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ACE Inhibitors

ACE Inhibitors. Charley Bruce. Plan. Indications Mechanism of action Side Effects Contraindications Metabolism Pharmacokinetics. Indications. Hypertension Heart Failure Diabetic Nephropathy Prophylaxis of Cardiovascular Events. Renin-Angiotensin-Aldosterone System. Hypertension.

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ACE Inhibitors

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  1. ACE Inhibitors Charley Bruce

  2. Plan • Indications • Mechanism of action • Side Effects • Contraindications • Metabolism • Pharmacokinetics

  3. Indications • Hypertension • Heart Failure • Diabetic Nephropathy • Prophylaxis of Cardiovascular Events

  4. Renin-Angiotensin-Aldosterone System

  5. Hypertension • Competitive inhibition of ACE • Reduced Angiotensin II production • Also… • ACE metabolises bradykinin • Brady kinin causes vasodilationtion • Less ACE = More bradykinin = Vasodilation

  6. Heart Failure • ACEi + B-blocker • Arterial and venous dilation • Improves peripheral haemodynamics • And therefore cardiac function • Improved survival, esp. if severe left vent. dysfunction

  7. Diabetic Nephropathy • Lowers systemic BP • Disturbed auto regulation of afferent • Reduces filtration fraction • Dilation of efferent arteriol • ?? Direct effect on glomerular permeability • Or reduced stretch? Diabetic nephropathy may be diffuse or nodular (Kimmelstiel-Wilson lesion). The early stages cause an elevated glomerular filtration rate with enlarged kidneys, but the principal feature of diabetic nephropathy is proteinuria. This develops insidiously, starting as intermittent microalbuminuria before progressing to constant proteinuria and occasionally nephrotic syndrome. Interesting article: Renoprotective Role of ACE Inhibitors in Diabetic Nephropathy… http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1025591/pdf/brheartj00006-0039.pdf

  8. Prophylaxis of cardiovascular events • Greater benefit if there is evidence of heart failure post MI • Mortality reduction of 25% over a year • Reduction in non-fatal reinfarction • Unknown mechanism

  9. Side Effects • First dose hypotension • Renal impairment • Dry cough • Angioedema • Hyperkalaemia

  10. Severe Hypotension • Postural hypotension • Diuretics • High dose loop = specialist supervision • First dose

  11. Renal impairment • Vasodilates efferent, lowers glomerular pressure • Reduces GFR • CONTRAINDICATED IN RENAL ARTERY STENOSIS • NSAIDs • Potassium-sparing diuretics

  12. Dry cough • 10-30% • More common in women • Can develop after months of treatment • Accumulation of bradykinins • Angiotensin II Receptor Antagonists can be given 2nd line.

  13. Hyperkalaemia • ACEi promotes K+ retention

  14. Contraindications • Hepatic impairment - metabolism • Renal impairment • Renal artery stenosis • Pregnancy • Breast feeding

  15. Metabolism and Pharmacokinetics • Usually a prodrug • Converted in the liver

  16. QUIZ!! • Where is ACE produced? • Why is there no reflex tachycardia?

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