Diuretics Flashcards
What type of drugs affect extracellular volume?
Effecting Neurohormonal regulators (RAAS, ADH)
Diuretics - target is within the kidney and the cells
Is urine production normally constant?
No
Why do we regulate urine production physiologically?
To maintain and osmotic - volume balance
How is urine production regulated physiologically?
Reabsorption and exchange by nephron.
120ml/min filtered –> 1ml/min urine
What is a Diuretic?
Any drug that will increase water/solute excretion
How do Diuretics work in the kidney?
Altered systemic physiology
Direct action on target cells
How does an osmotic diuretic work?
Eg. Mannitol
Filtered by the glomerulus but not readily reabsorbed.
Therefore this increases osmolarity of tubular fluid
Therefore this decreases water reuptake.
What similar effect does an osmotic drug have on the body?
Similar effect to hyperglycaemia
seen in diabetes mellitus patients
What are the uses of osmotic diuretics?
Therapeutic effects for any situation where there may be excess fluid in a tissue.
Acute Glaucoma/eye surgery
Cerebral oedema following trauma
Oliguria produced by renal failure.
Why would you not use osmotic diuretics for someone with a diseased/failing heart?
The osmotic diuretic would lead to an increase in extracellular fluid as more water is removed from the blood due to the osmolarity and therefore the heart has to work harder to maintain blood pressure.
What is oliguria?
When the nephron doesn’t produce enough urine.
Why would you treat oliguria with an osmotic diuretic?
To increase the fluid flowing through the nephron as it increases the osmotic pressure within the nephron so more fluid is drawn out and less is reabsorbed.
What are the direct drug effects of diuretics?
Action on tubule reabsorption processes (efficacy related to site of action)
Secreted into proximal tubule (not filtered)
Often to be to be filtered due to being bound to plasma proteins.
What are loop Diuretics?
Their action is sited at the loop of Henle
eg. Furosemide, ethacrynic acid
What is the mechanism of loop diuretics?
Wall of the ascending loop is full of protein transporters for ions.
The diuretic interferes with the transporters NKCC2
Therefore there is high concentration of ions in the lumen since they are not reabsorbed.
Therefore this changes the concentration of the interstitial space and therefore a reduce osmotic pull of water out of the nephron
Increased volume of urine produced
Why are loop diuretics acting on re-uptake process important for diuresis
Since roughly 25% of sodium filtered in the loop of Henle is reabsorbed which when blocked leads to a lot more sodium within the nephron and therefore water cannot escape
How are loop diuretics administered?
Via oral and IV
What is the rate of effect of loop diuretics?
Very rapid effects (minutes)
What side effects may occur with loop diuretics?
Dehydration if water loss is too great
Increased loss of other ions (Mg, Ca, H, K) leading to alkalosis and hypokalaemia
Deafness (ototoxicity)
What are some therapeutic uses of loop diuretics?
Heart failure/pulmonary oedema Renal failure Hypercalcaemia/kalaemia Hypertension Drug overdose (increased elimination)
What are the Thiazides?
Eg. Bendroflumethiazide
Also act at transporters
Where do the Thiazides work in the kidney?
Mechanism of action at transporters that transport Na and Cl from lumen into the body.
Found in the DCT
Why are thiazide diuretics less efficient to loop diuretics?
Since they act at the DCT mainly where sodium reabsorption is only about 5-10% and hence is not as effective as the 25% absorbed in the Loop of Henle
How are thiazides administered and how do they work?
Orally
Block Na/Cl cotransporter so less Na is absorbed from the filtrate.
This creates osmotic gradient for water to efflux back into the filtrate.
Increases urine
What are the side effects of Thiazides?
Increase excretion of other ions (Mg H K)
Decreased Calcium excretion (lead to kidney stones and disrupted electrical activity)
Erectile dysfunction
What are the therapeutic uses of thiazide diuretics?
Hypertension - decreased blood volume and vascular resistance
Heart failure/oedema
Why cant thiazides treat renal failure?
Level of effect of thiazides and the fact that they work further down in the nephron, means that the Loop of Henle tubes wont stay open and will collapse
What are potassium-sparing diuretics?
Eg. Spironolactone
Diuretics which dont lead to the loss of potassium ions.
What is the mechanism of action of potassium sparing diuretics?
Mineralocorticoid receptor antagonist
Therefore inhibits aldosterone action
Therefore has an action in the DCT and collecting ducts.
What are some therapeutic uses of potassium sparing diuretics?
Not usually used as a straight diuretic.
Hypertension due to elevated aldosterone (Conn’s Syndrome)
How are potassium sparing diuretics administered?
Orally
Active metabolites
What are some side effects of potassium sparing diuretics?
Hyperkalaemia
Action at other steroid receptors
Gynaecomastia
Sexual Dysfunction (due to abnormal hormone effects)
What is Gynaecomastia?
Breast growth (problem more in males)
What is amiloride/triamterene?
Type of potassium sparing diuretics that acts at the collecting duct.
What are the therapeutic uses of amiloride/triamterene?
Rarely used alone as a diuretic
How is amiloride administered?
Orally
What are the side effects of Amiloride?
Hyperkalaemia
Why would you use potassium sparing diuretics as diuretics if they are so weak?
Since other diuretics inhibit transporters by preventing uptake of sodium and potassium.
Leads to decreased K ions and hence may cause cardiac arrhythmias.
Why is a combination of a loop/thiazide diuretic with a potassium sparing diuretic important?
To prevent too much loss of K ions (hypokalaemia) and therefore may prevent cardiac arrhythmias.
