David Juurlink
@davidjuurlink.bsky.social
Internal Medicine, Clinical Pharmacology & Toxicology, and drug safety research at the University of Toronto. Inexplicably fortunate husband.
We've all seen firsthand how well opioids can work when first given. But they are at their pharmacologic best in the initial days of treatment.
Continue them for weeks, months, or years and the calculus becomes progressively less favourable.
Continue them for weeks, months, or years and the calculus becomes progressively less favourable.
October 27, 2025 at 6:28 PM
We've all seen firsthand how well opioids can work when first given. But they are at their pharmacologic best in the initial days of treatment.
Continue them for weeks, months, or years and the calculus becomes progressively less favourable.
Continue them for weeks, months, or years and the calculus becomes progressively less favourable.
Reposted by David Juurlink
Drs. Jessica Kent Rice @jessicakentrice.bsky.social & David Juurlink @davidjuurlink.bsky.social study on trends in opioid agonist therapy retention after non-fatal #OpioidOverdose: www.psifoundation.org/funded-resea... #InternationalOverdoseAwarenessDay #IOAD2025 @sunnybrookhsc.bsky.social
Funded Research - PSI Foundation
List of projects funded by PSI Foundation.
www.psifoundation.org
August 28, 2025 at 6:03 PM
Drs. Jessica Kent Rice @jessicakentrice.bsky.social & David Juurlink @davidjuurlink.bsky.social study on trends in opioid agonist therapy retention after non-fatal #OpioidOverdose: www.psifoundation.org/funded-resea... #InternationalOverdoseAwarenessDay #IOAD2025 @sunnybrookhsc.bsky.social
To sum up:
- Carbapenems lower VPA concentrations abruptly and dramatically
- They do this by tinkering with VPA metabolism
- Consider carbapenems in patients with severe VPA toxicity and those you expect to develop it
/end
- Carbapenems lower VPA concentrations abruptly and dramatically
- They do this by tinkering with VPA metabolism
- Consider carbapenems in patients with severe VPA toxicity and those you expect to develop it
/end
April 10, 2025 at 7:05 PM
To sum up:
- Carbapenems lower VPA concentrations abruptly and dramatically
- They do this by tinkering with VPA metabolism
- Consider carbapenems in patients with severe VPA toxicity and those you expect to develop it
/end
- Carbapenems lower VPA concentrations abruptly and dramatically
- They do this by tinkering with VPA metabolism
- Consider carbapenems in patients with severe VPA toxicity and those you expect to develop it
/end
In the second group, I start mero or erta early
It's conceptually similar to early alkalinization for ASA toxicity
/12
It's conceptually similar to early alkalinization for ASA toxicity
/12
April 10, 2025 at 7:04 PM
In the second group, I start mero or erta early
It's conceptually similar to early alkalinization for ASA toxicity
/12
It's conceptually similar to early alkalinization for ASA toxicity
/12
The second is people *expected* to get sick, generally those who ingest >300-400 mg/kg
/11
/11
April 10, 2025 at 7:02 PM
The second is people *expected* to get sick, generally those who ingest >300-400 mg/kg
/11
/11
The first is easy: the sickest of the sick
If you're contemplating hemo, you should be contemplating mero or erta
As I wrote:
/10
If you're contemplating hemo, you should be contemplating mero or erta
As I wrote:
/10
April 10, 2025 at 7:00 PM
The first is easy: the sickest of the sick
If you're contemplating hemo, you should be contemplating mero or erta
As I wrote:
/10
If you're contemplating hemo, you should be contemplating mero or erta
As I wrote:
/10
I wrote this review on the topic. It's not open access so I'll unpack the two scenarios where I think carbapenems should be considered.
/9
bpspubs.onlinelibrary.wiley.com/doi/abs/10.1...
/9
bpspubs.onlinelibrary.wiley.com/doi/abs/10.1...
BPS Publications
Severe valproic acid (VPA) overdose is characterized by coma (sometimes with cerebral oedema), respiratory depression, hypotension and metabolic abnormalities. Traditional management of VPA poisoning...
bpspubs.onlinelibrary.wiley.com
April 10, 2025 at 6:59 PM
I wrote this review on the topic. It's not open access so I'll unpack the two scenarios where I think carbapenems should be considered.
/9
bpspubs.onlinelibrary.wiley.com/doi/abs/10.1...
/9
bpspubs.onlinelibrary.wiley.com/doi/abs/10.1...
A few case reports describe using mero or erta for VPA toxicity, like this one
www.sciencedirect.com/science/arti...
/8
www.sciencedirect.com/science/arti...
/8
April 10, 2025 at 6:53 PM
A few case reports describe using mero or erta for VPA toxicity, like this one
www.sciencedirect.com/science/arti...
/8
www.sciencedirect.com/science/arti...
/8
What carbapenems so is inhibit APEH, abruptly and irreversibly
The net effect?
- a dramatic INCREASE in VPA-glucuronide (which is inert and eliminated by the kidney)
- a dramatic DECREASE in VPA concentrations
/7
The net effect?
- a dramatic INCREASE in VPA-glucuronide (which is inert and eliminated by the kidney)
- a dramatic DECREASE in VPA concentrations
/7
April 10, 2025 at 6:53 PM
What carbapenems so is inhibit APEH, abruptly and irreversibly
The net effect?
- a dramatic INCREASE in VPA-glucuronide (which is inert and eliminated by the kidney)
- a dramatic DECREASE in VPA concentrations
/7
The net effect?
- a dramatic INCREASE in VPA-glucuronide (which is inert and eliminated by the kidney)
- a dramatic DECREASE in VPA concentrations
/7
What's missing from that depiction is the reversibility of the lowermost pathway
Normally, the dominant metabolite (VPA glucuronide) is back-converted to VPA by acyl peptide hydrolase (APEH)
/6
Normally, the dominant metabolite (VPA glucuronide) is back-converted to VPA by acyl peptide hydrolase (APEH)
/6
April 10, 2025 at 6:52 PM
What's missing from that depiction is the reversibility of the lowermost pathway
Normally, the dominant metabolite (VPA glucuronide) is back-converted to VPA by acyl peptide hydrolase (APEH)
/6
Normally, the dominant metabolite (VPA glucuronide) is back-converted to VPA by acyl peptide hydrolase (APEH)
/6
We now know why this happens. It relates to how VPA is metabolized, which is generally represented like this:
/5
/5
April 10, 2025 at 6:52 PM
We now know why this happens. It relates to how VPA is metabolized, which is generally represented like this:
/5
/5
In 1997, Japanese doctors reported 3 children whose VPA levels plummeted after treatment with panipenem
/4
journals.lww.com/drug-monitor...
/4
journals.lww.com/drug-monitor...
April 10, 2025 at 6:51 PM
In 1997, Japanese doctors reported 3 children whose VPA levels plummeted after treatment with panipenem
/4
journals.lww.com/drug-monitor...
/4
journals.lww.com/drug-monitor...
Traditional management of VPA overdose?
- GI decontamination (mainly charcoal)
- L-carnitine for ↑NH₃
- Hemodialysis in the sickest of the sick
/3
- GI decontamination (mainly charcoal)
- L-carnitine for ↑NH₃
- Hemodialysis in the sickest of the sick
/3
April 10, 2025 at 6:51 PM
Traditional management of VPA overdose?
- GI decontamination (mainly charcoal)
- L-carnitine for ↑NH₃
- Hemodialysis in the sickest of the sick
/3
- GI decontamination (mainly charcoal)
- L-carnitine for ↑NH₃
- Hemodialysis in the sickest of the sick
/3
Most VPA overdoses manifest as just lethargy. But large ones (>400 mg/kg) get sick, with
- coma ± cerebral edema
- respiratory depression
- hypotension
- multiorgan dysfunction
- HAGMA
- hyperammonemia
And sometimes they die
/2
- coma ± cerebral edema
- respiratory depression
- hypotension
- multiorgan dysfunction
- HAGMA
- hyperammonemia
And sometimes they die
/2
April 10, 2025 at 6:50 PM
Most VPA overdoses manifest as just lethargy. But large ones (>400 mg/kg) get sick, with
- coma ± cerebral edema
- respiratory depression
- hypotension
- multiorgan dysfunction
- HAGMA
- hyperammonemia
And sometimes they die
/2
- coma ± cerebral edema
- respiratory depression
- hypotension
- multiorgan dysfunction
- HAGMA
- hyperammonemia
And sometimes they die
/2