2. Absorption
is the process by which a
drug enters the bloodstream without
being chemically altered
or
The
of
movement of a drug from its site
application
into
lymphatic system
the
blood
or
3. Mechanism of drug absorption
1. Passive diffusion
2. Carrier- mediated transport:
a) Active diffusion
b) Facilitated diffusion
3. Endocytosis
a) Pinocytosis
b) Phagocytosis
4. Exocytosis
5. Pore Transport (Filtration)
4. Passive Diffusion
water soluble drug (ionized or polar) is
readily absorbed via aqueous channels or
pores in cell membrane.
Lipid soluble drug (non ionized or non
polar) is readily absorbed via cell membrane
itself.
5.
6. Passive Diffusion
Characters
Common.
Occurs along concentration gradient. Non
selective
Not saturable
Requires no energy
No carrier is needed
Depends on lipid solubility.
Depends on pka of drug - pH of medium.
7. “The drug molecules diffuse from a region of higher
concentration to lower concentration until equilibrium is
attained & the rate of diffusion is directly proportional to
the concentration gradient across the membrane”.
8. Active Absorption
Relatively unusual.
Occurs against concentration gradient.
Requires carrier and energy.
Specific
Saturable.
Iron absorption.
Uptake of levodopa by brain.
9.
10. Passive transport
Along concentration
gradient
(From high to low)
No carriers
Active transport
Against concentration
gradient
(From low to high)
Needs carriers
Not selective
Not saturable
Selective, saturable
No energy
Energy is required
11. Facilitated Diffusion
Occurs along concentration gradient.
Requires carriers
Selective.
Saturable.
No energy is required.
12.
13. Active transport
Against concentration
gradient
(From low to high)
Carrier-mediated
facilitated diffusion
Along concentration
gradient
(From high to low)
Needs carriers
Needs carriers
Selective, saturable
Selective, saturable
Energy is required
No energy is required
14. It involves engulfing extracellular materials within a segment
of the cell membrane to form a saccule or a vesicle (hence also
called as corpuscular or vesicular transport) which is then
pinched off intracellularly.
15. Endocytosis - surrounding a substance with some of the
cell membrane and then, bringing it into the cell, within a
vacuole.
a)
Pinocytosis- bringing in liquids; “cellular drinking”
b)
Phagocytosis- bringing in solid-like food; “cellular eating”
Exocytosis -opposite to the pinocytosis
16. This process is important in the absorption of fat soluble
vitamins & in the uptake of nutrients.
17. Phagocytosis (“cellular eating”) a cell engulfs a particle
and packages it within a food vacuole
Pseudopod
of amoeba
Food being ingested
18. 3. Exocytosis - opposite of endocytosis.
a)
This is a way to rid cell of wastes.
b)
Restores the membrane, so the cell doesn’t shrink.
22. 1. Also known as convective transport, bulk flow or filtration.
2. Important in the absorption of low mol. Wt. (less than 100). Low
molecular size (smaller than the diameter of the pore) & generally watersoluble drugs through narrow, aqueous filled channels or pores in the
membrane structure.
e.g. urea, water & sugars.
3. The driving force for the passage of the drugs is the hydrostatic or the
osmotic pressure difference across the membrane.
Rate of absorption via pore Transport depends on the number & size of the
pores,
23.
Most drugs are absorbed in the small intestine,
because
It is the portal for absorption of nutrients into blood
It is surrounded by a very thin
with a large surface
area
membrane
24.
Rate - How rapidly does the drug get from its site of
administration, to the general circulation
Extent - How much of the administered dose enters
the general circulation
25.
Bioavailability of a drug is defined as the
amount / percentage /fraction of drug that is
absorbed from a given dosage form and reaches
the systemic circulation in unchanged form
following nonvascular administration.
26. PRINCIPLE
For drugs taken by routes other than the
i.v. route, the extent of absorption and
the bioavailability must be understood in
order to determine what dose will induce
the desired therapeutic effect. It will also
explain why the same dose may cause a
therapeutic effect by one route but a
toxic or no effect by another.
27.
DRUG RELATED FACTORS
Physical properties of the drug.
1.
2.
3.
1.
2.
3.
Physical state
Lipid /Water solubility
Concentration
Nature of the dosage form .
Particle size
Disintegration & Dissolution Time
Formulations
Route of drug administation .
29.
Physical state
Liquids are absorbed better than solids.
Crystalloids are absorbed better than colloids
Lipid and water solubility
Drugs in aqueous solution mix more readily than
those in oily solution with the aqueous phase.
At cell surface-lipid soluble drug penetrate more rapidly.
Example –bile salts assist the absorption of fat soluble vitamins in SI.
Concentration
Passive transport depends upon conc. i.e drug given in concentrated
form is absorbed faster.
30.
Particle size
Larger the particle slower the absorption and vice versa.
(EX.Antihelminthic-Bephenium)
Smaller size is imp. for absorption of
chloramphenicol,Griseofulvin, oral coagulants, tolbutamide,
spironolactone.
Dosage of the active drug can be reduced.
Disintegration & Dissolution Time
Rate of brake up of drug into granules is DI time
Rate at which drug goes into solution is DS time
DI is poor measure as Other factors- solvation, particle size,
form, saturation solubility can modify bioavailability.
31.
Formulations
Role of inert diluents –calcium,lactose, starch,lactate.
Method of formulation
Route of drug administation.
I.V Drug
Immediately
completely
Oral Drug
Delayed
incomplete
36.
The first-pass effect is the term
used for the hepatic metabolism of
a pharmacological agent when it is
absorbed
from
the
gut
and
delivered to the liver via the portal
circulation. The greater the firstpass effect, the less the agent will
reach the systemic circulation when
the agent is administered orally
37.
38.
Presence of other agents
Vitamin C enhances the absorption of iron.
Calcium retards absorption of tetracyclines.
Fat soluble vitamins absorption is delayed by liquid paraffin.
Enterohepatic cycling
Morphine…..
Area of absorbing surface
39.
Many drugs bind to plasma proteins in the blood
steam
Plasma protein binding limits distribution.
A drug that binds plasma protein diffuses less
efficiently, than a drug that doesn’t.
40.
Change in gastrointestinal pH
◦ Ketoconazole needs acidic conditions in gut
Drug binding in GI tract
◦ E.g. tetracycline and calcium
Change in gastrointestinal flora
◦ Antibiotics with OCs
Change in gastrointestinal motility
◦ Metoclopramide and digoxin
Malabsorption caused by other drugs
◦ Orlistat (Xenical) and fat soluble vitamins
Editor's Notes
G-I Tract - מערכת העיכול
Drugs can be ionised in an aqueous environment.
Non-ionised drug is more lipid soluble than ionised species.
Non-ionised species diffuse across cell membranes more easily than ionised species.
