💊 Haloperidol PK fact:
Lipophilic, distributes widely into brain & fat
Brain conc. = 10–30× higher than serum
Serum t½: ~15–30h
Brain t½: ~6.8 days
👉 Even weeks after stopping, brain levels may remain clinically relevant.
#PalliativeCare #MedEd #Pharmacology
💊FLIP-FLOP KINETICS📉
Have you ever wondered why immediate-release opioids reach steady state quickly, but modified-release formulations can take 2–3 days?
The answer lies in a fascinating pharmacokinetic phenomenon called flip-flop kinetics.
Let’s unpack it simply, using opioids as our guide
🧵
Visual representation:
=== 🔄 A Simple Analogy===
IR opioids = Drinking juice straight from a glass 🥤 — quick in, then slowly processed (comaparatively)
MR opioids = Drinking through a thin straw 🧃 — the body’s ready to process, but has to wait for it to arrive.
===🔍 Clinical Implications===
Don’t assume a long half-life = slow clearance — it could just be slow absorption.
Be cautious as kinetics may differ depending on formulation (IR v MR).
The time to reach steady state is delayed,
Often taking 2–3 days with modified-release opioids.
But because it's entering more slowly, the absorption becomes the rate limiting step — not elimination (see graph below)
This is flip-flop kinetics → where the usual roles are reversed
Here, the terminal half-life seen on the graph reflects absorption, not elimination. That’s why:
=== Modified-Release (MR) Opioids: Flip-Flop Kinetics ===
Now, consider sustained-release morphine or oxycodone.
The MR formulation slows the rate of absorption dramatically
Once the drug enters the bloodstream, it's now cleared comparatively quicker to the rate of absorption
As a result:
Steady state is reached in 4–5 elimination half-lives
Which may be as little as a day or less for some IR opioids
The terminal elimination phase of the plasma concentration-time graph reflects elimination
This is standard pharmacokinetics — absorption is fast, so elimination becomes the rate-limiting step (see graph below)
===Immediate-Release (IR)
Opioids: Standard Kinetics===
When you give a patient IR morphine the drug is absorbed quickly from the gut
The body eliminates it comparatively slower than the time taken for absorption
💊FLIP-FLOP KINETICS📉
Have you ever wondered why immediate-release opioids reach steady state quickly, but modified-release formulations can take 2–3 days?
The answer lies in a fascinating pharmacokinetic phenomenon called flip-flop kinetics.
Let’s unpack it simply, using opioids as our guide
🧵
💊 Haloperidol PK fact:
Lipophilic, distributes widely into brain & fat
Brain conc. = 10–30× higher than serum
Serum t½: ~15–30h
Brain t½: ~6.8 days
👉 Even weeks after stopping, brain levels may remain clinically relevant.
#PalliativeCare #MedEd #Pharmacology
Thanks to that open imidazole ring at low pH, it can be made into a stable injectable solution.
Most other benzos (diazepam, lorazepam) are poorly water soluble and need organic solvents like propylene glycol → which cause venous irritation. Midazolam avoids that.
In acidic environments (like in the injection solution), the ring is protonated → water-soluble → stable for IV prep.
At physiological pH, the ring closes → lipophilic → rapid CNS penetration → quick onset of action.
💡 Midazolam is actually water-soluble in its vial, but becomes lipid-soluble once it enters the body.
That’s unusual for a benzodiazepine. The trick lies in its imidazole ring 👇
💊💊ALFENTANIL💊💊
Alfentanil’s pKa ~6.5, much lower than fentanyl (~8.4) or morphine (~8.0)
At physiologic pH (7.4), ~90% of alfentanil exists in the unionised, lipid-soluble form → crosses the blood–brain barrier very rapidly
This explains why alfentanil has the fastest onset of action of any opioid
Oxford Case Histories Palliative Medicine - Google Books https://search.app/3WbLiPnPEdhSDvjR8
🎉 Excited to announce our new textbook, Oxford case histories in palliative medicine! 🎉
Dive into comprehensive insights and practical approaches to enhance patient care. Thank you to everyone who contributed 👏
📚 #PalliativeCare
Edited by palliative medicine physician Dr Jonathan Pickard, and consultant pharmacist Mr Jonathan Hindmarsh, 54 expert authors provide “diagnostic skills and clinical reasoning that helps temper knowledge and understanding with pragmatism and practicality in the face of life-limiting illness.”
It’s finally here! @oxfordunipress.bsky.social Oxford Case Histories in Palliative Medicine “guides medical professionals and trainees through 52 cases curated to illustrate the varied and often complex landscape of palliative medicine.”
oxford.ly/4hG4C9B
Psychostimulants and depression in palliative care:
A short thread 🧵
When prescribing dexamethasone, remember enzyme inducers, such as carbamazepine and phenytoin, can significantly reduce its serum levels. In some cases dexamethasone doses may need to be increased 2 - 4 fold! Particular caution needed in high risk indications such as MSCC!
When prescribing dexamethasone, remember enzyme inducers, such as carbamazepine and phenytoin, can significantly reduce its serum levels. In some cases dexamethasone doses may need to be increased 2 - 4 fold! Particular caution needed in high risk indications such as MSCC!
An option for bowel obstruction?
It’s still surreal to see our textbook available for preorder! 📚 Thank you to everyone who contributed. Excited to share this work and knowledge. #newbook #academia #palliativecare
They may cause agitation, psychosis, delirium hallucinations, insomnia (can be minimized by taking dose ≥ 8 hours before bed) and cardiac decompensation (in elderly patients with CV disease)
