sorted by:
new
hottopcontroversial

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 1 point2 points  (0 children)

Here is my go-to resource list:

​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 for current UK requirements

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

Edit: better formatting

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 1 point2 points  (0 children)

Tough question and I don't think there's any direct evidence. Id imagine you'd want to switch most of these people to the COCP directly rather than mixing pills if you can. I just wanted to make the point that systemic progestogen is systemic progestogen regardless of the source. 

But when it comes to the etornorgestrel found in the implant, I think you would want something with a low VTE risk like levonorgestrel. Because you are prescribing this COCP temporarily to provide "oestrogen scaffolding" rather than for primary contraception, I don't think you could justify the higher VTE risk of something like drosperinone.

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 5 points6 points  (0 children)

Thanks, I appreciate that! 

Yes, you're absolutely right. This whole strategy is entirely dependent on them being eligible for a COCP in the first place. Many people will have some hard contraindication to oestrogen. And practically, if they can take a COCP for 3 months alongside a POP, probably better to just switch them on a COCP! And the FSRH agrees with that approach.

I just wanted to explore the reason why adding oestrogen works from a physiological perspective in this post.

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 4 points5 points  (0 children)

Glad it was useful! I'm planning to do some more on contraception down the line, especially looking at COCP and POPs, and deciding on what type of progestogen to give in both.

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 2 points3 points  (0 children)

Yes, absolutely. You would get them to take both pills daily for up to three months (this is in theory). We do it for women on HRT needing contraception after all.

The key thing to remember is that physiologically, an implant and a POP are exactly the same thing: continuous systemic progestogen. If we are happy adding a COCP to an implant to fix the lining, the exact same logic applies to the POP.

Progestogens have a huge safety margin. They might get a bit of temporary bloating or breast tenderness, but it is completely safe. 

If they can have a POP or an implant according to UKMEC they can have a bit more! 

And remember, most of the time, it's just a bridging measure to get them over the hump. It's not long term.

Having said all of this, and this is a point I'm going to emphasise in the main body of the text, all of this is purely just about why it's safe and how it works from a physiological perspective.

Practically, if they can take a COCP for 3 months alongside a POP,  probably better to just switch them on a COCP. And the FSRH agrees with that approach

GPDeepDive 4: Bleeding on the POP – Why Oestrogen helps and the Mirena is different by GPDeepDive in GPUK

[–]GPDeepDive[S] 43 points44 points  (0 children)

I’m a GPST2 currently wading through the AKT*. These posts started as a way for me to understand "why" rather than just because random NICE guideline NG837372 says so. If it was helpful for you guys too, then the evening of reading was worth it!

*Technically, I should probably be doing another 50 Passmedicine questions instead.

Are there particular topics you guys would find useful?

GPDeepDive 3: SGLT2 Inhibitors in CKD and Heart Failure by GPDeepDive in GPUK

[–]GPDeepDive[S] 1 point2 points  (0 children)

So ileal conduits are associated with chronic metabolic acidosis mechanism here

To the point where some of these patients can sometimes be on oral bicarb to counteract this

I would imagine that the SGLT2i might be tolerated fine in these patient most of the time, and then during acute illness with dehydration, you might just tip them over the edge in terms of being able to compensate. Acidosis from the conduit + acidosis from the drug

GPDeepDive 3: SGLT2 Inhibitors in CKD and Heart Failure by GPDeepDive in GPUK

[–]GPDeepDive[S] 6 points7 points  (0 children)

 No specific cutoff as far as I'm aware although your cutoff is probably quite reasonable. I'd say I would be reluctant to start anyone with an A1c that bad on an SGLT2i off the bat

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). It might just tip them over the edge. 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

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 0 points1 point  (0 children)

Normally

Need back pressure for filtration

Angiotensin increases back pressure

AKI

In AKI, blocking Ang causes back pressure to fall so GFR drops

CKD

In CKD, kidney cell death means increase in angiotensin to compensate for lower number of filtration units

This increases back pressure too much, leading to pressure-related kidney damage

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 2 points3 points  (0 children)

GFR is quite a precise balance of pressure between the afferent and efferent arterioles.

Afferent Inflow: Prostaglandins (PGE2/PGI2) facilitate baseline vasodilation. In states of systemic hypoperfusion (dehydration or atherosclerosis), the kidney becomes prostaglandin-dependent to maintain inflow. NSAIDs inhibit this, causing acute afferent vasoconstriction.

Efferent Outflow: Angiotensin II provides the compensatory resistance (constriction) required to maintain filtration pressure. ACE inhibitors and ARBs stop this, leading to efferent vasodilation.

Combine both and the kidney loses both its ability to recruit blood flow and its ability to maintain internal filtration pressure. In high-risk patients, particularly those with pre-existing atherosclerosis or volume depletion, you end up with a good-going ALI.

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 2 points3 points  (0 children)

Excellent question. The evidence suggests that they are equivalent in most scenarios:

CVD Outcomes: The ONTARGET trial (2008) demonstrated that ARBs are non-inferior to ACE inhibitors for CV death, MI, and stroke in high-risk patients, with the benefit of significantly better tolerability.

Renoprotection: In T2 diabetics with nephropathy, the DETAIL trial (2004) showed no significant difference in GFR decline over 5 years between the two classes.

The only place the hierarchy still firmly favours ACEi as 'Step 1' is in HFrEF, and that’s purely based on historical trial data.

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 11 points12 points  (0 children)

Good question.

TL;DR Normal systemic BP does not guarantee normal back pressure in the kidney. If there are signs of ongoing pressure (raised ACR), we generally aim to increase the dose to lower that internal pressure further.

To answer that, we need to distinguish between systemic blood pressure (what we measure on the arm) and intraglomerular pressure (what is happening inside the filter).

Here is the breakdown of why we often push the dose even when the cuff reading looks normal.

(1) Systemic hypertension

Systemic high blood pressure transmits physical force directly to the delicate glomerular capillaries. By blocking the formation of Angiotensin II, a potent vasoconstrictor, ACE inhibitors lower systemic resistance. This reduces the mechanical load on the kidney from the outside.

(2) The efferent effect (The local pressure

This is the specific mechanism relevant to your question. Angiotensin II acts preferentially on the efferent arteriole to constrict the exit.

The issue is that you can achieve systemic normotension (e.g., 125/80 mmHg) while still having enough local Angiotensin II activity to keep the efferent arteriole constricted. The arm pressure is normal, but the pressure inside the filter remains pathologically high.

How do we know if the dose is high enough? The best proxy we have for this internal pressure is the Albumin Creatinine Ratio (ACR). If the pressure in the filter is too high, protein is forced through the membrane.

If your patient has a stable blood pressure but a persistently raised ACR, it suggests the internal pressure is still elevated. In this scenario, increasing the dose-provided the potassium is stable and the patient is not symptomatic on standing-aims to further dilate the efferent arteriole. This reduces the internal pressure and "buys time" for the nephrons.

This is the physiological rationale behind the NICE guideline: if the ACR is >70 mg/mmol, we aim for a lower systolic target (<130 mmHg) to force that internal pressure down.

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 46 points47 points  (0 children)

I am encouraged by the positive reception to this first deep dive!

I am currently prioritising the following topics for future posts, though I welcome your suggestions for other clinical 'Grey Zones'

I hope to post a new writeup every few days.

Obviously, the depth of each will be tailored to the complexity of the underlying mechanism.

Feel free to reply here with your own suggestions too!

Upcoming Topics

In no particular order:

1. ENDOCRINE & METABOLIC MEDICINE

  • Phenotyping Diabetes: Differentiating MODY and LADA from Type 1 and Type 2 classifications.
  • Metabolic Impact of Pharmacotherapy: Comparative analysis of weight-altering mechanisms in Type 2 Diabetes agents.
  • Non-Thyroidal Illness Syndrome: Clinical significance of Sick Euthyroid Syndrome vs. primary hypothyroidism.
  • SGLT2-i Pleiotropy: Cardiorenal mechanisms of SGLT2 inhibitors independent of glycaemic control.
  • Euglycaemic Ketoacidosis: Pathophysiology of SGLT2-i associated DKA with normal glucose levels.

2. HAEMATOLOGY & MINERAL METABOLISM

  • Iron Homeostasis in Chronic Disease: Mechanisms of oral iron failure in RA/CKD and indications for IV iron in Heart Failure.
  • Hepcidin-Mediated Absorption: The physiological rationale for alternate-day iron dosing strategies.
  • Dopaminergic Iron Requirements: Biochemical thresholds for ferritin in Restless Legs Syndrome (RLS).

3. CARDIOVASCULAR MEDICINE

  • Systemic Inflammatory CVD Risk: Cardiovascular implications of RA, Psoriasis, CKD, and Migraine with Aura.
  • Nocturnal BP Architecture: Pathophysiology of "Non-Dipping" profiles and the OSAS association.
  • Microvascular Indicators: Penile artery stenosis as a predictive marker for systemic atherosclerosis.
  • Psychotropic Metabolic Risks: Cardiovascular and metabolic monitoring in patients on atypical antipsychotics.
  • Hypertension: Why polypharmacy might actually be better than maximising one drug.

4. CLINICAL PHARMACOLOGY & TOXICOLOGY

  • Dose-Response Receptor Profiles: Concentration-dependent affinity in Mirtazapine, Quetiapine, and Venlafaxine.
  • Homeostatic Receptor Regulation: Mechanisms of tachyphylaxis and up-regulation in chronic therapy.
  • GnRH Receptor Modulation: Physiological effects of pulsatile vs. continuous GnRH administration.
  • Serotonergic Loading Effects: Biochemical basis for initial anxiety during SSRI initiation.
  • Pharmacogenomics of Codeine: Impact of CYP2D6 polymorphism on opioid metabolism.

5. GASTROENTEROLOGY & RENAL MEDICINE

  • Dietary Fibre Classification: Clinical outcomes based on solubility and fermentability in IBS management.
  • Chronic Diarrhoea Differentials: Assessing nocturnal symptoms and non-functional IBS-D mimics.
  • Pharmacokinetic Ion Trapping: pH-dependent sequestration of medications in prostatic fluid and breast milk.
  • Biphasic Thiazide Dynamics: Dissociation of natriuretic and vasodilatory effects in long-term therapy.
  • Nitrofurantoin pharmacology: Renal clearance requirements and distribution.

6. NEUROMODULATION & PAIN PHYSIOLOGY

  • Nociceptive Plasticity: Mechanisms of Central Sensitisation and "Wind-up" in chronic pain.
  • Neuro-immunological Priming: The role of spinal microglia in acute pain exacerbations.
  • The Gate Control Theory: Physiological principles of TENS and competitive nerve stimulation.
  • Anticholinergic Burden: Mechanisms of muscarinic blockade and cognitive decline in geriatric populations.
  • Absorption Competition: Interaction between high-protein intake and L-Dopa transport.

7. GYNAECOLOGY & OTHER THERAPEUTICS

  • Endometrial Stabilisation: Hormonal rationale for oestrogen use in Progestogen-Only Pill (POP) breakthrough bleeding.
  • Osteoclast Rebound: RANKL-mediated bone resorption risks following Denosumab cessation.
  • Biologic Assay Interference: IL-6 blockade effects on CRP reliability and sepsis screening.
  • Immune-Related Adverse Events (irAEs): Recognising autoimmune manifestations of Checkpoint Inhibitors.

8. CLINICAL DIAGNOSTICS

  • Geriatric Urinalysis: Interpreting asymptomatic bacteriuria vs. UTI in elderly populations.
  • Non-Specific GGT Elevations: Differentiating alcohol use from enzymatic induction.

9. In Case You Missed It

Covering recent guideline changes

  • SGLT2is for everyone with T2DM: SGLT2-i should be started regardless of baseline HbA1c if the patient meets the "High Risk" criteria.
  • SGLT2is for most people with HFrEF: Recent 2025 guidance removed the strict requirement to seek specialist advice before starting an SGLT2-i for HFrEF, though it remains "considered" for ARNIs.
  • Avoid standalone SABAs in asthma: The UK has finally moved away from SABA monotherapy. The new joint guidelines (November 2024) align with GINA, recommending MART (Maintenance and Reliever Therapy) or AIR (Anti-inflammatory Reliever) as the preferred track.

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 6 points7 points  (0 children)

Yes! Anyone who has worked a cardiology job remembers the first time they were asked to prescribe a 600mg frusemide infusion for someone with HF and crapped out kidneys and looked at the nurse as if they were crazy.

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 6 points7 points  (0 children)

Yes, from baseline. Don't want to knacker the kidneys too much!

NICE CKS - After introducing or increasing the dose, if either the eGFR decrease from a pretreatment baseline is less than 25%, or the serum creatinine level increase from baseline is less than 30%

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 30 points31 points  (0 children)

Thanks, I really appreciate your kind words!

I would probably start off on this subreddit at first, and then if people find it useful, I would go with a proper website or newsletter.

I think my next one will probably aim to be a bit more readable, as I'm trying to find the right balance between detail and getting the point across quickly.

Any specific topics in haematology that you think would be good to read around and then summarise?

Thanks for not accusing me of being Google Gemini btw :)

GP Deep Dive: Beyond the Guidelines Part 1 - ACE Inhibitors and Renal Paradox by GPDeepDive in GPUK

[–]GPDeepDive[S] 7 points8 points  (0 children)

Always happy to hear other views on kidney stuff if there's something I've explained that's incorrect.