Dr. Rathnakar U.P.

MD.DIH.PGDHM
Department of Pharmacology
Kasturba Medical College,
Mangalore
www.scribd.com

Dose






Drug in the plasma



Drug at the site of action



MOA & Effect- Adverse and Beneficial



Absorption




Distribution


Metabolism





Excretion
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Pharmacodynamics
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Topic Pharmacokinetics


Lecture 1: Absorption Drug passage across cell
membranes, Factors modifying absorption and
bioavailability.

Lecture 2: Drug distribution Volume of distribution, Plasma
protein and tissue binding and its clinical implications.

Lectures 3 & 4: Biotransformation Sites; Phases, examples,
Factors modifying it and its consequences, Enzyme induction
and inhibition and their clinical importance.

Lecture 5: Drug Elimination channels of drug excretion and
Factors modifying it. Kinetics of elimination.
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Pharmacokinetics
Branch of pharmacology, which deals with drug
absorption, distribution, metabolism and excretion

PK is the quantitative study of drug movement in,
through and out of the body
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PK-Membrane Transport
Mechanism by which drugs cross biological
membrane????????
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Filtration
Special transport
Passive
diffusion
Transport mechanisms
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Membrane Transport..

A. Passive diffusion
B. Filtration

C. Specialized transport

1. Carrier transport
Facilitated diffusion
Active transport
2. Endocytosis-pinocytosis
Size
Lipid solubility
Ionization
Concentration
gradient
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Passive diffusion

Bidirectional process,
Movement of molecules from higher to lower conc
[Down the gradient]
Lipid soluble drugs- Passive diffusion, after dissolving in
the lipid of cell membrane

Acidic drugs are unionized in acidic medium
Alkaline drugs are unionized in alkaline Medium
Unionized drugs are readily absorbed
More lipid soluble Diffuses quickly
Greater the difference in concn gradient Quicker
diffusion

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FILTRATION




Capillaries (Except in brain-Tight junction) have large
pores & most drugs filter through these.

Lipid insoluble drugs cross biological membranes by
filtration through these pores

Diffusion of drugs is dependent on Rate of Blood Flow

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Specialized transport: Carrier mediated
Drug + CARRIER in the membrane complex is
transported from one side of the membrane to other. Eg.
Calcium & iron absorption
Carrier transport
1. Specific,
2. Saturable,
3. Competitively inhibited by - which utilize the same
carrier.



A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
II. Pinocytosis
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Specialized transport: Carrier mediated
Facilitated diffusion
No energy required
Drug + carrier[SLC Transporter] in the membrane,
diffusion across the cell membrane.
Movement ONLY higher to lower conc [ALONG].
Eg. Glucose into muscles
A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
II. Pinocytosis
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Specialized transport:
Active transport

Movements of molecules Low conc. To high
conc.
Against the conc.gradient
Require energy.
P-glycoprotein
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ATP ADP
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A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
II. Pinocytosis
Specialized transport:
Active transport:Primary

Primary Active Transport
ATP Binding Cassette-Transporter
Only out of the cytoplasm
Energy derived from ATP
A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
a. Primary
b. Secondary
II. Pinocytosis
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ATP ADP
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Specialized transport:
Active transport

Energy derived from movement of
another substance
In the same direction- Symport
In opp.direction -Antiport

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ATP ADP
Symporter
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Antiporter
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A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
a. Primary
b. Secondary
II. Pinocytosis
Specialized transport:
Endocytosis





Pinocytosis; By formation of vesicles

A. Passive diffusion and Filtration

B. Specialized transport

I. Carrier transport
1. Facilitated diffusion
2. Active transport
II. Pinocytosis
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ABSORPTION
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Absorption
[Movement from site of administration to
circulation]
ORAL:
S.c, i.m: Absorbed by capillaries or lymphatics
Topical: Lipid solubility-Hyoscine, Fentanyl, GTN,
Nicotine, Testosterone, Estradiol
Cornea
Q.1.How much drug is absorbed?
Q.2.How much reaches syst.circulation?
Q.3.If 100% is not absorbed why?

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BA=30/150
First pass metabolism
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FACTORS INFLUENCING ABSORPTION

Solubility-dissolution
and disintegration
pH & Ionization
Concentration
Area of absorbing
surface
Vascularity
Diseases
Route-oral
Other drugs
Food
Efflux
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S.c and i.m
Lipid soluble
and insoluble
Large molecules
lymphatics
Heat-increases
Vasoconstrictors-
decrease

Topical
Lipid soluble
Bioavailability
Dose
Destroyed
in gut
Not
absorbed
Destroyed
by gut wall
Destroyed
by liver
to
systemic
circulation
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Absorption: Bio-Availability

The fraction [F] of administered dose of a
drug that reaches systemic circulation in
the unchanged form
I.V. 100% Bio-availablity
Oral-Not 100%. WHY?
1. Incompletely absorbed
2. First pass metabolism
i.m or s.c. also may be less
than 100% -Local binding
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Bioavailability
Fraction / proportion of
unchanged drug that
reaches systemic circulation
in unchanged form

Refers to rate & extent of
absorption of a drug from a
dosage form as determined
by its concentration-time
curve in blood or by its
excretion in urine
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Factors affecting bioavailability
Factors affecting absorption
First Pass Metabolism
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Physicochemical characteristics
of drugs

Solubility
Lipid soluble drugs
which are unionized
rapidly absorbed
e.g., thiopentone
sodium,
organophosphates
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Degree of ionization
Drugs: weak acids / weak bases
Membranes are permeable to the unionized form of drug
molecule, if it is lipid soluble
Degree of ionization varies with the pH of the absorbing
media.
Acids undergo ionization in alkaline pH
Bases ionize readily in acidic pH.
Acidic drugs remain unionized in acidic pH, these are better
absorbed from gastric mucosa e.g., aspirin and barbiturates.
At physiological pH (7.4), weak acids / weak bases remain partly
unionized and absorption is generally proportional to the lipid
solubility of the drug
Physicochemical characteristics
of drugs
5
pH and Ionization
4
pH & Ionization
[Ion trapping]
Acidic drug in acidic medium
Acidic
Unionized
Alkaline
Ionized
&
Trapped
3
Lumen
Wall
pH & Ionization
[Alkaline diuresis]
Acidic drug
is
Ionized
&
excreted
Alkalinize
the urine
2
Slowly disintegrating chemical complexes:
procaine penicillin
Oily preparations
Sustained release / Controlled release
preparations:
L-dopa
Transdermal:
e.g., ointments and patches
Methods to prolong drug
absorption
1
Pharmaceutical Equivalence
Contain the same active ingredients, identical in strength, dosage form, and route of
administration.
Eg. Tab.Metacin 500 mg and T.Crocin 500mg

Bioequivalence
Bioavailability of the active ingredient in the two products are same.
Eg. Metacin and Crocin

Therapeutic equivalence
Comparable efficacy and safety

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