medicines and the kidney Flashcards
summary of the nephron
bowmans capsule -filtration of all drugs of low molecular weight
PCT - ACTIVE TUBULAR secretion
loop of henle - reabsorption of water
DCT - passive tubular reabsorption
collecting duct - water soluble drugs and metabolites
Elimination of drugs and the kidney
Most drugs unless highly plasma protein bound freely filtered
Most drugs esp. weak acids actively secreted into proximal tubule
Lipid soluble drugs passively resorbed by diffusion across tubule- not excreted in urine a lot
Weak acids more easily excreted in alkaline urine and vice versa
Effect of Impaired Renal Function on Drug Therapy. what are the relevant factors
- Toxicity
- Ineffective treatment
- impaired drug absorption
- impaired elimination
- effect of renal dysfunction on hepatic drug metabolism
- increased tissue sensitivity
- protein binding
stages of chronic kidney disease
normal GFR >90 ml/min/1.73m2
early CKD GFR60-89 ml/min/1.73m2
moderate CKD GFR 30-59ml/min/1.73m2
severe CKD GFR 15-29 ml/min/1.73m2
endstage CKD GFR <15 ml/min/1.73m2
calculation of kidney function
Biochem labs report eGFR by MDRD formula
Prescribing based on CrCl (Cockcroft-Gault formula)
Similar but NOT the same
Dose Adjustment Options in Renal Decompensation
decrease dose - decreased peak concentration
increase dose interval - decreased trough concentration
what happens in accumulation of morphine and metabolites in renal disease
respiratory depression
selecting appropriate drugs in renal failure
drug that is predominantly eliminated via hepatic/biliary
less than 25% excreted unchanged in kidneys
no active metabolites
widespread therapeutic margin
disposition unaffected by protein binding changes or by fluid balance changes
drugs that are not nephrotoxic
Reduced clearance - leads to toxicity if the drug remains in the circulation at high concentrations. • This leads to accumulation of drugs and metabolites “normally” excreted and a change in the drug distribution. This leads to:
- Impaired drug absorption - fluid retention in the kidney with oedema of the bowel wall can lead to reduced absorption of drugs given orally.
- Decreased protein binding - proteinuria/albuminuria, causes decreased proteins available for binding to drugs in the plasma, hence increase plasma concentrations of that drug.
- Impaired kidney metabolism - some drugs are metabolised in the liver e.g. insulin. Impaired kidney function will lead to increased half lives of drugs, thus raising the plasma concentration with every dose.
• Prescribing drugs in CKD must be carefully monitored, with eGFR calculated to estimate renal function. There are 2 methods of dealing with dosage regimes:
- Decrease the dose, keeping the interval constant (lower peak concentrations)
- Keep the dose constant, and increase the dose interval. (lower trough concentrations)
what is Acute Tubular Necrosis
death of tubular epithelial cells and is one of the most common causes of acute kidney injury (AKI).
• Aminoglycosides (Gentamicin)
• NSAIDs
Glomerulonephritis
- inflammation of the glomerulus
• Gold salts
• Penicillamine •
Interstitial Nephritis
inflammation of the interstitium surrounding the tubules (acute/chronic) • Furosemide • NSAIDs • Penicillins • Thiazide
Nephrogenic Diabetes Insipidus
excessive thirst and excretion of large amounts of dilute urine.
• Lithium
• Demeclocycline
how do loop diuretics work
they are the most powerful of diuretics , capable of causing the excretion of 15-20% of filtered Na+
they act on the thick ascending loop of henle , inhibiting the action of NK2CL carrier in the lumen membrane e.g. furosemide
