Flashcards in CBD 7: Overdose Deck (16)
Resource for information on poisons/toxins
a) Which organ is the principal site of paracetamol toxicity?
b) How long does it take for toxicity to occur?
c) Which other organ is commonly affected in serious toxicity?
d) What is the toxic metabolite of paracetamol?
e) Stores of what chemical reduce the presence of this toxic metabolite?
f) Hence, how does NAC work?
g) And hence who is at greater risk of paracetamol toxicity?
h) What level is likely to be hepatotoxic?
b) 24 - 72 hours
f) NAC is a precursor to glutathione, hence increasing glutathione stores to reduce the amount of NAPQI
g) People with low glutathione stores:
- Cachectic patients - HIV/AIDS, cancer
h) > 16 (8 g)
You take blood for paracetamol levels at 0400 hours, 4 hours after he took the tablets. The level is 88mg/L.
You wonder whether you should start treatment with N-acetyl cysteine (NAC, Parvolex).
a) What factors increase the risk of hepatic toxicity?
b) In what cases should NAC be started immediately (before nomogram)?
c) Why are paracetamol levels taken at 4 hours and not immediately?
a) - Immunosuppresion, malnourishment
- Liver - alcohol use/alcoholism, chronic liver disease, taking hepatotoxic meds
- P450 activators - rifampicin, phenytoin, etc.
- Previous multiple paracetamol OD
b) The following make nomogram unreliable:
- Staggered overdose (overdose that is taken over a duration of 1 hour or more)
- Present > 8h after ingestion
- Not sure when the overdose was taken
c) Metabolism time to NAP-QI
b) Treatment line begins at....?
a) Paracetamol level (mg/L) vs. time (hours)
b) 4 hours
Paracetamol overdose: presentation
a) First 24 hours
b) Then classic symptoms and signs
a) - May be asymptomatic
- Non-specific GI symptoms (eg. nausea, vomiting)
b) Hepatic necrosis begins to develop after 24 hours:
- RUQ pain and jaundice
- Acute liver failure - bleeding, encephalopathy, jaundice, liver flap
- Renal failure - oliguria, etc.
- LFTs - elevated transaminases, raised PT, low albumin
- Renal failure - raised creatinine
- Lactic acidosis.
a) When should you generally treat with NAC?
b) NAC is generally 100% effective in preventing liver damage if given within...?
c) What is the dosing regimen for NAC?
d) When should charcoal be used?
a) - In general: wait for level and treat if above line
- Immediate treatment if > 8h post-ingestion, uncertainty over timing or staggered overdose
b) 8 hours
c) 3 consecutive IV infusions (total: 300mg/kg in 21 hrs):
- Loading dose: 150mg/kg over 1 hour,
- 50mg/kg over next 4 hours,
- 100mg/kg over next 16 hours
d) If ingestion within previous hour
Criteria for liver transplanation in paracetamol OD
b) Each criterion (HACK)
a) King's College liver transplantation criteria
- Hepatic encephalopathy (grade III or IV)
- Acidosis (pH < 7.3)
- Clotting (PT >100 or INR > 6.5)
- Kidney failure (Cr > 300)
Some time later Gary is receiving treatment with NAC. One of the nurses calls you to see him as he is flushed and has vomited. His observations are normal.
a) What is happening?
b) How should you manage?
c) Should you restart treatment once symptoms resolve?
d) If further reaction, consider...?
a) Allergic reaction to NAC
b) Stop NAC until symptoms resolve completely. Antihistamines, steroids, IV fluids, anti-emetics (only use adrenaline in anaphylaxis)
c) Yes, once symptoms of allergy resolve. Give half the original dose (most will not have a further reaction).
d) Oral methionine
Psych review post-overdose.
- Pierce Suicide Intent Scale:
If They Present After Failed Suicide, Let Suicidal Patient Relay Pertinent Details
Pierce Suicide Intent Scale:
Precautions taken (to not get caught)
Actions to gain help (not done)
Stated intent (at the time and now)
Reaction to act (guilty, remorseless?)
Death without medical treatment
Psych tool to predict suicide before attempt
- SAD PERSONS
S: Male sex
A: Age (<19 or >45 years)
P: Previous attempt
E: Excess alcohol or substance use
R: Rational thinking lost
S: Social supports lacking
O: Organized plan
N: No spouse
<4: low risk
4-6: medium risk
>6: high risk
a) Higher doses of drug required to achieve same effect
b) Stopping the drug leads to withdrawal symptoms
c) Rapidly diminishing response to successive doses of a drug, rendering it less effective
d) Lack of control over... the consumption of a drug, a particular behaviour, etc.
Alcohol dependence features: CANT STOP
C - Compulsion to drink alcohol
A - Aware of harm but continues to drink
N - Neglects other activities (e.g. self-care, social, work)
T - Tolerance to alcohol
S - Stopping drinking leads to withdrawal symptoms
T - Time pre-occupied with alcohol increases
O - Out of control use of alcohol
P - Persistent, futile attempts to cut down
Also - narrowing of repertoire with stereotyped drinking pattern
a) Who is more at risk of toxicity?
b) Chronic toxicity
c) Acute toxicity
f) Why might repeated doses or an infusion of naloxone be appropriate?
a) - Alcoholics
- Liver or renal impairment
- Elderly or frail
- Respiratory disease
b) - Constipation, nausea, loss of appetite, itching
- Signs of addiction - cravings, tolerance, etc.
- IVDU - track marks, etc.
c) - Hallucinations, drowsiness, pinpoint pupils, myoclonus
- Respiratory depression
d) - Urine toxicology - opiate level, other drugs
- Paracetamol and alcohol level
- Bloods: FBC, U+Es, LFTs, CK, ABG, etc.
e) - ABC - support airway and breathing; IV fluids
- IV naloxone (competitive antagonist at opioid receptor); give IM if no vein available; repeat if no response
f) - Naloxone has a short half life (~ 60 mins)
- The effects might wear off while the effects of the opiate are still in the system
- Hence, need to counterbalance with more/longer duration of naloxone
Opiate addiction: management
- Harm reduction
- Detox and maintenance
- Warn about withdrawal symptoms
- Relapse prevention
- Needle exchange
- Screen for blood-borne viruses
- Hep A/B vaccination
Detoxification and maintenance.
- Methadone (full agonist), or
- Buprenorphine (partial agonist/antagonist)
- cold sweats, tremor, nausea, vomiting, diarrhoea, abdominal pain, tachycardia, restless, insomnia
- Naltrexone (competitive opioid antagonist)