Nidhika kaundal presentation

Presented by :- Nidhika Kaundal
M. Pharma
1kaundalnidhika

 Excretion and types of excretion
 Processes of excretion
 Concept of clearance
 Factors affecting renal excretion or renal clearance
 Renal function and renal failure
 Dose adjustment in renal failure
8/25/2020 2kaundalnidhika

 Drugs or their metabolites are removed from the body by
excretion.
 Excretion is defined as the process whereby drugs or their
metabolites are irreversibly transferred from internal to
external environment.
 Excretion of drugs by kidney is called as renal excretion.

TYPES OF EXCRETION
RENAL
EXCRETION
NON RENAL
EXCRETION
EXCRETION BY
KIDNEYS
EXCRETION BY
LUNGS, BILIARY
SYSTEM,
SALIVARY
GLANDS, etc.

 Almost all drugs and their metabolites are excreted by the
kidney.
 Drugs such as gentamicin are eliminated by renal route only.
 Agents that are excreted in urine are water soluble, non
volatile, small in molecular weight(less than 500 Daltons),
agents that are metabolized slowly.

 The basic functional unit of kidney involved in excretion is the
NEPHRON.
 Each kidney comprises of 1 million nephrons.
 Each nephron is made up of the glomerulus, the proximal
tubule, the loop of Henle, the distal tubule and the collecting
tubule.

 It is a non selective, unidirectional process whereby most
compounds ionised or unionised, are filtered except those that
are bound to plasma proteins or blood cells.
 The driving force for filtration through the glomerulus is the
hydrostatic pressure of the blood flowing in the capillaries.
 The 25% of the cardiac output or 1.2 liters of blood/min that
goes to the kidneys via renal artery.
 Out of this 25% only 10% or 120 to 130 ml/min is filtered
through the glomeruli, the rate being called as glomerular
filtration rate (GFR).
 180 liters of protein and cell free ultrafilterate pass through

 The glomeruli each day , only about 1.5 litres is excreted as
urine
 The remaining being reabsorbed from tubules.
 Creatinine, inuline, mannitol, sodium thiosulphate are used to
estimate GFR.
 These agents are excreted by filtration and is neither secreted
nor reabsorbed.

 It is a carrier mediated process which requires energy for
transportation of compound against the concentration gradient.
 Mechanism of active tubular secretion:-
1.System for secretion of organic acids/anions:- penicillins,
salicylates, glucuronides, sulphates etc.
2. System for secretion of organic bases/ cations:- morphine,
hexamethonium, catecholamines, choline, histamine etc.
 Both the mechanisms are independent of each other.
 Process is bidirectional i.e,. agents may both be secreted as
well as reabsorbed actively., example uric acid.

 Process is unaffected by changes in pḤ and protein binding.
 It depend upon the renal blood flow i.e. drugs undergoing
active secretion have excretion rate values greater than normal
GFR value of 130 ml/min.
 Example:- Penicillin 500ml/min
Agents used to measure active tubular secretion is para amino
hippuric acid.
 Drug with greater rate of clearance will retard the excretion of
the other drugs with which it competes. Ex:- probenecid
inhibits the active tubular secretion of organic acid such as
penicillin.

 Tubular reabsorption occurs after the glomerulus filtration of
drugs.
 Takes place all along the renal tubule.
 Reabsorption of a drug indicates when the excretion rate
values are less than the GFR of 130 ml/min.
 Glucose get completely reabsorbed after filtration has a
clearance value of zero.
 Reabsorption results in an increase in the half life of a drug.
 Tubular reabsorption can either be an: active
process(endogenous:- electrolytes, glucose, amino acids) or
passive process(exogenous :- drugs).

 Varies between 4.5 to 7.5.
 Urine pḤ is depend upon diet, drug intake and
pathophysiology of the patient.
 Food rich in carbohydrate results in higher urinary pḤ whereas
proteins lower it.
 Drugs such as acetazolamide and antacids such as sodium
bicarbonate produces alkaline urine.
 Ascorbic acid makes urine acidic.

 Clearance is defined as the hypothetical volume of body fluids
containing drug from which the drug is removed or cleared
completely in a specific period of time
 It is expressed in ml/min.
clearance (Cl) = Elimination rate
plasma drug concentration

 Renal clerance (ClR) : It can be defined as the volume of blood
or plasma which is completely cleared of the unchanged drug
by the kidney.
clearance (ClR) = rate of urinary excretion
plasma drug concentration

Renal clearance
(ml/min)
Renal clearance
ratio
Mechanism of
renal clearance
examples
0 0 Drug filtered
and reabsorbed
completely
glucose
< 130 Above 0 below 1 Drug filtered
and reabsorbed
partially
Lipophilic drugs
130 1 Drug filtered
only
Creatinine,
inulin
>130 >1 Drug filtered as
well secreted
actively
Polar, ionic
drugs
650 5 Clearance equal
to renal plasma
flow rate
PAH

 Physiological properties of the drug.
 Plasma concentration of the drug.
 Distribution and binding characteristics of the
drug.
 Urine pH.
 Blood flow to the kidneys.
 Biological factors.
 Drug interactions.
 Disease states.

 Factors:- molecular size, pKa, lipid solubility.
 Molecular size
 Urinary excretion of unchanged drug is inversely related to its
lipophilicity.
Molecular weight(Dalton) Excretion pattern
Below 300 Excreted mainly in urine;
less than 5% excreted in
bile
Between 300-500 Excreted both in urine as
well as bile
Above 500 Excreted mainly in bile;
less than 5% is excreted
in urine

 This is because, a lipophilic drug is passively reabsorbed.

 Clearance is inversely related to apparent volume of
distribution (Vd).
 A drug with large Vd is poorly excreted in urine.
 Drug that are bound to plasma proteins behave as
macromolecules and thus cannot be filtered through
glomerulus.
 Only unbound or free drug appear in the glomerular filtrate.
 The renal clearance of oxytetracycline which is 66% unbound
is 99ml/min.
 Whereas doxycycline 7% unbound is 16ml/min

 The renal blood flow i.e., the increased perfusion increase the
contact of drug with the sites and hence enhance the
elimination.
 This is called perfusion rate limited.

 Difference in genetic , cardiac rhythm, alter drug excretion.
 Renal excretion is 10% lower in females than in males.
 In old age the GFR is reduced.
 In newborns the renal function is 30 % to 40% less in
comparison to adults.

 Alteration in P-D binding:- renal clearance of a drug
extensively bound to plasma proteins is increased after
displacement with another drug
ex:- gentamicin induced nephrotoxicity by furosemide
 Alteration of urine pH :-
Acidification of urine with ammonium chloride, methionine or
ascorbic acid enhances excretion of basic drugs.
Alkalinisation of urine with citrates, tartarates, bicarbonates, and
carbonic anhydrase inhibitor promote excretion of acidic
drugs.

 Cause of renal faliure are hypertension, diabetes
mellitus, hypovolemia, pyelonephritis,
nephroallergens
 Uraemia

 Renal function can be determined by measuring GFR.
 The agent should excreted in unchanged form by glomerular
filtration only.
 The agent should physiologically and pharmacologically inert.
 Both endogenous and exogenous substances have been used as
marker to measure GFR.
 The rate at which these markers are excreted in urine reflects
the GFR.
 Changes in GFR reflects renal dysfunction.

 Creatinine is an endogenous amine produced as a result of
muscle catabolism. It is excreted in urine by glomerular
filtration only.
 Normal Creatinine clearance value is 120 to 130ml/min.
 20 to 50ml/min denotes moderate renal failure.
 Below 10 ml/min indicates severe renal failure.
ClR = Rate of Creatinine excretion
Serum Creatinine in mg%

 The renal function(RF) can be calculated as:-
RF = ClCR of the patient
ClCR of a normal person
Where,
ClCR = Creatinine clearance in ml/min

 Drugs in patients with renal impairment have altered
pharmacokinetic profile.
 The renal clearance and elimination rate is reduced and the
elimination half life is increased
 alteration in apparent volume of distribution.
 Dosage regimen need not to be change when :
 RF is less then 0.7 of normal
 Drug dose = normal dose × RF

 Dose interval = normal interval in hours
RF

 Brahmankar D.M, Jaiswal B.S. Biopharmaceutics and Pharmacokinetics.
Vallabh Prakashan.2009.Reprint 2014.196-213.

Nidhika kaundal presentation

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