S4) Diuretics & Renal Pharmacology Flashcards
yWhat 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 (loss of bicarbonate) / hypokalemia (lose K at RomK channels)
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) because there is an increase in the activation of RomK to increase Enac so more K leaves
- causes direct dialation of veins that reduce preload
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 ‘ aquaretics’ e.g. lithium
ADH antagonists reduce concentrating ability of urine in collecting ducts
- tolvaptan → diuretic but not natriuretic, treat hyponatremia
- lithium → diuretic not a natriuretic
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
list some conditions diuretics are used for
- nephrotic syndrome
- odema
- hypertension
- chronic heart failure
- decompensated liver disease → ascites
what is the definition of aquaretic
loss of water without electrolytes
what are some adverse effects of loop diuretics
- dehydration, hypotension, hypokalaemia, hyponatremia,
who should you not prescribe loop diuretics to?
people with:
- hypokalaemia
- hyponatremia
- gout → can cause a build up of uric acid in joints (arthritis) as less urine so more concentrated
which drug interactions occur with loop diuretics
- aminoglycosides (gentamicin) can effect hearing
- digoxin → blurred yellow vision
- digoxin and lithium → both excreted via kidney so they compete with the diuretic so more will end up in blood
potassium sparing drug
- block Enac, Na not reabsorbed, reduced K excretion.
- adverse effects: hyperkalemia, potential arrhythmia
- people to avoid: Addisons (low aldosterone), anuria and hyperkalemia
- drug interactions: K sparing drugs, ACEi ARB
type 2 potassium sparing drug
- aldosterone antagonist/mineralcorticoid receptor antagonist
- aldosterone increases ENAc and Na/K/ATPase in principal cells of collecting duct so more Na reabsorbed and K excretion
- if this is antagonised then opposite happens and k gets absorbed
- adverse effects: gynaecomastia (blocks androgen receptor and reduces testosterone production), hyperkalamia
- people to avoid giving: Addisons (reduced aldosterone anyway), hyperkalemia
- drug interactions: alcohol, ACEi, amioride (too much K sparing then), ARBs
challenges with multiple drugs
potential sites where diuretic delivery to the renal tubule can be opposed
- Gut oedema → hard to absorb med (furosemide) decompensated heart failure
- blood → nephrotic syndrome → low albumin so drug can’t bind
- PCT → patient has CKD, maybe bad OAT (transports anions across)
