Renal Clearance and Nephrotoxicity

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Questions and Answers

Which process in renal clearance specifically involves the movement of drugs against an electrochemical gradient?

  • Secretion via organic anion transporters (correct)
  • Ultrafiltration
  • Resorption of lipophilic drugs
  • Secretion via organic cation transporters

What is the impact of NSAIDs on the kidneys regarding blood flow?

  • They have no effect on kidney blood flow.
  • They decrease blood flow by inhibiting prostaglandin production. (correct)
  • They restrict blood flow by blocking the afferent arteriole.
  • They increase blood flow through vasodilation of the efferent arteriole.

How do aminoglycosides primarily cause toxicity in renal tubular cells?

  • By blocking organic anion transporters.
  • By accumulating in lysosomes and impairing mitochondrial function. (correct)
  • By enhancing tubular resorption.
  • By decreasing the glomerular filtration rate.

Which of the following best describes the effect of diuretics on urine flow?

<p>They increase the rate of urine flow and promote excretion of Na and water. (C)</p> Signup and view all the answers

In what way do lipophilic drugs affect their own excretion in the kidneys?

<p>They are passively reabsorbed and poorly excreted. (C)</p> Signup and view all the answers

Which of the following is a consequence of NSAID-induced inhibition of prostaglandin production?

<p>Acute interstitial nephritis due to immune response. (B)</p> Signup and view all the answers

What type of transporter is involved in the secretion of basic drugs in the renal tubules?

<p>Organic cation transporters (A)</p> Signup and view all the answers

Which condition can arise as a result of nephrotoxic effects of aminoglycosides?

<p>Disruption of tubular transport mechanisms (D)</p> Signup and view all the answers

What is the primary mechanism of action for osmotic diuretics?

<p>Increasing osmolarity of the filtrate in glomerulus (A)</p> Signup and view all the answers

Which unwanted effect is associated with carbonic anhydrase inhibitors?

<p>Systemic acidosis (B)</p> Signup and view all the answers

What is a notable characteristic of loop diuretics?

<p>They cause significant electrolyte loss, particularly Na and K. (D)</p> Signup and view all the answers

What is the main indication for thiazide diuretics?

<p>Treatment of cardiac edema (D)</p> Signup and view all the answers

What effect do potassium-sparing diuretics have on potassium levels in the body?

<p>They cause hyperkalemia. (B)</p> Signup and view all the answers

Which class of diuretics acts mainly on the distal convoluted tubules?

<p>Thiazides (B)</p> Signup and view all the answers

What is the impact of aldosterone antagonists on electrolyte levels?

<p>They decrease Na reabsorption and promote K retention. (B)</p> Signup and view all the answers

Why must osmotic diuretics be administered intravenously?

<p>They are poorly absorbed through the gastrointestinal tract. (D)</p> Signup and view all the answers

Which of these drugs is known to inhibit gastric secretion?

<p>Magnesium hydroxide (A)</p> Signup and view all the answers

What is a common side effect of long-term use of thiazide diuretics?

<p>Hypomagnesemia (C)</p> Signup and view all the answers

What condition may arise from the self-limiting effects of carbonic anhydrase inhibitors?

<p>Systemic metabolic acidosis (D)</p> Signup and view all the answers

Which of these interventions is commonly used to treat rising intracranial pressure?

<p>Osmotic diuretics (D)</p> Signup and view all the answers

What can be a rebound effect of stopping potassium-sparing diuretics?

<p>Increased sodium retention (B)</p> Signup and view all the answers

What is the main benefit of combining different classes of diuretics?

<p>Maximizing diuretic effect at different renal sites (B)</p> Signup and view all the answers

What is the primary mechanism of action of proton pump inhibitors like omeprazole?

<p>Irreversibly bind to ATPase, inhibiting both basal and stimulated gastric secretion (D)</p> Signup and view all the answers

What is a common side effect of using bismuth to manage gastric issues?

<p>Diarrhea (C)</p> Signup and view all the answers

What condition is contraindicated for the use of metoclopramide?

<p>Vomiting due to obstruction (B)</p> Signup and view all the answers

How does charcoal assist in gastrointestinal treatment?

<p>Absorbs toxins and binds to bacteria (C)</p> Signup and view all the answers

What are the potential side effects of opiate medications like morphine when used as antidiarrheal agents?

<p>Decreased propulsion leading to constipation (B)</p> Signup and view all the answers

What is the mechanism of action for the drug sucralfate in gastrointestinal treatment?

<p>Provides mucosal protection (A)</p> Signup and view all the answers

Which drug acts as an antifoaming agent, breaking down bubbles in ruminants?

<p>Bloat guard (surfactant) (A)</p> Signup and view all the answers

What should be avoided when administering misoprostol?

<p>To pregnant animals in late gestation (A)</p> Signup and view all the answers

Flashcards

Renal Clearance

Volume of plasma containing a drug removed by the kidney per unit time.

Ultrafiltration

Process where small drugs pass from the blood into the glomerular filtrate.

Secretion

Active transport of drugs into the renal tubule.

Organic Anion Transporters

Carry acidic drugs out of the blood and into renal tubules.

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Organic Cation Transporters

Carry basic drugs out of the blood and into renal tubules.

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Resorption

Passive reabsorption of lipophilic drugs in the tubules.

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Nephrotoxicity

Kidney damage caused by certain drugs or substances.

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Aminoglycoside nephrotoxicity

Aminoglycosides damage renal tubular cells, especially in the PCT.

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NSAID nephrotoxicity

NSAIDS reduce kidney blood flow and cause interstitial nephritis.

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Diuretics

Increase urine flow and excretion of Na and water in filtrate.

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Diuretics

Drugs that increase urine production.

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Osmotic Diuretics

Diuretics that increase the osmolarity of the filtrate, reducing water reabsorption.

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Osmotic Diuretics Mechanism

Filtered into the glomerulus, but not reabsorbed; increasing osmolarity of filtrate in the PCT, decreasing sodium reabsorption in the descending loop and collecting ducts; drawing water into the urine.

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Carbonic Anhydrase Inhibitors

Diuretics that block the reaction of CO2 with H2O, preventing Na/H exchange, and reducing sodium and bicarbonate reabsorption.

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Loop Diuretics

Diuretics that inhibit Na, K, and 2Cl reabsorption in the thick ascending limb of Henle's loop.

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Loop Diuretics Mechanism

Inhibit sodium, potassium, and chloride reabsorption in the thick ascending limb of the loop of Henle; causing increased urine output and electrolyte loss.

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Thiazide Diuretics

Diuretics that inhibit sodium reabsorption in the distal convoluted tubule (DCT).

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Potassium-Sparing Diuretics

Diuretics that promote sodium loss without significantly reducing potassium.

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Aldosterone Antagonists

Diuretics that block aldosterone's effect in the collecting tubules, leading to sodium and water excretion, and potassium retention.

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Laxatives

Substances that promote bowel movements.

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Anti-emetics

Drugs that prevent or reduce nausea and vomiting.

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Anti-motility agents

Drugs that decrease intestinal motility, such as opiates, and atropine.

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Analgesics

Pain relievers.

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Magnesium hydroxide

Neutralizes stomach acid

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Aluminium hydroxide gel

Neutralizes stomach acid

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Alginates and simeticone

Reduce gas and indigestion

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Sucralfate

Protects stomach lining

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Activated charcoal

Absorbs toxins

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Bismuth

Reduces acid and protects stomach lining

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Kaolin/pectin

Absorbs toxins and coats stomach

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Ranitidine

Blocks histamine, reducing acid production

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Cimetidine

Inhibits histamine, reducing stomach acid 

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Omeprazole

Inhibits acid pump

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Lansoprazole

Inhibits acid pump

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Misoprostol

Reduces stomach acid, protects lining

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Apomorphine

Induces vomiting (emetic)

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Xylazine

emetic that's an alpha-2 agonist

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Ipecac Syrup

Induces vomiting

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Chlorpromazine

Stops vomiting

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Metoclopramide

Anti-emetic, increases stomach emptying

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Domperidone

Anti-emetic, increases gut motility

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Maropitant (Cerenia)

Anti-emetic (neurokinin-1 antagonist)

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Opiates

Decrease gut movement

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Loperamide (Imodium)

Slows gut movement (antimotility)

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Atropine

Slows gut movement (antimotility)

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Hyoscine (Buscopan)

Slows gut movement (antimotility)

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Methylcellulose

Increases stool bulk (laxative)

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Agar/bran

Increases stool bulk (laxative)

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Lactulose

Lowers gut pH, draws water into stool

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Cisapride

Increases gut movement

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Porcine pancreatic enzymes

Aid digestion of fats, proteins, carbs

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Prednisolone

Reduces inflammation

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Bloat Guard

Reduces gas bubbles

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Study Notes

Renal Clearance

  • Renal clearance is the volume of plasma containing a drug removed by the kidney per unit time.
  • Three fundamental processes are involved in renal clearance:
    • Ultrafiltration: small drugs pass through the glomerulus into the filtrate.
    • Secretion: drugs not passing through the glomerulus are transferred into the proximal and distal tubules by organic anion or cation transporters.
    • Reabsorption: lipophilic drugs are passively reabsorbed in the proximal/distal tubule due to their lipid-solubility.

Nephrotoxicity

  • Aminoglycosides: renal tubular cells, particularly in the PCT, are vulnerable.
    • They concentrate and reabsorb glomerular filtrate, leading to tubular cell toxicity.
    • Accumulate in lysosomes, impair mitochondrial function, increasing oxidative stress, and free radicals.
    • Interferes with tubular transport.
  • NSAIDs: the kidney autoregulates intra-glomerular pressure by modulating afferent and efferent arterial tone to preserve glomerular filtration rate (GFR) and urine output.
    • Prostaglandins normally dilate the afferent arteriole.
    • NSAIDs inhibit prostaglandin production, decreasing blood flow to kidneys, and potentially causing acute kidney injury.
    • Also cause acute interstitial nephritis (inflammation in kidney tissue) after period of NSAID exposure.

Diuretics

  • Diuretics increase urine flow and excretion of water and Na from the filtrate.
  • They decrease Na and usually Cl reabsorption.
  • Helpful for edema, acute kidney injury (AKI), forced diuresis, correcting ion imbalances.

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