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ACE inhibitors

Angiotensin Converting Enzyme (ACE) inhibitors: Mechanism of Action and Clinical Findings Angiotensin Converting Enzyme (ACE) Inhibitors Inhibits the conversion of angiotensin I to angiotensin IIà↓ serum angiotensin II levels Inhibits breakdown of bradykinin ↓ Activation of zona glomerulosa region of the adrenal cortex ↓ Aldosterone secretion from the adrenal cortex ↓ Expression of basolateral Na+/K+ pump and ↓ insertion of luminal Na+ channels in principal cells of the cortical collecting duct in kidney ↓ K+ secretion into urine ↑ Serum K+ concentration Hyperkalemia ↓ Activation of Na+/H+ exchanger in proximal convoluted tubule (PCT) of the kidney ↓ Na+ absorption into PCT and ↓ H+ excretion into lumen ↓ Na+ absorption into the blood ↓ Renal H2O reabsorption via osmosis ↓ Activation of paraventricular nuclei located in the hypothalamus ↓ Secretion of anti- diuretic hormone (ADH) into the capillaries of the posterior pituitary gland ↓ Aquaporin channel insertion at cortical collecting duct in kidney ↓ Renal H2O reabsorption à↑ serum bradykinin levels Vasodilation of efferent arteriole in kidneys ↓ Hydrostatic pressure within the glomerular capillaries ↑ Activation of cyclooxygenase-2 pathway ↑ Prostaglandin production ↓ Activation of angiotensin II type 1 receptors on surface of arteriolar smooth muscle ↓ Activity of G protein-coupled receptor intracellular secondary messenger cascade ↓ Systemic arteriolar vasoconstriction ↓ Total peripheral resistance (resistance to blood flow by systemic vasculature) ↓ Blood Pressure ↓ total blood flow perfusing kidneys Renal hypoxia ↑ Systemic arteriolar vasodilation ↓ Total peripheral resistance ↓ Blood Pressure ↓ Concentration of protein travelling through tubules for excretion ↓ Fraction of H2O filtered from glomerular capillaries into bowman’s capsule (start of the renal tubule) ↓ Filtration of blood contents through glomerular membranes Sensitization of airway vagal afferent receptors Stimulation of the cough center located in the medulla oblongata Cough ↓ Protein in urine High K+ levels surrounding the heart muscle cellsàchronic depolarization of the cardiomyocyte cell membrane àalters cardiomyocyte conduction (complex mechanisms) Cardiac Arrythmias (see relevant slide on Hyperkalemia: Clinical Findings) ↓ Effective arterial blood volume Authors: Nicole Brockman Reviewers: Emily Wildman, Austin Laing Adam Bass*, Yan Yu* * MD at time of publication Renal tubules have relatively less water compared with the peritubular capillaries ↓ H2O reabsorption from the renal tubule back into the blood ↑ Serum creatinine, ↓ estimated glomerular filtration rate Renal nephron injury and dysfunction Acute Kidney Injury (rise in creatinine >26.5umol/L in <7 days) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 10, 2022 on www.thecalgaryguide.com

Angiotensin Converting Enzyme (ACE) inhibitors: Mekanisme Kerja dan Temuan Klinis

Angiotensin Converting Enzyme (ACE) inhibitors: Mekanisme Kerja dan Temuan Klinis