Surprised to see losartan topping this list.

When starting an ARB, losartan is the last option I'd go with, for one simple reason.

🧵 /1

https://twitter.com/WahajAmanMD/status/1774419137239900500

Losartan is a prodrug with two active metabolites, both of which have weirdly cryptic names.

Most of the hypotensive response is mediated by EXP3174 (usually abbreviated E-3174).

/2

shorturl.at/ehiuB

"Is this serotonin syndrome or NMS?"

In a patient with hyperthermia, altered mental status and neuromuscular abnormalities, evaluating 3 factors makes the distinction easier

🧵

/1 #1: The drugs

SS: 5-HT agonists, either in large amounts (OD) or in combination - SSRIs, some TCAs, MAOIs (incl. linezolid), opioids, St. John's wort, MDMA, Li⁺, others

NMS: D2 blockers - antipsychotics, metoclopramide; also, withdrawal of dopamine agonists (eg. L-dopa)

/2

Saddened to learn of the death of David Bailey, Canada's first four-minute-miler and the scientist who discovered, by sheer serendipity, that grapefruit juice interacts with dozens of medications.

I'll tell the story as David related it to me.

theglobeandmail.com/canada/article…

/1 In the late 80s, David was running a volunteer study to determine whether alcohol influenced the effect of felodipine.

To mask the taste of alcohol, he tried mixing it with various juices: orange, grape, apple. None of those worked.

/2

Hearing reports of a mass poisoning event related to a Markham restaurant, possibly involving aconite

Aconitine is a highly toxic alkaloid derived from the genus Aconitum (monkshood, wolfsbane and others)

Quick thread:

/1 Effects occur quickly and are chiefly GI, neurologic and cardiac

GI:
- nausea, vomiting, cramping

Neurologic:
- numbness (face and mouth, progressing to limbs)
- muscle weakness
- coma

Cardiac:
- hypotension, life-threatening arrhythmias

tandfonline.com/doi/abs/10.108…

/2

So, who knew that dimenhydrinate (Dramamine, Gravol) is actually two drugs?

A short drug history thread.

/1 The antihistamine diphenhydramine (Benadryl) was developed in 1940.

It was effective but very sedating, which is why it’s marketed even today as over-the-counter sleep aids like Nytol.

/2

Since posting this last week I've spoken with dozens of colleagues who have the same concern.

https://twitter.com/DavidJuurlink/status/1469633841971494912

Guy's and St. Thomas' Hospital in London now has 350(!) staff off work due to COVID, 25% more than just one day earlier.

theguardian.com/world/2021/dec…

If anything should move young people to get vaccinated, it's the seemingly endless number of tragic stories about young people who regret not being vaccinated.

Like this pregnant 39 y.o. woman in an ICU 800 km from her husband and children.

cbc.ca/news/canada/br… Or this couple in their 40s who left behind four children.

independent.co.uk/news/world/ame…

Still seeing stuff like this, even from MDs and nurses.

“Lots of COVID patients in ICU are fully vaccinated” is put forth as evidence the vaccines don't work.

It's an easy inference to draw. And it's wrong.

/1 Imagine you live in a city of 1 million people.

Most of the city's population is fully vaccinated. Let’s say 95%.

(Yes that’s unrealistically high. Just making a point.)

/2

I have a specific concern about third doses of vaccine that I’m not sure has received enough attention.

The issue is myocarditis.

/1 Let’s assume vaccine-induced myocarditis is immunologically mediated, as clustering after second doses clearly suggests.

Why would we not expect the incidence of myocarditis to be higher, or the manifestations more severe, if third doses are widely deployed?

/2

ACIP's slides on mRNA vaccines and myocarditis are now available cdc.gov/vaccines/acip/…

Hard to argue this isn't causal The signal by age and dose is not ambiguous

Should management of VITT include a short course of ibrutinib?

Thread:

/1 Most guidance on VITT management focuses on 3 main strategies:

- Avoidance of heparin & platelet transfusions
- A short course of IVIG
- DOACs as first line anticoagulants

/2

Yes, the AstraZeneca vaccine-thrombosis association is causal.

The temporal relationship is strong, it’s not seen with mRNA vaccines, and there’s a plausible mechanism analogous to heparin-induced thrombocytopenia (HIT)

nejm.org/doi/full/10.10… As with HIT, these are unusual clots: they occur in odd places (brain, abdomen) and in arteries as well as veins.

They’re more serious than the run-of-the mill clots we see all the time.

Carbapenem antibiotics reduce valproic acid (VPA) concentrations quickly and dramatically

Why does this happen?

/1 The carbapenem-VPA interaction was first described in 1997

Here, an 8-year-old girl with a seizure disorder and pneumonia is treated with panipenem

Thereafter, her [VPA] falls from 30.1 µg/mL (209 µM) to 1.53 µg/mL (11 µM)

academic.oup.com/jac/article/39…

/2

This report of a physician who died after receiving COVID vaccine offers a useful lesson in the importance of thinking more critically about does and what does not constitute a drug reaction.

/1
usatoday.com/story/news/hea… Briefly, the MD noticed petechiae (tiny areas of bleeding into the skin, as seen in image) 3 days after vaccination. He was diagnosed with ITP (immune thrombocytopenic purpura).

People with ITP have profoundly low platelets and can bleed spontaneously as a result.

/2

Grateful to the editors of @CanFamPhysician and @CPJ_RPC for jointly retracting two publications on the safety of codeine during breastfeeding journals.sagepub.com/doi/full/10.11… Story by @rachelmendleson here: thestar.com/news/investiga…

Last week I was interviewed for a podcast about hydroxychloroquine.

As we were wrapping up, the producer interjected and asked “Some doctors say it works, others say it doesn’t. As a layperson, who should I believe?”

Great question. Here's the answer.

/1 To know whether a drug “works” or not, we need to test it.

How? By giving it to people and watching what happens to them.

We look for any benefits (the things we hope the drug does) as well as any side effects.

/2

In @AnnalsofIM, we report what appears to be a novel drug interaction: rosuvastatin toxicity precipitated by canagliflozin.

I’ll walk through the case and discuss suspected mechanisms.

acpjournals.org/doi/10.7326/L2…

/1 A 76-year-old woman presented to our hospital with new-onset muscle pain and impaired ambulation.

On exam she had severe muscle weakness. Labs revealed CK 13,262 and ALT 1017.

She was on rosuvastatin, and statin toxicity was the obvious diagnosis.

/2

This thread of drug-specific tips has generated a series of podcasts with @JAMA_current's Ed Livingston (@ehlJAMA). I'll append them here as they are released.

https://twitter.com/DavidJuurlink/status/1145489525751369732

First up: penicillin allergy edhub.ama-assn.org/jn-learning/au…

A colleague died this week. Todd Mainprize, our Division Head of Neurosurgery. I didn’t know him that well, but we crossed paths several times over the years. Since learning of his death, our last encounter has played out several times in my head. It was maybe a year ago and some of the details are fuzzy. The patient was admitted under me, and he was in the ED waiting for a bed on the ward. His brain MRI revealed a vascular abnormality so we got neurosurgery involved.

Some thoughts on the repurposing of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus infection. /1 How might CQ or HCQ help with COVID-19?

Potential mechanisms include:

- inhibiting viral replication
- ↑endosomal pH required for cell fusion
- ↓viral binding to target cells by impairing glycosylation of the ACE2 receptor
sciencedirect.com/science/articl… /2

With a crop of new interns hitting the wards tomorrow, here are ten (somewhat random) #TipsForNewDocs with a focus on drugs. Feel free to suggest others.

Thread —> 1. Most patients who report a penicillin allergy don’t actually have one. Rather than blanket avoidance, use the history to guide your approach. jamanetwork.com/journals/jama/… by @ericashenoy, @EricMacyMD et al.