Drugs Which Affect the Kidney Flashcards
What are two modes of action for diuretics?
- Direct action on the cells of the nephron ( more common)
- Modification of content of the filtrate
List 4 situations which you would use diuretics?
- hypertension
- CHF
- liver cirrhosis
- renal disease
- premenstrual oedema
- toxic oedema
- increase the elimination of drugs
- rapid weight loss (abuse)
What are the 5 classes of diuretic agents?
- Carbonic anhydrase inhibitor
- Osmotic diuretic
- Loop diuretics
- Thiazide and Thiazide-like diuretics
- Potassium-sparring diuretics: (Non-) Aldosterone antagonists
Where is the main site of action for the class of diuretics: carbonic anhydrase inhibitors
- the proximal tubule
Where is the main site of action for the class of diuretics: Osmotic diuretics
- Proximal tubule
- Descending Loop of Henle
(water permeable parts of the nephron)
Where is the main site of action for the class of diuretics: Loop diuretics?
- Ascending Loop of Henle
Where is the main site of action for the class of diuretics: Thiazide and Thiazide-like diuretics?
- Early distal tubule
Where is the main site of action for the class of diuretics: Potassium-sparing diuretics
- Late distal tubule
- Early collecting tubule (duct)
Describe the action of Loop Directs
- Inhibits the action of NKCC2 in the thick ascending Loop of Henle
- Na+, K+ and Cl- not reabsorbed from the tubule
- reduced Na+ reabsorption leads to rapid and significant diuresis
- the osmotic gradient isn’t created in the medulla –> less water being reabsorbed from descending limb of LOH
- urine output from 200 to 1200 ml in 3 hours
When would use of Loop diuretics be clinically indicated?
- Acute pulmonary oedema
- Chronic Heart Failure
- Cirrhosis of the liver
- Resistant hypertension
- reduced urine production (oliguria)*
- Nephrotic syndrome
- Acute kidney syndrome
What are the unwanted effects of Loop diuretics?
- Dehydration
- Hypokalaemia: K+ loss leading to low plasma K+
- Metabolic alkalosis: due to H+ loss in urine
- Hypokalaemia can potentiate the effects of cardiac glycosides (increase output force of the heart and increase HR acts on Na/K pump)
- Deafness: when used with aminoglycoside antibiotics
Describe the action of Thiazide diuretics
- Inhibit the Na/Cl co-transporter in the distal tubule
- cause moderate but sustained Na+ secretion with increased water excretion
- well-absorbed from GI tract and long duration of action: up to 24h
Give examples of thiazide and thiazide-like diuretics and their indications?
- Bendroflumethiazide: useful for mild/moderate heart failure
- Chlortalidone: preferred for ascites due to cirrhosis of stable patients; oedema due to nephrotic syndrome
Thiazide-like diuretics
- Indapamide: preferred for hypertension
- Metolazone: good combined with loop diuretics, good for Oedema
- Xipamide: lowers BP with less side effects, good for Oedema
What are the unwanted effects of Thiazide diuretics and what drug is used for the least unwanted effects?
- Plasma K+ depletion
- Metabolic alkalosis: due to urinary H+ loss
- Increased plasma uric acid- gout
- Hyperglycaemia
- Increased plasma cholesterol (with long term use)
- Male impotence (reversible)
Indapamide
What are the symptoms and clinical features Mild Hypokalemia?
- Loop Diuretics and Thiazide diuretics
- fatigue
- drowsiness
- dizziness
- muscle weakness
What are the symptoms and clinical features Severe Hypokalemia?
- abnormal heart rhythm
- muscle paralysis
- death
Describe the action of Potassium-Sparing diuretics: Aldosterone antagonists
- aldosterone antagonist in the distal tubule
- used short-term fro Heart failure and Oedema
- Spironolactone (or Epleronone) is metabolised to canrenone (active form)
- acts as a competitive inhibitor for aldosterone receptor
- reduce Na+ channel formation and its absorption from the distal tubule
- limited diuretic action, takes several days to take effect as its affecting the protein expression on distal tubular cells
What are the unwanted effects of the Potassium-sparing diuretic drug Spironolactone?
- Hyperkalaemia: needs regularly monitoring
- Metabolic acidosis (increased plasma H+)
- GI upsets (peptic ulceration)
- Gynaecomastia, menstrual disorders, testicular atrophy
- Eplerenone produces less unwanted effects than spironolactone
What is the use of Triamterene and Amiloride?
- weak diuretics best used in combination with potassium depleting-diuretics to limit hypokalaemia
- blocks luminal Na+ channel which aldosterone acts on to produce its main effect
What is the main unwanted effect of Potassium-sparing diuretics Triamterene and Amiloride?
- hyperkalaemia
- metabolic acidosis
- GI disturbance
- skin rashes
What diuretic combinations can be used to avoid hypokalemia?
Loop diuretics with spironolactone
- Lasilactone®: furosemide + spironolactone
Loop diuretics with amiloride or triamterene
- Co-amilofruse: furosemide + amiloride
Thiazides with spironolactone
- Co-flumactone: hydroflumethiazide + spironolactone
Thiazides with amiloride or triamterene
- Co-amilozide: hydrochlorothiazide + amiloride
Diuretics containing K+
Describe the action and indicated use of the diuretic type: Carbonic Anhydrase Inhibitors
- what are the unwanted effects
- Blocks NaHCO3 reabsorption in the Proximal tubule
- weak diuresis
Used for:
- glaucoma (reduces intraocular pressure)
- epilepsy (reduces volume and pressure of CSF)
Unwanted effects:
- metabolic acidosis (due to excretion of HCO3-)
- enhances renal stone formation (alkaline urine)
Describe the action and indicated use of Osmotic diuretics.
- give an example
- what are the unwanted effects?
- Mannitol
- non-absorbable solute undergoes glomerular filtration
- excreted within 30-60min
- diuresis begins within 30-60 mins and persists for 6-8h
Used for:
- cerebral oedema
- glaucoma (eye thing)
- osmotic diarrhoea if given orally
- acute renal failure
Unwanted effects:
increases plasma volume can’t be used in those with hypertension
