Diuretics

Diuretics
Hypertension, Congestive Heart Failure , Diabetes, Cirrhosis and Renal Failure

Objectives
I. Review renal structure and function II. Neurohumoral regulation of water (ECF) & electrolyte balance III. Pharmacotherapy that acts at the kidney A. Loop diuretics B. Thiazide diuretics C. Carbonic Anhydrase Inhibitors D. K+- sparing diuretics E. Osmotic diuretics F. Others IV. Therapeutic uses

I. Structure/Function

Germann and Stanfield Fig. 19.2

The Nephron: Tubular Component
Bowman’s Capsule (Glomerulus) Proximal C T Proximal Straight Tubule Loop of Henle Descending Ascending

Distal C T
Collecting Duct
Germann and StanfieldFig 19.3

Renal Processes

Germann and Stanfield Fig 19.7

• Sympathetic nerves
• ANP

II. Neurohumoral Regulation of Renal Blood Flow

– NE onto 1 on afferent arteriole to decrease RBF & GFR

– increase GFR by dilation of afferent arteriole

• ADH – decrease RBF and GFR by constriction • NO
– dilates & increases RBF

• Endothelin, adenosine & ATP – constricts and decreases RBF - via stretch of vessels • Angiotensin II
– constricts afferent & efferent* (at HIGH doses) – ? GFR

II. Electrolyte-Water Balance and Regulation
• Neurohumoral Regulation
– Renin-Angiotensin- Aldosterone System (RAAS) – ADH (Anti-Diueretic Hormone) aka Vasopressin – ANP

Na Handling and ECF

Na+ Reabsorption in PCT

Germann and Stanfield Fig 20.13

Na+ Reabsorption in DCT

Germann and Stanfield Fig 20.13

Urea & Water Reabsorption:

Germann and Stanfield. Fig. 20.5

Juxtaglomerular Apparatus

Germann and Stanfield Fig 19.5

Renin - Angiotensin
• Macula Densa senses tubular fluid flow and fluid [Na+]
– Low renal blood flow --> Low tubular fluid flow ---> low tubular fluid [Na+]

• Activation of B1 Adr R on JG cells • Reduced blood pressure in preglomerular vessels  Results in release of renin from juxta-glomerular cells

Angiotensin II
• AT1 and AT2 GPCR
– Negative feedback

•