Pharmacology and the Kidney Flashcards by Esme Cosham

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)

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What are effects of aldosterone?

Sodium and water retention, potassium excretion –> increases blood pressure

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What do beta blockers inhibit?

Renin release

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Side effect of ACE inhibitors?

Cough - can cause bradykinin accumulation (as ACE normally breaks down bradykinin)

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What is bradykinin?

A vasodilator

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What drugs may be used instead of ACEi?

Angiotensin II receptor antagonists (but less data available for these drugs)

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What type of cells contain renin?

Granular cells

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What is renin release stimulated by?

Decreased pressure in afferent arteriole

Sympathetic nervous system

Changes in conc of chloride, osmotic conc

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What is effect of ACEi?

Inhibit conversion of angiotensin I to angiotensin II so inhibit the vasoconstrictive effects of angiotensin II

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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

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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

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What is the intra-glomerular pressure?

Pressure responsible for filtration

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What are the indications that ACEi is needed?

Hypertension, cardiac failure, CKD

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What are possible side effects of ACEi?

Hypotension (consider holding if AKI or risk of AKI)

Hyperkalaemia

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How may ACEi lead to hyperkalaemia?

Decreased aldosterone levels (aldosterone normally increases levels of potassium released in urine)

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What are examples of ACEi?

Ramipril
Lisinopril

(tend to end in -pril)

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What are dangers of ACEi surrounding pregnancy?

Warn woman taking that she must not get pregnant as these can cause foetal abnormalities

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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

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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.

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What are indications that ARBs are needed?

Hypertension
Cardiac failure
CKD (reduces intra-renal pressure)

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What are possible side effects of ARBs?

Hypotension (consider holding if AKI or risk of AKI)

- Hyperkalaemia

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How may ARBs lead to hyperkalaemia?

Decreased aldosterone levels (aldosterone normally increases levels of potassium released in urine)

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What are examples of ARBs?

Valsartan

- Irbesartan

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Are there similar dangers of ARBs with pregnancy?

Yes

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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 !

Pharmacology and the Kidney Flashcards

(71 cards)