Flashcards in Pharmacology Deck (105)
How do diuretics increase urine flow?
Inhibit electrolyte reabsorption:
- Mainly Na+ in nephron
-> So reduced water reabsorption
What causes oedema?
- Rate of ISF formation
- Rate of ISF absorption
What is ISF formation proportional to?
(Pc - Pi) - (πp - πi)
- Pc is capillary hydrostatic pressure
- Pi is ISF hydrostatic pressure
- πp is capillary oncotic pressure
- πi is ISF oncotic pressure
What is the main constituent of πp?
Plasma proteins (Mainly albumin)
How does Nephrotic syndrome cause oedema?
How does CHF cause oedema?
How does hepatic cirrhosis cause ascites (intraperitoneal oedema)?
Reduced hepatic blood flow
-> Increased portal system pressure
-> Increased Pc -> Ascites
Reduced albumin production -> Decreased πp
How does increased ISF formation lead to further oedema?
1. Blood volume and cardiac output reduced
2. RAAS Activation (as there is renal hypoperfusion)
3. Sodium and water retention
4. Increased blood volume
5. Increased Pc and further decreased πp
What sort of oedema does CHF cause?
Pulmonary (+/- peripheral)
What drugs block Na+ reabsorption in the PCT?
Carbonic anhydrase inhibitors
What drugs block Na+ reabsorption in the Loop of Henle?
What drugs block Na+ reabsorption in the DCT?
What drugs block Na+ reabsorption in the collecting duct?
Where do most diuretics act, the apical membrane or the basolateral membrane?
What drugs are transported into the filtrate by Organic Anion Transporters (OATs)?
- Loop diuretics
What drugs are transported into the filtrate by Organic Cation Transporters (OATs)?
In regards to OATs, how do organic anions enter the cell at the basolateral membrane?
Exchange for α-ketoglutarate
How is the [α-ketoglutarate]i kept high?
Transported into cell via a Na+-dicarboxylate transporter:
- Na+ from Na+/K ATPase
How do organic anions enter the lumen at the apical membrane?
Via the Multidrug Resistant Protein 2 (MRP2)
And via OAT4 (in exchange for α-ketoglutarate)
Why do thiazides predispose to gout?
Uric acid competes with thiazides at MRP2:
- Increases [Uric acid]p -> Gout
How do organic cations move across the basolateral membrane?
Diffusion (if uncharged)
Organic Cation Transporters
How do organic cations enter the lumen at the apical membrane?
Organic Cation+/H+ antiporters (OCTN)
What transporter do Loop diuretics block in the thick ascending loop of the Loop of Henle? How do they do this?
The Na+/K+/Cl- co-transporter:
Put the following steps of the pharmacophysiology of how loop diuretics work:
- Filtrate is less dilute in thick ascending limb of Loop of Henle
- Increased calcium and magnesium excretion
- Reduced tonicity of medullary ISF
- Diuretic binds to Cl- site on NKCC2
- Increased Na+ load in DCT and CD
- Potassium loss
1. Diuretic binds to Cl- site on NKCC2 in TAL of Henle
2. Reduced tonicity of medullary ISF
3. Filtrate is less dilute in thick ascending limb of Loop of Henle
4. Increased Na+ load in DCT and CD
5. Potassium loss
6. Increased calcium and magnesium excretion
What percentage of filtered Na+ is excreted on the use of IV loop diuretics?
Loop diuretics have an indirect vasodilator action which makes them useful in pulmonary oedema. What are the possible mechanisms by how this works?
Increase levels of vasodilating prostaglandins?
Reduce response to Angiotensin II and NA?
Open K+ channels in resistance vessels?
-> Reduced Calcium influx -> Relaxation
Loop diuretics are strongly bound to plasma proteins, how does this affect their transport into the nephron lumen?
They rely heavily on OATs
True or false; Loop diuretics are poorly absorbed from the GI tract?
Which of the following is not a major use of loop diuretics:
- Acute pulmonary oedema (IV)
- Chronic kidney failure
- Ankle oedema
- Hepatic cirrhosis with ascites
- Nephrotic syndrome