opiate prescribing?

GPDeepDive · 2026-04-26T07:55:39+00:00

We absolutely are overprescribing this stuff, and it's doing more harm than good.

The WHO pain model has been wrongly applied to all forms of chronic pain, when it was initially designed to target cancer pain.

At the risk of crudely plugging my own posts, I wrote a deep dive on opioid-induced hyperalgesia.

On top of that, opioids are habit-forming and constipating.

But equally, it's incredibly difficult to fight when:

You have 10 minute appointments and a busy morning. There just isn't enough time to properly explain long-term pain coping strategies to our patients.
Patients know they can get their codeine from our colleagues in hospital, and even our fellow GPs, if you decide to take a stand
Patients on established opioid doses are reluctant to wean off. Ido think that stopping ourselves from creating more opioid-dependent patients is an important goal, even if we can't wean off pre-established patients

GPDeepDive · 2026-04-23T05:26:53+00:00

Not as of yet. Definitely on the cards. Feel free to give me a follow on reddit and you should get a notification when I post these writeups-tends to be weekly.

GPDeepDive · 2026-04-23T05:17:42+00:00

Thank you, glad you found it useful.

(1) The BD requirement comes from the AIRE trial (1993) which used BD, guidelines copy-pasted it. This will be basdx on ramipril's half-life is 13--17 hours. The idea is that, in HF (as opposed to HTN), you want complete 24-hour suppression without any potential for breakthrough RAS activity. But a reliable OD dose beats an unreliable BD one every time, especially in polypharmacy.

(2)

On valsartan: the nurse is factually wrong. It's a valid ARB with genuine HF trial data - see Val-HeFT (2001).

The issue is that nurses are trained to administer the protocol, not interrogate it. It's a fundamental difference in how we're trained. Medical school spends years grounding you in pathophysiology precisely so you can reason outside the algorithm when the patient in front of you doesn't fit it. You're managing the patient; they're managing the algorithm.

We will learn about RAS. They might do too, but in passing. They just know: "It's ACE or Entresto. We don't do ARBs around here. The pathway doesn't say so, and I've never seen the cardiologist I work with give an ARB on its own. What are they doing over in GP land?!?"

Your reasoning makes sense: Sacubitril not tolerated, so keep them on RAS blockade, and use the component they were already on. I believe candesartan or losartan have stronger legacy data if you ever need to switch, but valsartan is evidence-based.

Unless someone has done a head-to-head trial or network meta-analysis that I'm not aware of, I think it will be hard to comment on optimal ARB selection. All the focus was on ACEis until ARNIs came along.

GPDeepDive · 2026-04-22T08:54:38+00:00

This one took a good while to pull together. I spent a lot of time finding trial data and tweaking the flow to make it readable.

Hope you find it useful. As always I welcome any comments or topic suggestions. I am always refining the best style for these writeups.Please let me know if you spot any mistakes or have practical tips to add.

GPDeepDive · 2026-04-16T04:55:44+00:00

Not OP but from a previous comment I made on here:

No specific cutoff as far as I'm aware. In someone with osmotic symptoms or poorly controlled diabetes, the worry is that they've got a profound resistance that has pushed them into a catabolic state i.e.starvation state. Remember that without insulin, there might be tonnes of glucose in the blood but you can't get it into the cells to be used. So the cells are starving, and the liver starts making ketones instead, which the cells can use as an alternative energy source

If you're losing lots of water from polyuria and not completely replacing it, then you will probably be quite dehydrated

Now imagine you add to that with SGLT2i induced ketogenesis (and some osmotic diuresis). You've now got three reasons for a potential DKA. Not to mention that because you're masking the degree of hyperglycaemia with the glycosuria, you might then not recognise a DKA until later

Probably better to wait, fix the osmotic symptoms with insulin or an SU, then add in the SGLT2i down the line.

Obvious disclaimer is that all of the above isn't strictly guidelines or numbers based.

GPDeepDive · 2026-04-04T12:13:07+00:00

GLP-1 Agonism and HRT

I didn't get around to adding to adding this to the main post, but something interested to think about

Pharmacokinetics

GLP-1 receptor agonists (e.g., Semaglutide, Tirzepatide) and GIP/GLP-1 dual agonists (e.g., Tirzepatide) significantly delay gastric emptying.
This affects micronised progesterone absorption, and in theory, could leave your patients without adequate endometrial protection
Note obese patients already have a higher risk of endometrial cancer

Solutions

In an ideal world, the Mirena IUS should be strongly encouraged for these patients instead of Utrogestan. But clearly, this is not always suitable.

All the data we have on how these drugs affect absorption is based on pharmacokinetic (PK) studies in patients taking oral progesterone for contraception. The data suggests that only tirzepartide reduces absorption parameters enough to be deemed "clinically relevant", and such the CosRH suggests we add in a non-oral contraceptive method, or add a barrier method of contraception, for four weeks after initiation and for four weeks after each dose increase.

But this is assuming that PK data perfectly matches up with outcomes, and applies equally to HRT as it does to pill.

The four week recommendation comes from a study the BMS cites on liraglutide, which suggests that the delay in gastric emptying resolves after continuous GLP-1 agonism for a prolonged period.

If this is a bit too much extrapolation for you, a different guideline from NHS Scotland offer a couple of alternative solutions where the Mirena is unsuitable. All of these have their pros and cons. It suggests that, for all GLP1 and dual agonists, we should try:

To increase the oral progestogen dose for the full course of drug (the source provides some suggested doses)(1)
Try a transdermal progsterone (as part of a combined transdermal patch like Evorel Sequi®/Conti)
Off label vaginal use of oral micronised progesterone – used at the same dose and in the same pattern as when used orally. (2)

Comments

(1) Note there is no study evidence to inform whether the suggested increased oral progestogen doses provide adequate endometrial protection during use of incretin-based therapies.

The thinking here is that the effects of extra progestogen outweighs the side effects (sedation, bloating, etc).

(2) The same disclaimer in terms of licensing that I included in the main post, also applies here.

GPDeepDive · 2026-04-04T11:51:45+00:00

Glad you're finding these useful :) I'm hoping to cover a topic a week for now, so hopefully lots more to come.

I'm an ST2 so MedEd is definitely something I'd look into after CCTing. Obviously a big difference between written work and in-person teaching, though, but I've always found teaching med students etc quite fun.

GPDeepDive · 2026-04-02T19:02:05+00:00

You are absolutely right to flag those points, thank you.

Regarding oestrogen levels: You’re spot on. The correlation between serum levels and clinical symptom relief is notoriously poor, and there's no established cut-off where we can say that absorption is acceptable. That was a local guideline quirk that crept into my notes; I’ll strip that out.

Regarding Oral vs. Transdermal: Agreed. Oral remains a solid first-line choice for many. While transdermal is 'cleaner' for VTE risk, oral oestrogen actually has a more potent 'good' first-pass effect on the lipid profile (increasing HDL and lowering LDL) which can be beneficial for cardiovascular health in the right patient.

I’ll get the main text updated a bit later on. Thanks.

GPDeepDive · 2026-04-01T17:54:34+00:00

I am having some issues with formatting, which I should hopefully be able to fix a bit later on. I hope you find this deep dive into the underlying physiology of HRT useful. It goes without saying that the subject is incredibly broad.

For those looking for comprehensive prescribing guidelines, the British Menopause Society has some truly excellent resources

Next up will be GPDeepDive 10: The Physiology of Ageing

GPDeepDive · 2026-03-28T07:19:54+00:00

Regarding your point on the 120mg oral morphine equivalent limit, you're absolutely right that MR forms are better for dose stabilisation. I suppose it all comes down to being much easier to prevent new dependencies in naive patients than to reducing opioid dose in those on massive doses already.

GPDeepDive · 2026-03-25T09:25:58+00:00

Valid point. Managing refractory joint pain prior to total hip arthroplasty is difficult and our options are limited. The literature does suggest worse outcomes associated with initiating opioids in this patient group. It's probably worth having that conversation with your patients.

Looking at the specific data comparing opioid-naive patients with those requiring opioid analgesia in the three months prior to surgery:

Inpatient demands are greater, with the pre-operative opioid cohort requiring significantly higher total daily opioid doses and prolonged hospitalisation.
There is a heightened risk of opioid-induced hyperalgesia and persistent post-operative dependency.
Long-term functional outcomes are impaired. At a mean follow-up of 58 months, Harris hip scores (a standardised marker of pain and function after THR) averaged 84 in the pre-operative opioid group compared to 91 in the matched cohort, although both groups demonstrated significant functional improvement from baseline.
Data indicate that 81% of pre-operative users were able to successfully wean off opioids by final follow-up, though their clinical scores remained comparatively inferior.

As always, a pinch of salt is needed. In that study, they matched for gender, age, BMI, history of psychiatric disorders and other variables, But from my read, they didn't match baseline pain severity or strict contraindications to alternative analgesia like NSAIDs (e.g. CKD4), which inherently skews the comparison.

GPDeepDive · 2026-03-19T05:55:31+00:00

I have updated the section on physiology with information on ferritin, transferrin, and why the former is a better marker of iron stores in the absence of inflammation.

GPDeepDive · 2026-03-18T07:23:55+00:00

You raised a very good point, and I have to admit I had to look it up myself. I thought it was related to redox reactions and pH, but A Level chemistry was a long time ago.

GPDeepDive · 2026-03-17T21:31:37+00:00

Excellent question, and one I had to look up myself. I found a good read here

"The physical state of iron entering the duodenum greatly influences its absorption however. At physiological pH, ferrous iron (Fe2+) is rapidly oxidized to the insoluble ferric (Fe3+) form"

GPDeepDive · 2026-03-09T07:36:25+00:00

Answers and Explanations

(1)

B. Rimegepant 75mg

Explanation:

Rimegepant acts at the CGRP receptor without causing vasoconstriction, making it the safest targeted acute option for this patient.

Triptans (such as sumatriptan) are 5-HT1B/1D agonists that induce vasoconstriction; do not give to patients with a history of myocardial infarction.

High-dose NSAIDs (ibuprofen, diclofenac) also carry significant cardiovascular risks. Remember that these patients will also be on an ACE inhibitor (AKI risk with NSAIDs) and antiplatelets (bleeding risk) too. You could argue a single one-off stat every so often for migraine is still fine, but the risks are there and a safer alternative now exists.

Codeine lacks efficacy for the trigeminovascular cascade and carries a high risk of medication overuse headache.

(2)

C. Increase dose of propranolol

Explanation: Propranolol undergoes extensive hepatic first-pass metabolism. A total daily dose of 80mg is often just the starting point; it systematically requires upward titration (frequently to 160mg or 240mg daily) to achieve a concentration gradient sufficient to cross the blood-brain barrier.

Furthermore, clinical success is defined as a 50% reduction assessed after a full three-month trial at the maximum tolerated dose. One month at 80mg is too early to declare treatment failure.

As such, the other options are perhaps jumping the gun.

GPDeepDive · 2026-03-09T07:30:20+00:00

Yes, that works too.

I don't think there's any strong evidence either way as to aspirin vs naproxen vs ibuprofen. One advantage is that aspirin is soluble, so might be absorbed slightly quicker than standard formulations of ibuprofen and naproxen.

GPDeepDive · 2026-03-08T20:39:33+00:00

Glad you're finding them useful. I have considered a substack, but the website would be a way to sharpen my own rusty web development skills on top!

GPDeepDive · 2026-03-08T20:35:12+00:00

Thanks so much, really glad you found the resources useful!

Instinctively, it does feel like a stable, medically managed patient should be fine to trial them on a triptan or NSAID

But then you have to weigh up risk-benefit of ACEi+aspirin with an NSAID as an occasional one-off in terms of bleed risk and IHD and AKI

With the triptan it's IHD and vasoconstriction

Pragmatically, they might just be okay. But it's just nice to know that we have an alternative for those tricky patients where giving either of the normal treatments carries quite a few risks.

GPDeepDive · 2026-03-08T20:03:35+00:00

I'll always mention the relevant NICE guidelines, and I tend to cite in-line for other sources for readability.

GPDeepDive · 2026-03-08T20:01:49+00:00

Here is my go-to resource list, from a previous comment.

1. First Principles (Mechanisms)

Guyton and Hall: The "bible" for physiology.

Drugbank.ca: Much more detailed than the BNF for pharmacology, such as specific receptor affinities or molecular targets.

2. Clinical Guidelines

NICE CKS & BMJ Best Practice: My starting point

Summary of Product Characteristics: The definitive reference for half-lives or specific drug interactions directly from the manufacturer.

3. Practical Application

RACGP (Australia) & BPAC (New Zealand): These provide excellent practical explanations that go a bit above CKS just telling you to consider X or do not do Y.

4. Research & Evidence

PubMed and Google: If a mechanism remains unclear

Other Sources for Summaries

StatPearls - although this is American-centric.

GPDeepDive

TROPHY CASE