Renal Pharmacology Flashcards
List three disease states in which you get oedema
Nephrotic syndrome
Congestive heart failure
Hepatic cirrhosis with ascities
List 6 factors that contribute to oedema
- Increased hydrostatic pressure
- Reduced oncotic pressure within blood vessels
- Increased tissue oncotic pressure.
- Increased blood vessel wall permeability e.g. inflammation;
- Obstruction of fluid clearance in the lymphatic system
- Changes in the water retaining properties of the tissues themselves.
How to thiazides and loop diuretics get into the cell at its apical membrane?
Pass into filtrate bound by plasma proteins. They are then secreted by organion anion transporters into the filtrate.
Are thiazide diuretics acidic or basic drugs?
Acidic
After secretion, is the concentration of the diuretic in the filtrate higher or lower than that of the blood.
Higher concentration in the filtrate.
Where do loop diuretics work?
Thick ascending limb of the loop of henle
What channel do loop diuretics block?
Na+/K+/2Cl- co-transport
Briefly describe the mechanism of action of loop diuretics.
- Na+/K+/2Cl- co-transporter blocked
This stops sodium from being reabsorbed into the tubular epithelium. - The tonicity if the medullary interstitium is decreased
- Because magnesium and calcium reabsorption in the thick ascending limb is dependent on the positive lumen voltage gradient set up by potassium recycling through renal outer medullary potassium channel, loop diuretics also inhibit their reabsorption.
Where on the Na+/K+/2Cl- co-transporter do loop diuretics bind?
Cl- site
Name two loop diuretics
Furesomide
Bumetanide
`How would you administer furesomide in acute pulmonary oedema?
IV
Why is there increase excretion of magnesium and calcium with loop diuretics.
The reabsorption of these is dependant on the positive voltage gradient set up by pottassium recycling.
Is the tonicity of the medulla interstitium increased or decrease by loop diuretics?
Decreased.
What other indirect action do loop diuetics have, other that diuresis?
Venodilator action
Are loop diuretics acidic or basic drugs?
Acidic
Which drugs create a stronger diuresis; thiazide or loop diuretics?
Loop
List some adverse effects of loop diuretics
Hypokalaemia Metabolic alkalosis Hypovolaemia Hypotension Depletion of calcium and magnesium Hyperuricaemia (causes gout)
What channel do thiazide diuretics block?
The Na+/Cl- co transporter
Where do thiazide diuretics bind on the Na+/Cl- channel?
Cl- site.
What indirect action do thiazide diuretics have on blood vessels?
Vasodilator
What two conditions are thiazide diuretic most often used in?
Mild heart failure
Hypertension
Where is the nephron do thiazide diuretics work?
Distal convoluted tubule
Name two thiazide diuretics
Bendroflumetazide
Hydrochlorothiazide
Briefly describe the mechanism of thiazide diuretics
Bind to Cl- aspect on Na/Cl channel and inhibit its action. This means sodium is not reabsorbed and therefore neither is water.
Which diuretic causes depletion of calcium.
Loop. Thiazides do not cause deplection of calcium.
Which diuretic is more likely to cause erectile dysfunction
Thiazided
Why might diuretics cause a metabolic alkalosis?
H+ ions are washed away by increasing urinary flow.
What does aldosterone do at a cellular level in the kidneys?
It is a steroid hormone and so acts via cytoplasmic recpetors to increase the synthesis of the Na+/K+ ATPase.
It also increases synthesis of a protein that activates the epithelial Na+ channel
Overall would increase sodium retention
How does ADH work?
A peptide hormone which acts via G protein coupled receptors to increase the number of aquaporins (water channels) in the cell membrane.
Why do thiazide and loop diuretics cause hypokalaemia?
Pottassium is excreted into the filtrate in response to sodium being reabsorbed.