Drug absorption

1. DR FAHAD
DRUG
ABSORPTIO
N

2. DRUG ABSORPTION
• ABSORPTION: THE TRANSPORT OF A DRUG
FROM ITS SITE OF ADMINISTRATION TO
THE BLOOD STREAM
• DRUGS ARE EITHER WEAK ACID OR WEAK
BASES

3. DRUG MOVEMENT
THROUGH MEMBRANES
DRUG AS A WEAK ACID
.
For drugs weak acids are defined as neutral molecules
that can reversibly dissociate into an anion (-ive charge
molecule) and a proton (a hydrogen ion)
EXAMPLE
ASPIRIN
C8H702COOH C8H702COO-
+ H+
(NEUTRAL ASPIRIN) (ASPIRIN
ANION) (PROTON)

4. DRUG MOVEMENT THROUGH
MEMBRANES
DRUGS AS A WEAK BASE
For drugs weak base is a neutral molecule that can
form a cation (+ively charged molecule) by combining
with a proton
H+ + Weak Base Cation
EXAMPLE
Pyrimethamine
C12H11C1N3NH3(CATION)
C12H11C1N3NH2 (NEUTRAL) + H+
Drug can be ionized in the aqueous solution but only
the non-ionized (uncharged) species is lipid soluble
cross the membrane

5. MECHANISM OF DRUG
ABSORPTION
1. PASSIVE ABSORPTION
2. ACTIVE TRANSPORT

6. PASSIVE ABSORPTION
A. SIMPLE DIFFUSION
B. FACILITATED DIFFUSION
C. FILTRATION

7. PASSIVE
ABSORPTION

8. A) SIMPLE DIFFUSION
Aqueous solution of the drug molecule diffuse through the
membranes by first dissolving in the aqueous (hydrophilic)
part of the membrane, then dissolve in the lipid part
THE TRANSPORT OF THE DRUG MOLECULES FOLLOWS
A CONCENTRATION GRADIENT
EXAMPLE------ Drug like weak organic acids, bases, alcohol,
urea
etc are transported through simple diffusion

9. SIMPLE DIFFUSION……
CLASSIFICATION OF SIMPLE DIFFUSION
1. CONVECTIVE TRANSPORT
2. ACID/BASE DIFFUSION
3. ION PAIR TRANSPORT

10. SIMPLE DIFFUSION……
CONVECTIVE TRANSPORT (also called pore
transport )
Transport of the drug takes place through the pores
in the biological membranes
The drug molecule dissolve in the aqueous medium
and move through the pores called aqua porins.
(Transport channels for water )
Several human aqua porins have been indentified in
various system organs
EXAMPLES
DEXTROSE, FRUCTOSE, ORGANIC
ELECTROLYTES, UREA AND DRUGS (CIMETIDINE,
ATENOLOL, MANNITOL)

11. SIMPLE DIFFUSION……
ACID/BASE DIFFUSION
Weak Acid
Example ---- ASPIRIN
Weak Base
Example ------ AMPHETAMINE

12. SIMPLE
DIFFUSION……
ION PAIR TRANSPORT
 Absorption Of Highly Ionized Organic Compounds.
 Combine With ENDOGENOUS SUBSTANCES
which carry an OPPOSITE CHARGE to form ANION
PAIR COMLEXES
Once transported the complex then breaks up
releasing the drug and the endogenous substance,
which is now again available to form complex with
more drugs
Examples:
SULPHONAMIDES, QUININE,
PROPRANOLOL

13. B) FACILITATED DIFFUSION
Using transporter to move drug molecule from high
concentration to low concentration across the cell
membrane.
CONCENTRATION GRAGIENT DEPENDANT

14. FACILITATED DIFFUSION……
TYPES OF FACILITATED DIFFUSION
CHANNEL MEDIATED
CARRIER MEDIATED

15. FACILITATED
DIFFUSION……
CHANNEL MEDIATED
Special types of channel proteins called facilitated
proteins (fps) are involved in this type of transport
 Drug molecules of specific shapes and size
come in contact with the outer receptor site of the
channel, the channel open and the drug molecule is
allowed to pass through the channel (Key Hole)
THIS PORCESS IS ENERGY NON-DEPENDENT
(PASSIVE)
Examples: ANTICANCER, ANTIVIRAL DRUGS

16. FACILITATED
DIFFUSION……
CARRIER MEDIATED
This Is Similar To The Mechanism Of Active
Transport EXCEPT THAT IT DOES NOT
OCCUR AGAINST A CONCENTRATION
GRADIENT.
EXAMPLES
VITAMIN B12 COMPLEX WITH INTRINSIC
FACTOR
The complex then combines with a carrier for
transport across the cell membrane
 CEPHALEXIN
 CAPTOPRIL

17. C) FILTRATION
 The process of transport of substances (H20,
ions and some polar and non polar molecules
of low Molecular weight through PORES in the
cell membranes by means of their osmotic
pressure gradient.
 DRUGS ADMINISTERED PARENTALLY (I/M)
CAN PENETERATE USING THIS MECHANISM

18. ACTIVE
TRANSPORT

19. ACTIVE TRANSPORT
CLASSIFICATION
1-PRIMARY ACTIVE TRANSPORT (UNIPORT)
2-SECONDARY (CO-TRANSPORT)
3-ENDOCYTOSIS

20. PRIMARY ACTIVE
TRANSPORT
A SINGLE MOLECULE IS TO BE
TRANSPORTED
 Each drug or group of drug needs specific carrier
 It is energy dependent
 Proceeds against the concentration gradient (from
region of low concentration to high concentration)
 Energy is provided by ATP
 Carrier can be located on the external surface of the
membrane and appear to be an enzyme
 Drug molecule plus carrier complex once transported,
the carrier dissociates releasing the drug
 The carrier return to its original surface for further drug
molecule transport

21. SECONDARY (CO-
TRANSPORT)
When the carrier protein transport two substances
(one is transported primarily and the other
secondarily) the process is called co-transport
EXAMPLES
Na- Glucose Co Transport
Na- Amino acid Co Transport

22. SECONDARY (CO-
TRANSPORT)
CO-TRANSPORT SYSTEM CAN BE
SYMPORT
ANTIPORT
SYMPORT---- Both the substances move across the
membrane in the same direction
ANTI-PORT---- Both the substances are transported
across the membrane in opposite directions
Examples
Na/K ATPase: Na is expelled outside and K inside

23. ENDOCYTOSIS
The drug molecule is engulfed by the cell membrane
and carried into the cell.
Endocytosis permits very large or very lipid-insoluble
chemical to enter cell
TYPES OF ENDOCYTOSIS
1. PINOCYTOSIS
2. RECEPTOR MEDIATED ENDOCYTOSIS
3. PHAGOCYTOSIS
4. TRANSCYTOSIS

24. ENDOCYTOSIS
PINOCYTOSIS
Small particles up to 75nm
Mostly occur in GIT
Engulfment of small solid particles of drug by the
membrane vesicles
 Forming vacuoles or vesicles
EXAMPLES
VITAMIN A, D, E, K (mostly the fat soluble drugs)

25. ENDOCYTOSIS ……
RECEPTOR– MEDIATED
ENDOCYTOSIS
Occur in many cells of the body
Ligand (any molecule or ion that binds to the protein surface
by non-covalent bond, drug molecule, foreign substance)
The ligand (drug) combine with the specific receptor
The Ligand- Receptor Internalize Across The Cell Membrane
Within the endosome the ligand dissociates from receptors
 The receptor is then re cycled to the plasma membrane
EXAMPLES
Proteins, Polysaccharides, Nucleic Acids,
Iron …..Transferrin
LDL particles ….the liver cell

26. ENDOCYTOSIS ……
PHAGOCYTOSIS
Engulfment of particles larger than 500nm
Mechanism is similar to that of pinocytosis
 Absorption of polio and other vaccines from GIT

27. ENDOCYTOSIS
……
TRANSCYTOSIS
 Drug is internalized by the surface membrane
 Transported as such without any degradation
 The engulfed substance (drug) secreted on the
opposite side of the cell membrane
EXAMPLES
Vaccines

28. FACTORS
MODIFYING DRUG
ABSORPTION

29. FACTORS MODIFYING DRUG
ABSORPTION
1. CHEMICAL NATURE OF THE DRUG
2. PH OF THE MEDIUM
3. PHYSICAL STATUS OF THE DRUG/DOSAGE FORM
4. ROUTE OF ADMINISTRATION
5. SURFACE AREA
6. BLOOD FLOW / SUPPLY
7. FOOD CONTENT IN THE STOMACH
8. WATER/MILK TAKEN WITH DRUG
9. GIT MOTILITY
10. CONCENTRATION OF THE DRUGS
11. PRESENCE OF THE OTHER DRUGS/AGENTS IN THE STOMACH
12. DRUG FORMULATION

30. FACTORS MODIFYING
ABSORPTION
CHEMICAL NATURE OF THE DRUG
A- LIPID---- WATER SOLUBILITY
 Diffusion of a non- electrolyte drug across a cell
membrane is dependent on its lipid solubility
 Lipid soluble drug absorb quickly
 Water soluble drugs absorb poorly
B-DEGREE OF IONIZATION
Especially in case of weak electrolytes
Un-ionized drug is lipid soluble and diffusible
Ionized drug is less lipid soluble and less diffusible

31. FACTORS MODIFYING
ABSORPTION
PH OF THE MEDIUM
Acidic drugs … rapidly absorbed from the stomach …
non ionized form in the acidic medium of the stomach.
Basic drugs ….. reach the alkaline medium of the small
intestine …. non-ionized form… absorbed quickly
EXAMPLES---- Aspirin (Stomach )
Morphine, Quinidine, Ephedrine (Intestine)
(Note:- Insulin, Corticotropins etc when taken orally are
destroyed by the gastric juice or intestinal enzymes)
THESE DRUGS SHOULD NOT BE TAKEN ORALLY

32. FACTORS MODIFYING
ABSORPTION
PHYSICAL STATUS OF THE DRUG/DOSAGE FORM
Drugs in liquid form is readily absorbed than solid state
A drug in solution form is absorbed much easily than
suspension form (Adrenalin, Penicillin And Insulin )
When protamine is added to insulin to form suspension,
the rate of absorption of insulin is reduced
Absorption of solid (tablets, capsules ) depends on the
rate of disintegration and dissolution
The particle size: the smaller the particle size the better
will be its absorption (Corticosteroids, Chloramphenicol
And Griesofulvin)

33. FACTORS MODIFYING
ABSORPTION
ROUTE OF ADMINISTRATION
In descending order
 I/V
 I/M
 I/PERITONEAL
 HYPODERMIC
 SUBLINGUAL
 ORAL
 RECTAL
INHALATION

34. FACTORS MODIFYING
ABSORPTION
SURFACE AREA
 Larger the surface area available for
absorption (absorption surface): greater will be
rate and extent of absorption
 Examples Of Large Surface Areas---
 PULMONARY ENDOTHELIUM
 PERITONEAL SURFACE
 SMALL INTESTINE (10-14 FT)

35. FACTORS MODIFYING
ABSORPTION
BLOOD FLOW / SUPPLY
Greater the blood supply to a part of GIT, greater
will be absorption of the drug
Maximum blood supply ==== stomach
Massage at the site of injection increase blood flow
and increases absorption of the drug
Cooling the area of injection slows drug absorption
In case of circulatory failure, (shock) drug
absorption may be very slow

36. FACTORS MODIFYING
ABSORPTION
FOOD CONTENT IN THE STOMACH
Presence of food in the stomach delays drug
absorption
 Fatty meals prolongs the emptying time of the
stomach
 Drugs taken with fatty meals will reach late for
absorption in the intestine
Fatty meals increase absorption of Vit: A & D,
propranolol, metoprolol (lipophilic drugs)
Absorption increases in the presence of food
Presence of Vit: D helps absorption of calcium from
the stomach

37. FACTORS MODIFYING
ABSORPTION
WATER/MILK TAKEN WITH DRUG
 Intake of water decreases the viscosity of the drug in
GIT, which favors better drug absorption
EXAMPLES-----
Aspirin
 Theophylline
 Erythromycin
if taken with water, their absorption will be increased
 With Milk …. Tetracycline === absorption decreased
(non absorbable complexes with calcium )

38. FACTORS MODIFYING
ABSORPTION
GIT MOTILITY
Increase in motility == decreased drug absorption
REASON= lesser contact time available to the drug for
absorption at the absorption site in the GIT
Decrease In Git Motility Beyond The Physiological
Limits = decreases drugs absorption
REASON= lesser chance of drug dissolution and
subsequent absorption

39. FACTORS MODIFYING
ABSORPTION
CONCENTRATION OF THE DRUGS
The more concentrated the drug, the more will be its
absorption and vice versa
REASON
The Principle Of Osmosis (The Concentration Gradient )
From High Conc. To The Lower Conc.
Drug from a concentrated medium flows to a diluted
medium

40. FACTORS MODIFYING
ABSORPTION
PRESENCE OF THE OTHER
DRUGS/AGENTS IN THE STOMACH
1- Presence of some drugs in the GIT affects the absorption of
other drugs
EXAMPLES ----
VIT: C enhances absorption of IRON from intestine
Phytates retard absorption of IRON from intestine
2- Absorption of fat soluble vitamins is reduced in the
presence of liquid paraffin
3- Calcium present in milk and antacids containing aluminium
form insoluble complexes with tetracycline, reducing its
absorption.

41. FACTORS MODIFYING
ABSORPTION
DRUG FORMULATION
EXCIPIENT-substances like lactose, sucrose, starch,
calcium phosphate or lactate are added in formulating
powder or tablets.
Excepients are pharmacologically inactive substances.
These are added to improve drug stability
Added to tablets to cause them swell with water and
disintegrate into fine particles
These will interfere with the absorption of the drugs.