effect of benzos in minutes
IV bolus over 15s
Repeat as shorter acting than benzos
What is flumazenil contraindicated in
Patients on TCAs (precipitates seizures)
If on benzos for seizure control or elevated IC
When is flumezanil most useful
Iatrogenic overdose with chronic resp disease - prevent intubation and ventilation
TCA poisoning epidemiology
6% of overdoses
High fatality
100-200 deaths a year
Anticholinergic effects from TCAs
Hot dry skin
Dilated pupils
Tachy
Urinary retention
Agitation
Delirum
Fits
Coma
Hypertonia, hyperreflexia
Sodium channel effects and alpha adrenoreceptor effects of TCAs
Na channel blocker -> cardiac arrhtyhmias, conduction block, prolonged QRS and QT intervals
Hypotension - aa antagonism
Investigations for TCAs
U+Es
Blood glucose
ABG
ECG
Constant cardiovascular monitoring
What QRS duration on ECG in TCA overdose thresholds for risk
> 160ms (4 small squares) = v high risk arrhtyhmias
120ms (3 small squares) = specific urgent action
V BROAD
Action when large TCA overdose or initial abnormal ECG
CCU or ITU
Treatment options TCA overdose
Gastric decontamination
Enhance elimination - MDAC
Activated charcoal in both
Why can activated charcoal still be effective at gastric decontamination over one hour after TC voerdose
TCAs delay gastric emptying due to anticholingergic effects - charcoal can still be effective
What tricyclics can MDAC be beneifical in
amitryptilline, nortryptilline
When give sodium bicarbonate in TCA overdose
Acidosis
Wide QRS complex - 120ms
Arrhtyhmias
WHy is sodium bicarb given in TCA overdose
Correct metabolic acidosis - arrhythmias more likely if pH<7.4
How treat arrhythmias from TCA overdose
Na bicarb
Correct K+
If NaBicarb fails -> DC cardioversion or overdrive pacing IF patient unstable
What medications must not use in TCA overdose
Anti-arrhythmic drugs - may worsen arrhythmias
What use to treat seizures from TCA overdose
Diazepam or lorazepam
If fail - paralysis, mechanical ventialtion
Examples of antidepressants more safe in overdose than TCAs
SSRIs - citalopram, escitalopram, fluoxetine, paroxetine, sertraline
SNRI - venlafaxine
NaSSa (noradrenergic and serotonergic) - mirtazipine
NaRI - noradrenaline reuptake inhbite - reboxetine
RIMA - MAOi - mocolbemide
Serotonin syndrome features
Cognitive behavioural changes (agitation, confusion, hallucinations, coma)
Neuromuscular dysfunction (tremor, teeht, grinding, myoclonus, hyperreflexia)
Autonomic dysfunction (tachycardia, fever, hyper/hypotnesion rapid changes between, flushing, diarrhoea)
Others - comitting, seizures, hyperpyrexia, rhabdomyolysis, renal faikure, coagulopathies
Triad of SS syndrome
Congitive behavioural changes
NM dysfunction
Autonomic dysfunction
Often only few symptoms present so high level of clinical suspicion
Early signs of iron overdose
0-6 hrs
N+V
Abdo pain
Diarrhoea bloody
Massive GI fluid loss
Delayed efffects of iron poisoning
Black offensive stools
Drowsines/coma
Fits
Cirulatory collapse
Late - 2-4 days after iron overdose presentation
Acute liver necrosis due to build uo
Renal failure
What forms weeks after iron overdose
Gastric strictures
Investigations iron overdose
History - amount of elemental iron taken
Iron concentration (4 hrs after+ monitor)
FBC
U+Es
Bicarbonate - daily monitor
Glucose
Clotting - daily monitor
LFTs (hepatotoxicity)
What amount is a serious iron overdose
> 10mg/kg
Iron concentration when measured
After at least 4 hours
Repeat after 2-3 hours
What see in FBC in iron
Leucocytosis - raised WCC
What see effect onglucose in iron overdose
Hyperglycaemia
What gastric decontamination can give in iron poisoning
ONLY gastric lavage - activated charcoal ineffective
If large overdose
Which poisoning is activated charcoal ineffective in
Iron overdose
How does desferroxamine work
Binds to iron and chelates -> ferrioxamine - water soluble and excreted in urine (red discolouration)
Adverse effects of desferrioxamine
Hypotension and pulm oedema
What is desferrioxamine CI in
Renal failure - cleared by kidney turns wee red
When is desferroxamine used in iron poisoning (criteria)
V severe iron toxicity
Fits, coma, circulatory collapse
GI symptoms - leucocytosis, hyperglycaemia, high iron concentration >3mg/l
Supportive care for iron poisoning
IV fluids if hypo
Antiemetics if vomitting
Fits - diazepam/lorazepam
Correct acidosis w bicarb
Dialysis if renal failure
Where are organophosphate compounds most commonly poisoned
Major cause worldwide esp in south east asia
Mechanism of organophosphate compounds
Block cholinesterase enzymes esp acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) -> ACCUMULATION of acetylcholine at muscarinic receptors and nicotinic receptors and CNS -> increased activity
Cholinergic crisis features (organophosphate overdose) muscarinic effects
Too much acetylcholine
DUMBBBELS
Muscarinic effects
Diarrhoea
Urination
Miosis
Bradycardia
Bronchorrhoea, Bronchospasm
Emesis
Lacrimation
Salivation
Sympathetic NS
Mydriasis, HPTN, tachycardia
Re-entrant dysrhtyhmias
Cardiorespiratory arrest
Cholinergic crisis nicotinic effects
Respiratory difficulty - resp arrest, diaphragmatic weakness
Muscle weakness -fasciculations, clonus, tremor
Stimulation -of sympathetic NS
What stimulation of sympathetic nervous system causes in cholinergic crisis
Mydriases, HPTN, tachycardia, re-entrant dysrhythmias
Cardio-respiratory arrest
CNS effects with organophosphate poisoning
Malaise
Memory loss
Confusion
Disorientation
Delirium
Seizures
Resp centre depression or dysfunction
Coma
Initial management of organophosphate poisoning
ABC -
AW L lateral postion
Give oxygen
IV access x2
What are the antidotes for organophosphates
Atropine
Pralidozime/obidozime
What effects do atropine reduce from organophosphate poisoning
Bronchorrhoea, bronchospasm, salivation, abdominal colic
When should stop giving atropine
Every 10 minutes until signs of atropinisation develop - flushed red skin, tachycardia, dilated pupils, dry mouth
Triggers for giving atropine
Pinpoint pupils
Sweating
Difficulty breathing
What may be required in first 24 hours of orgaophosphate poisoning with atroping
Infusion or v large doses
Examples of cholinesterase reactivators
Pralidoxime, obidoxime
When does pralidoxime work
Within a short time period depending on type of organophosphate - otherwise complex of ACH and OP ‘aged’ and it cannot be reversed
Supportive care in organophosphate poisonning
Clearning the AW
Esure adequate ventilation
High flow O2
Manage ICU
Atropine - excesive secretions
Diazepam - seizures
Investigations organophosphate poisoning
ECG
U+Es
Glucose
Red cell cholinesterase activity
What test measures severity of organophosphate poisoning
Red cell cholinesterase activity
What is most helpful in determining severity of poisoning with organophosphates
Severity of clinical symptoms is more important than red cell cholinesterase activity - wide inter-individual range cholinesterase activity
ECG of benzodiazapine overdose
transient first and second degree block and QT prolongation
What effect does metoclopramide have on gastric emptying and why is it helpful?
Increases - speeds up absorption of other drugs
What drugs delay gastric emptying
CAs
Opiates
Antimuscarinics
Why dont give clarithromycin IV
Reaction at site
V good bioavailability orally - no need ot give IV
How do you know to step down from oral to IV abtibiotics
Decreasing white cell count
Stable CRP (not rising - CRP lag)
Apyrexial
What drugs do antacids make less orally bioavailable
Quinolones
Tetracyclines
Up to 70%
Why do thiazide like diuretics cause lithium accumulation
Thiazides cause diuresis and initial sodium loss
Compensatory sodium retention in proximal tubules
Proximal tubules do not distinguish sodium from lithium
Lithium also retained and accumulates
How do ciprafloxacin/clarithromycin interact with theophylline
INhibitors of CYP450
Dose of theophylline reduced and levels monitored
What macrolide doesnt interfere with wafarin
Azithromycin
Why can ACE inhibitors cause angio-oedema
Release of bradykinin
What mental health medication can cause galactorrhea
Antipsychotics eg risperidne - raise prolactin -> galactorrhea
Which antibioticscan cause childhood teeth staining if taken during pregnancy
Tetracyclines
When measure paracetamil overdose vs treat immediately
Explanation:
All patients taking an acute overdose more than 75 mg/kg should have their paracetamol concentration measured to determine whether acetylcysteine is indicated.
If presenting late i.e more than 8 hours, acetylcysteine should then be started before the results are available.
Stimulant vs TCA presentation after overdose
Both - dilated pupils, HR increase, low BP
TCA - dru skin, absent bowel sounds
Stimulant - increased bowel sounds, sweating
Is sodium valproate a CYP450 inhibitor
Yes
Is pancreatitis a side effect of sodium valproate
Yes
Phenytoin info around drug
Narrow therapeutic index
Inducer of CYP450
Highly protein bound
Hypotension and arrhythmias if given IV
