Renal pharmacology

Question 1

What is renal clearance of drugs?

Answer 1

volume of plasma containing the drug removed by the kidney per unit time

Question 2

Describe glomerular filtration of drugs

Answer 2

Most drugs are small so can cross glomerulus freely
Drugs bound to albumin cannot cross

Question 3

Describe active tubular secretion of drugs

Answer 3

Drugs can be transferred into tubular lumen by non-selective carrier systems:
- organic anion transporter (OATs) - acidic drugs against electrochemical gradient
- organic cation transporters (OCTs) - organic based drugs down gradient

Question 4

Describe passive tubular resorption of drugs

Answer 4

Lipid soluble drugs are poorly excreted as they are reabsorbed
Drug excretion is influenced by degree of ionisation and urinary pH:
- ionised drugs cannot cross plasma membrane
- acidic drugs are more rapidly excreted if urine is alkaline
- basic drugs are more rapidly excreted if urine is acidic

Question 5

How can aminoglycosides cause nephrotoxicity?

Answer 5

Cause tubular cell toxicity by:
- accumulating in lysosome of PCT epithelial cells
- impair mitochondrial function => increasing oxidative stress and free radicals
- interfere with tubular transport

Question 6

Describe the interactions between NSAIDs and the kidney

Answer 6

Prostaglandins dilate afferent arteriole
NSAIDs (COX2 inhibitors) block prostaglandin production => decrease blood flow to kidneys => acute kidney injury

NSAIDs can induce an immunological reaction after a period of exposure => inflammatory cells infiltrate kidney interstitium => acute interstitial nephritis => AKI

Question 7

How can a non-toxic drug cause toxicity due to dosage?

Answer 7

Multiple repeated doses results in increasing plasma concentration and potentially toxicity
Decreasing dose frequency allows levels to return to normal

Question 8

why is drug clearance an important consideration in elderly patients or those with renal disease

Answer 8

Drugs removed predominantly by renal excretion are liable to cause toxicity
Polar drugs remain in lumen and get progressively more concentrated - these drugs need special care in patients with renal function

Question 9

What are diuretics?

Answer 9

drugs that increase the rate of urine flow and excretion of Na+ and water from filtrate
Decrease the reabsorption of Na and Cl from filtrate
Cause increased water loss (secondary to Na excretion)

Question 10

What are the different groups of diuretics

Answer 10

Osmotic diuretics
Loop diuretics
Thiazides
Amiloride
Spironolactone

Question 11

Describe the mechanism of action of osmotic diuretics

Answer 11

Indirectly act on cells of nephron:
- drug is filtered in glomerulus but cannot be reabsorbed
- increase the osmolarity of filtrate
- water is retained in urine to maintain osmotic balance
- => decreases concentration Na+ in lumen and decreases reabsorption of Na+
IV administration

Question 12

What is the effect of osmotic diuretics if given orally?

Answer 12

Will not be absorbed
cause water to be retained in intestines => diarrhoea

Question 13

What are the indications of osmotic diuretics (mannitol)

Answer 13

forced diuresis (intoxication, impending kidney failure)
Emergency treatment of acutely raised intracranial or intraocular pressure

Question 14

What are the unwanted effects of osmotic diuretics

Answer 14

transient expansion of extracellular fluid volume
hyponatraemia (acute)

Question 15

Describe the mechanism of action of action of loop diuretics

Answer 15

Act from within the tubule:
- Na+, K+ and Cl- enter blood by a co-transport system
- loop diuretics act on NKCC2 symporter in the thick ascending loop of LoH
- inhibits Na, K and Cl reabsorption => diuresis

Interfere with tubular feedback control of GFR => no decrease of GFR

Question 16

Describe the pharmacokinetics of loop diuretics

Answer 16

Tightly bound to plasma protein:
- do not pass directly into glomerular filtrate
- secreted into tubule by organic anion transporters
- action reduced if proteinuria is present

Rapid onset of action - 30 mins after administration

Question 17

What are the unwanted effects of loop diuretics e.g., flurosemide?

Answer 17

excessive water loss
Na and K loss following long-term use
Hypocalcaemia
Adaptive changes in circulation - RAAS activation

Question 18

Describe the mechanism of action of thiazides

Answer 18

Act from within tubule:
- bind to Cl- site of distal tubule Na/Cl co-transport system
- inhibit Na+ reabsorption
- inhibit water reabsorption

Question 19

What are the unwanted effects of thiazides?

Answer 19

adaptive changes in circulation
K loss following long-term use

Question 20

What is the action of potassium-sparing diuretics?

Answer 20

Triamterene and amiloride
Act from within tubule:
- directly block epithelial Na+ channel
- inhibits Na+ reabsorption in collecting ducts
- promotes loss of Na+ and water without depleting K+

Question 21

What are the unwanted effects of potassium sparing diuretics?

Answer 21

hyperkalaemia

Question 22

What is the mechanism of action of aldosterone antagonists (diuretics)

Answer 22

Spironolactone
Act from within tubule:
- tubule cells are impermeable to Na+ in absence of aldosterone
- spironolactone competes with aldosterone at its receptor
- causes milk diuresis and potassium retention

Question 23

Describe the pharmacokinetics of spironolactone

Answer 23

Well absorbed after oral administration and extensively metabolised by the liver to active metabolite
Slow onset of action - effects peak after 2-3 days

Question 24

What are the indications for use of thiazides?

Answer 24

oedema
heart failure

Question 25

What are the indication for use of loop diuretics?

Answer 25

oedema
heart failure
forced diuresis (intoxication, renal failure)

Question 26

What is the best way to keep your girlfriend happy

Answer 26

Buy chicken gyozas
Make brownies
Back scratches
Massage her sore back and shoulders