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1. ELIMIMATION OF DRUGS
SUBMITTED TO SUBMITTED BY
Dr. Manoj Sharma Yogesh Yadav
Associate Professor M Pharmacy ( 1st Sem)
(Pharmacology)

2. CONTENT
o INTRODUCTION
o NEPHRON ANATOMY
o RENAL EXCRETION
Glomerular filtration
Tubular Secretion
Tubular Reabsorption
o NON RENAL EXCRETION
o CONCEPT OF CLEARANCE
o FACTORS AFFECTING RENAL EXCRETION

3. INTRODUCTION
ELIMINATION OF DRUGS is refer as removal of drugs and its metabolites from internal to
external environment.
The principle organs of excretion are kidneys.
Excretion by kidneys is called as Renal Excretion.
Excretion of organs other than kidneys such as lungs, biliary ,salivary glands, skin or dermal ,
genital organ excretion is known as Non-Renal Excretion.
Glomerular filtration and active tubular secretion facilitate the drug excretion whereas tubular
reabsorption decreases drug excretion.
Rate of renal excretion = (rate of filtration + rate of secretion) – rate of reabsorption

4. Nephron
• Microscopic structure and functional unit of
kidney.
• Compose of renal corpuscle and a renal tubule.
• The renal corpuscle consists of a tuft of
capillaries called a glomerulus and a cup-shaped
structure called Bowman's capsule.
• Healthy adult has 1 to 1.5 million nephrons in
each kidneys.
• Precursor- Metanephric blastema.
• They cleanse the blood of toxins and balance the
constituents of the circulation to homeostatic set
points through the processes of filtration,
reabsorption, and secretion.

7. RENAL EXCRETION
• Almost all drugs and their metabolise are excreted
by the kidneys . Excretion of drugs and their metabolite
through kidney called as Renal Excretion.
• The basic functional unit of kidney involved in excretion
is nephron .
• Each nephron is made up of glomerulus , proximal tubule ,
loop of Henle , distal tubule and the collecting tubule .
• Principle processes that determine urinary excretion of a
drug are :
1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption

9. o Glomerular Filtration
• Begins at glomerulus
• Consist of a capillary network surrounded by Bowman’s
Capsule.
• Small pores perforate the capillary walls.
• Drugs are forced through these pores. This driving force
for filtration through the glomerulus the hydrostatic
pressure of the blood flowing in the capillaries .
• This process moves drugs from blood to tubular urine.
• Most compounds ionized and unionized are filter except
those that are bound to plasma proteins or blood cells.

10. o Tubular Secretion
• Drugs are pumped from the blood to tubular urine via active transform systems.
• An area of lower concentration towards an area of higher concentration .
• Requires energy .
• Unaffected by changes in Ph of urine and protein binding .
• Tubular cells contain P- glycoprotein in their membranes , which pump drugs
into urine .
• Most of acidic drugs e.g. – penicillin , diuretics , probenecid etc and basic drugs
e.g. quinine , procaine , morphine etc are secreted through this.
• .

11. o Tubular Reabsorption
• Blood vessels to the glomerulus meet up the
renal distal tubule .
• Here , concentration of drugs in the blood are
lower than drugs in the tubule.
• This concentration gradient acts as a driving
force to move drugs from the tubule back in the
blood(reabsorption) .
• Strongly basic and strongly acidic drug remain in
ionized form at any Ph of urine and excrete out.

12.  CONT…..
• Weekly acidic e.g. salicylate , barbiturates in acidic urine remain
mainly in unionized form and easily reabsorbed if the Ph of urine is
made alkaline by sodium bicarbonate than these drugs get ionized
and excrete easily .
• Weak basic drugs e.g. morphine , amphetamine etc in alkaline urine
remain in unionized form and easily reabsorbed . If the Ph of urine
made acidic by vitamin c ascorbic acid the basic get ionized and
excreted easily .

13. Non Renal Excretion
• Nonrenal clearance is all drug removal
pathways excluding those related to the
kidneys.
• It Includes:
 Biliary excretion
 Pulmonary Excretion
 Salivary Excretion
 Mammary Excretion
 Skin Excretion
 Gastrointestinal Excretion

14. Biliary Excretion
• Transporters are also present in the canalicular membrane of the hepatocyte and these
actively secrete drugs and metabolites in to bile e.g. the organic anion transporting
polypeptides the p- glycoprotein transport system and the multi drug resistance associated
protein drug in bile inters the gastrointestinal track after storage in the gallbladder .
• It may then be excreted from the body by the stools.
• A drug excrete in the bile may be reabsorbed from the gastrointestinal tract or a drug
conjugated may be hydrolyzed by gut bacteria liberating original drug which can be
returned to the general circulation.
• Such recycling may continue until the drug either undergoes metabolic changes in the
liver is the excreted by the kidney or both.

15. Cont..
• Such enterohepatic recycling if
extensive may prolong significantly
the preaches of a drug and it's effects
with in the body pair to elimination
by other pathways
• Orally administered activated
charcoal and /or anion exchange
resins have been used clinically to
interrupt the enterohepatic cycling
and trap drug in the gastrointestinal
tract
• Cholesteric disease states in which
normal bile flow is reduced will
influence drug elimination by this
route resulting in risk of drug
toxicity.

16. Pulmonary excretion
• Gases and other volatile substance such
as general anesthetics than inter the
body primarily through the respiratory
that can be expected to be excreted by
route No specialized transport system
are involved in the loss of substances
expired air simple diffusion across cell
membrane is predominant
• The rate of loss of gases is not constant
it depends on the rate of respiration and
pulmonary blood flow
• The degree of solubility of a gas in blood
also will affect the rate of gas loss Gases
such a nitrous oxide which are not very
soluble in blood will be excrete rapidly
that is almost the rate at which the
blood delivers the drug to the lungs
Ethanol which have a relatively high
blood gas solubility is excreted very
slowly by the lungs

17. Salivary excretion
• The pH of saliva various from 5.8 to 8.4 unionized lipid soluble drug are
excreted passively.
• The bitter taste in the mouth of a patient is indication of drug excreted .
• Some basic drug inhibit saliva secretion and are responsible for mouth
dryness .
• Compounds excreted in saliva are caffeine, phenytoin, theophylline.

18. Mammary excretion
• Milk consist of lactic secretion which is rich in fats and proteins .
• Excretion of drug milk is important as it gains entry in breasts feeding infants.
• pH of milk it's various from 6.4 to 7.6 free un-ionized and lipid soluble drugs diffuse passively
• Highly plasma bound drug like diazepam is less secreted in milk.
• Amount of drug excreted in milk is less than 1 % and fraction consumed by infant is to less to
produce toxic effects. Some potent drug like barbiturates and morphine may induce toxicity
• The excretion of drugs in breast milk can be a concern for lactating mothers because of the
exposure this causes to infants who are breastfeeding.

19. Skin excretion
 Drugs excreted through skin via sweat
follows pH partition hypothesis .
 Excretion of drug through skin may lead to
urticaria dermatitis .
 Compound like benzoic acid , salicylic acid
alcohol and the heavy metals like lead ,
Mercury and arsenic are excreted in sweat .

20. Gastrointestinal Excretion
• Excretion of drugs through GIT usually
occurs after parenteral administration.
• Water soluble and ionized form of
weakly acidic and basic drugs are
excreted in GIT.
• Drugs like Nicotine and Quinine are
excreted in stomach.
• Drugs excreted in GIT are reabsorbed
in systemic circulation and undergo
recycling.

21. Concept of clearance
• Clearance is defined as " hypothetical volume of body fluid containing drug from
which the drug is removable or cleared completely in a specific period of time •
• Clearance(cl) = Elimination rate / Plasma drug concentration.
• It is expressed in ml/ min.
• Applied to or organs involved in drug elimination and referred to as renal
clearance , hepatic clearance pulmonary clearance biliary clearance and so on.
• Total body clearance - is the sum of individual clearance by all eliminating organs
• Total body clearance = CL(liver)+ CL (kidney)+ CL (lungs)+ CL x

22. Renal clearance
• Major organ for almost all drug and
metabolite excretion.
• Renal clearance (cl R) - can be defined as
the volume of blood or plasma which is
completely clearance of the unchanged
drug by the kidney per unit time.
• Clr = Rate of urinary excretion / Plasma
drug concentration
• Clr = Rate of (filtration + secretion -
reabsorption ) Plasma drug concentration
• Renal clearance ratio - Clr of drug / Clr of
creatine

23. Factors Affecting Renal Clearance
• 1 . Physicochemical properties of drug
• 2. plasma concentration of the drug
• 3. Distribution and binding characteristics of the Drug
• 4. Urine pH
• 5. Blood flow to the kidney
• 6. Biological factor.
• 7. Drug interactions
• 8. Disease states

24.  Plasma concentrations of drug
• Affects glomerular filtration and reabsorption .
• actively reabsorbed drugs excrete in urine only when there concentration in
the glomerular filtrate > active reabsorption capacity e.g. glucose
 Physicochemical chemical properties of drug
Molecular size
• Drugs with molecular weight <300 water soluble are excreted in kidney
• Molecular weight 300 to 500 Dalton are excreted both through urine and bile
 Distribution and binding characteristics of drug
• Drugs that are bound to plasma proteins behave as macromolecules are
cannot be filtrated through glomerulus. Only unbound or free drug appear
glomerulus filtrate .
• Protein bound drug has long lives.

25.  Blood flow to the kidney
• Important in case of
• Drugs excreted by glomerular filtration only
• Drugs that are actively secreted
• in actively secreted drugs renal clearance perfusion rate limited
 Biological factors
• Age, sex species strain difference etc alter the Excretion of drug
Sex- renal Excretion 10% lower in female then in male
Age - the renal Excretion in new-born is 30- 40% less in comparison to adults.
Old age - The GFR is reduced and tubular functions is altered which results slow
excretion of drug and prolonged half live

26.  Drug interactions
• Any drug interaction that result in alteration of binding characteristics renal body flow ,active
secretion , urine pH , intrinsic clearance and forced diuresis would alter renal clearance of drug.
• Alteration in protein drug binding: Gentamycin induced nephrotoxicity by Furosemide.
• Complexation of active secretion: Phenylbutazone + hydroxyhexamide Prolong action.
 Disease state
Renal Dysfunction
• Greatly impairs the elimination of drugs especially those that are primarily excreted by kidney
some of the causes of renal failure are B.P , diabetes pyelonephritis.
Uraemia
• Characterized by the impaired GFR accumulation of fluids And proteins metabolites also impaired
the excreted of the drugs half life increased resulting in drug accumulation and increased toxicity.

27. References
• Stefanie.Buck@oregonstate.edu
• Biopharmaceutics and clinical pharmacokinetics by Milo Gibaldi, 4th ed.; 1991.
• WWW.GOOGLE.COM
• Brahmankar MD,Jaiswal S.,Biopharmaceutics & Pharmacokinetics- A teratise
• Shargel L.,Susanna W., Applied Biopharmaceutics and Pharmacokinetics.
• Applied Biopharmaceutics and Pharmacokinetics – Leon Shargel, Sussana Wu-Pong, Andrew
B.C. Yu, 6th Edition, Mc Graw Hill Inc.Chapter -6 Page -107 to 127
• https://accesspharmacy.mhmedical.com/content.aspx?bookid=513&sectionid=41488024
• Pharmacology for Dentistry 2nd edition- Veena Nayak, Tara V Shanbhag, Smita Shenoy.

28. THANK YOU
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