Renal pharmacology Flashcards Preview

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Flashcards in Renal pharmacology Deck (27):

What are the two major components of fluid balance in capillaries?

Capillary pressure

Oncotic pressure

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What changes in fluid balance will cause oedema?

Increased capillary pressure

Decreased oncotic pressure


What is nephrotic syndrome?

A disorder of filtration that allows large plasma proteins to enter the filtrate


How does a decrease in oncotic pressure cause oedema?

The decrease in oncotic pressure allows an increase in interstitial fluid

This reduced blood volume and thus cardiac output (Frank-Starling mechanism)

RAAS is activated

Sodium and water are retained

This increases capillary pressure, leading to more oedema

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How does heptic cirrhosis with ascites cause oedema?

Increased pressure in the hepatic portal vein, combined with decreased production of albumin, causes loss of fluid into the peritoneal cavity and oedema (ascites)
Activation of the RAAS occurs in response to decreased circulating volume

Sodium and water retention causes increased capillary pressure


Where do loop diuretics have their effect and against which co-transporter?

Thick ascending limb of the loop of Henle

Na+/K+/Cl- transporter

The ascending limb loses its diuretic effect


Where do thiazide diuretics have their effect and on what transporter?

The distal convoluted tubule

Na+/Cl- co-transport


Where do potassium-sparing diuretics have their effect and on which transporter?

Na+/K+ exchange on collecting tubule


What happens to the concentration of plasma protein with diuretic use?

Concentration increases due to the decreased volume (excretion of water)

This increases plasma oncotic pressure and water/oedema is drawn back into the capillaries


What kind of drugs do organic anion transporters deal with?

Negatively charged, acidic drugs

e.g. thiazide and loop diuretics


What kind of drugs do organic cation transporters deal with?

Positively charged, basic drugs


How are organic anions (OA-) transported into the filtrate using organic ion transporters?

At the basolateral membrane, OA- enters the cell by diffusion or in exchange for α-KG using OATs
qα-KG is transported into cell (against a concentration gradient) via a Na+-dicarboxylate (NaDC) transporter

OA- is transported into the lumen either via multidrug resistance protein 2 (MRP2), or OAT4 (in exchange for α-KG) 

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How do organic cations (OC+) enter the filtrate?

At the basolateral membrane organic cations (OC+) enter the cell either by diffusion, or OCT, (both driven by negative potential of cell interior and against a concentration gradient)

At the apical membrane, OC+ enters the lumen via either multidrug resistance protein 1 (MRP1), or OC+/H+ antiporters (OCTN) 

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How do loop diuretics work?

Inhibit the Na+/K+/2Cl- carrier by binding to the Cl- site and thus:
Decrease the tonicity of the interstitium of the medulla

Prevent dilution of the filtrate in the thick ascending limb

Increase the load of Na+ delivered to distal regions of the nephron (causing K+ loss)

Increase excitation of Ca2+ and Mg2+

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What are some examples of loop diuretics?

Furosemide and Bumetanide


How do loop diuretics enter the nephron?

Organic anion transport mechanism


What are some of the adverse affects of loop diuretics?


Shift in acid-base towards alkaline side (metabolic alkalosis) – caused by increased H+ secretion from intercalated cells in collecting tubule


Hypocalcaemia and hypomagnamesia



What is the mechanism of action of thiazide diuretics?

Inhibit the Na+/Cl- carrier by binding to the Cl- site and thus:

Prevent the dilution of filtrate in the early distal tubule

Increase the load of Na+ delivered to the collecting tubule (causing K+ loss)

Increase reabsorption of Ca2+ 

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How much sodium do loop diuretics cause to be excreted?



How much filtered sodium do thiazide diuretics cause to be excreted?



What are some examples of thiazide diuretics?

Bendroflumethiazide (bendrofluazide) and hydrochlorothiazide


Which diseases are thiazide diuretics widely used in?

Mild heart failure



What are some of the adverse affects of thiazide diuretics?


Metabolic alkalosis



Male sexual dysfunction

Impaired glucose tolerance


What is the mechanism that causes hypokalaemia with diuretic use?

Increased sodium in the filtrate caused by diuretic use causes enhanced reabsorption of sodium

Resulting charge separation makes lumen more negative and causes depolarisation

Increased driving force on K+ across the lumenal membrane leads to enhanced secretion of K+ (Secretion of H+ is similarly affected)

K+ and H+ washed away in urine - diuretics cause increased urine output

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How do potassium-sparing diuretics amiloride and triamterene work to prevent hypokalaemia caused by other diuretics?

Block the apical sodium channel decrease Na reabsorption, preventing the depolarisation that drives K+ secretion 


How do spironolactone and epinerleone work to prevent hypokalaemia?

Compete with aldosterone to bind to intracellular receptors causing:
1. decreased gene expression and reduced synthesis of a protein mediator that activates Na+ channels in the apical membrane (site 1)
2. decreased numbers of Na+/K+ATPase pumps in the basolateral membrane (site 2)


When are aldosterone antagonists used?

Heart failure
Primary hyperaldosteronism (Conn’s syndrome)
Resistant essential hypertension
Secondary hyperaldosteronism (due to hepatic cirrhosis with ascites)