Pharmacology and the Kidney Flashcards
Describe the RAAS system
- Blood pressure drops
- Renin released by the kidneys
- Angiotensinogen produced by the liver is converted to angiotensin I by renin
- ACE convert angiotensin I to angiotensin II in the lungs
- (Effects of angiotensin II - vasoconstriction)
- Aldosterone released by adrenal cortex (effects of aldosterone)
What are effects of aldosterone?
Sodium and water retention, potassium excretion –> increases blood pressure
What do beta blockers inhibit?
Renin release
Side effect of ACE inhibitors?
Cough - can cause bradykinin accumulation (as ACE normally breaks down bradykinin)
What is bradykinin?
A vasodilator
What drugs may be used instead of ACEi?
Angiotensin II receptor antagonists (but less data available for these drugs)
What type of cells contain renin?
Granular cells
What is renin release stimulated by?
Decreased pressure in afferent arteriole
Sympathetic nervous system
Changes in conc of chloride, osmotic conc
What is effect of ACEi?
Inhibit conversion of angiotensin I to angiotensin II so inhibit the vasoconstrictive effects of angiotensin II
How does ACEi act on the kidneys?
Act on efferent arteriole (prevents vasoconstriction due to lack of angiotensin II)
This modulates intra-glomerular pressure and increases sodium and water excretion
Why does ACEi act on efferent arteriole?
The efferent arteriole has a smaller diameter in the basal state; as a result, further constriction at this site will produce a greater increase in resistance than at the afferent arteriole.
This decreases pressure
What is the intra-glomerular pressure?
Pressure responsible for filtration
What are the indications that ACEi is needed?
Hypertension, cardiac failure, CKD
What are possible side effects of ACEi?
Hypotension (consider holding if AKI or risk of AKI)
Hyperkalaemia
How may ACEi lead to hyperkalaemia?
Decreased aldosterone levels (aldosterone normally increases levels of potassium released in urine)
What are examples of ACEi?
- Ramipril
- Lisinopril
(tend to end in -pril)
What are dangers of ACEi surrounding pregnancy?
Warn woman taking that she must not get pregnant as these can cause foetal abnormalities
What is effect of angiotensin receptor blockers (ARBs)?
Inhibit vasoconstrictive effect of angiotensin II on receptor
- Acts on efferent arteriole
- Modulates intra-glomerular pressure
- Increases sodium and water excretion
Why do ARBs act on efferent arteriole?
The efferent arteriole has a smaller diameter in the basal state; as a result, further constriction at this site will produce a greater increase in resistance than at the afferent arteriole.
This decreases pressure.
What are indications that ARBs are needed?
- Hypertension
- Cardiac failure
- CKD (reduces intra-renal pressure)
What are possible side effects of ARBs?
- Hypotension (consider holding if AKI or risk of AKI)
- Hyperkalaemia
How may ARBs lead to hyperkalaemia?
Decreased aldosterone levels (aldosterone normally increases levels of potassium released in urine)
What are examples of ARBs?
- Valsartan
- Irbesartan
Are there similar dangers of ARBs with pregnancy?
Yes
What are diuretics?
Drugs that increase salt and water excreted in urine
What are osmotic diuretics?
Inhibits reabsorption of water and sodium in regions of the kidney that are highly permeable to water
What are carbonic anhydrase inhibitors?
Weak diuretics, with the main site of action in the proximal tubular lumen and cell.
Reduce formation of bicarbonate and H+ ions by inhibiting carbonic anhydrase
This reduces bicarb and N+ reabsorption via the Na+/HCO3- cotransporter so promotes renal excretion of Na+, K+, bicarb and water.
How do loop diuretics work?
Inhibit the Na+/K+/2Cl co-transporter in the loop of Henle (in the kidney). This reduces Na, Cl and K reabsorption leads to increased loss in the urine, water follows this so excess water is lost
How can loop diuretics ease symptoms of oedema?
Less fluid remains in bloodstream which eases symptoms of oedema (accumulation of fluid) due to heart failure
What are thiazides?
A weak diuretic
How do thiazides work?
Promote diuresis by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron
Inhibits sodium uptake so increases excretion of sodium and water
What are indications that loop diuretics are required?
- CKD
- Nephrotic syndrome
- Hypertension
- Cardiac failure
What are possible side effects of loop diuretics?
- Hypovolaemia
- Hypokalaemia (can be used with potassium sparing diuretic)
What are indications that thiazides are required?
- CKD
- Nephrotic syndrome
- Hypertension
- Cardiac failure
What are possible side effects of thiazides?
Hypovolaemia
What is effect of Spironolactone?
Inhibits aldosterone
This prevents sodium reabsorption in exchange for potassium
What is spironolactone also referred to as?
Potassium sparing diuretic
What are the indications that spironolactone is required?
- Cardiac failure
- Liver cirrhosis (ascites)
What is ascites?
Abnormal buildup of fluid in the abdomen
What is common cause of ascites?
High blood pressure in the veins that bring blood to the liver (portal hypertension), which is usually due to cirrhosis.
What are possible side effects of spironolcatone?
Hyperkalaemia
What is amiloride?
Potassium sparing diuretic
How does amiloride work?
Inhibits sodium reabsorption in exchange for potassium
Removes sodium and water
What are the most potent diuretics?
Loop diuretics
When is amiloride is required?
To prevent hypokalaemia
What are possible side effects of amiloride?
Hyperkalaemia
How is vitamin D activated?
Hydroxylated in liver and then kidneys into calcitriol
What is effect of calcitriol?
Increase absorption of dietary calcium and phosphorus
How do healthy kidneys deal with calcium and phosphorus?
Decrease excretion of calcium
Increase excretion of phosphorus
If vitamin D is not activated, what happens?
Poor absorption of dietary calcium
Parathyroid glands sense low blood calcium and increase PTH secretion
This causes bones to release calcium and phosphorus –> can lead to bone disease and osteoporosis
What are vitamin D analogues?
A form of synthetic vitamin D
Hydroxylated by liver to active form
What are effects of vitamin D analogues?
Increases uptake of calcium and phosphate from gut
What are possible side effects of vitamin D analogues?
- Hypercalcaemia
- Hyperphosphataemia
What is erythropioetin?
Stimulates erythropoiesis. Produced by cells in the interstitium of the kidneys.
What is erythropioetin secretion stimulated by?
Hypoxia
Erythropioetin is given as a subcutaneous injection when eGFR drops below what?
eGFR < 15
What are potential side effects of erythropiotein?
- Hypertension (can lead to strokes)
- Pure red cell aplasia (rare)
What does reduced renal perfusion lead to?
Decreased transglomerular pressure, therefore decreased GFR
How do prostaglandins act on kidney?
Vasodilate afferent arteriole (to increase flow)
How do NSAIDs affect kidney?
Inhibit prostaglandins (reduce perfusion which can be dangerous)
What is effect of RAAS system on efferent arteriole? What does this lead to?
Vasoconstriction (Ag II), this increases transglomerular pressure and restores GFR
What is effect of ACEi and ARBs on efferent vasoconstriction?
Inhibit this which decreases transglomerular pressure and decreases GFR
What are dangers of ACEi and ARBs in AKI?
Can induce renal failure
Are penicillins excreted by the kidneys?
All penicillins except Flucloxacillin are excreted by the kidneys
What can accumulation of penicillin lead to?
CNS side effects (including seizures)
What can accumulation of opioid analgesics due to poor renal excretion lead to?
Accumulation of active metabolites (especially morphine, pethidine and codeine) can lead to increased incidence of CNS side effects and respiratory depression
What are the opiates with minimal renal excretion?
- Fentanyl
- Oxycodone
- Hydromorphone
What can accumulation of digoxin lead to?
Bradycardia, visual disturbances, mental confusion
Aggravates hyperkalaemia
What can accumulation of hypoglycaemic agents lead to? How can this be reduced?
Hypoglycaemia
- Aggravates hyperkalaemia
- Reduce dose
- Monitor drug level
What can accumulation of metformin lead to?
Poor excretion by kidneys leads to lactic acidosis and hypoglycaemia
What herbal medicines are implicated in interstitial nephritis?
Chinese herbal medicines with aristocholic acid implicated in interstitial nephritis
Cat’s Claw has anti-inflammatory properties
implicated in causing AKI and hypotension with antihypertensives
Remember to ask patient !
