DR.

SAMAH MOHAMED
ELAIDY
1. Drug Elimination
(Clearance).
2. Secretion of Drugs.
3. Activation,
Inactivation and
Biotransformation of
Drugs.
4. Secretion of Hormones.
 It is controlled by the following factors:
Renal Blood Flow and Glomerular
Filtration:
▪ Increased by: vasodilators, digoxin, methyl
xanthines.
▪ Decreased by: vasoconsrictors, ACEIs, ARBs, β-
blockers, verapamil.
C. Changes of PH of the Filtrate:
▪ Acidic drugs (e.g. salicylates) are better
eliminated in alkaline urine.
▪ Basic drugs (e.g. Atropine) are better eliminated
in acidic urine.
▪ Acidification of urine is produced by: Ascorbic
acid , ammonium chloride.
▪ Alkalization of urine is produced by: sodium
bicarbonate, sodium lactate, sodium citrate.
 Tubular secretion of drugs or body
excreta (e.g. uric acid) occurs in the
proximal convoluted tubules, as:
▪ Acidic drugs (Anions): penicillins, thiazides, loop
diuretics, salicylates.
▪ Basic drugs (Cations): atropine, quinidine,
morphine, amiloride.
 Some drugs inhibit the tubular secretion
of other drugs→↑plasma levels of the
latter, as:
▪ Probenicid inhibits tubular secretion of penicillins,
cephalosporins →Beneficial effect.
▪ Quinidine inhibits tubular secretion of digitalis
→digitalis toxicity.
 Some drugs inhibit the tubular secretion
of other drugs→ inhibit their
 In the kidney vitamin D is
converted to its active form
[1,25(OH)2 Cholecalciferol], by 1-
alpha-hydroxylase enzyme.
 Some drugs are inactivated in the
kidney, as imipinem (beta lactam
antibiotic) is inactivated by renal
dihydropeptidase (DHP).
 Oxidation of salicylates and
acetaminophen in renal tissues
shares for pathogenesis of renal
toxicity of these drugs.
 Small molecular weight protein and
polypeptides (e.g. insulin) are
 As, secretion of
erythropoeitin (EPO), to
stimulate bone marrow or
RBCs production.
 So, in CRF, anemia is a
sign, which can be
treated by EPO.
A. Parathyroid Hormone (PTH):
▪ Stimulates reabsorption of calcium from DCT.
▪ Inhibits phosphate reabsorption from all
segments of nephron.
▪ Stimulate 1-alpha-hydroxylase enzyme →
↑ active form of vitamin D.
B. Calcitonin:
▪ Inhibits reabsorption of calcium and phosphate
from all segments of nephron.
C. ADH (Vasopressin):
▪ Increasing permeability to water in DCT and
collecting tubules.
▪ Used in treatment of diabetes insipidus (pituitary
type).
D. Aldosterone:
A. Renin:
▪ Secreted by juxtaglomerular apparatus.
B. Prostaglandines:
▪ PGE2 (medullary)
▪ PGI2 (cortical)
▪ PGF2α
▪ PGD2
▪ Thromboxane A2 (TXA2)
C. Endothelins:
▪ ET1, ET2, ET3, acting on ETA&ETB
receptors.
▪ Their levels increase in acute and
chronic renal failure.
1. Absorption:
▪ Impaired due to nausea and vomiting of
uremia.
▪ Some unabsorbable drugs are absorbed
(e.g.aminoglycosides).
2. Volume of Distribution (Vd):
▪ May be ↑or ↓, leading to change in total
dose required (=serum conc. X Vd).
3. Protein Binding:
▪ Some patients are hypoproteinemic (e.g.
nephrotic syndrome), thus increasing free
drug level, and needing dose adjustment,
esp. in highly protein-bound drugs.
▪ In CRF, excess H+ ocuppy the receptor sites
for acidic drugs (e.g. sulpha, penicillin,
Changes in PK and PD of drugs in cases
of impaired renal function
1. Metabolism &
Biotransformation:
 Small molecular weight protein
and polypeptides (e.g. insulin)
should be reduced in diabetics
with renal impairment.
5. Renal clearance of drugs:
 ↓ due to accumulation of drugs
or their metabolites.
 They are drugs induced impairment of renal
functions, which could be:
Pre-Renal Insult:
▪ By drugs decreasing RBF, as:
▪ Drugs induced hypovolemia, e.g. loop
diuretics.
▪ Drugs lowering cardiac output, e.g. Β-
blockers.
3. Renal Insult:
A. Acute Tubular Necrosis (ATN):
• Direct nephrotoxicity resulting from
prolonged use of: aminoglycosides,
amphotericin B.
B. Acute Tubulo-interstitial Nephropathy
(ATIN):
• Cell-mediated hypersensitivity
Nephrotoxic Drugs
A. Chronic Tubulo-interstitial
Nephropathy (CTIN):
• Induced by: aspirin, paracetamol
(analgesic nephropathy), lithium,
cisplatin, cyclosporins.
B. Immune Complex Mediated
Glomerulonephritis:
• As: Penicillamine.
C. Nephrotic syndrome:
• Induced by: heavy metals (e.g. gold,
mercury), Penicillamine, lithum, NSAIDs,
captopril, probenicid, rifampicin.