Drugs with Adverse Effects on Renal Function Flashcards
three main mechanisms by which drugs can have adverse effects on the kidneys
reducing extracellular fluid volume
direct effects on renal blood vessels
toxic effects on renal cells
most obvious cause of dehydration causing damage to kidney function
diuretics
what happens in the kidneys when extracellular fluid volume decreases significantly
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
two drugs classes most likely to have direct affects on renal blood flow
those affecting RAS - e.g. ACEis and ARBs
NSAIDs
two important presentations of toxicity
acute tubular necrosis
acute interstitial nephritis
early signs of diuretic-induced dehydration
thirst
dizziness - especially after sitting up
reduced urinary volume
signs of dehydration
decreased skin turgor
reduced BP
postural hypotension
investigations for dehydration monitoring
blood tests that demonstrate impaired renal function (e.g. increased urea and creatinine)
pathway of dehydration
- ↓ 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
pathway of dehydration
- ↓ 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
drugs which cause diarrhoea
laxatives
proton pump inhibitors
antibiotics
others
which three conditions when combined with ACEis and ARBs are most likely to cause renal impairment
dehyrdation
systemic arterial hypotension
renal artery stenosis
how do NSAIDs interfere with renal function
inhibit generation of prostaglandins E2 and I2 which have a role in regulating vasomotor tone and tubular transport
function of PGE2 and PGI2
vasodilators that enhance glomerular perfusion
inhibit sodium-potassium-chloride co-transporter in the TAL of LoH
under what condition is the actions of PGE2 and PGI2 up-regulated
when glomerular perfusion is threatened
who is most at risk of impaired renal function due to NSAIDs
elderly
those who take drugs which affect RAS (ACEis or ARBs)
contraindications of NSAIDs
hypertension
heart failure
three main mechanisms of direct toxic damage on kidneys
acute tubular necrosis
acute interstitial nephritis
tubular dysfunction
what is acute tubular necrosis
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
non-drug causes of acute tubular necrosis
bacterial sepsis
renal ischaemia
drug causes of acute tubular necrosis
aminoglycoside antibiotics
amphotericin B
calcineurin inhibitors
chemotherapeutic agents
aciclovir
poisins
radiocontrast media
what is acute interstitial nephritis
where there is an acute hypersensitivity reaction manifesting as inflammation in the interstitial spaces around the renal tubules
clinical features of acute interstitial nephritis
low grade fever
skin rash
eosinophilia
protein and white blood cells in urine
common drug causes of acute interstitial nephritis
antibiotics
NSAIDs
PPIs
what is tubular dysfunction
when drugs have direct affects which alter tubular function without inducing acute tubular necrosis
effect of lithium on kidney funciton
can compete with other cations in tubular cells and cause polyuria secondary to impairing urine concentrating ability
effect of cumulative exposure to heavy metals (e.g. lead, mercury, arsenic, cadmium)
impaired tubular function
excessive loss of glucose, amino acids, phosphate and small proteins which would normally be reabsorbed
