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8 REABSORPTION
Excretion only BASES
3. Tubular Fluid pH
is time required 4. Tubular Fluid
Volume
4 to clear 50%
of drug.
A Nephron is the functional
2 EXCRETION
t 1/2 unit of the Kidney.
1
0 1 2 3 4 5 6 7 8
TIME (hours)
Glomerular Filtration II
Glomerular Filtration I
Non Saturable process.
Kidney blood flow is about 650 ml/min.
Drug Clearance is often proportional to GFR.
Glomerulus filters about 20% (130 ml/min). [GFR]
GFR is reduced in : newborn, elderly, kidney
GFR is a good measure of Kidney function.
and heart disease.
180 L filtered/day but 99% reabsorbed (urine = 2 L) Reduced GFR: lower drug dose, increase
dose interval or both.
Most non-protein drugs are filtered.
1
Tubular Reabsorption [Passive] Tubular Reabsorption [Active]
Drug moves from nephron lumen to blood. Movement of agent from urine to blood.
Drugs cross membrane by passive diffusion (Fick’s Law). 99% of agent reabsorbed by active transport:
sodium, glucose, amino acids, uric acid.
99% of water reabsorbed increases drug level in lumen.
Problem: High plasma uric acid level in gout.
Change urine pH to increase drug ionization and excretion .
Treatment: Block reabsorption of uric acid with:
NaHCO3 increases pH and ionization of acids: aspirin, PB. probenecid or aspirin since these agents
saturate uric acid carriers.
NH4 Cl lowers pH and increases ionization of bases: codeine,
amphetamine, meperidine (not used clinically).
Two separate carrier- mediated systems for bases and acids. Penicillin secretion is readily blocked with Probenecid.
Bases: acetylcholine, histamine, atropine, meperidine , etc. Saturation of carriers at high drug doses.
Acids: salicylate, penicillin, probenecid, cephalosporins , etc. Protein-bound drugs in plasma are readily secreted.
2
Renal Drug Clearance III Renal Drug Clearance IV
U V P
CL = [130 ml/min] [1 ml/min] / 1 mg/ml] = 130 ml/min
3
Biliary Drug Excretion I
Hepatic Drug Clearance II Cell Plate
Not readily cleared in their first-pass through the liver. Secretion of various agents:
Na, Bile Acids, PL and
Clearance regulated by metabolism rather than blood flow. Cholesterol produces bile.
Liver
Drug uptake and metabolism Orally administered drugs that are not absorbed:
Gallbladder Hepatic Duct Cholestyramine
Portal Vein Drug secretion and hydrolysis
Cystic Duct
Common Bile Duct Stomach (pH 1 -3) traps bases (codeine)
Duodenum Liver Drug reabsorption
Portal Vein
Superior Mesenteric
Intestine (pH 6 -8) traps acids (aspirin)
Common Bile
Vein Duct
Prolonged duration of action.
Superior Mesenteric
Vein
Small Intestine
Inhibit cycling (cholestryamine)
Drug → Small Intestine
Enterohepatic Cycle
Agent toxicity (indomethacin)
4
Minor Routes of Drug Excretion
Pulmonary Drug Excretion
Drugs are primarily excreted by passive diffusion.
[Drug in Lung Blood] / [Drug in Lung Air] = λλ
Salivary Gland drug excretion may produce toxicity to
Low λλ drugs such as Nitrous Oxide (λλ = 0.5) oral mucosa and teeth.
Short duration of action and rapid elimination. Mammary Gland drug excretion will contaminate milk
[mother and cows] consumed by individuals.
High λλ drugs such as methoxyflurne (λλ = 12)
Sweat Glands major route of drug elimination in person
Long duration of action and slow elimination. who profusely sweats (professional athlete or outside
worker in hot and humid conditions).
Elimination rate inversely proportional to λλ