Clinical Toxicology Flashcards
What are the two most common things people go to the ED for overdosing on?
Antidepressants
Benzos
Among non-opioid analgesic overdoses, what is the most common culprit at 78%?
Paracetamol
What’s the take home message about toxic pharmacokinetics?
We can’t compare them with therapeutic level pharmacokinetics. We need to know how they behave PK-wise at toxic levels. I.e. “ADME during overdose”.
In what kinds of preparations have the most rapid absorption and what are the typical culprits?
Liquid preparations -
Paracetamol, chemicals, pesticides.
Why would the effects of anticholinergic overdoses be delayed?
Reduces gut absorption, because that’s characteristic of anticolinergics.
Recall anti-cholinergic = atropine-like = sympathetic overbalance.
What two common overdose stuffs have anticholinergic effects?
Antihistamines, TCAs
Where do we need to monitor >17 hours for toxic effects?
Sustained release preparations.
What’s a common sustained-release drug often overdosed on?
calcium-channel blockers
Paracetamol isn’t hepatotoxic. Why do we worry about liver damage in paracetamol overdose?
NAPBQI binds to hepatocytes with hepatotoxic consequences. Liver damage can result.
NAPBQI Question:
In paracetamol overdose, the K pathway experiences abnormally high flux as the W pathway and M pathways are saturated.
Microsomal,
Glucuronidation; Sulphation
NAPBQI Question:
Normally the K pathway has an ample supply of R for the portion of paracetamol it metabolises. NAPBQI can rapidly conjugate to R and get pissed out. But when overworked, R is depleted and the hepatotoxic intermediate metabolise NAPBQI accumulates.
Microsomal; glutathione
A Y is a tool indicate whether to treat for liver toxicity, based on Cp and hours-post-ingestion.
Nomogram
A nomogram is what?
A graph of Cp (paracetamol) vs. hours-since-ingestion with safe zones and danger zones marked out, indicating whether or not to treat for liver toxicity.
What pharmacokinetic quality means serum levels can rise abruptly in progressively higher doses?
High protein-binding.
What is the serum-level profile for a high-Vd (typically very lipophilic) drug?
[early toxicity because of a] rapid increase upon entry into the bloodstream, with progressive reduction due to redistribution.
What is the significance of a high Vd drug in terms of management strategy and why?
E.g. someone’s in cardiac arrest because they’ve overdosed on TCAs. What do you know you have in store?
EARLY TOXICITY because of rapid entry to the bloodstream, but that THE GAME’S NOT OVER once it’s under control, since we’re still wary of the toxicant reentering the blood compartment.
Re TCA overdose: We’re gonna be resuscitating for cardiac arrest, but we’re gonna be at it for a while because the causative agent is gonna keep leeching from the body back into the blood keeping cardiac conduction fucked.
Apart from protein binding, what can knock serum levels up abruptly in overdose? What’s a typical example?
Hepatic metabolism can get saturated, knocking 1st order kinetics to zero-order kinetics.
Example: aspirin (Pka 3.0), renal clearance only mechanism during OD.
Pharmacodynamics question:
What’s an important example of receptor-density modification and what’s the danger?
Opioids. Famously they induce physical tolerance by increasing receptor endocytosis and degradation.
Overdose wise - big problems occur AFTER WITHDRAWAL, during which receptor density has recuperated, when the user takes an identical dose.
Apart from receptor-density changes, what is a major pharmacodynamic concept?
Loss of specificity.
As a cross-over with antidepressants, relate TCA overdose symptoms to four losses of specificity.
ALPHA2 BLOCKADE - hypotension (vasodilation)
NA(v) BLOCKADE - disrupted conduction problems
mAChR BLCOKADE - ANTICHOLINERGIC
GABA2 BLOCKADE - lowered seizure threshold
Toxicodynamics question:
List the four blockades that occur with decreased TCA specificity during overdose?
Alpha2,
GABA2,
mAChR, p
Na(V)
Most ODs are very undifferentiated upon presentation. What are the practical steps to take when someone admits with an overdose?
ABC - airway, breathing, circulation; check O2 sat.
Check for hypoglycaemia.
Do a toxicology screen.
OD deaths are uncommon.
What are the three pharmacological steps in responding to an OD?
Hinder absorption
Help elimination
Give antidote where possible.
How long after ingestion is it too late for charcoal therapy?
1-2 hours. It really only helps with [non-polar] stuff that’s STILL in the GI tract.