Pharmacology Flashcards
What general effects does a diuretic have on the body?
- Increases urine output
- Inhibits the reabsorption of electrolytes
- Used to enhance excretion of salt and water in conditions where there there is an increase in the volume of interstitial fluid.
What is the basic mechanism of a diuretic?
- in the presence of a diuretic, water and salt output is increased
- blood leaving the kidney is haemoconcentrated
- plasma protein concentration is increased and therefore oncotic pressure is increased
- Blood in periphery sucks the fluid from the interstitial fluid.
What pressures are involved in Oedema?
- Capillary oncotic pressure
- Capillary hydrostatic pressure
- Interstitial hydrostatic pressure
- Interstitial oncotic pressure
What happens when capillary hydrostatic pressure is increased?
Interstitial fluid increases –> may lead to oedema
What happens when interstitial oncotic pressure is reduced?
Fluid moves more easily into interstitium –> may lead to oedema
Define nephrotic syndrom
Disorder which causes the kidney to pass too much protein
What conditions can cause oedema?
- Nephrotic syndrome
- Congestive heart failure
- Hepatic cirrhosis
How does nephrotic syndrome produce oedema?
Decreased plasma protein concentration causes a reduction in the plasma oncotic pressure. Fluid therefore flows into interstitial fluid more easily leading to oedema and a decreased in blood volume and cardiac output. In turn, this activates RAAS leading to formation of angiotensin II causing the release of aldosterone which increases reabsorption of electrolytes and later –> OEDEMA
Where are the sites of action of the different types of diuretics?
- Proximal convoluted tubule = Carbonic anhydrase inhibitors
- Ascending Limb of the Loop of Henle = Loop Diuretics
- Distal convoluted tubule = Carbonic anhydrase inhibitors
- Distal convoluted tubule (Na/Cl- co-transporter) = Thiazide diuretics
- Collecting ducts (Na/K+ exchanger) = Potassium sparing diuretics
Which site of the membrane does most diuretics work at?
Apical membrane
How do they enter the filtrate?
- Glomerular filtration not bound to plasma protein
- Secretion via transport process in proximal tubule
- Organic anion transporter
- Organic cation transporter
What type of drugs are associated with Organic anion transporters
Acidic drugs
What type of drugs are associated with Organic Cation Transporters
Basic/positive drugs
The concentration of a diuretic in the blood is greater than the concentration in the filtrate? True or False
False
Organic anion transporter moves substances from the basolateral membrane to the apical membrane, True or False
True
How to organic ions enter the cell on the basolateral membrane?
Enter the cell in exchange for a-ktogluterate
How does a-ketogluterate enter the cell?
Enters via NaDC channel where sodium enters the cell coupled with a-ketogluterate
How does organic anions enter the lumen on the apical membrane?
Multridrug Resistance protein MRP2/4
How do organic cations enter via the basolateral membrane?
Organic cation enters the cell via organic cation transporter 2
How do organic cations enter the lumen via apical membrane
OC+ enters lumen via MDR1 or OC/H+ antiporters (MATE)
Which transporter does Loop Diuretics work on
Triple transporter (Na+/K+/2Cl-)
Which part of the Nephron does loop diuretics act upon?
Ascending thick limb of the Loop of Henle
What effect does a loop diuretic have upon sodium concentration in the medulla
Sodium is not able to enter the tubular cell on the apical membrane then enter the medulla where it increases the tonicity. Therefore the tonicity of the medulla is reduced, preventing dilution of filtrate in the thick ascending limb. Increases Na+ load delivered to distal regions
Does loop diuretics cause a loss of K+?
Yes, increased load of Na+ delivered to the distal regions of the nephron. K+ is exchanged for Na+ and no further opportunity for K+ to be reabsorbed so is excreted in the urine.
