Drugs and the Kidney Flashcards
Tubular secretion of drugs is independent of protein binding. T/F?
True
Glomerular filtration of drugs depends on GFR and protein binding. T/F?
True
Weak acids are more easily secreted into urine of what pH?
Alkaline pH
Why are lipid soluble drugs not excreted to any great extent in the urine?
They are passively reabsorbed by diffusion across the tubule
In which part of the kidney tubule are weak acid drugs most actively secreted?
PCT
Which formula is used to calculate a drug dose in light of impaired GFR?
Cockcroft Gault formula
What effect does chronic kidney disease have an the metabolism of drugs such as CNS depressants and antihypertensives?
Increased sensitivity to these drugs
What effect does chronic kidney disease have an the metabolism of drugs such as diuretics and urinary antibacterials?
Reduced sensitivity to these drugs
Why is the increased sensitivity to opiates in patients with impaired renal function significant?
It causes significant respiration depression
Give examples of some drugs which have enhanced adverse effects in the presence of chronic kidney disease?
Digoxin
Potassium-sparing diuretics
Biguanides
Sulphonylureas
Reduced excretion of drugs due to chronic kidney disease leads to enhanced toxicity. Give example of drugs for which this is a problem?
Opiates / CNS depressants
Aminoglycosides
Digoxin
Aciclovir
When is dose adjustment in renal failure required?
When the drug has at least a 50% renal clearance and a low therapeutic index
Give examples of some drugs whose dose needs adjusted in renal failure?
Aminoglycosides Lithium Amphotericin Metofrmin ACE inhibitors Methotrexate
What are the ideal qualities of a drug for use in patients with renal failure?
Predominately secreted by liver
<25% excretion unchanged
No active metabolites
Wide therapeutic index
Disposition unaffected by protein binding or fluid balance changes
Response unaffected by tissue sensitivity changes
Not nephrotoxic
How can NSAID use result in acute kidney injury?
The prostaglandins produced by these drugs can cause afferent arteriole dilation and an increase in GFR
Give examples of drugs which can cause acute tubular necrosis?
Aminoglycosides Amphotericin B Cisplatin NSAIDs Radiocontrast media Paracetamol
Give examples of drugs which can cause renal tubular acidosis?
Acetaxolamide
Amphotericin B
lithium
Give examples of drugs which can cause interstitial nephritis?
Allopurinol Azathioprine Frusemide NSAIDs Penicillins Sulphonamides Thiazides Vancomycin
Give examples of drugs which can cause nephrotic diabetes insipidus?
Lithium
Demeclocycline
Give examples of drugs which can cause renal papillary necrosis?
Aspirin
NSAIDs
What are some of the generic causes of nephrotoxicity?
Pre-renal acute kidney injury
Glomerular damage
Tubular damage
Ureteric obstruction
What is the presentation of nephrotoxicity?
Acute kidney injury Chronic renal failure Nephrotoxic syndrome Lupus-like syndrome Nephrogenic diabetes insipidus Fluid overload Uraemia
Give examples of loop diuretics
Bumetanide
Furosemide
Give an example of a thiazide diuretic
Bendroflumethazide
Give an example of a potassium sparing diuretic?
Spironolactone
What part of the nephron is the site of action of a loop diuretic?
Thick ascending loop of Henle
What part of the nephron is the site of action of a thiazide diuretic?
Cortical DCT
What part of the nephron is the site of action of a potassium sparing diuretic?
Distal DCT and collecting duct
What is the clinical use of loop diuretics?
Odema
Acute renal failure
Hypertension
Hypercalcaemia
What is the clinical use of thiazide diuretics?
Hypertension
Oedema
Hypercalcaemia
Nephrogenic diabetes insipidus
What is the clinical use of potassium sparing diuretics?
Potassium conservation
Oedema
Hyperaldosteronism
Hypertension
Loop diuretics can cause ototoxicity in high doses.T/F?
True
Which transporter do loop diuretics work on?
The sodium/potassium/2chloride transporter
What is the action of amiloride?
A sodium channel blocker - blocks the ENaC channel in the collecting duct
What are the potential side-effects of thiazide and loop diuretics?
Non-specific GI upsets
Hypersensitivity reactions
Metabolic effects (hypokalaemia, rate retention, glucose intolerance)
Ototoxicity
Glomerular filtration will filter non-protein bound drugs of a molecular weight below…?
20kDa
What is the name of the type of transporter which aids the secretion of acidic drugs?
Organic anion transporter (OAT)
What is the name of the type of transporter which aids the secretion of acidic drugs?
Organic cation transporter (OCT)
Carrier-mediated transport in the secretion of drugs in the kidney tubule can achieve maximal drug clearance even when most of the drug is bound to plasma proteins. T/F?
True
How can one drug affect the rate of renal excretion of another drug?
By altering protein binding and hence altering filtration of the drug
Inhibiting tubular secretion of the drug
Altering urine flow and/or pH
