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DIURETICS & BLOOD PRESSURE MANAGEMENT

PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson. Mehrad Saeb, Susanta Dan, Meng Lin & Kavi Mahalingam. DIURETICS & BLOOD PRESSURE MANAGEMENT. Outline. Review of renal anatomy and physiology Hypetension Introduction to diuretics Uses of Diuretics & BP management

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DIURETICS & BLOOD PRESSURE MANAGEMENT

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  1. PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson Mehrad Saeb, Susanta Dan, Meng Lin & Kavi Mahalingam DIURETICS & BLOOD PRESSURE MANAGEMENT

  2. Outline • Review of renal anatomy and physiology • Hypetension • Introduction to diuretics • Uses of Diuretics & BP management • Classes of Diuretics • Loop diuretics • Thiazides • Osmotic diuretics • Potassium Sparing diuretics • Carbonic Anhydrase inhibitors • Adverse Effects

  3. Kidney • Kidney • Excretion of wastes • Acid-base homeostasis • Osmolality regulation • Blood pressure regulation • Hormone secretion • Functional Unit • Nephron

  4. Renal Physiology • Renal processes • Filtration • At glomerulus (GFR) • Reabsorption • Water, electrolytes • Active tubular secretion • Organic acids and bases

  5. Reabsorption

  6. Hypertension • Chronically increased systemic arterial pressure. Commonly due to abnormally reduced arteriolar radius. • More than 95% of hypertension patients: causes unknown • Defined: • Arterial blood pressure >140/90 mm Hg • Treatment: • Low sodium diet • Diuretic drugs

  7. Congestive Heart Failure • Collection of signs and symptoms that occur when the heart fails to pump an adequate cardiac output. • May be due to many causes • Pumping against chronically elevated arterial pressure (Hypertension) • Failing heart -> decreased GFR + elevated aldosterone • Virtual absence of sodium in urine • Net result: edema

  8. Diuretics • Drugs to treat diseases characterized by renal retention of salt and water. Essentially increase volume of urine excreted by inhibiting sodium/water reabsorption. • Applications • Treatment of hypertension • Reduction of edema to treat congestive heart failure, liver cirrhosis and certain kidney diseases • Treatment of drug toxicity and overdose

  9. Diuretics • Function: • Block sodium and water reabsorption • Site of Action: • Tubules of kidney; exact location varies with drug. • Classes: • Loop diuretics • Thiazides • Osmotic diuretics • Potassium Sparing diuretics • Carbonic Anhydrase inhibitors

  10. Loop Diuretics Furosemide • Widely used Diuretics • Mechanism of Action • Blocks Na+/K+/2Cl- Symporter • Site of Action: Ascending Limb • Pharmacokinetics • Administrated as IV or Oral • Rapid onset • Therapeutic Uses • Pulmonary edema caused by congestive heart failure or renal insufficiency • Hypertension.

  11. Thiazides Class of diuretics often used to treat hypertension  First-line of treatment in the US Peak action is 4-6 hours Block Na+ and Cl- symporter in the distal convoluted tubules

  12. Adverse Effects • Hypotension • Allergy • Renal failure • Pregnancy: breast milk contamination • Electrolyte Imbalances • Dehydration • Loss of volume • Hypokalemia • Hyperuricemia

  13. Summary • Hypertension: Arterial blood pressure >140/90 mm Hg, chronic condition, hugely unknown, and may lead to congestive heart failure • Diuretics treat diseases characterized by renal retention of salt and water via increased volume of urine excreted • Site of action: tubules of kidney; exact location vary with drug. • Classes: Loop, Thiazides, Osmotic, Potassium Sparing and Carbonic Anhydrase inhibitors • Loop;: • Site of action: Ascending limb • block Na+/K+/2Cl- Symporter thereby reducing reabsorption , increasing urine output leading to lower BP • Thiazide: • Site of Action: Distal convoluted tubule • block Na+/Cl- symporter and thereby inhibit reabsorption, leading to increase urine output, lower body sodium level and lower BP • Adverse effects - Hypotension, Allergy, Renal failure, Pregnancy: breast milk contamination, Electrolyte Imbalances, Dehydration, Loss of volume, Hypokalemia, Hyperuricemia

  14. References • DiPiro, J.T., Talbert, R.L., Hayes, P.E. Et al. Pharmacotherapy: A Pathiophysiological Approach, 8th ed. McGraw-Hill Co., In., NY, 2008. • Duarte JD, Cooper-DeHoff RM (June 2010). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Rev Cardiovasc Ther 8 (6): 793–802. doi:10.1586/erc.10.27. PMC 2904515. PMID 20528637. • One Stop Gate: One Stop Gate to Success. Diuretics. Accessed 15 October 2012. <http://www.onestopgate.com/gate-study-material/pharmaceutical-science/medicinal/diuretics-1.asp>. • Piascik, M.T. The Pharmacology of Diuretic Drugs. Accessed 15 October 2012. <http://www.uky.edu/~mtp/Diuretic_Drugs.htm>. • Rais-Bahrami K, Majd M, Veszelovszky E, Short B (2004). "Use of furosemide and hearing loss in neonatal intensive care survivors". Am J Perinatol21 (6): 329–32. • Schlatter E., R. Greger and Weidtke C. (1983) Effect of “high ceiling” diuretics on active salt transport in the cortical thick ascending limb of Henle's loop of rabbit kidney. European Journal of Physiology. 396(3): 210-217. • Thomas MC (February 2000). "Diuretics, ACE inhibitors and NSAIDs--the triple whammy". Med. J. Aust.172 (4): 184–5. • Eric P. Widmaier. Hershel Raff. Kevin T. Strang. “Vander’s Human Physiology 11th ed”. McGaw-Hill: 2008.

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