Renal Pharmacology

Question 1

bioavailability (F)

Answer 1

*fraction of orally administered medication (%) reaching systemic circulation
*IV therapy = 100%; PO = variable
*bioavailability is affected by:
-route of administration
-barriers to absorption (vomiting, reduced stomach acidity, gut wall edema)
-transit time (reduced peristalsis)
-blood flow/supply
-co-administration of other drugs/food (phosphate binders)

Question 2

volume of drug distribution (Vd)

Answer 2

*ratio of drug concentration in tissues relative to blood
*based on drug and patient characteristics:
-lipophilic + tissue-bound: large Vd
-hydrophilic: small Vd, remains in blood
*highly affected by protein binding:
-generally, only unbound (free) drug causes pharmacologic response (and toxicity)

Question 3

metabolism changes in renal patients

Answer 3

*non-renal elimination may increase, remain unchanged, or decrease:
-metabolism is unpredictable
-oxidation may be compensatorily increased
-reduction and hydrolysis often slowed
*many drugs have active metabolites that still require renal elimination (tramadol, meperidine, allopurinol); accumulation of metabolites can cause toxicities

Question 4

renal drug clearance

Answer 4

*excretion is affected by filtration, secretion (proximal tubules), and reabsorption (proximal and distal tubules)
*metabolism: CYP 450
*when renal function deteriorates, filtration + secretion + reabsorption are less effective, leading to reduced drug clearance

Question 5

drug classes that are commonly adjusted for in patients with renal dysfunction

Answer 5

*antihypertensives (atenolol, ACEi/ARBs)
*oral hypoglycemics (metformin, glyburide)
*antimicrobials
*analgesics (NSAIDs, morphine)
*statins
*seizure medications (phenytoin)

Question 6

morphine contraindications in ESRD

Answer 6

*morphine may accumulate active metabolites, leading to toxicity
*excreted 4% as unchanged parent drug; the majority is excreted as GLUCURONIDE active metabolites:
-morphine 3-glucuronide
-morphine 6-glucuronide
-active metabolites are more potent and accumulate in patients with renal dysfunction, causing prolonged narcosis and side effects

Question 7

aminoglycosides & acute kidney injury - pharmacology

Answer 7

*aminoglycosides: gentamicin, tobramycin, amikacin
*filtered at glomerulus
*saturable uptake and binding to proximal tubule cells
*accumulation disrupts mitochondrial function and protein processing → direct tubular toxicity
*therapeutic drug monitoring is critical (high dose, extended interval is generally preferred)

Question 8

nephrotic syndrome - pharmacology impacts

Answer 8

*deficiency of albumin in blood due to excretion of albumin in the urine
*very little data on drug excretion
*decreased protein binding → increased free fraction:
-potentially increased excretion in normal renal clearance
-decreased excretion in CKD, potentially increased risk of toxicity

Question 9

furosemide pharmacology in nephrotic syndrome

Answer 9

*extensively bound to albumin
*furosemide-albumin complex is actively secreted in proximal tubule
*decreased albumin (hypoalbuminemia due to nephrotic syndrome) → decreased furosemide secretion and decreased furosemide activity