Renal pharmacology Flashcards
(26 cards)
What is renal clearance of drugs?
volume of plasma containing the drug removed by the kidney per unit time
Describe glomerular filtration of drugs
Most drugs are small so can cross glomerulus freely
Drugs bound to albumin cannot cross
Describe active tubular secretion of drugs
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
Describe passive tubular resorption of drugs
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
How can aminoglycosides cause nephrotoxicity?
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
Describe the interactions between NSAIDs and the kidney
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
How can a non-toxic drug cause toxicity due to dosage?
Multiple repeated doses results in increasing plasma concentration and potentially toxicity
Decreasing dose frequency allows levels to return to normal
why is drug clearance an important consideration in elderly patients or those with renal disease
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
What are diuretics?
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)
What are the different groups of diuretics
Osmotic diuretics
Loop diuretics
Thiazides
Amiloride
Spironolactone
Describe the mechanism of action of osmotic diuretics
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
What is the effect of osmotic diuretics if given orally?
Will not be absorbed
cause water to be retained in intestines => diarrhoea
What are the indications of osmotic diuretics (mannitol)
forced diuresis (intoxication, impending kidney failure)
Emergency treatment of acutely raised intracranial or intraocular pressure
What are the unwanted effects of osmotic diuretics
transient expansion of extracellular fluid volume
hyponatraemia (acute)
Describe the mechanism of action of action of loop diuretics
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
Describe the pharmacokinetics of loop diuretics
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
What are the unwanted effects of loop diuretics e.g., flurosemide?
excessive water loss
Na and K loss following long-term use
Hypocalcaemia
Adaptive changes in circulation - RAAS activation
Describe the mechanism of action of thiazides
Act from within tubule:
- bind to Cl- site of distal tubule Na/Cl co-transport system
- inhibit Na+ reabsorption
- inhibit water reabsorption
What are the unwanted effects of thiazides?
adaptive changes in circulation
K loss following long-term use
What is the action of potassium-sparing diuretics?
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+
What are the unwanted effects of potassium sparing diuretics?
hyperkalaemia
What is the mechanism of action of aldosterone antagonists (diuretics)
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
Describe the pharmacokinetics of spironolactone
Well absorbed after oral administration and extensively metabolised by the liver to active metabolite
Slow onset of action - effects peak after 2-3 days
What are the indications for use of thiazides?
oedema
heart failure
