Diuretics Flashcards
What are the classic diuretics?
- hydrochlorothiazide (thiazide)
- furosemide, ethacynic acid (loop)
- spironolactone (potassium sparing)
What are the solute/ water excretion altering diuretics? (not clinically useful as diuretics)
- mannitol (osmotic diuretic)
- acetazolamide (carbonic anhydrase inhibitor)
- tolvaptan (vasopressin receptor antagonist)
- dapagliflozin (sodium/glucose co-transport 2 inhibitor)
The interest of diuretics is in what?
- renal solute excretion (sodium and water)
- blocks sodium reabsorption - water will follow later
What is the aim of therapy with a diuretic?
- only need to decrease sodium reabsorption a few percent
- change of 5% has a great effect (1250 mol/day of Na is excreted and therefore this would represent a loss of 9 litres of extracellular fluid loss)
What drugs act on the proximal tubule of the kidney?
- mannitol, unreabsorbed glucose, dapagliflozin, and acetazolamide
What drugs work on the ascending loop of henle?
- furosemide
What drugs work on the distal tubule?
- metolazone
What drugs work on the collecting duct?
- spironolactone
- conivaptan
What are examples of thiazide diuretics?
- hydrochlorthiazide, metolazone and chlorthalidone
Where is the primary site action of thiazide diuretics concentrated and what is their effect?
- works in the distal tubule to: increase NaCl excretion (decreases reabsorption) and decreases Ca excretion (increases reabsorption) - loop diuretics do the opposite
What is the proximal tubular effect of thiazide diuretics?
- there is some - normally not very important, compensation in the loop of henle
- important when combined with loop of diuretic
- may decrease blood pressure without a perceivable volume loss (low dose is usually effective - also decreased toxicity)
If we want to conserve calcium in a patient, we should put the patient on a ___ diuretic
thiazide
do not want to put on a loo diuretic because it will dump calcium and exacerbate a bone disorder
What is the process of action that thiazide diuretics have on blood pressure control?
thiazide diuretics -> increase NaCl excretion -> decrease blood volume and decrease cardiac output -> tolerances? -> blood volume and CO returns to normal -> blood pressure stays down and may decrease further -> (Cox decrease in TPR = decrease in BP)
What are the general problems associated with thiazide diuretics?
- increased incidence of other risk factors for CV disease
- hyperglycemia (decrease insulin resistance, decrease tissue utilization)
- increased LDL levels
- increased incidence of erectile dysfunction
- plasma volume contraction due to increased urine loss
- increased proximal tubule reabsorption, response to fluid loss —> increased lithium, urea reabsorption
What are the used of thiazide diuretics?
edema and hypertension
What are the advantages of the use of thiazide diuretics?
- orally active, low toxicity and no postural hypotension
- potentiate other antihypertensive drugs
What are the three examples of loop diuretics?
- furosemide
- bumetanide
- ethacrynic acid (non sulfonamide)
What are the two formulations that loop diuretics can be in?
- oral and IV
Loop diuretics should increase the production of ______
prostaglandin
Loop diuretics are useful in acute ________ as they vasodilate veins.
pulmonary edema
____ may decrease function of loop and thiazide diuretics
NSAIDs
Loop diuretics increase the Na, Cl, and K excretion and what two minerals follow?
- Mg and Ca
Loop diuretics inhibit the renal diluting ability and abolished the renal concentrating ability, so the urine becomes ____ or _____
isotonic or slightly dilute
What are the main problems associated with loop diuretics?
- deafness: never combine with amino glycoside antibiotics
- chronic dilutional hyponatremia
- due to excrete of an isotonic urine
What are the uses of loop diuretics?
- good in renal insufficiency (GFR <50 ml/mim)
- edema (pulmonary), hypertension (not as sole medication), hypercalcemia (opposite to thiazides), heart failure
Is potassium depletion due to thiazide/loop diuretics a problem in healthy patients?
- no, it is not — only a problem is low potassium is already a problem (heart failure, cirrhosis, etc)
What is the two major causes of electrolyte disturbances?
- Secondary hyperaldosteronism (due to plasma volume depletion)
- increase renin, increase A2, increase aldosterone
- Na reabsorption at the expense of K (and H) loss - Increased distal delivery
- increased distal delivery- due to inhibition of Na reabsorption in loop and distal tubule
- collecting tubules therefore increase Na reabsorption to conserve sodium
* * see slide 16
What are some treatments for potassium depletion?
- dietary intake (apricots, bananas)
- potassium chloride tablets - chloride salt - dilute solution
- slow potassium tablets - ulceration
- emergencies
- iv KCl - repeat cautiously until potassium rinses - potassium sparing diuretics
- weak diuretics
- give with other diuretics to decrease K loss
- may cause hyperkalemia
- never combine with K supplements
- spironolactone (blocks aldosterone receptor, prevents cardiac remodelling- may delay progression of failure)
- triamterene (decrease sodium permeability - have limited use)
Wha other medications are known to increase plasma potassium concentrations?
- Beta- adrenoreceptor antagonists, ACEI’s, ARB’s may also increase plasma potassium concentrations
- beta- adrenoreceptor antagonists decrease potassium from entering the cells
Amiloride and triamterene block ___ from entering into the collecting tubule/duct
Na
Spironolactone blocks _____ from entering into the collecting tubule/duct
aldosterone
Explain extracellular volume depletion as an electrolyte disturbance?
- furosemide: kidney is unable to concentrate or dilute, so urine is excreted and is isotonic
- inability to concentrate urine (can simply drink more water to excrete solutes)
- inability to dilute urine (ingest a hypotonic solution, and excrete an isotonic urine. There is a net loss of electrolytes including plasma sodium. Chonic dilution hyponatremia)
Thiazides ___ calcium excretion (good for hypocalciuria)
decrease
Furosemide ___ calcium excretion and is good to hypercalcemia
increases
Volume depletion and increased proximal tubule reabsorption causes an increase in uric acid ____. What can this lead to?
excretion
Can lead to gout
When a person is taking both lithium as we’ll as diuretics, you can see a _____ in proximal tubular reabsorption
increase (we are concerned here about toxicity)
What are the clinical uses for diuretics?
- used for edema forming conditions and arterial hypertension
- also for treating hepatic cirrhosis and cardiac failure
Describe tissue edema?
- fluid shift into the extracellular space that has exceeded 3-4 L - due to salt and water retention
- loop diuretics are preferred for this - if there is no response, check for serum chloride concentration
Fluid excreted in the urine is taken from the ______ - need to allow time for this to be replaced by the interstitial fluid (edematous)
vascular space
What is the first line single therapy for treating hypertension?
thiazide diuretic
What are the risks of using a thiazide diuretic in treating hypertension?
- can increase LDL, can increase plasma glucose (not metabolically neutral)
- good as second medication to treat sodium and water retention - common side effect go other anti-hypertensives
How are diuretics useful to treat hepatic cirrhosis?
- sodium/water accumulates in the abdomen and/or tissue
- abdominal fluid movement into vascular space may be a concern
- slower than fluid movement from interstitial to vascular space
- aggressive treatment will remove fluid faster from the vascular space than can be replaced by the abdominal fluid
What is the role of diuretics in cardiac failure?
- fluid retention increases vascular volume
- helps to increase preload and stimulate the heart
- as failure continues so does fluid retention
- preload increases to levels causing edema
- diuretics decrease vascular volume
- -successful tx of heart failure requires adequate control of vascular volume
What are osmotic diuretics?
- osmotically active components in the plasma
What are the properties for a perfect osmotic diuretic?
- filtered
- not reabsorbed
- pharmacologically inert
- resistant to alteration
- osmotically active compounds hold onto water (high urine volume- little sodium)
What are the few uses for osmotic diuretics (mannitol and glycerol)
- vascular surgery
- renal transplant
- ophthalmological procedures
What is the example of carbonic anhydrase inhibitors?
- acetazolamide
Describe carbonic anhydrase inhibitors?
- very weak diuretics
- inhibits carbonic anhydrase (decreases reabsorption of bicarbonate in proximal tubular cells, increases bicarbonate excretion-with some sodium)
What are the uses for carbonic anhydrase inhibitors?
- in severe alkalosis (increases renal excretion of bicarbonate)
- alkalization of filtrate ionizes acidic drugs - ionization increases renal excretion (salicylate)
- acute motion sickness
- increasing excretion of weak acids
- glaucoma - decreases aqueous humor formation
What does antidiuretic hormones do?
- increases water reabsorption (no effect on electrolytes)
What is an example of an antidiuretic hormone antagonist?
- conivaptan
What does conivaptan do?
blocks the ADH receptor in the collecting tubules - increases water excretion (without electrolytes)
_____ is increased in heart failure and syndrome of inappropriate ADH secretion. The chronic increased water reabsorption may produce hyponatremia
vasopressin
What is an example of a sodium glucose co-transport 2 inhibitor?
dapagliflozin
Where is the major site of glucose reabsorption for the sodium glucose co-transport 2 inhibitor?
proximal tubule
Blocking the sodium glucose co-transport increases what?
- urinary excretion of glucose
associated with a small decrease in plasma glucose
Sodium glucose co-transport 2 inhibitors are associated with what?
- with a decrease in blood pressure and weight
