Drug Overdose Flashcards
What happens to the Paracetamol when is taken at a normal dose?
It gets conjugated
*conjugates are harmless - filtered out by the kidney and completely safe
What happens when normal paracetamol metabolic pathways become saturated?
Normal pathways (safe pathways): 1) glucuronyl transferase 2) phenolsulphotranseferase
When normal pathways get saturated (overwhelmed by OD)-> 3rd pathway activated (it is called N-acetyl-p-benzoquinoneimine) -> NAPQI produced -> it destroys hepatocytes in the liver
How does the body get rid of NAPQI?
It combines with Glutathione -> that conjugates NAPQI and gets rid of it (by removing it from the body)
What do we give in paracetamol OD/ what’s the physiological princple?
We want to increase Glutathione dose -> so we can conjugate NAPQI (harmful metabolites of paracetamol in OD)
For that purpose we give N-acetylcysteine
What is the timeframe to give N-acetylcysteine after paracetamol OD?
within 4 hours from OD
What do the inducers do?
Induced cytochrome P450 -> more metabolism -> other drugs (that are metabolized) are less effective
Cytochrome P450 inducers
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- *C**arbemazepines
- *R**ifampicin
- *A**lcohol (chronic)
- *P**henytoin
- *G**riseofulvin (anti-fungal)
- *P**henobarbitone
- *S**ulphonylureas / St John’s Wort (alternative remedy for depression)
Cytochrome P450 inhibitors
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- *S**odium valproate
- *I**soniazid
- *C**imetidine
- *K**etoconazole
- *F**luconazole
- *A**lcohol (acute - binge drinking)
- *C**hloramphenicol
- *E**rythromycin
- *S**ulfonamides
- *C**iprofloxacin
- *O**meprazole
- *M**etronidazole
*grapefruit juice
What do cytochrome p450 inhibitors do?
Cytochrome p450 inhibitors -> inhibit liver metabolism -> other drugs are less metabolised -> toxicity (overdose/accumulation may occur)
What is the connection between the inducer of cytP450 and paracetamol OD?
As more liver CytP450 activity -> more activation of pathway that produce NAPQI = more dangerous
Treatment protocol for paracetamol
(to treat or not to treat)
Drug paracetamol level is taken 4 hours after the OD -> to check what blood Paracetamol level is
If it is above the line -> treat with NAC (N-acetylcysteine)
If the blood level of Paracetamol is below -> then do not treat *at that point perhaps enough glutathione to metabolise paracetamol + side effects of having NAC
Side effects of NAC treatment
NAC = N-acetylcysteine
- nausea/ vomiting
- bronchospasm
- anaphylactoid reation* - rash (in about 20% of people)
*anaphylactoid reaction is anaphylaxis - like picture but not mediated by IgE but by direct release of inflammatory mediators from mast cells
Do we treat paracetamol OD if we do not know when a person took OD, confusion about where the levels of Paracetamol fall on the ‘treatment line’?
If there is confusion - we treat
What groups of the patients are at high risk of toxic effects of Paracetamol?
High risk of toxic effects of Paracetamol = due to low glutathione stores
- alcoholics
- immunosuppressed
- malnourished
Best investigations for a person coming with Paracetamol OD
- Paracetamol level
- LFT -> to check liver function and bilirubin
- INR -> to make sure clotting is not affected (synthetic function)
- U&Es -> to ensure that there is no multi-organ failure
- glucose -> if pt has low GCS/mental state - to role out that cause of pt state
- ABG -> always to do with a patient with low GCS
- metabolic flap test -> to check if encephalopathy has happened
Paracetamol OD management
if taken <1 hour ago
Activated Charcoal
MoA: it is going to the stomach and absorbs paracetamol particles
*but effective only if a drug is in the stomach
Main treatment for Paracetamol OD
- how much / when
- what do we do
NAC (N-acetylcysteine)
- take blood (levels of Paracetamol) -> give NAC
- 3 x bags of NAC over 21 hours
- repeat bloods afterwards
* to check if they are in ‘safe zone’
What’s a ‘safe zone’ following NAC treatment?
After treatment with NAC -> we check the bloods
‘safe zone’ is:
- INR <1.3
- ALT <2 X upper limit abnormal
Then, they are likely to recover - not dangerous state for the liver
*if not within ‘safe zone’ limit -> give more NAC over 16 hours and keep patient for another day
What do we need to do before discharging a patient with Paracetamol OD?
We need to arrange psychological review (mental health team)
What is the last resort in the treatment of Paracetamol OD?
Liver transplant
What criteria are used to determine who should be referred for an immediate liver transplant?
King’s criteria
to determine who should receive a liver transplant after acute or chronic paracetamol induced severe liver injury
What are the most important King’s College criteria for liver transplant
- pH <7.3 or lactate >3.5 after fluids -> indicates metabolic acidosis due to liver failure
OR all 3 of:
- INR >6.5
- Creatinine >300 -> renal dysfunction
- hepatic encephalopathy - grade III or IV -> low GCS and liver flap
*All these are signs of severe liver damage
Common examples of benzodiazepines
- Diazepam
- Lorazepam
- Midazolam
- Zopiclone
- Flunitrazepam / Rohypnol
Uses of benzodiazepines
- anxiolytic
- sedative
- hypnotic
- anticonvulsant
- muscle relaxant
