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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.