S4) Diuretics & Renal Pharmacology Flashcards
What are the four broad functions of the kidney?
- Regulatory
- Excretory
- Endocrine
- Metabolism
What are the three regulatory functions of the kidney?
- Fluid balance
- Acid-base balance
- Electrolyte Balance
What does the kidney excrete?
- Waste products
- Drug elimination (glomerular filtration & tubular secretion)
Identify four endocrine secretions of the kidney
- Renin
- Erythropoetin
- Prostaglandins
- 1-alpha calcidol
Which substances does the kidney metabolise?
- Vitamin D
- Polypeptides e.g. insulin
- Drugs e.g. morphine, paracetamol
What are the seven different types of diuretic drugs acting on the kidney?
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides
- K+ sparing diuretics
- Aldosterone antagonists
- ADH Antagonists
Describe the actions and effects of carbonic anhydrase inhibitors
- Sodium bicarbonate diuresis
- Excretion of Na+, K+ and PO3
- Metabolic acidosis / hypokalemia
Describe the actions and effects of osmotic agents
- Filtered at glomerulus
- Increase osmotic gradient throughout nephron
- Excessive water loss
- Hypernatraemia
Describe the actions and effects of loop agents
- Thick ascending limb loop of Henle
- Inhibit NaCl reabsorption
- Concurrent Ca/Mg excretion
- Hypokalaemia (CD)
Describe the actions and effects of thiazides
- Inhibits NaCl reabsorption
- Promotes Ca reabsorption
- Hypokalaemia
- Hyperuricaemia
Describe the actions and effects of aldosterone antagonists e.g. spironolactone
- Inhibits Na+ retention (Na-K ATPase / Na+ flux)
- Blunts K+ and H+ secretion
- Androgenic cross-reactivity
What is the action of aldosterone on the kidney
Aldosterone increases expression of ENaC and Na/K/ATPase in principal cells of the collecting duct
Describe the actions and effects of ADH antagonists e.g. lithium
ADH antagonists reduce concentrating ability of urine in collecting ducts
Explain how the following substances have diuretic action:
- Alcohol
- Caffeine
- Alcohol – inhibits ADH release
- Caffeine – ↑GFR and ↓ tubular Na+ reabsorption
Identify four generic adverse drug reactions from diuretics
- Anaphylaxis / photosensivity rash
- Hypovolaemia & hypotension
- Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)
- Metabolic abnormalities
Identify 5 common specific ADRs from thiazides
- Gout
- Hyperglycaemia
- Erectile dysfunction
- ↑LDL & TG
- Hypercalcaemia
Identify 3 common specific ADRs from spironolactone
- Hyperkalaemia
- Impotence
- Painful gynaecomastia
Identify 4 common specific ADRs from furosemide (loop diuretic)
- Ototoxicity
- Alkalosis
- ↑LDL & TG
- Gout
Identify a common specific ADRs from bumetanide (loop diuretic)
Myalgia
Explain the effect of ACE Inhibitors interacting with K+ sparing diuretics
Increased hyperkalaemia → cardiac problems
What is the effect of aminoglycosides interacting with loop diuretics?
- Ototoxicity
- Nephrotoxicity
Explain the effect of digoxin interacting with thiazide and loop diuretics
Hypokalaemia → increased digoxin binding & toxicity
What is the effect of β- Blockers interacting with thiazide diuretics?
- Hyperglycemia
- Hyperlipidemia
- Hyperuricaemia
What is the effect of steroids interacting with thiazide & loop diuretics?
Increased risk of hypokalaemia
What is the effect of lithium interacting with thiazide & loop diuretics?
- Lithium toxicity (thiazides)
- Reduced lithium levels (loop)
What is the effect of carbamazepine interacting with thiazide diuretics?
Increased risk of hyponatraemia
Which diuretics are commonly used to treat hypertension?
- Thiazide diuretics (vasodilatation as well as diuresis)
- Spironolactone
Which diuretics are commonly used to treat heart failure?
- Loop diuretics
- Spironolactone (non-diuretic benefits)
Which diuretics are commonly used to treat decompensated liver disease?
- Spironolactone
- Loop diuretics
Which diuretics are commonly used to treat nephrotic syndrome?
- Loop diuretic (often big doses needed)
- ± Thiazides
- ± K+ sparing diuretic / K+ supplements
Which diuretics are commonly used to treat Chronic Kidney Disease?
- Loop diuretics
- ± Thiazide-like
- Generally avoid K+ sparing diuretics
Describe the process and requirements for diuretic delivery to renal tubule e.g. furosemide
- Blood flow to proximal tubule must be intact (transport via albumin)
- Proximal tubule must be functioning to transport furosemide across
- TAL must be intact to respond to furosemide
In four steps, describe the clinical approach to treat a patient with refractory oedema
⇒ Check salt intake
⇒ IV furosemide (if gut oedema likely)
⇒ Find minimum effective dose
⇒ Give repeated bolus or infusion (short t1/2)
Describe the relationship between diuretic drugs and kidney function in terms of adverse reactions
- Drugs may reduce kidney function by direct/indirect toxicity
- Drugs may accumulate to toxic levels if they are excreted through the kidneys and renal function is impaired
Identify four potentially nephrotoxic drugs
- Aminoglycosides e.g gentamicin
- Vancomycin (IV only)
- Aciclovir
- NSAIDs
Identify four drugs which can exacerbate renal dysfunction
- ACE-Inhibitors
- Diuretics
- NSAIDs
- Metformin
What are the three steps involved in managing hyperkalaemia?
⇒ Identify a cause
⇒ ECG
⇒ Treatment
Describe the three steps in the emergency treatment of hyperkalaemia
⇒ Protect the heart → calcium gluconate
⇒ Lower serum K+ → insulin / dextrose
⇒ Remove K+ from body → calcium resonium
