Drug Distribution & Factors Affecting DistributionVijay Kevlani
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Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues.
Drug Distribution & Factors Affecting DistributionVijay Kevlani
To have the full content of slide, kindly download it and convert it to ppt form.
Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues.
Drug distibution, significance, steps in Drug distribution, Factors affecting,physiochemical properties of drug, volume of distribution,protein binding, mechanism of protein drug binding
What Is Disposition?
What Is Distribution?
Steps In Drug Distribution
Factors Affecting Distribution Of Drugs
Physiological Barriers To Distribution
Volume Of Distribution
Specific Tracers Or Markers
Methods For Studying Drug Distribution Pattern
D M Brahmankar and Sunil B.Jaiswal Biopharmaceutics and Pharmacokinetics A Treatise
"Physiological Barriers" by Debanjan Chatterjee & Abhishek Roy Debanjan Chatterjee
Various Physiological barriers as a protective of drug , & their related Bio pharmaceutical action pharmacokinetic action the list of drugs and other relevant details
Drug distibution, significance, steps in Drug distribution, Factors affecting,physiochemical properties of drug, volume of distribution,protein binding, mechanism of protein drug binding
What Is Disposition?
What Is Distribution?
Steps In Drug Distribution
Factors Affecting Distribution Of Drugs
Physiological Barriers To Distribution
Volume Of Distribution
Specific Tracers Or Markers
Methods For Studying Drug Distribution Pattern
D M Brahmankar and Sunil B.Jaiswal Biopharmaceutics and Pharmacokinetics A Treatise
"Physiological Barriers" by Debanjan Chatterjee & Abhishek Roy Debanjan Chatterjee
Various Physiological barriers as a protective of drug , & their related Bio pharmaceutical action pharmacokinetic action the list of drugs and other relevant details
1. Distribution of drug
2. Factor affecting of drug
3. Protein binding of drug
4. Factors affecting of protein binding of drug
5. Significance of protein drug binding
6. Volume of distribution
This PowerPoint presents information about the Distribution of the Drug process in the Body. This includes Definitions and Factors that affect the Distribution process. An explanation of Tissue permeability of Drugs. And Steps involved in this distribution process.
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2. After the drug enters in to the systemic circulation by different routes the
drug is subjected to number of process called DISPOSITION
(arrangements/transfer)
The 2 major dispositions are
a) DISTRIBUTION: is a reversible process of transfer of drug between
compartments
b) ELIMINATION: is a irreversible loss of drug from the body.
Distrib
uted in
the
body
Drug &
metabo
lites in
plasma
elimin
atiion
metab
olized
3. DISTRIBUTION
Reversible transfer of drug between 2 compartments, since the
process is carried out by the circulation of blood, one of the
compartment is always the BLOOD or PLASMA, and other
represents the E.C.F or body tissues.
So now we can describe distribution as reversible transfer of drug
between blood and E.C.F fluids or Tissues.
Distribution is a PASSIVE process(driving force is conc. Gradient)
between blood and e.c.f tissues.
This process occurs by diffusion of free drug until EQUILIBRIUM is
achieved.
CAPILLARY CELL
4. Significance :-
☺☺☺ Pharmacological action of drug depends upon its
concentration at the site of action
Thus distribution plays important role in
♫ onset of action
♫ Intensity of action
♫ Duration of action to☺o
5. Capillary carrying blood along with drug
Cell-1 Cell-2 Cell-3 Cell-4
Distribution of drug is not uniform through out the body because different tissues
receive the drug from plasma at different rates,
The differences are due to a number of factors:
6. Factors affects the drug distribution
1). tissue permeability of drug
a. physicochemical property – i) molecular size
ii) pKa
iii) o/w partion coefficient
b. physiological barriers
2). Organ tissue size and perfusion rate
3). Binding of drug to tissue components
a. with blood components
b.with extravascular tissue proteins
4). Miscellaneous factors
a. age
b.Pregnancy
d.Obesity
e.Diet
f.Disease states
g.Drug interaction
1). TISSUE PERMEABILITY OF THE DRUGS:
• if the blood flow to entire body was rapid and uniform, difference in degree of
distribution between tissues is a sign of difference in tissue permeability of the drug
and the process will be TISSUE PERMEABILITY RATE-LIMITED.
•The tissue permeability of drugs depend on PHYSICOCHEMICAL properties of drug
as well as PHYSIOLOGIC barriers that restrict diffusion of drug in to tissues.
7. a. PHYSIOCHEMICAL PROPERTIES OF THE DRUG:
Molecular size
Degree of ionization
Partition coefficient
Drugs having molecular size of less than 500-600 Daltons easily cross
the capillary membrane to diffuse in to the extracellular interstitial fluids.
However penetration of drugs from e.c.f to cell is the function of
molecular size , ionization constant and lipophilicity of drug.
Only small water soluble molecules of size below 50 Daltons enter cell
through aqueous filled channels, where as larger size molecules enters
through specialized transports.
In case of degree of ionization , a drug that remains unionized at the pH
values can penetrate the cells more rapidly.
So the drugs which ionize at plasma pH cannot penetrate the lipoidal
cell membrane and hence TISSUE PERMEABILITY is the rate limiting
step in distribution.
In case of partition coefficient, drugs having same 0/w ratio but differ in
extent of ionization having different penetration power
Less ionized drugs>more ionized drugs
+ +- +-
13. PERFUSION RATE:
It is defined as the volume of blood that flows per unit time, per
unit volume of the tissue
ORGAN/TIISUE % OF BODY
VOLUME
BLOOD
FLOW
(ml/min)
HIGHLY PERFUSED
1. Lungs 0.7 5000
2. Kidney 0.4 1250
3. Brain 2.0 700
MODERATELY PERFUSED
4. muscles 42.0 1000
5. Skin 15.0 350
POORLY PERFUSED
6. Fat(adipose tissue) 10.0 200
7. Bone( skeleton) 16.0 250
14. BRAIN
ADIPOSE TISSUE
HIGHLY
PERFUSE
D TISSUE
LESS
PERFUSE
D TISSUE
I.V injection
So The extent to which the drug is distributed in a
particular tissue or organ depends up on the size of the
tissue as well tissue/blood partition coefficient of the
drug.
Redistribution
15. 3).Binding of drug to tissue components
a) Binding of drug to blood components;-
i) Plasma protein bindings
Human serum albumin:-acidic drug
ά1- acid glycoprotein :-basic drugs(impra)
Lipoproteins :-basic, lipophilic drugs(chlorpromazine)
ά1-Globuline :-steroids like corticosterone ,vit-B12
ά2-Globuline :-vit-A,D,E,K,cupric ions.
Hemoglobin :-Phenytoin, phenothiazines.
ii) Blood cells bindings:-
RBC : drugs like, phenytoin,phenobarbiton binds with Hb
,imipramine,chlorpromazine binds with RBC Cell wall
AB Ligand
binding site
Free
drug
Bound
drug
16. b.with extra vascular tissue proteins
40% of total body weight comprise of vascular tissues
Tissue-drug binding result in localization of drug at specific
site in body and serve as reservoir
As binding increases it also increase biological half life.
Irreversible binding signify drug toxicity. (carbamazepine-
agranulocytosis)
liver>kidney>lungs>muscle>skin>eye>bone>Hair, nail
17. AGE:
Differences in distribution pattern of a drug in different age groups are
mainly due to differences in:
a) Total body water-which is greater in infants.
b) Fat content-is also higher in infants and elderly.
c) Skeletal muscles-are lesser in infants and elderly.
d) Plasma protein content -low albumin content in both infants and elderly.
PREGNANCY:
During pregnancy, the growth of uterus, placenta and fetus increases the
volume available for distribution of drugs.
The fetus represents a separate compartment in which a drug can
distribute.
OBESITY:
In obese persons, the high adipose tissue content can take up a large
fraction of lipophilic drugs despite the fact that perfusion though it is low.
18. DISEASES STATES:
A number of mechanisms may be involved in the alteration of drug
distribution characteristics in disease states:
a. Altered albumin and other drug binding protein concentration.
b. Altered or reduced perfusion to organs or tissues.
c. Altered tissue pH.
DRUG INTERACTIONS:
Drug interactions that affect distribution are mainly due to differences in
plasma protein or tissue binding of drugs.
19. Quiz Yourself
1. DISTRIBUTION: is a irreversible process of transfer of drug
between compartments T/F
2. A drug that remains unionized at the pH values can penetrate
the cells more slowly T/F
3. Distribution is a active process T/F
4. Since BBB is lipoidal barrier, it allows only the drugs having
low o/w partition coefficient to diffuse actively. T/F
5. Placental barrier is as effective a barrier as BBB T/F
6. ---------- drugs will bound to the glycoproteins.