71. Pharmacology - Renal Pharmacology

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Questions and Answers

Which diuretic class primarily inhibits carbonic anhydrase in the proximal tubule?

Carbonic anhydrase inhibitors (correct)

Osmotic diuretics

Thiazide diuretics

Loop diuretics

What is the primary site of action for thiazide diuretics?

Proximal tubule

Collecting tubule

Distal convoluted tubule (correct)

Loop of Henle

Which diuretic class is typically classified as potassium-sparing?

Loop diuretics

Aldosterone antagonists (correct)

Osmotic diuretics

Thiazides

What is a potential side effect of NSAIDs on kidney function?

Acute kidney injury Signup and view all the answers

Which hormonal system is targeted by drugs that influence renal function?

Renin-angiotensin-aldosterone system Signup and view all the answers

Which mechanism is primarily associated with loop diuretics?

Inhibition of NKCC2 in the ascending loop of Henle Signup and view all the answers

What role do pharmacologic agents that stimulate mitochondrial biogenesis play in kidney function?

They promote cellular energy production. Signup and view all the answers

Which pathway is NOT involved in the regulation of renin secretion?

Cortical feedback pathway Signup and view all the answers

Which pharmacologic agent is primarily considered an indirect modulator of the RAS pathway?

Diuretics Signup and view all the answers

What is the role of the AT1 receptor in the context of the RAS system?

Mediates the effects of angiotensin II Signup and view all the answers

Which of the following is a key enzyme in the RAS pathway that could serve as a pharmacologic target?

Renin Signup and view all the answers

What adverse renal effect is associated with the use of NSAIDs?

Acute renal failure Signup and view all the answers

What is the function of aquaporins in the thin descending limb of Henle's loop?

Passive reabsorption of water Signup and view all the answers

Which segment of the nephron is primarily responsible for the active reabsorption of 15–25% of filtered Na+/K+/Cl−?

Thick ascending limb Signup and view all the answers

What class of diuretics specifically acts on the thick ascending limb of Henle's loop?

Loop diuretics Signup and view all the answers

How does the distal convoluted tubule regulate calcium reabsorption?

Under parathyroid hormone control Signup and view all the answers

What is the role of vasopressin (ADH) in the medullary collecting duct?

Control water reabsorption Signup and view all the answers

Which function is NOT associated with the proximal tubule?

Very high secretion of water Signup and view all the answers

What is the primary mechanism of sodium reabsorption in the cortical collecting tubule?

Na channels coupled to K+ secretion Signup and view all the answers

Which segment has a very low capacity for solute reabsorption and is primarily responsible for Na+ and Cl− reabsorption?

Distal convoluted tubule Signup and view all the answers

What percentage of filtered Na+ is typically reabsorbed in the cortical collecting tubule?

2–5% Signup and view all the answers

What is the primary site of action for thiazides in the nephron?

Distal convoluted tubule Signup and view all the answers

Which type of cells in the collecting tubule are primarily responsible for secreting H+?

Intercalated cells (a subtype) Signup and view all the answers

Which of the following statements regarding Na+ transport in Principal cells is correct?

Na+ entry predominates, creating a lumen-negative potential. Signup and view all the answers

What is a key feature of the intercalated cells in the collecting tubule?

They can be divided into two distinct subtypes based on ion transport. Signup and view all the answers

What is the consequence of upstream diuretics increasing Na+ delivery to the collecting tubules?

Increased K+ secretion Signup and view all the answers

What characteristic of thiazides was discovered shortly after their introduction?

Inhibition of NaCl transport primarily Signup and view all the answers

Which ion primarily drives the transport of Cl– ions into the blood within Principal cells?

Na+ ions Signup and view all the answers

What role do principal cells primarily serve in the collecting duct?

Reabsorption of water and Na+ Signup and view all the answers

What unusual feature do thiazides and carbonic anhydrase inhibitors share?

Both contain an unsubstituted sulfonamide group. Signup and view all the answers

In the context of ion transport across membranes in Principal cells, which of the following statements is accurate?

Na+ entry leads to paracellular transport of Cl– and K+. Signup and view all the answers

What is the primary effect of GILZ on ENaC activity in the cell membranes of the distal tubule and collecting duct?

Enhances active ENaC availability Signup and view all the answers

What determines the permeability of principal cells to water in the collecting duct?

Presence of antidiuretic hormone (ADH) Signup and view all the answers

Which statement correctly describes the role of vasopressin receptors in the kidney?

V2 receptors stimulate cAMP production to enhance water reabsorption Signup and view all the answers

What is the outcome of the absence of ADH on the collecting tubule and duct?

Formation of dilute urine Signup and view all the answers

Which type of diuretics are classified as potassium-sparing?

ENaC inhibitors Signup and view all the answers

Which substance is a competitive antagonist to aldosterone?

Spironolactone Signup and view all the answers

What is a significant characteristic of triamterene in terms of pharmacokinetics?

Short half-life with extensive hepatic metabolism Signup and view all the answers

The decrease of which specific signaling pathway is influenced by GILZ?

ERK signaling Signup and view all the answers

What effect do K+-wasting diuretics like loop and thiazide diuretics have on serum potassium levels?

They can lead to hypokalemia Signup and view all the answers

What is the role of AQP2 channels in the nephron?

Regulate water reabsorption Signup and view all the answers

Study Notes

Renal Pharmacology 1 & 2 - Learning Objectives

Identify different classes of drugs that modify kidney function, and apply knowledge of their mechanisms of action to understand normal kidney function.
Identify different classes of diuretic agents and their actions on specific nephron segments.
Differentiate diuretic classes based on cellular site of action, mechanisms, effects on sodium, volume, and acid-base balance.
Distinguish potassium-sparing from potassium-wasting diuretics and their uses.
Describe drugs used to alter fluid balance.
Identify targets in the renin-angiotensin-aldosterone system that affect renal function.
Evaluate potential side effects of NSAIDs on kidney function.
Explain the use of drugs stimulating mitochondrial biogenesis in kidneys and their impact on kidney function.

Renal Pharmacology 1 & 2 - Lecture Outline

Introduction
Diuretics
- Overview: Formation of urine, diuretic action sites.
- Proximal tubule: Carbonic anhydrase inhibitors, osmotic diuretics.
- Loop of Henle: Loop diuretics, NKCC2.
- Distal convoluted tubule: Thiazides, NCC, Ca2+ reabsorption.
- Collecting tubule system:Aldosterone, ENaC, and ADH.
Potassium-wasting and potassium-sparing diuretics.
Drugs that alter water balance: ADH agonists and antagonists.
Drugs targeting the renin-angiotensin system (RAS).
Effects of NSAIDs on renal function.
Pharmacologic agents that modulate mitochondrial biogenesis.
Summary

Renal Pharmacology 1 & 2 - Question 1

Pharmacologic agents can be investigative tools to understand normal physiological function.
Specific proteins are sometimes only studied through inhibition of their activity.
Genetic mutations in proteins can markedly alter their activity e.g., Polycystins in ADPKD.

Renal Pharmacology 1 & 2 - Question 2

Repetition of learning about drugs is useful, as the mechanisms of action in various nephron segments will be later applied to understand disease processes in the M2 curriculum.
Example: Diuretics, drugs targeting the RAAS, Vaptans (used for hypertension).
Drugs that modulate mitochondrial biogenesis are used to treat acute and chronic kidney injury.

Renal Pharmacology 1 & 2 - Diuretics A. Overview

Diuretics are drugs that increase urine volume.
Natriuretics cause increased renal sodium excretion.
Aquaretics increase excretion of solute-free water.
Osmotic diuretics and ADH antagonists are aquaretics, but not directly natriuretic.
More recently, urea transport blockers have been developed, increasing urea excretion but not electrolyte excretion.

Renal Pharmacology 1 & 2 - Sites of Action of major diuretic agents

Carbonic anhydrase inhibitors (PCT).
Osmotic agents (PCT, thin descending limb, CD).
Loop agents (TAL).
Thiazides (DCT).
Aldosterone antagonists (CT).
ADH antagonists (CD).
Adenosine (Glomerulus, PCT, TAL, CD).

Renal Pharmacology 1 & 2 - Major Segments of the Nephron and their functions (Table 1)

Lists nephron segment functions, water permeability, drug targets, and major actions
Includes glomerulus, proximal convoluted tubule (PCT), proximal straight tubules, thin descending limb, thick ascending limb, thin limb of Henle's loop, distal convoluted tubule, cortical collecting tubule, medullary collecting duct.

Thiazides were researched as carbonic anhydrase inhibitors but are now primarily known for inhibiting NaCl transport in the DCT, not NaHCO3.
Still retain some carbonic anhydrase inhibitory activity.
All thiazides have an unsubstituted sulfonamide group.

Renal Pharmacology 1 & 2 - Collecting Tubule System: Aldosterone, ENaC, and ADH

Principal cells are the major sites of Na+, K+, and water transport in the collecting tubule system.
Intercalated cells (α and β subtypes) are the main sites for H+ or HCO3- secretion, respectively.
H+-ATPase and Cl-/HCO3- exchangers have reversed membrane localizations in α and β intercalated cells, respectively.

Renal Pharmacology 1 & 2 - Potassium-wasting and Potassium-sparing Diuretics

Loop diuretics and Thiazides cause K+ loss (hypokalemia).
ENaC inhibitors (e.g., Amiloride, Triamterene) and aldosterone antagonists (e.g., Spironolactone) help conserve K+.
Amiloride and Triamterene are direct Na+ influx inhibitors in the cortical collecting tubule.

Renal Pharmacology 1 & 2 - Drugs that alter water balance: ADH agonists and antagonists

ADH (arginine vasopressin) agonists are often used in diabetes insipidus and enhance ADH function.
ADH antagonists are used in syndromes of inappropriate ADH secretion, or situations needing reduced ADH effects;
- Examples are Lithium and Demeclocycline.
- More recent drugs are Vaptans (e.g., Tolvaptan, Satavaptan, Lixivaptan, Mozavaptan)

Renal Pharmacology 1 & 2 - Effects of NSAIDs on renal function

NSAIDs inhibit COX-1 and/or COX-2, which reduces prostaglandin production.
Reduced prostaglandins can lead to ischemia, glomerular filtration decline, and acute kidney injury (AKI).
NSAID use with reduced eGFR may increase risk of AKI.

Renal Pharmacology 1 & 2 - Pharmacologic agents that modulate mitochondrial biogenesis

Sirtuins (SIRT1 or SIRT3) activators are commonly used to improve kidney function.
These agents are found in both natural compounds (e.g., resveratrol) and synthetic derivatives.
SIRT activators improve renal function by reducing apoptosis and preserving mitochondrial function.

Renal Pharmacology 1 & 2 - Summary of key diuretic agents

Summary of different diuretic classes, mechanism of action, and effects.
Includes carbonic anhydrase inhibitors, loop diuretics, thiazides, potassium-sparing diuretics, osmotic diuretics and vasopressin antagonists.

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Description

This quiz tests your knowledge of the pharmacology related to diuretics and their effects on kidney function. It covers various classes of diuretics, the renin-angiotensin system, and the mechanisms through which these drugs operate. Perfect for students studying renal pharmacology or related medical fields.