Drugs And The Kidneys Flashcards
(41 cards)
A large proportion of acute kidney injury (AKI) is drug/chemical induced. This is because the kidneys are susceptible to 4 things. What are they?
- Vascularity
- Large SA for binding + transport
- Reabsorption of water from kidneys which concentrates some drugs in the nephron
- Main route of excretion for most drugs
What should you consider when prescribing for patients with renal disease?
- How the renal impairment affects handling/effective of drug: drugs may accumulate to toxic levels if excreted through kidneys in renal impairment
- Could the drug worsen the renal impairment: i.e. avoid nephrotoxic drugs (e.g. aminoglycosides like gentamicin can be directly toxic to tubular cells)
Why do problems occur with medications in patients with impaired renal function?
Reduced renal excretion of drug
Side-effects poorly tolerated (e.g. increased K+)
Increased sensitivity to some drugs
Some drugs less effective (e.g. diuretics like furosemide)
How can you avoid/minimise problems when prescribing drugs to patients with renal impairment?
Reducing dose/frequency
Considering alternative drugs (e.g. different antibiotic to aminoglycoside)
What are dose adjustments of drugs based on?
Severity of renal impairment
Proportion of drug eliminated by renal excretion (some may be more liver dependent)
Toxicity of drug/’safety margin’ (therapeutic window)
In what 3 patient groups must more accurate measures of GFR be used than eGFR?
Elderly patients (>75 yrs)
Toxic drugs
Patients at extremes of weight
What 3 pieces of practical advice can be given for prescribing drugs?
Check BNF for individual drug advice
Be aware that renal function normally declines with age when prescribing to elderly
Understand limitations of eGFR (+ other measures) + how this can be misleading
What are the prescribing considerations for patients on dialysis?
Need specialist advice
Some drugs will be removed by dialysis + may lead to loss of therapeutic effect
No longer have to worry about nephrotoxic effects (advantage as machine has taken over kidney function)
How does urine pH affect speed of drug excretion?
Most drugs weak acids or bases:
Alkaline urine will more readily ionise acidic drugs (+ vice versa) -> ionised substances (polar) are more water soluble -> easier to excrete via kidneys (urine pH can be manipulated for treatment e.g. aspirin is a weak acid so infuse sodium bicarbonate to increase excretion in poisoning)
What are diuretics and what are they commonly used for?
Substance that promotes formation (excretion) of urine most commonly by promoting renal excretion of Na+ (natriuresis)
Commonly used for conditions associated with oedema + hypertension
What are the 6 types of diuretic (in decreasing number of importance from top to bottom)?
Loop Thiazide (+ related) K+ sparing Carbonic anhydrase inhibitors Osmotic ADH antagonists
Where is Na+ reabsorbed in the nephron?
100% filtered ->
~65% in PT
~25% in ascending loop of henle
~8% in DT + collecting duct
Where is water reabsorbed in the nephron?
~65% in PT
~20% in descending loop of henle
~15% in cortical + medullary collecting ducts
Why are diuretics that act on the more proximal area of the nephron more powerful?
More Na+ is still in the tubule fluid at this stage as less has been reabsorbed so there is more to play with (if Na+ is affected, water will follow as a general rule)
How do carbonic anhydrase inhibitors work?
Inhibit carbonic anhydrase in PT but have weak diuretic action as only small amount of Na+ normally reabsorbed in this way
Also prevents secretion of H+ (side effect could be metabolic acidosis)
E.G. acetazolamide
Why is carbonic anhydrase needed in the reabsorption of Na+/water?
HCO3- ions from tubular lumen cannot be directly transported into tubular cells. Secreted H+ is needed to covert HCO3- -> H2CO3. H2CO3 is broken down to CO2 + H20 via CA action which can now go into tubular cells. In tubular cells, H2CO3 is reformed and then so is HCO3- and H+. HCO3- is co-transported into blood with Na+/water. Therefore, with CA blocked, HCO3-, Na+ and water cannot be reabsorbed via this route.
When are carbonic anhydrase inhibitors used?
Not usually for diuretic effect but used:
- To reduce intraocular pressure e.g. in glaucoma (aqueous humour production requires HCO3- secretion/isoform of enzyme in eye)
- Mountain sickness prophylaxis (although unlicensed)
How do osmotic diuretics work?
Increase osmolality of filtrate preventing water reabsorption; act best where most osmotic reabsorption occurs i.e. PT + descending LOH
E.G. mannitol
What are the main uses of osmotic diuretics?
Not used for diuretic effect but used to:
Decrease intracranial pressure
Decrease intraocular pressure e.g. in glaucoma
How can glucose act as an osmotic diuretics and what can happen in disease states as a result of this?
Glucose is usually filtered + reabsorbed by SGLT
If Tm is exceeded (e.g. uncontrolled DM), glucose is excreted in urine + prevents water reabsorption
-> diuresis + polyuria
How is the mechanism of action of loop diuretics?
Act on thick ascending LOH by inhibiting the Na+K+Cl- co-transporter by competing with Cl- binding decreasing NaCl reabsorption decreasing osmotic concentration in medulla + ADH mediated H20 absorption -> increased NaCl delivery to distal tubules will increase Na+ uptake by principal cells + so loss of K+ and H+ (Ca2+ & Mg2+ reabsorption reduced too)
E.G. furosemide
Why are loop diuretics so powerful?
Potentially can excrete ~25% of the filtered load of Na+
Why are loop diuretics not filtered but secreted directly into the PT? What does this mean for them?
Because they bind to plasma proteins so:
- Effective in renal impairment
- May be less effective in nephrotic syndrome where is a large amount of albumin (leakage of plasma proteins due to impaired filtration barrier) in the tubular lumen so the drug will bind to that rather than the NaKCl transporter it should bind too
What are the main uses of loop diuretics and their selected side effects?
Peripheral oedema (e.g. CHF)
Acute pulmonary oedema (due to vasodilator effect)
Resistant hypertension
Side effects: hypovolaemia/hypotension, hyponatraemia/hypokalaemia + ototoxicity (hearing loss in high doses)
