💊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 🧵

💊Venlafaxine and blood pressure💊 A dose-dependent link between venlafaxine and elevations in blood pressure has been suggested by some studies. Additionally, case reports have implicated venlafaxine as the precipitating cause for hypertensive crisis in some individuals.

Exciting news! Due to pharma funding, ASPCP conference tickets are now just £30. 🎉 Open to everyone—members and non-members! A great opportunity to connect, network, and hear from top speakers. We appreciate your continued support! #ASPCP #PalliativeCare #Conference eventbrite.co.uk/e/aspcp-ann…

💥Prescribing cascade of the day💥 1. Patient started on regular ibuprofen leading to gastritis (with nausea) and iron deficiency anaemia. 2. Commenced on regular metoclopramide for nausea. Subsequently developed restless leg syndrome (RLS), secondary to both metoclopramide and iron deficiency. 3. Later commenced on pramipexole for RLS. Developed aggressive / impulsive behaviours (likely impulse control disorder secondary to dopamine agonist pramipexole). 4. Afterwards, patient commenced on risperidone...... 😱

Gastrografin is the go-to water-soluble contrast for treating adhesive small bowel obstruction (ASBO). Each 100 mL has 10g sodium diatrizoate & 66g meglumine diatrizoate (osmolarity: 2150 mOsm/L). It works by drawing water into the bowel, reducing edema, and boosting muscle contractions to relieve ASBO.

**Neuroendocrine effects of opioids** ➡️ Opioids impact the hypothalamic-pituitary-adrenal axis: leading to ↑ prolactin, ↓ sex hormones, rarely secondary adrenal insufficiency. ➡️ Opioid-induced hypogonadism can lead to sexual dysfunction, fatigue, depressed mood, bone loss and infertility. ➡️ Trials for testosterone replacement in male patients have shown mixed results. Some benefits for pain/emotional functioning, but no clear benefit for sleep, mood, or sexual/physical functioning. ➡️ VHA study: Testosterone treatment ↓ all-cause mortality, major adverse cardiovascular events, anemia, hip fractures in long-term male opioid users. ➡️ Clinical context matters: unclear relevance for cancer patients, but hypogonadism symptoms may affect quality of life. ➡️ Clinicians should assess testosterone levels in males and consider treatment if appropriate. ➡️ Limited data for female patients. ➡️ Postmenopausal symptoms and symptoms of fatigue, depressed mood, and sexual dysfunction should be assessed if clinically appropriate. ➡️If there is no contraindication to estradiol treatment, blood levels of sex hormones should be measured, and a trial of estrogen therapy should be considered if levels are low.

Duloxetine for Chemotherapy induced peripheral neuropathy (CIPN): ➡️ Initially proven effective in a double-blind trial with 231 patients. ➡️ Participants had painful CIPN, with pain scores >4/10 persisting for 3+ months. ➡️ Randomized to duloxetine (30 mg daily for 1 week, then 60 mg daily for 4 weeks) or placebo. ➡️ Pain scores measured weekly via Brief Pain Inventory, Short Form (BPI-SF). ➡️ Other endpoints: QOL assessed by FACT-GOG NTX and EORTC QLQ-C30, plus nonpainful symptoms. ➡️ After 5 weeks, a 2-week washout period occurred, followed by crossover to the alternate treatment. ➡️ Duloxetine group had a larger average decrease in pain score (1.06 vs. 0.34, p = 0.003). ➡️ Greater improvement in functional/QOL scores and reduced foot numbness/tingling (41% vs. 23%). ➡️ Well tolerated with no significant differences in toxicities. ➡️ More effective for oxaliplatin-induced than taxane-induced neuropathy. Additional small trials: ➡️ One trial: venlafaxine, duloxetine, or placebo for CIPN; duloxetine showed more reduction in neuropathy. ➡️ Japanese trial: duloxetine outperformed vitamin B12 in 34 patients. ➡️ Phase II trial: duloxetine was inferior to pregabalin in 80 patients with taxane-related CIPN. Guidelines: 2020 ASCO: clinicians may offer duloxetine for CIPN. 2020 ESMO/EONS/EANO: recommend duloxetine for neuropathic pain. ☀️ Benefit is modest but notable ☀️

🤢🤮Opioid induced N&V🤮🤢 ➡️ Nausea often occurs with the start of opioid therapy but usually resolves quickly. ➡️ Persistent nausea is less frequent and may include other symptoms like dry mouth, reflux, anorexia, early satiety, and bloating. ➡️ Individual responses to opioids vary; one might tolerate oxycodone better than morphine and vice versa. ➡️ Opioids can cause nausea via: ✅chemoreceptor trigger zone, ✅vestibular sensitivity, and ✅delayed gastric emptying. ✅Constipation, stool impaction, as well as taste and texture of chosen formulation may also cause or worsen symptoms. ➡️ Opioid rotation or changing administration routes (e.g., oral to subcutaneous) may help with persistent nausea. ➡️ Persistent nausea often responds well to antiemetics, the choice of which should be guided by the likely underlying mechanism by which the opioid has induced nausea and vomiting. Chemically mediated / CTZ = haloperidol; gastric stasis = prokinetic (domperidone or metoclopramide); vestibular sensitivity (cyclizine); constipation (laxatives); taste / palatability = change formulation)