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Yr 4 - ACC > Paracetamol Overdose & Alcohol Withdrawal > Flashcards

Paracetamol Overdose & Alcohol Withdrawal Flashcards

1
Q

What is the therapeutic dose of paracetamol in adults?

A

1g QDS

Max of 4g per day

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2
Q

How is paracetamol metabolised?

A

1) 95% of paracetamol undergoes glucuronidation: creates water-soluble paracetamol conjugate that is eliminated in urine

2) 5% metabolised using cytochrome P450 enzymes to a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).

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3
Q

What is the toxic metabolite of paracetamol?

A

N-acetyl-p-benzoquinone imine (NAPQI)

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4
Q

How is the toxic NAPQI excreted?

A

NAPQI binds to glutathione (another protein in the body) –> becomes a mercapturate derivative

This is a non-toxic metabolite that gets excreted in the urine.

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5
Q

How can paractamol overdose be toxic?

A

1) In large amounts of paracetamol, production of NAPQI can significantly exceed the body’s detoxification capacity due to the finite amount of glutathione available.

2) Excess NAPQI binds to the hepatocytes causing mitochondrial injury

3) May cause acute liver failure or even death.

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6
Q

What are the 3 different types of paracetamol overdose?

A

1) Acute overdose

2) Staggered overdose

3) Therapeutic excess

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7
Q

What is an acute paracetamol overdose?

A

Excess amounts of paracetamol ingested over less than one hour, usually in the context of self-harm.

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8
Q

What is a staggered paracetamol overdose?

A

Excess amounts of paracetamol ingested over LONGER than one hour, usually in the context of self-harm.

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9
Q

What is a ‘therapeutic excess’ paracetamol overdose?

A

Excess paracetamol ingested with the intent to treat pain or fever and without the intent of self-harm.

Paracetamol is ingested above the licensed daily dose and more than or equal to 75mg/kg in 24 hours.

This can involve excessive doses of the same paracetamol product or the inadvertent use of multiple paracetamol-containing products simultaneously.

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10
Q

Can paracetamol toxicity result from normal yes?

A

Rarely - possibly due to the idiosyncratic differences between individuals’ enzyme activities during the metabolism process.

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11
Q

What are some risk factors for paracetamol overdose?

A

1) History of self harm

2) History of frequent or repeated use of medication for pain relief

3) Low body weight (<50 kg): unintentional overdose may occur due to a low body weight not being accounted for when prescribing

4) Cytochrome P450 inducers

5) Glutathione deficiency

6) Malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days

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12
Q

Give some examples of P450 enzyme inducers

A
  • phenytoin
  • carbamazepine
  • rifampicin
  • chronic alcohol excess
  • St John’s Wort
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13
Q

Acute alcohol intake vs chronic in risk of developing hepatotoxicity in paracetamol overdose?

A

Acute alcohol intake - not associated with an increased risk of developing hepatotoxicity and may actually be protective.

Chronic - increased risk of hepatotoxicity

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14
Q

What are some risk factors for a glutathione deficiency

A

Malnourishment:
- Eating disorders
- Alcohol use disorder
- Psychiatric disorders
- Chronic illnesses reducing nutritional intake

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15
Q

Early clinical features of paracetamol overdose?

A

N.B. paracetamol is often combined with opioids (e.g. codeine and dihydrocodeine); thus, a concomitant opioid toxidrome may be present.

Typical early clinical features (<12 hours) include:
- Potentially asymptomatic
- Nausea and vomiting
- Mild/moderate abdominal pain/tenderness

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16
Q

Late clinical features of paracetamol overdose (12-36 hours)?

A
  • Moderate/severe abdo pain
  • Metabolic acidosis
  • Jaundice
  • AKI
  • Hepatic encephalopathy
  • Coma
  • Bruising or systemic haemorrhage may indicate coagulopathy secondary to impaired hepatic clotting factor production
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17
Q

Not all patients will require investigation following a paracetamol overdose (see management section).

If indicated, what are some potential lab investigations?

A

1) Paracetamol concentration*

2) Liver function tests

3) INR

4) Urea and electrolytes

5) Plasma bicarbonate

6) Plasma glucose

7) Full blood count

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18
Q

How can acetylcysteine affect lab tests in paracetamol overdose?

A

Some laboratory analysers may underestimate paracetamol concentration by as much as 40% if the blood test is taken during treatment with acetylcysteine.

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19
Q

Give some examples of patients that require hospital assessment following paracetamol overdose

A

1) presence of symptoms e.g. jaundice

2) deliberate paracetamol overdose for self-harm (regardless of dose)

3) ingested dose >75 mg/kg over 1 hour or less

4) all staggered paracetamol overdoses

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20
Q

In the minority of patients who present within 1 hour, what can sometimes be given?

A

Activated charcoal

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21
Q

Management of an acute paracetamol overdose (i.e. ingested over one hour or less) if presenting within 8 hours of ingestion?

A

1) Wait four hours from the last ingestion, then take blood samples

2) Start acetylcysteine if 4-hour paracetamol level is above the treatment line, or evidence of liver injury (usually raised ALT)

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22
Q

How long should you wait after paracetamol ingestion to measure blood levels?

A

4 hours

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23
Q

what can be used to determine if blood paracetamol level needs treatment?

A

Use paracetamol treatment graph

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24
Q

What is plasma paracetamol conc that indicates treatment at 4 hours after ingestion?

A

100 mg/litre

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25
Q

What is plasma paracetamol conc that indicates treatment at 8 hours after ingestion?

A

50 mg/litre

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26
Q

Management of an acute paracetamol overdose (i.e. ingested over one hour or less) if presenting within 8-24 hours of ingestion?

A

1) Take blood samples immediately

2) If ≥150mg/kg ingested (or unknown amount) or symptomatic: start acetylcysteine while waiting for results

3) If <150mg/kg ingested: wait for results, start acetylcysteine if paracetamol level above the treatment line, or evidence of liver injury (usually raised ALT)

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27
Q

Management of an acute paracetamol overdose (i.e. ingested over one hour or less) if presenting >24 hours of ingestion?

A

1) Take blood samples immediately

2) If ≥150mg/kg ingested (or unknown amount) or symptomatic: start acetylcysteine while waiting for results

3) If <150mg/kg ingested: wait for results, start acetylcysteine if ALT raised, INR >1.3 (in the absence of other cause) or paracetamol detected, jaundiced, hepatic tenderness

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28
Q

In patients who present 8-24 hours after ingestion of an acute overdose, what amount of paracetamol ingested indicates the need for immediate acetylcysteine?

A

> 150 mg/kg

Give acetylcysteine even if the plasma-paracetamol concentration is not yet available.

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29
Q

In patients who present >24 hours after ingestion of an acute overdose, what would indicate the need to start acetylcysteine?

A

1) Ingested >150 mg/kg

2) Jaundiced

3) Hepatic tenderness

4) Raised ALT

5) INR >1.3

30
Q

Management of all patients with a staggered paracetamol overdose (i.e. ingested >1 hour)?

A

1) Start acetylcysteine treatment immediately

2) Take blood samples four hours after the last ingestion

3) Consider discontinuing acetylcysteine if low risk of hepatotoxicity: paracetamol concentration <10mg/L, normal ALT, INR <1.3 and asymptomatic

31
Q

Management of all patients with a therapeutic excess paracetamol overdose?

A

1) If symptomatic: start acetylcysteine treatment immediately

2) Management of therapeutic excess depends on the patient’s weight and quantity of paracetamol consumed within the last 24 hours

32
Q

How is acetylcysteine given in paracetamol overdose?

A

IV acetylcysteine infusion over one hour.

33
Q

Why is acetylcysteine given IV in paracetamol overdose?

A

to prevent/lessen liver damage secondary to a paracetamol overdose

34
Q

When is acetylcysteine most effective in paracetamol overdose?

A

Within 8 hours of paracetamol ingestion.

35
Q

How can excessive dosage of acetylcysteine be avoided in obese patients?

A

Use a ceiling weight of 110kg

36
Q

Main adverse effect of IV acetylcysteine?

A

Commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release.

37
Q

Management of anaphylactoid reaction to IV acetylcysteine?

A

Generally treated by stopping the infusion, then restarting at a slower rate.

38
Q

What are the 2 cetylcysteine regimens used in the UK?

A

1) Standard 21-hour regimen: 150mg/kg over one hour, then 50mg/kg over four hours, then 100mg/kg over 16 hours

2) Modified 12-hour Scottish & Newcastle Acetylcysteine Protocol (SNAP) regimen: 100mg/kg over two hours, then 200mg/kg over 10 hours

39
Q

In paracetamol overdose during pregnancy, how should:

a) toxic dose be calculated?
b) acetylcysteine dose be calculated?

A

a) using the patient’s pre-pregnancy weight

b) using the patient’s actual pregnant weight.

40
Q

3 treatment options in paracetamol overdose?

A

1) activated charcoal

2) N-acetylcysteine

3) liver transplant

41
Q

Criteria for liver transplant following paracetamol overdose (i.e. paracetamol liver failure)?

A

1) Arterial pH < 7.3, 24 hours after ingestion

OR all of the following:
2) prothrombin time > 100 seconds
3) creatinine > 300 µmol/l
4) grade III or IV encephalopathy

42
Q

What tests are required BEFORE stopping acetylcysteine in a paracetamol overdose?

A

Tepeat blood tests (including paracetamol concentration, INR, and LFTs).

43
Q

Is a previous anaphylactic reaction to acetylcysteine a contraindication for further treatment?

A

No - consider prophylactic treatment with antihistamines

44
Q

Further management of deliberate overdose once patient is medically fit for discharge?

A

Psychosocial assessment of their needs and risks by a specialist mental health professional.

45
Q

Complications of excessive ingestion of paracetamol?

A

1) N&V
2) Abdo pain
3) Acute liver failure
4) Renal impairment
5) Death

Significant complications are rare due to the availability of acetylcysteine (a highly effective antidote).

46
Q

What criteria is used to identify which patients with fulminant hepatic failure should be referred for liver transplantation?

A

The King’s College Criteria (KCC)

47
Q

Pathophysiology behind alcohol withdrawal?

A

1) chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors

2) alcohol withdrawal is thought to be lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission)

48
Q

Clinical features of alcohol withdrawal at:

a) 6-12 hours
b) 36 hours
c) 48-72 hours

A

a) tremor, sweating, tachycardia, anxiety

b) seizures

c) delirium tremens: coarse tremor, confusion, delusions, auditory & visual hallucinations, fever, tachycardia

49
Q

Management of alcohol withdrawal?

A

1) may need to admit patient (especially those with a history of complex withdrawals from alcohol)

2) give chlordiazepoxide, typically as part of a reducing dose protocol

50
Q

What benzo is preferable in patients with hepatic failure for alcohol withdrawal?

A

Lorazepam

51
Q

1st line medical management of alcohol withdrawal?

A

benzodiazepines e.g. chlordiazepoxide

52
Q

What 2 questionnaires can be used in alcohol excess?

A

AUDIT & CAGE

53
Q

What signs may be seen on examination in chronic alcoholism?

A
  • Palmar erythema (red palms)
  • Dupuytren’s contracture (nodules and pitting on ligaments of the hand which can prevent the fingers from straightening properly)
  • Spider naevi (swollen blood vessels with a central red spot and spider web type appearance typically seen on the face, neck or upper arms)
  • Gynaecomastia (enlarged breasts in men)
  • Testicular atrophy
  • Usually a small shrunken liver, but this may be enlarged earlier in the disease
  • A hepatic flap may occur in severe liver disease
  • An enlarged spleen
  • Caput medusae
54
Q

What triad is seen in Wernicke’s encephalopathy?

A
  • ataxia
  • ophthalmoplegia (usually lateral gaze palsy)
  • confusion
55
Q

How does Korsakoff’s syndrome present?

A
  • irreversible anterograde and retrograde amnesia
  • confabulation
56
Q

What criteria is needed for the diagnosis of alcohol excess?

A

ICD-10 definition - 3 or more needed

  • compulsion to drink
  • difficulties controlling alcohol consumption
  • physiological withdrawal
  • tolerance to alcohol
  • neglect of alternative activities to drinking
  • persistent use of alcohol despite evidence of harm
57
Q

Give 2 examples of drugs that can be used in chronic withdrawal of alcohol (i.e. preventing relapse)?

A

1) disulfram
2) acamprosate

58
Q

Role of disulfram in alcohol excess?

A

Promotes abstinence

Alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase.

Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms.

59
Q

Contraindications for disulfram?

A

1) IHD
2) Psychosis

60
Q

Role of acamprosate in alcohol withdrawal?

A

Reduces craving.

Is a weak antagonist of NMDA receptors.

61
Q

What is alcoholic ketoacidosis?

A

A non-diabetic euglycaemic form of ketoacidosis.

62
Q

Who does alcoholic ketoacidosis occur in?

Pathophysiology?

A

It occurs in people who regularly drink large amounts of alcohol.

1) Often alcoholics will not eat regularly and may vomit food that they do eat, leading to episodes of starvation.

2) Once the person becomes malnourished, after an alcohol binge the body can start to break down body fat, producing ketones.

3) Hence the patient develops a ketoacidosis.

63
Q

Typical features of alcoholic ketoacidosis?

A

1) metabolic acidosis

2) elevated anion gap

3) elevated serum ketone levels

4) normal or low blood glucose

64
Q

Management of alcoholic ketoacidosis?

A

Saline & thiamine

65
Q

How does ataxia in Wernicke’s typically present?

A

Particularly truncal ataxia, which manifests as an unsteady gait and difficulties in maintaining an upright posture. Limb ataxia can also be present but is generally less prominent.

66
Q

Clinical features of Wernicke’s?

A

Triad:
- Nystagmus
- Confusion
- Ophthalmoplegia: unilateral or bilateral dysfunction of eye movement, often affecting the lateral rectus and medial rectus muscles

Others:
- Memory deficits
- Apathy or agitation
- Hypothermia
- GI symptoms
- Tachycardia

67
Q

Differentials for Wernicke’s?

A
  • Delirium tremens
  • Hepatic encephalopathy
  • Stroke
  • Normal pressure hydrocephalus
68
Q

what triad is seen in normal pressure hydrocephalus?

A

1) mental state changes
2) gait instability
3) urinary incontinence

69
Q

Management of Wernicke’’s?

A

WE is managed through urgent administration of parenteral (not oral) thiamine for a minimum of 5 days.

Oral treatment should follow parenteral treatment.

70
Q
A

Yr 4 - ACC (73 decks)

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