Drug overdose

Question 1

What causes hepatic problems in paracetamol overdose?

Answer 1

The toxic metabolite N-acetyl­ p-benzoquinone imine (NAPQI) results from depletion of glutathione stores, causing fulminant hepatic necrosis after several days

Question 2

How can paracetamol overdose present?

Answer 2

No symptoms
Nausea and vomiting
Loin pain
Haematuria and proteinuria
Jaundice
Abdominal pain
Coma
Severe metabolic acidosis

Question 3

How do you manage paracetamol overdose if ingestion < 1 hour ago + dose > 150 mg/kg?

Answer 3

Activated charcoal

Question 4

How do you manage paracetamol overdose if ingestion < 4 hours ago?

Answer 4

Wait until 4h to take level + treat with NAC based on level

Question 5

How do you manage paracetamol overdose if ingestion within 4-8 hours + dose > 150mg/kg?

Answer 5

Start NAC immediately if there is going to be a delay of > 8 hours obtaining paracetamol level

Question 6

How do you manage paracetamol overdose if ingestion within 8-24 hours + dose > 150mg/kg?

Answer 6

Start NAC immediately

Question 7

How do you manage paracetamol overdose if ingestion > 24h?

Answer 7

Start NAC immediately if:
1) Jaundice
2) RUQ tenderness
3) Elevated ALT
4) INR > 1.3
5) Paracetamol concentration is detectable

Question 8

How do you manage paracetamol overdose if staggered?

Answer 8

Start NAC immediately

Question 9

How do you decide whether to treat paracetamol overdose with NAC?

Answer 9

Based on a normogram - if paracetamol levels are above the treatment line then start NAC

Question 10

When should NAC be started regardless of normogram?

Answer 10

1) Patient presents after 16h
2) Uncertainty about timing
3) Staggered overdose

Question 11

What is a side effect of NAC?

Answer 11

NAC is associated with anaphylactoid reactions -these are not true anaphylactic reactions and can usually be managed by stopping the infusion temporarily and then restarting at a lower rate

Question 12

When else would you administer NAC immediately?

Answer 12

If there is increased risk of toxicity:
1) Patient on long-term enzyme inducers
2) Regular alcohol excess
3) Pre-existing liver disease
4) Glutathione-deplete states: eating disorders, malnutrition and HIV

Question 13

What is the UK treatment normogram threshold for paracetamol overdose at 4 hours?

Answer 13

100 mg/L in all groups

Question 14

What are symptoms of SSRI overdose?

Answer 14

1) Prolonged QT (risk of TdP)
2) CNS depression
3) Seizures

Question 15

What are the two key additional symptoms that should prompt concern about serotonin syndrome?

Answer 15

1) Hyperreflexia
2) Pyrexia

Question 16

How is SSRI overdose managed?

Answer 16

1) Cooling
2) Fluids
3) Benzodiazepines
4) Intensive therapy support

Question 17

Are SNRIs e.g. venlafaxine more or less toxic than SSRIs?

Answer 17

More toxic bc also inhibits noradrenaline reuptake

Question 18

What are the symptoms of TCA overdose?

Answer 18

1) Metabolic acidosis
2) CNS depression
3) QRS widening (due to sodium channel blockade)
4) Arrhythmias

Question 19

How do you manage TCA overdose?

Answer 19

1) IV sodium bicarbonate (if QRS widened)
2) Supportive ± ITU

Question 20

What are the symptoms of opiate overdose e.g. heroin?

Answer 20

1) Itching
2) Miosis
3) Hypoventilation leading to respiratory arrest

Question 21

How do you manage opioid overdose?

Answer 21

IV/IM naloxone - usually titrated to the point of adequate respiratory function

Question 22

What are the key considerations with naloxone?

Answer 22

1) Be aware that reversal can be immediate, precipitating agitated behaviour due to withdrawal effects
2) The half-life of naloxone is shorter than most opiates (~20min) so repeat dosing ± an infusion may be required

Question 23

What are the signs of cocaine use?

Answer 23

Potent sympathomimetic
1) Euphoria
2) Hypervigilance
3) Tachycardia
4) Hypertension

Question 24

What are the signs of cocaine toxicity?

Answer 24

1) Severe agitation
2) Myocardial infarction
3) Arrhythmias
4) Seizures
5) Intracranial bleeding

Question 25

How do you manage cocaine overdose?

Answer 25

Supportive - benzodiazepines ± GTN

Question 26

What type of drug is amphetamine?

Answer 26

Sympathomimetic (same as cocaine)

Question 27

What are features of amphetamine toxicity?

Answer 27

1) Pyrexia
2) Hyponatraemia
3) Rhabdomyolysis
4) Renal failure
5) Multi organ failure
+ similar toxidrome to cocaine:
1) Severe agitation
2) Myocardial infarction
3) Arrhythmias
4) Seizures
5) Intracranial bleeding

Question 28

How is amphetamine overdose managed?

Answer 28

1) Active cooling
2) Fluid resuscitation
3) Benzodiazepines
4) ITU support
5) Manage MDMA pyrexia with dantrolene

Question 29

What are examples of hallucinogenics?

Answer 29

1) Phencyclidine (PCP)
2) Psilocybin (mushrooms)
3) Lysergic acid diethylamide (LSD)

Question 30

What are the effects of hallucinogenics?

Answer 30

Profound short and longer term psychiatric effects incl. hallucinosis + psychosis

Question 31

How do you treat hallucinogenic effects?

Answer 31

1) Supportive
2) Care in a quiet calm environment
3) ± benzodiazepines

Question 32

What is the active ingredient in cannabis?

Answer 32

Tetrahydrocannabinol (THC)

Question 33

What are the clinical effects of cannabis?

Answer 33

1) Lethargy
2) Psychomotor retardation
3) Postural hypotension
4) Slurred speech
- Synthetic cannabinoids can have much more profound and prolonged neuropsychiatric effects

Question 34

How do you manage cannabis use?

Answer 34

Supportive

Question 35

How does serotonin syndrome present?

Answer 35

1) Restlessness
2) Diaphoresis (excessive sweating)
3) Tremor
4) Fever
5) Shivering
6) Myoclonus/hyperreflexia
7) Confusion
8) Convulsions
9) Death

Question 36

How do some antidepressants need to be specifically cross-tapered to avoid serotonin syndrome?

Answer 36

1) MAOIs to any other antidepressant - withdraw and wait two weeks (time taken for monoamine oxidase to be replenished)
2) Do not co-administer clomipramine + SSRIs or venlafaxine
3) Beware of fluoxetine interactions - may still occur for 5 weeks after stopping due to long half life

Question 37

What is a key drug interaction that can cause serotonin syndrome?

Answer 37

Sertraline + tramadol

Question 38

When does serotonin syndrome present?

Answer 38

First couple of months of starting SSRI, drug interactions, cross-tapering