Renal Pharmacology: Diuretics PDF

11/6/24 Renal Pharmacology: Diuretics Kelly Elmore, DNP, APRN-CRNA Mary Baldwin University NAP Advanced Pharmacology for Anesthesiology Practice I Spring Semester 1 Renal Anatomy & Physiology Review 2 Renal Functions Formation, co...

11/6/24 Renal Pharmacology: Diuretics Kelly Elmore, DNP, APRN-CRNA Mary Baldwin University NAP Advanced Pharmacology for Anesthesiology Practice I Spring Semester 1 Renal Anatomy & Physiology Review 2 Renal Functions Formation, concentration & dilution of urine Fluid & electrolyte homeostasis ○ Osmolarity ○ Plasma, ECF volumes Acid-base balance 3 1  11/6/24 Renal Functions Clearance ○ Removal from systemic circulation ○ Elimination of toxins and metabolites Hormone production ○ Renin ○ __________________________________________ ○ Vitamin D3 4 Basic (Internal) Renal Anatomy https://www.nursingtimes.net/clinical-archive/renal/renal-system-1-the-anatomy-and-physiology-of-the-kidneys-23-01-2023/ 5 https://nurseslabs.com/urinary-system/ https://thecomicalanatomist.com/category/urinarysystem/kidney_anatomy/renal- corpuscle/ 6 2  11/6/24 Basic Renal Tubular Anatomy https://courses.lumenlearning.com/suny-dutchess-ap1/chapter/nephrons-structure/ 7 Regulation of Renal Blood Flow ~25% of cardiac output per minute ○ Renal artery → lobar, interlobar arteries → arcuate, interlobular arteries ○ Afferent & efferent arterioles (= capillary beds) ○ Interlobular, arcuate veins → interlobar, lobar veins → renal veins 8 Regulation of Renal Blood Flow Autoregulation ○ RBF maintained between _____________________________ mmHg ○ Direct relationship between RBF and glomerular filtration ○ Below MAP 50, filtration ceases ○ Myogenic mechanisms ○ Override of SNS 9 3  11/6/24 Hormonal Influence Aldosterone ○ Distal reabsorption of Na+, H2O ○ Distal secretion of K+** Antidiuretic hormone ○ Increases distal tubular & collecting duct permeability to H2O ○ Vasoconstrictor 10 Hormonal Influence Renin/Angiotensin ○ Conversion to angiotensin II causes vasoconstriction ○ Reabsorption NaCl, H2O ○ Secretion of K+ ○ Aldosterone release ○ ADH release 11 MemoryMaster Knowledge Check Blood is delivered to the glomerular capillaries through what vessels? Blood is carried away from the glomerular capillaries through what vessels? Which blood vessels supply the loop of Henle? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.77 12 4  11/6/24 https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system 13 Renin-Angiotensin-Aldosterone-System What perioperative conditions might activate the RAAS? What drugs tend to inhibit RAAS activation? How might you prevent or treat these conditions? 14 Hormonal Influence Atrial natriuretic peptide (atria muscles) ○ Natriuresis, diuresis (Na+ excretion, water excretion) ○ Decreased Na+ reabsorption ○ Vasodilation Brain natriuretic peptide (primarily ventricular muscles) C-type natriuretic peptide (vessel wall endothelial cells) Urodilatin (lower urinary tract) 15 5  11/6/24 Hormonal Influence Natriuretic peptide common actions ○ Arterial, venous ____________________________________ ○ Increased RBF ○ Increased GFR ○ Inhibit renin, aldosterone release ○ Inhibits action of NE, angiotensin, _________________________ 16 Hormonal Influence Renal prostaglandins ○ ______________________________________ during ischemia ○ Stimulate release of renin and aldosterone (RAAS activation) ○ Regulate sodium and water balance (excretion, reabsorption) ○ Trigger inflammation ○ Prostaglandin E2, prostacyclin (PGI2), thromboxane A2 can modulate renal effects of other hormones 17 Acid-Base Balance Metabolic component of acid-base buffering Regulates plasma pH Regulates urine pH ○ Maintains > 4.5 ○ Buffers bind H+ ○ eg, ammonia (NH3), phosphate (HPO4) https://www.merckmanuals.com/professional/multimedia/video/overview-of-the-role-of-the-kidneys-in-acid-base- balance#:~:text=The%20kidneys%20have%20two%20main,they%20balance%20the%20bloodstream's%20pH. 18 6  11/6/24 Acid-Base Balance https://www.merckmanuals.com/professional/multimedia/video/overview-of-the-role-of-the-kidneys-in-acid-base- balance#:~:text=The%20kidneys%20have%20two%20main,they%20balance%20the%20bloodstream's%20pH. 19 Acid-Base Balance https://www.merckmanuals.com/professional/multimedia/video/overview-of-the-role-of-the-kidneys-in-acid-base- balance#:~:text=The%20kidneys%20have%20two%20main,they%20balance%20the%20bloodstream's%20pH. 20 Acid-Base Balance https://www.merckmanuals.com/professional/multimedia/video/overview-of-the-role-of-the-kidneys-in-acid-base- balance#:~:text=The%20kidneys%20have%20two%20main,they%20balance%20the%20bloodstream's%20pH. 21 7  11/6/24 Acid-Base Balance https://doctorlib.info/physiology/physiology-2/66.html 22 Acid-Base Balance https://doctorlib.info/physiology/physiology-2/66.html 23 Urine Filtrate Formation https://www.lecturio.com/concepts/glomerular-filtration/ 24 8  11/6/24 Filtration - Renal Corpuscle Passive movement of water, small dissolved molecules from plasma into BC filtrate No RBCs No large proteins Various competing hydrostatic and colloid osmotic pressures 25 Filtration - Renal Corpuscle Glomerular filtration rate ○ 180 L/day filtered (178 L reabsorbed) ○ Varies depending on age, sex, body size ○ Determined by measuring clearance of filtration markers (solutes) ○ Increased by increased renal blood flow, afferent arteriole vasodilation, efferent arteriole vasoconstriction ○ Decreased by decreased RBF, afferent constriction, efferent dilation 26 Reviewing the Effects of NSAIDs & ACEI/ARBs on Renal Blood Flow How do NSAIDs work? https://www.grepmed.com/images/5959/nsaids-effects-renal-aceiarb-kidney 27 9  11/6/24 Filtration https://www.khanacademy.org/test-prep/mcat/organ-systems/the-renal- https://www.osmosis.org/learn/Glomerular_filtration system/a/renal-physiology-glomerular-filtration 28 Next Steps in Urine Filtrate Formation ________________ ________________ Movement of substances from tubular Movement of substances from plasma into filtrate back to plasma tubular filtrate H2O, electrolytes, glucose, amino acids Organic anions, drugs, foreign substances, Active mechanisms etc. ○ eg, Na/K ATPase Active mechanisms Passive mechanisms Passive mechanisms ○ eg, diffusion, osmosis 29 https://pediaa.com/difference-between-filtration-and-reabsorption/ 30 10  11/6/24 MemoryMaster Knowledge Check Renal ischemia and stress stimulates the production of what local mediators to maintain renal blood flow and urine output? How does GFR change if the efferent arteriole dilates more than the afferent? How does GFR change if the efferent arteriole constricts more than the afferent? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.77 31 Proximal Convoluted Tubule https://www.osmosis.org/learn/Proximal_convoluted_tubule 32 https://www.uptodate.com/contents/image?imageKey=NEPH%2F75301 Loop of Henle https://www.osmosis.org/notes/Renal_electrolyte_regulation#page-4 33 11  11/6/24 Distal Convoluted Tubule & Collecting Duct H2O Urea HCO3 https://www.osmosis.org/notes/Renal_electrolyte_regulation#page-5 34 Final Step… Excretion 35 MemoryMaster Knowledge Check What is the most important determinant of antidiuretic hormone (ADH) release? How does urine volume and osmolality change with ADH release? What stimulates the release of renin? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.77-79 36 12  11/6/24 MemoryMaster Knowledge Check Does angiotensin II constrict the afferent arteriole, efferent arteriole, or both? What are the three major (first) renal tubular processes? Which of these three requires energy (ATP or “pump”)? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.77-79 37 38 39 13  11/6/24 1. 2. 3. 4. https://en.wikipedia.org/wiki/Glomerular_filtration_rate 40 Diuretics 41 Introduction to Diuretics Among most commonly prescribed drugs Primary therapeutic effect → ____________________________________________ ○ Promotes urinary loss of Na and H2O ○ Reduction in plasma volume ○ Reduction in blood pressure 42 14  11/6/24 Introduction to Diuretics Uses ○ HTN* ○ CHF* ○ Kidney disease ○ Liver disease (eg, cirrhosis) ○ ICP management ○ IOP management 43 Introduction to Diuretics https://tmedweb.tulane.edu/pharmwiki/doku.php/diuretic_pharm 44 Carbonic Anhydrase Inhibitors - Acetazolamide Block carbonic anhydrase activity Primarily in PCT, also CD Weak diuretic primarily for decreasing intraocular pressure https://doctorlib.info/physiology/physiology-2/66.html 45 15  11/6/24 Carbonic Anhydrase Inhibitors - Acetazolamide Decreases reabsorption of Na+, HCO3-, water ○ Natriuresis ○ Diuresis ○ _______________________________________ urine Increases K+ excretion Increases Cl- reabsorption 46 Carbonic Anhydrase Inhibitors - Acetazolamide Side effects ○ Metabolic __________________________________ ○ Hypokalemia ○ Hyperchloremia ○ Kidney stones ○ Fatigue ○ Paresthesias 47 https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/cainhibitor.png?id=diuretic_pharm 48 16  11/6/24 Osmotic Diuretics Primarily in PCT, descending limb of Loop (permeable to H2O) Mannitol*, urea, isosorbide, glycerin https://www.osmosis.org/learn/Osmotic_diuretics 49 Osmotic Diuretics Inert chemical substances freely filtered by glomerulus Increase osmolarity of fluids ________________________________________ May prevent perioperative renal failure in acute tubular necrosis ○ Vasodilates, improves RBF ○ Removes renal toxins, necrotic debris ○ Scavenger of free O2 radicals - may prevent cellular injury 50 Osmotic Diuretics Side effects ○ ________________________________________________ Caution in LV dysfunction, pulmonary edema Risk of worsening cerebral edema in pts with non-intact blood brain barrier ○ Hypovolemia with long-term use ○ Hypokalemia ○ Hyponatremia ○ Thrombophlebitis with PIV infiltration 51 17  11/6/24 Osmotic Diuretics - Mannitol Sugar alcohol - does not cross cell membranes Dose ________________________________________ IV IV onset 10 - 15 min. Reduces increased ICP ~60 - 90 min. Duration 6 - 8 hrs. 52 https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/mannitol.png?id=diuretic_phar m 53 Loop Diuretics Block Na/K/2Cl cotransporter Thick ascending limb of Loop https://www.uptodate.com/contents/mechanism-of-action-of- diuretics?search=loop%20diuretics&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 54 18  11/6/24 Loop Diuretics Decreases reabsorption of Na+, K+, Cl-, water ○ Natriuresis ○ Diuresis ○ Hypokalemia Decreases reabsorption of Ca2+, Mg2+ 55 Loop Diuretics Most potent diuretics ____________________________________________ formation & release ○ Venodilation à reduces preload ○ Less vasodilation than thiazides → less effective at lowering HTN Furosemide (Lasix)*, torsemide, ethacrynic acid, bumetanide 56 Loop Diuretics Uses ○ HTN ○ Edema (heart, renal, & hepatic failure, pulmonary & cerebral) ○ Hyperkalemia ○ Hypercalcemia Acute tolerance ○ RAAS activation ○ Heart failure patients often resistant ○ May require addition of thiazides 57 19  11/6/24 Loop Diuretics Side effects ○ ________________________________________ ○ Hyponatremia ○ Hypocalcemia ○ Hypomagnesemia ○ Metabolic alkalosis 58 Loop Diuretics Side effects ○ HOTN, renal ischemic injury ○ Hyperuricemia, gout ○ ________________________________, tinnitus ○ Increase nephrotoxic effects of aminoglycosides, cephalosporins 59 Loop Diuretics - Furosemide Dose: ___________________________________ Up to max 200 mg per dose Highly bound to albumin (90%) Onset 5 - 10 min. Duration 2 - 6 hrs. 60 20  11/6/24 https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/loops.png?id=diuretic_pharm 61 Thiazide Diuretics Block the Na/Cl cotransporter Distal convoluted tubule https://www.uptodate.com/contents/image?imageKey=NEPH%2F64975 62 Thiazide Diuretics Decreases reabsorption of Na+, Cl-, water ○ Natriuresis ○ Diuresis Increases excretion of K+ Increases reabsorption of Ca2+ 63 21  11/6/24 Thiazide Diuretics Uses ○ 1st line for HTN Decrease fluid volume, cardiac output, vasodilation ○ Edema (cardiac, renal, & hepatic failure) ○ Hypocalcemia, Ca2+ containing renal stones Hydrochlorothiazide*, chlorothiazide, chlorthalidone, indapamide 64 Thiazide Diuretics Side effects ○ _______________________________________** ○ Hyponatremia ○ Hypercalcemia ○ Hypochloremia, hypomagnesemia, hypophosphatemia ○ Hyperuricemia 65 Thiazide Diuretics Side effects ○ Metabolic _______________________________________ ○ Hypovolemia, HOTN ○ ______________________________________________ Glucose intolerance Insulin resistance ○ Cross-reactivity in sulfa allergy 66 22  11/6/24 https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/thiazides.png?id=diuretic_phar m 67 Potassium-Sparing Diuretics Primarily cortical collecting duct, also DCT Decrease K+ excretion https://www.uptodate.com/contents/mechanism-of-action-of- diuretics?search=loop%20diuretics&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 68 Potassium-Sparing Diuretics Epithelial Na+ channel (ENaC) blockers ○ Decrease reabsorption of Na+, water ○ Triamterene, amiloride https://www.uptodate.com/contents/mechanism-of-action-of- diuretics?search=loop%20diuretics&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 69 23  11/6/24 Potassium-Sparing Diuretics Aldosterone receptor antagonists ○ Decrease reabsorption of Na+, water ○ Inhibit Na+/K+ ATPase ○ Spironolactone, eplerenone https://www.uptodate.com/contents/mechanism-of-action-of- diuretics?search=loop%20diuretics&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 70 Potassium-Sparing Diuretics Side effects ○ _______________________________________** ○ Hyponatremia ○ Risk metabolic acidosis ○ Dehydration, HOTN ○ Gynecomastia, decreased androgen levels ○ Dry skin, rash 71 https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/ksparing.png?id=diuretic_phar m 72 24  11/6/24 Dopamine Receptor Agonists D1 receptor activation ○ Increases cAMP ○ Inhibits Na+/H+ exchange ○ Inhibits Na+/K+ ATPase ○ Natriuresis ○ Maintains, increases RBF, GFR https://www.semanticscholar.org/paper/Dopamine-and-renal-function-and- blood-pressure-Armando-Villar/87fe07228f60c0e5317ad97adb963db00f878272 73 Dopamine Receptor Agonists Higher doses - sympathetic activation ○ Beta cardiac stimulation ○ Alpha vasoconstriction Dopamine*, fenoldopam 74 Dopamine Receptor Agonists - Fenoldopam Selective D1-agonist ○ Moderate activity at alpha-2 ○ No effect on D2, beta, alpha-1 ○ Increases RBF ○ Decreases SVR Short-term treatment of severe HTN, renal protection (high-risk) Fast-acting 1/2 life 10 min. 75 25  11/6/24 MemoryMaster Knowledge Check What is the main side effect of thiazides? Spironolactone works primarily on what renal tubule segment? How and where do thiazide diuretics work? How does this differ from loops? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.168-169 76 MemoryMaster Knowledge Check What are the main metabolic disturbances produced by acetazolamide? How and where does acetazolamide work? Which diuretic may cause pulmonary edema and CHF? Valley answersAnesthesia.(2023). Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.168-169 77 MemoryMaster Knowledge Check What are the main metabolic disturbances produced by furosemide? How does furosemide promote venodilation? Which diuretics may cause ototoxicity, and which patients are at greatest risk? Valley Anesthesia.(2023). answers Memory for the student nurse Master: anesthetist Questions (33rd and ed.). P.168-169 78 26  11/6/24 79 80 Anesthetic Considerations 81 27  11/6/24 Perioperative Medication Management No current consensus or guidelines on continuance Consider individualized approach ○ HTN ○ HF (acute, chronic, decompensated?) 82 Perioperative Medication Management Assess fluid volume status ○ Risk greater hypovolemia with long NPO time ○ Additive vasodilation with anesthetics Assess electrolytes ○ Hypokalemia - greatest risk Arrhythmia risk, potentiates muscle relaxants, risk paralytic ileus 83 Assessing Perioperative Risk 84 28  11/6/24 Perioperative Management Maintain renal blood flow ○ Minimize perioperative conditions which decrease RBF ○ _______________________________________________ ○ Minimize use of vasodilators ○ Reduce sympathetic stimulation ○ Minimize increases in intrathoracic, intraabdominal pressures ○ Renal ischemia may occur with normal MAP ○ Urine output can be poor predictor of function 85 Perioperative Management Avoid/minimize nephrotoxic agents ○ __________________________________________ ○ Contrast agents ○ Many antivirals & antibiotics ○ Many others… 86 87 29  11/6/24 END! 88 References https://tmedweb.tulane.edu/pharmwiki/doku.php/diuretic_pharm https://www.pharmacy180.com/article/high-ceiling-%28loop%29-diuretics-1199/ https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/loops.png?id=diuretic_pharm https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/ksparing.png?id=diuretic_pharm https://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/thiazides.png?id=diuretic_pharm https://www.uptodate.com/contents/perioperative-medication-management https://www.ncbi.nlm.nih.gov/books/NBK553144/ https://www.uptodate.com/contents/image?imageKey=NEPH%2F64975 https://doctorlib.info/physiology/physiology-2/66.html https://www.grepmed.com/images/5959/nsaids-effects-renal-aceiarb-kidney 89 References https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system https://courses.lumenlearning.com/suny-dutchess-ap1/chapter/nephrons-structure/ https://nurseslabs.com/urinary-system/ https://thecomicalanatomist.com/category/urinarysystem/kidney_anatomy/renal-corpuscle/ https://www.nursingtimes.net/clinical-archive/renal/renal-system-1-the-anatomy-and-physiology-of-the-kidneys-23-01- 2023/ https://www.merckmanuals.com/professional/multimedia/video/overview-of-the-role-of-the-kidneys-in-acid-base- balance#:~:text=The%20kidneys%20have%20two%20main,they%20balance%20the%20bloodstream's%20pH. https://doctorlib.info/physiology/physiology-2/66.html 90 30  11/6/24 References https://en.wikipedia.org/wiki/Glomerular_filtration_rate https://www.khanacademy.org/test-prep/mcat/organ-systems/the-renal-system/a/renal-physiology-glomerular-filtration https://pediaa.com/difference-between-filtration-and-reabsorption/ https://www.osmosis.org/learn/Proximal_convoluted_tubule https://www.osmosis.org/notes/Renal_electrolyte_regulation#page-4 https://www.uptodate.com/contents/image?imageKey=NEPH%2F75301 https://www.osmosis.org/notes/Renal_electrolyte_regulation#page-5 Valley Anesthesia.(2023). Memory master: Questions and answers for the student nurse anesthetist (33rd ed.). 91 31