L1 - PK Renal disease & dose adjustment Flashcards
(13 cards)
Renal function - 2
- Regulate body fluids & Electrolytes
- Remove metabolic & drug waste
Renal disease & Drug relation:
Renal disease & Drug relation:
Renal disease will alter the clearance, which can cause the drug to accumulate, possibly leading to toxic effects
Common causes of kidney failure – 6
- Pyelonephritis: Inflammation, deterioration of pyelonephrons due to infection, antigens.
- Hypertension: Chronic overloading of kidney with fluid & electrolytes may lead to kidney insufficiency
- Diabetes Mellitus: Disturbance of sugar metabolism & acid-base balance may lead to degenerative renal disease
- Nephrotoxic drugs/metals: Certain drugs taken chronically may cause irreversible kidney damage (aminoglycosides, phenacetin, heavy metals)
- Hypovolemia: Reduction in renal blood flow will lead to renal ischemia & damage
- Neophrallergens: Certain compounds may produce an immune type of sensitivity reaction with nephritic syndrome (quartan malaria nephrotoxic serum)
Renal impairment - 3
- Uremia: glomerular filtration impaired (decreased renal drug excretion, accumulation: excessive fluid, blood nitrogenous products), caused by acute diseases, trauma
- Alterations in PK processes: distribution (Vd, protein binding), elimination (biotransformation, renal excretion) - alters therapeutic & toxic responses
- Requires special dosing considerations
PK Considerations (uremic patients) -5
- PO BA may decrease, drugs with high 1st pass effect may have increased BA
- accumulation of metabolites (weak acids: decreased, weak bases: less affected), changes in total body water, increase in Vd
- increased elimination half-life (t1/2) DUE TO REDUCED GFR
- Total body Cl reduced (reduced GFR & reduced hepatic clearance).
- Drug dosage regimen: estimation of remaining renal function, prediction of Clt, aim to prevent accumulation
Renal disease treatment - Common assumptions - 4
- ClCr: accurately measures degree of renal impairment:
- Nonrenal drug elimination (constant): Unchanged from GI tract, but liver may be affected
- Drug absorption (constant): Normal Cl may include active secretion, passive filtration
- Unaltered drug protein binding: may be altered (accumulation urea, nitrogenous wastes, metabolites)
Filtration rate of markers reflects GFR - 3
- Inulin: fructose polysaccharide (time consuming; IV infusion until constant ss plasma level)
- Creatinine: endogenous substance (creatine phosphate-muscle metabolism). Eliminated primarily by glomerular filtration, but may be actively secreted, higher GFR than with inulin
- Blood urea nitrogen (BUN): urea (end product of protein catabolism, excreted through the kidney, commonly used)
Assumptions for Clcr: Daily anabolic production of creatinine in the liver is constant
Synthesis of creatinine in liver is not constant in Hepatic insufficiency, making Creatinine a poor marker
Assumptions for Clcr: Daily anabolic conversion in striatal muscle is constant & other non constant sources of creatinine production do not exist - 2
- Production & release of creatinine from muscle directly proportional to Lean Body Weight (Weight - fat); difficult to estimate; usually IBW (Ideal Body Weight) used as index of muscle mass
- Interindividual variability between IBW & Cr production (muscle mass constitutes a reduced fraction of IBW in certain populations:
A) Cr urinary excretion: lower in females, neonates, elderly, patients with cachexia, muscular dystrophies, paralysis.
B) Muscle mass: larger fraction in athletes & obese
C) Change in metabolic production of Cr in muscle due to administration of drugs (i.e. trimethoprim).
D) Exogenous sources of Cr e.g. meat
Assumptions for Clcr: Creatinine is filtered freely by the kidney & is not secreted or reabsorbed - 2
- Creatinine undergoes active tubular secretion
- In disease states that primarily affect the glomeruli (e.g. hypertension): significant contribution of tubular secretion- overestimation of GFR by ClCr
Assumptions for Clcr: The measurement of creatinine in serum & urine is accurate – 2
Both can interfere with measurement of creatinine in serum & urine
1. Diseases (i.e. diabetic patients & Jaffe enzymatic colorimetric method)
2. Drugs (i.e. cefoxitime) interfere with measurement of Cr in biological fluids
Assumptions for Clcr: Urine collection is complete - 2
- Overcollection, under collection, degradation of Cr in stored samples: alter Clcr
- Patient compliance
Creatinine clearance calculation methods – 2
- Crockcroft & Gault method:
ClCr = ((140-age) x body weight (kg))/[Serum Creatinine] - Nomogram: age is connected to weight, & then the serum creatinine is drawn over the R line, connecting to the clearance.
