Diuretics and Renal Pharmacology Flashcards
Outline the key aspects renal physiology
R – regulatory = fluid balance, acid-balance balance, electrolyte balance
E – excretory = waste products, drug elimination (glomerular filtration, tubular secretion)
E – endocrine = renin, EPO, prostaglandins, 1-alpha calcidol
M – metabolism = vit D, insulin, drugs
Which drugs can act on the renal tubules?
Carbonic anhydrase inhibitors
Osmotic Diuretics
Loop Diuretics
Thiazides
Potassium sparing diuretics
Aldosterone antagonists
ADH Antagonists
Outline Na handling in the kidney
- PCT = Na/H transporter, Na/co-transporters, 65% Na reabsorbed
- TALLH = NKCC2, 25% Na reabsorbed
- DCT = NCCT, 5% Na reabsorbed
- CD = ENaC, aldosterone effects
Discuss carbonic anhydrase inhibitors
PCT
If you block this you just get more reabsorption downstream so not particularly effective at blocking Na
Also blocking bicarb reabsorption (promote acidosis)
Outline Loop diuretics
TALLH
Block NKCC2
Block 25% Na reabsorption
Very effective for getting rid of excess fluid
Are used in hypercalcemia pts – due to concurrent Ca/Mg excretion
Furosemide
Outline Osmotic agents
Hold water in filtrate
Glucose, urea
Drug = mannitol – stops reabsorption of water
Discuss Thiazide diuretics
DCT
Block 5% Na reabsorption
Effect K – due to ENaC
Discuss Aldosterone antagonists
CT
Inhibits ENaC
Spironolactone
Bind intracellular aldosterone receptor = decreases expression of ENaC + Na/K/ATPase in principle cells
Outline ADH antagonists
Effects free water reabsorption – most pts polyuric and dehydrated
Lithium
Explain alcohols diuretic action
Inhibits ADH release
How does caffeine increase water loss?
Increases GFR, decreases tubular Na reabsorption
What adverse drug reactions can take place when using diuretics?
Anaphylaxis
Hypovolaemia/hypotension
Electrolytic disturbance
Metabolic abnormalities
Outline the possible drug interactions
ACEi/K sparing diuretic = hyperkalaemia = cardiac arrythmia
Aminoglycosides/loop diuretics = nephrotoxicity
Beta blockers/thiazide diuretics = hyperglycemia
Outline the use of diuretics in hypertension
Thiazide diuretics (vasodilatation as well as diuresis)
Spironolactone
Loop diuretics
Outline the use of diuretics in heart failure
Loop diuretics
Spironolactone
What diuretics are used in liver disease?
Loop diuretics
Spironolactone
What diuretics are used in nephrotic syndrome?
Loop diuretics
+/- thiazides
+/- potassium-sparing diuretic / potassium supplements
What diuretics are used in CKD?
(Decreased GFR leads to salt and water retention)
Loop diuretics
+/- thiazide-like
Generally avoid K+-sparing diuretics
What should be checked in refractory oedema?
= does not respond to Na deitary restriction + diuretics
Check salt intake (24 hour Na excretion if necessary)
Give furosemide iv if gut oedema likely
Find minimum effective dose
Give repeated bolus or infusion (short t1/2)
Why do thiazides cause hyponatraemia and hypokalaemia?
Relates to the concentrating gradient down the kidney
25% Na reabsorbed from TAL – to interstitium = hypertonic interstitum
Thiazides block 5% Na reabsorbed in DCT = hypertonic medulla interstitum
As you become hypovolemic = RAAS, ADH activated
ADH more affective if hypertonic = now absorbing water
Outline the problems of prescribing in renal failure
Drugs may reduce kidney function by direct or indirect toxicity
Drugs may accumulate to toxic levels if they are excreted through the kidneys and renal function is impaired
What drugs are potentially nephrotoxic?
Aminoglycosides: e.g gentamicin
Vancomycin (intravenous only)
Aciclovir
NSAIDs
Name some drugs that can cause problems with renal dysfunction
ACE-Inhibitors
Diuretics
NSAIDs
Metformin – can make you acidotic
How do NSAIDs affect renal perfusion?
Inhibits PG vasodilation at AA
How do ACEi/ARB affect renal perfusion?
Inhibits Ang II vasoconstriction at EA
What are the causes of hyperkalaemia?
Excess intake
Movement out of cels = acidosis, hypetonicity, tissue damage
Reduced urine loss = reduced GFR, reduced secretion in CD
Drugs = RAASi, NSAIDs, ENaC blockers
How is hyperkalaemia managed?
Identify cause
ECG
Treatment:
1) protect heart = calcium gluconate
2) lower serum K+ = insulin/dextrose
3) remove K+ from body = Ca resonium
