Drugs and the Kidneys Flashcards
What are the three processes involed with drug excretion by the kidneys?
- Glomerular filtration
- Passive tubular reabsorption
- Active tubular secretion
What is Nephrotic Syndrome?
Non-specific kidney disorder:
Proteinuria, Hypoalbuminaemia, Oedema
Increased permeability of glomerulus
How can distribution of drug be affected by renal impairment?
Changes in hydration state of the patient - (drugs with small volume of distribution affected = gentamicin): particularly important when using IV fluids, diuretics or intermittent renal replacement therapy
Alterations in protein binding - Hypoalbuminaemia, or uraemia: compete with drugs to bind with albumin
Alterations in tissue binding (e.g. Phenytoin) if unbound drug pharmacologically active, in patients with renal impairment: need to consider altered serum albumin conc and decreasing binding affinity
How may insulin dosing be affected by CKD?
Insulin normally freely filtered by kidney
Insulin clearance falls in CKD, so lower doses or cessation of insulin therapy may be necessary
Also decreased caloric intake, due to uraemia-induced anorexia
How are the following affected in renal impairment?
Glomerular filtration
Tubular secretion
Reabsorption
All reduced:
Glomerular filtration: Higher plasma levels
Tubular secretion: Higher plasma levels
Reabsorption: Higher concentrations in urine
Which drug group needes to be prescribed with extreme caution in patients with renal impairment?
Opitates: Morphine Sulphate
Potential accumulation of morphine-6-glucuronide - renally excreted active metabolite)
How does uraemia affect the body’s response to different drugs?
- Increased sensitivity to drugs acting on the CNS e.g. benzodiazepines
- Increased risk of GI bleeding with irritant drugs - NSAIDs
- Increased risk of hyperkalaemia with drugs such as potassium-sparing diuretics
What is the difference between eGFR and GFR absolute?
GFR absolute for patients who have a BSA of <1.73m2
without modification, eGFR will likely overestimate kidney function in patients with BSA of <1.73m2
When is it appropriate to use eGFR and Creatinine Clearance?
For most drugs for patients of average build and height
When is appropriate to use GFR absolute or CrCl using appropriate body weight?
Nephrotoxic drugs with small safety margins
Patients with extremes of weight
Name two drugs which have loss of effectiveness with renal failure
Nitrofurantoin (antibiotic for UTI) - needs renal secretion into urinary tract
Bendroflumethiazide (diuretic for HTN) - inhibits renal tubular absorption of Na and Water, needs to be excreted into renal tubule in DCT
Name 4 different drug groups that may cause pre-renal AKI
Haemodynamic - vasodilator effect on efferent glomerular arterioles:
- ACE inhibitors (Ramipril, Lisinopril)
- ATII inhibitors (Losartan, Candesartan)
Volume depletion:
- Laxatives and Diuretics - Excessive (Furosemide and Bumetanide)
- NSAIDs (Ibrupofen, Naproxen, Diclofenac)
How do NSAIDs affect patients with renal disease?
They impair ability of renal vasculature to adapt to falls in perfusion pressure or to an increase in vasoconstrictor balance
Prostaglandins (blocked by NSAIDs) produced in response to pain → potent vasodilators to maintain renal circulation
How are potassium levels affected by kidney disease? and what pathological effects are there?
Potassium excretion affected, so K+ in upper limits of normal
ECG changes, VF and cardiac arrest
What are the drug causes of hyperkalaemia?
ACE Inhibitors
ATII inhibitors
NSAIDs
Potassium Supplements
Spironolactone (potassium sparing diuretic)
Amiloride (diuretic)
Loop diuretics - furosemide, bumetanide
Thiazide diuretics - bendroflumethiazide
What anti-rejection drugs used in kidney transplants are renally toxic?
Ciclosporin
Tacrolimus
Causes intense vasoconstriction → fall in perfusion and fall in GFR
