The document discusses various mechanisms of drug excretion from the body. The major sites of excretion include the kidneys, gastrointestinal tract, lungs, saliva, sweat, milk, and bile. Renal excretion occurs through glomerular filtration, tubular secretion, and tubular reabsorption. Molecular weight and protein binding influence the degree of filtration. Active tubular secretion is the most effective excretion mechanism for some drugs like penicillin. As people age, renal function declines, increasing drug half-lives. Renal failure further increases half-lives dramatically. Biliary excretion and enterohepatic recirculation can form drug reservoirs due to intestinal reabsorption of conjugated metabolites. Lung excretion occurs

2. Excretion:
is the passing out of a drug from
the body in any form, present
systemically.

3. Sites of Excretion
Renal:
Kidney
Others:
GIT
Lungs
Saliva
Sweat
Milk

4. Renal Excretion
Filtration:
Secretion:
Reabsorption:
Variety of Organic
Acids & Bases are
secreted here.

5.  All water soluble substances;
Total amount excreted through kidney in
the
urine is the sum of:
 Total Glomerular Filtration +
 Tubular Secretion +
 Tubular Reabsorption
Tubular Filtration

6. Molecular weight for majority of the drugs is
< 20,000 so are filtered easily ( --- if free.)
Warfarin is 99% bound so only 1-2% filtered;
99% filtrate is reabsorbed,
but reabsorption depends upon
lipid-solubility & non-ionization.

7. Ionized drugs are trapped in the urine &
then excreted
e.g;
Digoxin,
Aminoglycosides

8. After 35 years of age:
↓ GFR & in renal concentrating capacity
so drugs are not so easily eliminated leading to
↑ t½
e.g., Digoxin t½ becomes > 54 h ( usual 36 h ).
In renal failure:
its t½ increases to 4 - 5 times ( 140 – 175 h )

9. is the most effective mechanism:
Active secretion: e.g., Penicillin.
(almost all clear in first go through renal tubules)
even plasma protein bound drugs are
completely eliminated by it.
Passive tubular reabsorption:
Non-ionized & lipid soluble drugs
Tubular Secretion
Carrier molecules (SLC, OCT 1, OCT2, OAC)

10. Probenecid decreases penicillin
secretion so prolonging its action.
( compete with Penicillin )
OCT2 …. Cisplatin ….. Nephrotoxicity
Cimetidine Compete … Nephrotoxicity
Carboplatin Less toxic ….. Not excreted by OCT2
Salicylates decreases secretion of
Probenecid & Sulfinpyrazone.

11. Role of Ionisation affect in
EXCRETION
 Permiation
 Steady-state distribution between aqueous
compartments

12. By Ion trapping
Aspirin ( pKa 3.5) would be concentrated
4 times in Renal tubule (pH 4.5 -…) with
respect to plasma (pH 7.4 )

13. Actually Does not happen because:
1: Total Impermeability to charged species is not
realistic
2: Compartments rarely approach equilibrium
6000 fold in plasma (pH 7.4 ) with respect to
Gastric content( pH 3.3 – 4.0 )

14.  Urinary Acidification (by Ammonium Chloride)
(in diazepam Overdosage)
 Urinary Alkalinisation (by sodium carbonate)
( In Aspirin Overdosage),
Acetazolamide???(C/I)

15. Why Sodium Bicarbonate is Preferred
(MUST BE) over acetazolamide for
Urinary Alkalinisaton in
Aspirin overdosage ???

16. More Na+ and
H2O,esp. Cl-
going down & reabsorbed leading to Hyperchloremic Metabolic Acidosis.
Acetazolamide etc.

17. Sodium Bicarbonate
Increase Plasma pH … (Alkaline),
Aspirin become more ionized, So can not
cross BBB.
Acetazolamide
Reduce Plasma pH i.e. become acidic
so Aspirin become unionized in plasma,
So can cross BBB,

18. Biliary Secretion &
Enterohepatic Circulation

19. Liver cells transfer drugs from plasma to bile
 Similar transport system as renal tubules
 OCTs (organic Cation Transporter) …. SLC
 OATs (Organic Anion Transporter) …. .SLC
 P-glycoproteins (P-gp) …… ABC
Hydrophilic drug conjugates (Glucuronides) are
concentrated in bile & delivered in intestine
 Erythromycin,
 Rifampin,
 Ampicillin,
 Tetracyclines,
 Oral Contraceptives. (ethinylestradiol)
 Morphine,

20. Enterohepatic Circulation
 Hydrophilic drug conjugates (Glucuronides) are
concentrated in bile & delivered in intestine &
are hydrolyzed by intestinal flora, active drug
is released once again and is reabsorbed
from the intestine.
 This cycle is repeated again and again
 This effect create a “reservoir” of circulating drug.
Up to 20% of total drug.

21. Effect of antibiotic Treatment
Failure of contraception

22.  Vecuronium ( non-depolarizing NMJ blocker)
Mainly excreted unchanged in bile

23. Rifampicin
 Absorbs from GIT
 Slowly deacetylated, retaining its biological
activity
 Both forms are secreted in bile
 Deacetylated form is not reabsorbed
 Eventually …. Drug leaves the body through
faeces.

24. Intestine
Anthracine purgatives: Senna, Cascara, etc.
Active metabolite absorbed in the small intestine, after
hydrolysis an active “principles” are liberated which
are excreted in the large gut.
( where it irritate & produce purgation )
Heavy metals: Lead, Arsenic, Iron, etc.
excreted in the feces through bile.
Rifampicin Slowly deacetylated …..in bile …… in faeces

25. Lungs
Volatile General Anesthetics: Halothane, etc. N2O
Paraldehyde: 70%-80% metabolized in the liver
which is exhaled, remaining excreted
in the urine.
(In hepatic failure ↑ed in expired air )
Alcohol: Most of it is excreted through
kidney & lungs

26. Skin:
Mercury,
Arsenic
Saliva:
Rifampin,
Lithium,
K-iodides

27. Breast
By passive diffusion, more lipid soluble and
less protein bound drugs are better distributed
Like:
 Tetracyclines, (C/I in lactation children. WHY?)
 Isoniazid,
 Diazepam,
 Opioid,
 Penicillins,
 Chloramphenicol,
 Anti-cancers.

28. Drugs sedreted in PCT by OAT &OCT
OAT
 Furosemide
 Penicillin
 Probenacid
 Methotrexate
 Indomethacin
 Thiazide diuretics
OCT
 Morphine
 Dopamine
 Pethedine
 Quinine
 Amiloride
 Triamterine

29. Drugs mainly excreted unchanged in urine
 Up to 100-75%
 Furosemide
 Gentacin
 Methotrexate
 Atenolol
 Digoxin
 Up to 75-50%
 Cimetidine
 Neostigmine
 Oxytetracycline

30. MCQ
“A three year child ingested large dose of
diphenhydramine, a basic drug ( pKa 8.8).
It is capable of entering most of the body
tissues including brain. Which of the
following statement regarding over-
dosage of diphenhydramine is correct?”

31. 1. Hemodialysis only effective therapy.
2. Absorption of the drug would be faster from
stomach than from small intestine
3. More of the drug would be ionized at blood pH
than at stomch pH.
4. Urinary excretion would be accelerated by
giving NH4Cl
5. Urinary excretion would be accelerated by
giving NaHCO3
4

32. Thanks