Antihypertensives Chad Byworth

Hypertension What is hypertension? Blood pressure of greater than 140 systolic or 90 diastolic, confirmed in primary care by ambulatory monitoring of > 135/85 What are the long-term complications of HTN? Renal FailureRetinopathy Coronary Artery DiseaseHeart Failure Stroke

RAAS

ACEi Ramipril, Lisinopril, Captopril Inhibit angiotensin converting enzyme, preventing conversion of angiotensin I to angiotensin II Side Effects Cough Angioedema Hyperkalaemia Contraindications Aliskiren Caution in renal artery stenosis & CKD

ARBs Losartan, Valsartan Block type 1 angiotensin II receptors reducing aldosterone secretion and inducing vasodilation Side Effects Hyperkalaemia Dizziness due to hypotension Contraindications Aliskiren Caution in renal artery stenosis & CKD

CCBs - Dihydropyridines Amlodipine, Nifedipine Block L-type calcium channels with selectivity for smooth muscle cells leading to vasodilation (also induce a mild natriuresis) Side Effects Headache Peripheral oedema Reflex tachycardia Contraindications Unstable angina Aortic stenosis Cardiogenic shock

α and β blockers Not used as first line antihypertensives. α-blockers Doxazosin Side Effects Postural hypotension Syncope Drowsiness Also used to treat BPH β-blockers Bisoprolol, Atenolol Side Effects Bradycardia Conduction abnormalities GI disturbance Contraindicated in asthma

Other antihypertensives These would be started under specialist advice: Hydralazine Highly specific arterial vasodilator Minoxidil Potassium channel agonist → smooth muscle relaxation Nitrates (GTN, Isosorbide, Sodium nitroprusside) Not used in the management of chronic hypertension but are used to treat hypertensive emergencies

Renal Physiology and Diuretics Harvey Davies

The Kidney  Functions of the Kidney  Excretion of waste  Reabsorption of vital nutrients  Acid-Base Homeostasis  Osmolality Regulation  Blood Pressure Regulation  Hormone Secretion  The kidney filters 180L per day, but only 1-2L of urine produced per day

The Nephron

Diuretics - MoA  Loop Diuretics  Inhibit Na + and Cl - reabsorption in the Loop of Henle by blocking Cl - binding site (NKCC)  Reduces the hypertonic renal medulla, leading to bulk water loss

Diuretics - MoA  Thiazide Diuretics  Inhibit Na + and Cl - reabsorption in the Distal Convoluted Tubule (NCC)  As water follows ionic gradient, water is lost too  Often used in conjunction with another diuretic

Diuretics - MoA  Potassium-Sparing Diuretics  Aldosterone Antagonists  Aldosterone normally adds sodium channels to principle cells of the collecting duct (through mineralocorticoid receptors)  Spironolactone prevents aldosterone from entering the principal cells, preventing sodium and water reabsorption  Epithelium Sodium Channel Blockers  Amiloride directly blocks the epithelial sodium channel (ENaC) thereby inhibiting sodium and water reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the kidneys

Diuretics - MoA

Management of Hypertension