Drugs with Adverse Effects on Renal Function

Question 1

three main mechanisms by which drugs can have adverse effects on the kidneys

Answer 1

reducing extracellular fluid volume
direct effects on renal blood vessels
toxic effects on renal cells

Question 2

most obvious cause of dehydration causing damage to kidney function

Answer 2

diuretics

Question 3

what happens in the kidneys when extracellular fluid volume decreases significantly

Answer 3

arteriole blood pressure decreases
protective mechanisms initiated - renin-angiotensin system activated and SNS activated
brain, heart and kidneys protected
continued decrease in perfusion will eventually result in glomerular filtration rate falling which means waste products can’t be cleared

Question 4

two drugs classes most likely to have direct affects on renal blood flow

Answer 4

those affecting RAS - e.g. ACEis and ARBs
NSAIDs

Question 5

two important presentations of toxicity

Answer 5

acute tubular necrosis
acute interstitial nephritis

Question 6

early signs of diuretic-induced dehydration

Answer 6

thirst
dizziness - especially after sitting up
reduced urinary volume

Question 7

signs of dehydration

Answer 7

decreased skin turgor
reduced BP
postural hypotension

Question 8

investigations for dehydration monitoring

Answer 8

blood tests that demonstrate impaired renal function (e.g. increased urea and creatinine)

Question 9

pathway of dehydration

Answer 9

• ↓ plasma volume
• ↓ venous return to the heart
• ↓ arterial blood pressure
• ↓ tissue perfusion
• changes sensed by arterial baroreceptors and low pressure stretch receptors in the heart
• protective reflexes initiated - activation of SNS and RAS
• SNS causes vasoconstriction and ↓ perfusion of kidneys
• ↓ perfusion reduces blood supply to glomeruli
• ↓ filtration due to ↓ hydrostatic pressure in glomerular capillaries
• ↓ GFR
• ↓ volume of urine produced
• this preserved threatened fluid volume

Question 10

pathway of dehydration

Answer 10

• ↓ plasma volume
• ↓ venous return to the heart
• ↓ arterial blood pressure
• ↓ tissue perfusion
• changes sensed by arterial baroreceptors and low pressure stretch receptors in the heart
• protective reflexes initiated - activation of SNS and RAS
• SNS causes vasoconstriction and ↓ perfusion of kidneys
• ↓ perfusion reduces blood supply to glomeruli
• ↓ filtration due to ↓ hydrostatic pressure in glomerular capillaries
• ↓ GFR
• ↓ volume of urine produced
• this preserves threatened fluid volume

Question 11

drugs which cause diarrhoea

Answer 11

laxatives
proton pump inhibitors
antibiotics
others

Question 12

which three conditions when combined with ACEis and ARBs are most likely to cause renal impairment

Answer 12

dehyrdation
systemic arterial hypotension
renal artery stenosis

Question 13

how do NSAIDs interfere with renal function

Answer 13

inhibit generation of prostaglandins E2 and I2 which have a role in regulating vasomotor tone and tubular transport

Question 14

function of PGE2 and PGI2

Answer 14

vasodilators that enhance glomerular perfusion
inhibit sodium-potassium-chloride co-transporter in the TAL of LoH

Question 15

under what condition is the actions of PGE2 and PGI2 up-regulated

Answer 15

when glomerular perfusion is threatened

Question 16

who is most at risk of impaired renal function due to NSAIDs

Answer 16

elderly
those who take drugs which affect RAS (ACEis or ARBs)

Question 17

contraindications of NSAIDs

Answer 17

hypertension
heart failure

Question 18

three main mechanisms of direct toxic damage on kidneys

Answer 18

acute tubular necrosis
acute interstitial nephritis
tubular dysfunction

Question 19

what is acute tubular necrosis

Answer 19

process of direct injury to the renal tubules resulting in dysfunction and death of the cells and obstruction of the tubules caused by cellular debris

Question 20

non-drug causes of acute tubular necrosis

Answer 20

bacterial sepsis
renal ischaemia

Question 21

drug causes of acute tubular necrosis

Answer 21

aminoglycoside antibiotics
amphotericin B
calcineurin inhibitors
chemotherapeutic agents
aciclovir
poisins
radiocontrast media

Question 22

what is acute interstitial nephritis

Answer 22

where there is an acute hypersensitivity reaction manifesting as inflammation in the interstitial spaces around the renal tubules

Question 23

clinical features of acute interstitial nephritis

Answer 23

low grade fever
skin rash
eosinophilia
protein and white blood cells in urine

Question 24

common drug causes of acute interstitial nephritis

Answer 24

antibiotics
NSAIDs
PPIs

Question 25

what is tubular dysfunction

Answer 25

when drugs have direct affects which alter tubular function without inducing acute tubular necrosis

Question 26

effect of lithium on kidney funciton

Answer 26

can compete with other cations in tubular cells and cause polyuria secondary to impairing urine concentrating ability

Question 27

effect of cumulative exposure to heavy metals (e.g. lead, mercury, arsenic, cadmium)

Answer 27

impaired tubular function
excessive loss of glucose, amino acids, phosphate and small proteins which would normally be reabsorbed