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)ZQFSUFOTJPO Tanya Jayakar tanya.jayakar21@imperial.ac.uk8IBU▯XFsSF▯HPJOH▯UP▯DPWFS▯ • What is hypertension? • Why do I care? • QRISK & cardiovascular risk • What can I d? • CCB • ACEi • ARB • Thiazides • Treatment guidelines (NICE) • Pharmacokinetics • Pro-drugsHypertension???8IP▯IBT▯IZQFSUFOTJPO A. Lucy measured her blood pressure at home once as 149/85 B. Kamal’s blood pressure was 162/92 at the GP , but 134/78 average with ABPM C. Niamh’s NP was 138/121 when measured by the nurse in clinic D. Kal has been measuring his blood pressure twice daily at home and it was around 118/848IP▯IBT▯IZQFSUFOTJPO A. Lucy measured her blood pressure at home once as 149/85 B. Kamal’s blood pressure was 162/92 at the GP , but 134/78 average with ABPM C. Niamh’s BP was 138/121 when measured by the nurse in clinic D. Kal has been measuring his blood pressure twice daily at home and it was around 118/84Hypertension: so what?8IFSF▯EP▯$$#T▯BDU▯GPS▯UIFJS▯BOUJ▯IZQFSUFOTJWF▯FGGFDU A. Kidneys B. Heart C. Vascular smooth muscle D. Brain8IFSF▯EP▯$$#T▯BDU▯GPS▯UIFJS▯BOUJ▯IZQFSUFOTJWF▯FGGFDU A. Kidneys B. Heart C. Vascular smooth muscle D. Brain$$#T Mechanism of action Amlodipine, felodipine Block L-type calcium channels, predominantly on vascular smooth muscle Dihydropyridine type calcium channel blockers Results in decrease in calcium influx and downstream demonstrate a higher degree of vascular selectivity inhibition of myosin light chain kinase and prevention of cross-bridge formation Resultant vasodilation reduces peripheral resistance Side effects • Ankle oedema • Constipation • Palpitations • Flushing/headache8IJDI▯PG▯UIF▯GPMMPXJOH▯TUBUFNFOUT▯JT▯DPSSFDU A. ARBs cause a dry cough B. Both ACEis and ARBs inhibit renin production C. ACEis prevent vasoconstriction while ARBs reduce aldosterone production D. Both ACEis and ARBs can cause hyperkalaemia8IJDI▯PG▯UIF▯GPMMPXJOH▯TUBUFNFOUT▯JT▯DPSSFDU A. ARBs cause a dry cough B. Both ACEis and ARBs inhibit renin production C. ACEis prevent vasoconstriction while ARBs reduce aldosterone production D. Both ACEis and ARBs can cause hyperkalaemia"$&J▯BOE▯"3# Mechanism of action ACE: Ramipril, Lisinopril, Perindopril ACEi-> prevents conversion of Ang I to Ang II ARB: Losartan, Irbesartan, Candesartan ARB-> non-competitive antagonists at AT1 receptor on kidneys and vasculature Most ACE inhibitors (not lisinopril) are prodrugs so require hepatic activation to have an effect eGFR and serum K+ must be regularly monitored when prescribing ACE inhibitors. Losartan and candesartan are also prodrugs. ARBs are not as effective antihypertensives as ACEi Side effects • Hypotension • Hyperkalaemia (care with K+ supplements or K+ sparing diuretics) • Foetal injury (avoid in pregnant women) • Renal failure (in renal artery stenosis patients) • Urticaria (hives)/angioedema (swelling under skin) • ACEi: cough due to bradykininACE is involved in breakdown of bradykinin. ACEi cause accumulation of bradykinin and prostaglandins which stimulate cough receptors8IJDI▯PG▯UIF▯GPMMPXJOH▯TUBUFNFOUT▯JT▯DPSSFDU A. Thiazides have a long lasting diuretic effect B. Thiazides act in the proximal convoluted tubule C. Thiazides cause more dilute urine production D. Thiazides cause increased Cl- excretion in the urine8IJDI▯PG▯UIF▯GPMMPXJOH▯TUBUFNFOUT▯JT▯DPSSFDU A. Thiazides have a long lasting diuretic effect B. Thiazides act in the proximal convoluted tubule C. Thiazides cause more dilute urine production D. Thiazides cause increased Cl- excretion in the urine5IJB[JEFT Mechanism of action Bendro-flumethiazide (thiazide) Block Na+ Cl- cotransporter in early DCT Indapamide (thiazide-like) Ø Na+ and Cl- reabsorption inhibited Ø Osmolarity of tubular fluid increases, decreasing Lose diuretic effects in 1-2 weeks of treatment the osmotic gradient for water reabsorption in Continuing antihypertensive action appears to be due collecting duct to vasodilating properties (more pronounced for thiazide-like diuretics) Side effects Hypokalaemia Hyponatraemia Metabolic alkalosis (increased H+ excretion) Hypercalcaemia Hyperglycaemia (hyperpolarised pancreatic beta cells) Hyperuricaemia8IJDI▯PG▯UIF▯GPMMPXJOH▯DPSSFDUMZ▯NBUDIFT▯UIF▯ ESVH▯UP▯UIF▯TUBHF▯▯▯IZQFSUFOTJPO▯QBUJFOU A. Muhammad is 45, of Middle Eastern origin and has T2DM; ACEi B. Calorine is 35, of British Asian origin and has no comorbidities; CCB C. James is 65, an Irish Traveller and has no comorbidities; ARB D. Harmony is 73, of Afro-Carribean origin and has T2DM; Thiazide8IJDI▯PG▯UIF▯GPMMPXJOH▯DPSSFDUMZ▯NBUDIFT▯UIF▯ ESVH▯UP▯UIF▯TUBHF▯▯▯IZQFSUFOTJPO▯QBUJFOU A. Muhammad is 45, of Middle Eastern origin and has T2DM; ACEi B. Calorine is 35, of British Asian origin and has no comorbidities; CCB C. James is 65, an Irish Traveller and has no comorbidities; ARB D. Harmony is 73, of Afro-Carribean origin and has T2DM; Thiazide)PX▯UP▯BQQSPBDI▯B▯)5/▯QSFTDSJCJOH▯2 1. Do they have T2DM? -> YES: ARB (Afro-Caribbean) or ACEi 2. Are they of Afro-Caribbean origin? -> YES: CCB 3. Are they over 55? -> YES: CCB 4. NO: ACEi 5. If they’re already medicated: add whatever they don’t have NO THIAZIDES FOR DIABETICS1IBSNBDPLJOFUJDT8IJDI▯PG▯UIF▯GPMMPXJOH▯DBO▯CF▯EFEVDFE▯GSPN▯ UIF▯UBCMF A. A day after taking the tablet, there is no felodipine left in the body B. It could be appropriate to take a dose of amlodipine every 2 days C. After 12 hours, no amlodipine is detectable in the plasma D. The kidneys remove 11mL/min/kg of amlodipine from the plasma8IJDI▯PG▯UIF▯GPMMPXJOH▯DBO▯CF▯EFEVDFE▯GSPN▯ UIF▯UBCMF A. A day after taking the tablet, there is no felodipine left in the body B. It could be appropriate to take a dose of amlodipine every 2 days C. After 12 hours, no amlodipine is detectable in the plasma D. The kidneys remove 11mL/min/kg of amlodipine from the plasma1SP▯ESVHT Ramipril (&most ACEis) Lisinopril5)"/,▯:06▯ Please fill in the Feedback form! Name: T anya Jayakar Email: tvj21@ic.ac.uk tion=imperial-pharmacology-ning/feedback/anonymous?organisa society&keyword=ecdb6d067f045960da2d5b4bHypertension •Angiotensin converting enzyme inhibitors (Ramipril, Lisinopril, Perindopril) •Calcium channel blockers (Amlodipine, Felodipine) •Thiazide or thiazide-like diuretics (Bendro-flumethiazide (thiazide), Indapamide (thiazide-like)) •Angiotensin receptor blockers (Losartan, Irbesartan, Candesartan)