drugs which affect the kidney: diuretic agents Flashcards
1
Q
what types of drugs can affect the kidney? 9
A
- ACE inhibitors
- Anticancer drugs
- Antiviral agents
- Aminoglycosides
- Beta blockers
- Lithium
- NSAIDs
- Radiocontrast media
- Vasodilators
2
Q
what are diuretic agents? 4
A
- Any compound that causes the excretion of an increased volume of urine from the body
- A drug which increases the excretion of both fluids and solutes
- Natriuretic= increases Na+ excretion
- Kaliuretic= increase K+ excretion
3
Q
what do diuretics do to the kidney? 3
A
- Increase excretion of Na+ and water by the kidneys:
- They reduce reabsorption of Na+ from the filtrate
- They increase water loss secondary to Na+ excretion
4
Q
what do aquatic agents do?
A
- increase urine excretion without increasing Na+ excretion
5
Q
what are the modes of action of diuretics? 2
A
- Direct action on the cells at the nephron (more common)
- Modification of content of the filtrate
6
Q
why do we use diuretics? 12
A
- Reduce circulating fluid volume
- Removal of excess body fluid (oedema)
- Hypertension
- Chronic heart failure
- Liver cirrhosis
- Renal disease
- Premenstrual oedema
- Toxic oedema
- Increase elimination of drugs
- Rapid weight loss. (abuse)
- Glaucoma (reduces intra-ocular pressure)
- Epilepsy (reduces pressure of CSF
7
Q
describe the reabsorption of water and Na+? 2
A
- 5% of water is reabsorbed
99. 4% of Na+ is reabsorbed
8
Q
what are the different classes of diuretic agents? 5
A
- Carbonic anhydrase inhibitors= proximal tubule
- Osmotic diuretics= proximal tubule, descending loop of Henle
- Loop diuretics= ascending loop of Henle
- Thiazides and thiazide like diuretics= early distal tubule
- Potassium- sparing diuretics (aldosterone antagonists, non-aldosterone antagonists) = late distal tubule, early collecting tubule
9
Q
describe loop diuretics? 4
A
- Most effective diuretics available
- Often called high-ceiling diuretics: lead to torrential urine flow
- Inhibit the Na+/K+?2Cl- transporters (NKCC2) in the thick ascending limb of the loop of Henle: this reduces reabsorption of Na+, K+ and Cl-
- Reduced Na+ reabsorption leads to rapid and profound diuresis: a single dose can increase urine volume from 200 to 1,2000 ml over 3 hours
10
Q
what are the clinical uses of loop diuretics? 6
A
- Acute pulmonary oedema
- Chronic heart failure
- Cirrhosis of the liver
- Resistant hypertension
- Nephrotic syndrome
- Acute kidney injury
11
Q
what are the unwanted effects of loop diuretics? 5
A
- Dehydration
- K+ loss leading to low plasma K+ (hypokalaemia)
- Metabolic alkalosis (due to H+ loss in the urine)
- Hypokalaemia can potentiate effects of cardiac glycosides
- Deafness (when used with aminoglycoside antibiotics)
12
Q
describe the sodium-potassium exchange in the DT? 3
A
- Loop diuretics cause increased Na+ delivery to the distal tubule
- This is exchanged for K+ in the DT which is excreted in the urine
- This K+ loss contributes to the hypokalaemia associated with loop diuretics
13
Q
describe thiazide diuretics? 5
A
- Act in the distal tubule to inhibit the apical Na+/Cl- co-transporter
- Cause moderate but sustained Na+ excretion with increased water excretion
- Moderately powerful diuresis: but maximum diuresis produced is considerably lower than that produced by loop diuretics
- Well absorbed from the GI tract and long duration of action: up to 24 hours
- Main thiazide is Bendroflumethiazide= useful for moderate/mild heart failure
14
Q
describe thiazide- like diuretics? 2
A
- Similar but different molecular structures
- Indapamide- preferred for resistant hypertension due to lower incidence of unwanted effects
15
Q
what are the clinical uses of thiazide and thiazide like diuretics? 3
A
- Hypertension
- Oedema
- Mild heart failure
16
Q
what are the unwanted effects of thiazide and thiazide like diuretics? 6
A
- Plasma K+ depletion (due to urinary K+ loss)
- Metabolic alkalosis (due to urinary H+ loss)
- Increased plasma uric acid- gout
- Hyperglycaemia (increased blood glucose)
- Increased plasma cholesterol (with long term use)
- Male impotence (reversible)
17
Q
describe why hypokalaemia can be a problem? 3
A
- Due to increased loss of K+ in the urine, loop diuretics and thiazides can cause hypokalaemia
- Mild= fatigue, drowsiness, dizziness, muscle weakness
- Severe= abnormal heart rhythm, muscle paralysis, death
18
Q
describe potassium sparing diuretics? 3
A
- Potassium sparring diuretics can avoid this problem by acting on distal tubules to inhibit Na+ reabsorption however K+ is not secreted into the distal tubule
- Two subcategories:
- Aldosterone antagonists (eplerenone, spironolactone)
- Non-aldosterone antagonists (amiloride, triamterene)
19
Q
describe spironolactone and eplerenone? 5
A
- Spironolactone is metabolised to canrenone (its active metabolite)
- A competitive antagonist of aldosterone (mineralocorticoid) receptor
- Reduces Na+ channel formation and its absorption from the distal tubule
- Limited diuretic action (not as potent as loop diuretics or thiazides)
- As mechanisms depends on reduction of protein expression in distal tubular cells, effects normally take several days to develop
20
Q
what are the clinical uses of spironolactone and eplerenone? 4
A
- Heart failure
- Oedema
- Short term use
- Can also be used for resistant hypertension but some concerns over long- term use due to possible incidence of cancer
21
Q
what are the unwanted effects of spironolactone and eplerenone? 5
A
- Hyperkalaemia (increased plasma K+ levels)- needs to be monitored regularly)
- Metabolic acidosis (due to increased plasma H+)
- GI upsets (peptic ulceration reported)
- Gynaecomastia, menstrual disorders, testicular atrophy
- Eplerenone produces less unwanted effects than spironolactone
22
Q
describe triamterene and amiloride? 3
A
- Weak diuretics act on distal tubule to inhibit Na+ reabsorption and decrease K+ excretion
- Blocks luminal Na+ channel by which aldosterone produces its main effects
- Of little therapeutic use alone but are useful in combination with potassium depleting diuretics as they limit hypokalaemia
23
Q
describe the unwanted effects of triamterene and amiloride? 4
A
- Hyperkalaemia
- Metabolic acidosis
- GI disturbances
- Skin rashes
24
Q
why do we use diuretics in combination? 6
A
- To increase diuretic effect:
- Some patients do not respond well to just one type of diuretic for unknown reasons
- Combinations of diuretics with different sites of action can sometimes provide synergistic action which can become complicated
- .
- To avoid the unwanted effects of hypokalaemia (reduces plasma K+ levels):
- Combinations of loop diuretics or thiazides with potassium sparing diuretics
- Diuretic preparations containing K+
25
what are the different diuretic combinations to avoid hypokalaemia? 4
- Loop diuretics and spironolactone
- Loop diuretics with amiloride or triamterene
- Thiazides with spironolactone
- Thiazides with amiloride or triamterene
26
describe carbonic anhydrase inhibitors? 4
- Acetazolamide
- Block’s sodium bicarbonate reabsorption in the PT
- These were the earliest diuretics developed
- Causes only weak diuresis so not now used commonly
27
describe the use of carbonic anhydrase inhibitors?
- Glaucoma
| - Epilepsy
28
describe the unwanted effects of carbonic anhydrase inhibitors? 2
- Metabolic acidosis (due to excretion of HCO3-)
| - Enhances renal stone formation (due to alkaline urine)
29
describe osmotic diuretics? 4
- Mannitol
- Non-resorbable solute which undergoes glomerular filtration
- Excreted within 30-60 minutes
- Diuresis begins in 30-60 minutes and persists for 6-8 hours
30
what are the clinical uses of osmotic diuretics? 4
- Treatment of raised intercranial pressure (cerebral oedema)
- Treatment of intraocular pressure
- If given orally can cause osmotic diarrhoea which eliminates toxins
- May be useful for treatment of acute renal failure
31
what are the unwanted effects of osmotic diuretics?
- Presence in blood also exerts osmotic pressure leading to increased plasma volume so can’t be used in patients with hypertension
32
describe water as a diuretic? 3
- Under normal conditions, increased water intake leads to an increase in the volume of urine excreted
- Process is controlled by ADH which is the most important hormone in regulating water balance
- Normally some ADH is present in the circulation maintaining urine volume at around 1.5L/day
33
describe ADH antagonists? 7
- Potential ADH antagonists:
- Investigational drugs which inhibit the effects of ADH at the collecting tubule
- Two non-selective agents (orally active) = lithium and demeclocycline
- Toxicity is a problem:
- Can cause diabetes insipidus
- Renal failure reported for both Li+ and demeclocycline
- Li+ can cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction and leucocytosis
- Demeclocycline shouldn’t be used in patients with liver disease
34
describe an agent which inhibits ADH release?
- Alcohol (although tolerance develops rapidly so diuresis is not sustained)
35
describe an agent which increases ADH release? 4
- Nicotine
- Ether
- Morphine
- Barbiturates
36
describe Xanthine's? 5
- Commonly found in tea of coffee
- Produce their weak diuretic effect by increasing cardiac output
- Possibly also some vasodilation of the glomerular afferent arteriole
- Results in increased renal and glomerular blood flow which increases glomerular filtration rate and urine output
- Rarely used clinically due to gastric irritant effects (but theophylline used clinically as a bronchodilator for asthma)
