6 Diuretics and Renal Pharmacology Flashcards
Identify four endocrine secretions of the kidney
- Renin
- Erythropoetin
- Prostaglandins
- 1-alpha calcidol - vitamin D
Which substances does the kidney metabolise? (3)
- 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 (2) and side effects (2) of carbonic anhydrase inhibitors
Actions:
- Sodium bicarbonate diuresis
- Excretion of Na+, K+ and PO3
Side effects:
- Metabolic acidosis
- Hypokalemia
Describe the actions and side effects of osmotic agents
Name an example of an osmotic agent.
Actions:
- Filtered at glomerulus
- Increase osmotic gradient throughout nephron
- Excessive water loss
Side effects:
- Hypernatraemia
Example:
- Mannitol
Describe the actions and effects of aldosterone antagonists.
Name an example:
- Competes with aldosterone at mineralcorticosteroid receptor
- Aldosterone increases expression of ENaC and Na/K/ATPasein principal cells of the collecting duct
Example:
Spironolactone (potassium sparing)
Describe the actions and side effects of loop diuretic.
Name 2 examples.
Actions:
- Thick ascending limb loop of Henle
- Inhibit NaCl reabsorption (block Na/K/2Cl co-transporter)
- Concurrent Ca/Mg excretion
Side effects:
- Hypokalaemia (CD)
Examples:
- Bumetanide
- Furosemide
Describe the actions and side effects of thiazides.
Name 2 examples.
Actions:
- Inhibits NaCl reabsorption
- Promotes Ca reabsorption
Side effects:
- Hypokalaemia
- Hyperuricaemia
Examples:
- Bendroflmethiazide
- Indapamide
Identify 5 common specific ADRs from thiazides
- Gout
- Hyperglycaemia
- Erectile dysfunction
- ↑LDL & TG
- Hypercalcaemia
Outline the action of ADH antagonists. (aquaretics)
Give 2 examples
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 3 common specific ADRs from spironolactone
- Hyperkalaemia
- Impotence
- Painful gynaecomastia (male breasts)
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? Why are loop diuretics not usually used?
- Thiazide diuretics (vasodilatation as well as diuresis)
- Spironolactone
(Loop diuretics) - don’t work well as body compensates quickly
Which diuretics are commonly used to treat heart failure?
- Loop diuretics
- Spironolactone (non-diuretic benefits)
(ACE inhibitors/ ARBs)
(Beta- blockers)
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
(Alkalosis and kalliuretic effects potentially beneficial)
Kalliuretic= getting rid of potassium in urine)
Describe the process and requirements for diuretic delivery to renal tubule e.g. furosemide
Need to consider these when it comes of delivering drugs because if gut oedema for examples- fluid overloaded anyway so drug not well absorbed
- Blood flow to proximal tubule must be intact (transport via albumin)
- Proximal tubule must be functioning to transport furosemide across
- Thich Ascending Limb must be intact to respond to furosemide
In four steps, describe the clinical approach to treat a patient with refractory oedema
(Refractory oedema= peripheral oedema that does not respond to dietary sodium restriction and combined diuretic treatment including a loop diuretic, often caused by an evident underlying cardiac or pulmonary condition)
⇒ 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 (2 important points to consider)
- 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 (antiviral)
- NSAIDs
Identify four drugs which can exacerbate renal dysfunction
- ACE-Inhibitors
- Diuretics
- NSAIDs
- Metformin
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
What do the terms natriuretic and aquaretic mean? (vs diuretic)
Natriuretic- peeing sodium
Aquaretic- peeing water only
Diuretic- peeing urine
Fill in the missing labels showing which drugs work at which site:
Useful table for drug-drug interactions with diuretics:
Apart from spironolactone, give another example of a potassium sparing diuretic and state how is works:
Amiloride
Block ENaC at luminal surface of renal tubule
What are carbonic anhydrase inhibitors used to treat?
- Glaucoma
- Mountain sickness
(BUT tolerance builds up in 2-3 days)
Mannitol is an osmotic agent (diuretic), what is it used for?
(need to be careful as patients can become hypernaetraemic)
Used as diuretic in ITU to 1) relieve ICP and to 2) force urine production in people with acute (sudden) kidney failure
What are SGLT2 inhibitors used for?
Treating type 2 diabetes
Get rid of uric acid
