A seminar on ALTERED KINETICS IN RENAL DISEASES. BY A.SRILATHA ( M.Pharm I sem ). Department of Pharmaceutics BLUE BIRDS COLLEGE OF PHARMACY (Affiliated to Kakatiya University)
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(M.Pharm I sem )
Department of Pharmaceutics
BLUE BIRDS COLLEGE OF PHARMACY
(Affiliated to Kakatiya University)
Pharmacokinetics involves the kinetics of drug absorption, distribution & elimination(excretion & metabolism).
Statistical methods are used for pharmacokinetic parameter estimation and data interpretation.
Disease affects the way drugs are absorbed,distributed,excreted and metabolized. Renal disease directly affects drug excretion but also affects drug binding. Hepatic disease affects drug metabolism.
Renal dysfunction greatly impairs the elimination of drugs especially those that are primarily excreted by the kidneys. Some of the causes of renal failure are hypertension, diabetes mellitus, hypovolemia, pyelonephritis, nephrotoxic agents such as amino glycosides, phenacetin and heavy metals such as lead and mercury.
Uraemia characterized by impaired GFR and accumulation of fluids and protein metabolites also impairs renal clearance of drugs. In both these conditions the half lives of the drugs are incresed, as a result drug accumulation and toxicity may result.
Several drugs and endogenous substances have been used as markers to measure GFR.These markers are carried to the kidney by the blood via the renal artery and are filtered at the glomerulus.
Criteria necessary for using a drug to measure GFR
Inulin, a fructose poly saccharide fulfills most of the criteria listed above and is therefore used as a standard reference for the measurement of GFR. Clearance Creatinineis used most extensively as a measurement of GFR. In humans, creatinine is mainly filtered at the glomerulus with no reabsorption.Blood urea nitrogen (BUN) is a commonly used clinical diagnostic laboratory test for renal disease, urea is the end product of protein catabolism and is excreted through the kidney, normal BUN ranges from 10-20mg/dl.Higher BUN levels indicate the presence of renal disease.
It is an endogenous amine produced as a result of muscle catabolism.
Excreted unchanged in the urine by GFR.An advantage of this test is that it can be correlated to steady state concentration of creatinine in plasma and no needs no collection of urine.Normal values adjusted to 1.73m2 body surface area range from 100-125ml/min. Creatinine clearance values of 20 -50 ml/min, indicates moderate renal failure, values less than 10ml/min indicates severe renal failure.
Eg: Relationship between total clearance and renal function (creatinine clearance) for three drugs that are excreted in the urine to different degrees in patients with normal renal function. Vertical line shows clearances and half-lives when renal function is reduced to one-sixth of normal. Renal disease has the largest effect on drug A and the smallest effect on drug C.
t ½ =0.693 Vd/Cl.
It indicates that the half life is dependent on Vd and Cl.
vd and Cl are the independent variables.
Drugs elliminated almost entirely by the kidneysDrugs elimination entirely unchanged by the kidney (fu=1) (e.g.gentamicin)for these drugs, doses should be reduced in direct proportion to the degree of impairment in creatinine clearance.
Drugs that are eliminated partly by the kidney and partly by the metabolism
Drugs that are extensively excreted unchanged in urine, alteration of the renal function will alter the drugs elimination rate. Many drugs or their metabolites are eliminated partly or completely by the kidneys, thus the usual dosage regimens may need to be adjusted to provide safe and effective treatment for patients with impaired renal function. So i conclude that determination of renal function is important to monitor the dosage regimen.
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