protien binding

1. DRUGINTERACTION
• Presented by:
• Karthik swamy bm
• M PHARM 2nd sem(pharmaceutics)
• Under guidance of:
• HAFSA MADAM
• Mod.rel drug delivery
system
• V.L COLLEGE OF PHARMACY
• RAICHUR

2. Content
• Pharmacokinetic
• Drug interaction
• Factor contributing to drug interactions
• protein binding of drug
• Effect of protein binding interaction
• Effect of tissue binding interaction

3. Pharmacokinetics
• Pharmacokinetics is a study of what the body
does to drug.
• It is a science of kinetics of ADME.
• It is also defined as movement of drug in the body.
• Elimination occur by two processes Metabolism
and Excretion.

4. Drug Interactions
• When the pharmacological activity of a drug is altered by
the concomitant use of another drug or by the presence of
some other substance.
• The drug whose activity is affected by such an interaction
is called as the object drug.
• The agent which precipitates such an interaction is
referred to as the precipitant. Drug interactions include
1. Drug-drug interactions.
2. Food-drug interactions, for example, inhibition of
metabolism of several drugs by grapefruit juice

5. 3. Chemical-drug interactions, for example,
interaction of a drug with alcohol, tobacco or
environmental chemicals.
4. Drug-laboratory test interaction, for example,
alteration of diagnostic laboratory test results by
the presence of drug.
5. Drug-disease interactions, for example, worsening
of disease condition by the drug.

6. Factors Contributing to Drug
Interactions
• Some of the more important risk factors that lead
to drug interactions include
1. Multiple drug therapy
2. Multiple prescribers
3. Multiple pharmacological effects of drug
4. Multiple diseases/Predisposing illness
5. Poor patient compliance
6. Advancing age of patient
7. Drug related factor

7. Protein binding of drug
• The phenomenon of complex formation with proteins is
called as protein binding of drugs.
• The formation of a drug–protein complex is often named
drug–protein binding.
• The drug protein binding may be of two types
1) Reversible
• When the drug bind the protein with weaker chemical bonds
such as hydrogen bond or vander waal’s forces.
2) Irreversible
• Irreversible drug protein binding is usually a result of
chemical activation of the drugs, which then attaches
strongly to the protein or macromolecules by covalent
chemical bonding

8. BINDING OF DRUGS TO BLOOD
COMPONENTS
• Albumin
• Alpha 1-Acid Glycoprotein
• Lipoprotein
• Erythrocytes (RBC)
• Immunoglobulins
The extent or order of binding of drugs to
various plasma proteins is: Abumin > alpha1
Acid Glycoprotein > Lipoproteins > Globulin

9. Effect of protein binding interactions
Apparent volume of distribution :
It is defined as the hypothetical volume of body fluid into
which a drug is dissolved or distributed. It is called as
apparent volume because all parts of the body equilibrated
with the drug do not have equal concentration.
Effect Of Protein Binding On The Apparent Volume Of
Distribution :
• The extent of drug protein binding affects VD.
• Drugs that are highly bound to plasma proteins have a low
fraction of free drug (fu = unbound or free drug fraction).
• The plasma protein-bound drug does not diffuse easily and is
therefore less extensively distributed to tissue

10. • Drugs with low plasma protein binding have larger fu,
generally diffuse more easily into tissues, and have a
greater volume of distribution.
• Drugs such as furosemide, sulfisoxazole, tolbutamide, and
warfarin are bound greater than 90% to plasma proteins
and have a VD value ranging from 7.7 to 11.2 L per 70-kg
body weight.
• Basic drugs such as imipramine, nortriptyline, and
propranolol are extensively bound to both tissue and
plasma proteins and have very large VD values.

11. Displacement of drugs from plasma proteins can affect the
pharmacokinetics of a drug in several ways : directly
increase the free (unbound) drug concentration as a
result
• 1. Reduced binding in the blood;
• 2. Reaches the receptor sites directly, causing a more
intense pharmacodynamic (or toxic) response;
• 3. Causing a transient increase in VD and decreasing
partly some of the increase in free plasma drug
concentration;
• 4. More drug diffusion into tissues of eliminating
organs, particularly the liver and kidney, resulting in a
transient increase in drug elimination

12. Effect Of Protein Binding On
Elimination Of Drug :
• Protein binding decreases the renal excretion of the drugs
and enhance the biological half –life. Only the free drugs
excreted through filtration for example tetracycline.
• The binding of drugs in extravascular organs decreases
their concentration in blood and thereby shows their
elimination by liver, kidney and lungs.
• However, the binding of drug to plasma protein may retard
the elimination of drugs depending on the mechanism of
elimination, for example the binding of drug to the plasma
protein lowers their unbound concentration in blood and
thereby decreases their rate of elimination by glomerular
filtration and by inefficient transport system in the kidney.

13. • Binding to plasma protein would decreases the rate of
elimination of lipid soluble drugs that diffuse rapidly
from the glomerular filtration back into the blood, even
though they are rapidly transported by active transport
system.
• In addition, the binding of drug to plasma protein
would also decreases the rate of drug metabolism by
relatively inactive enzyme system in liver.

14. Effect Of Protein Binding On Patient
With Kidney Disease :
• Albumin is primarily responsible for the binding of
acidic drugs whereas basic drugs appear to bind
preferentially to AAG (alpha-amino glycoprotein).
• The low concentration of albumin and AAG in
patients with liver disease indicates the inability of
the liver to synthesize these drug-binding proteins.
• Impaired binding of acidic and basic drugs is well
documented in patients with liver disease.

15. • The albumin concentrations in the transplant patients were
low despite stable biochemical liver tests. Because albumin
is primarily responsible for binding of acidic drugs, liver
transplant patients would not be able to bind acidic drugs as
efficiently as the normal subjects.
• However, the AAG concentrations were elevated in all the
transplant patients studied. AAG is an acute-phase reactant
and is primarily synthesized in the liver.
• AAG concentrations are known to increase in plasma.

16. Effect Of Protein Binding On Patients
With Hepatic Disease :
• Protein binding affects distribution.
• The impaired liver is unable to synthesize
plasma proteins (albumin) adequately.
• Liver impairment causes accumulation of
substances (bilirubin) that displace drugs from
protein-binding sites.
• A statistics on this case shows that liver disease
patients with normal concentration of albumin
and bilirubin have unbound percentages of
frusemide similar to those in healthy subjects

17. Effect of tissue binding interactions TISSUE
BINDING OF DRUGS (TISSUE LOCALIZATION OF
DRUGS)
• A drug can bind to one or more of the several tissue components.
Tissue-drug binding is important in distribution from two
viewpoints :
• It increases the apparent volume of distribution of drugs in
contrast to plasma protein binding which decreases it.
• Tissue-drug binding results in localization of a drug at a specific
site in the body (with a subsequent increase in biological half-life).
This is more so because a number of drugs bind irreversibly with
the tissues (contrast to plasma protein-drug binding); for example,
oxidation products of paracetamol, phenacetin, chloroform, carbon
tetrachloride and bromobenzene bind covalently to hepatic tissues.

18. Factors influencing localization of
drugs in tissues include :
1. lipophilicity and structural features of the drug,
2. perfusion rate
3. pH differences, etc.
• Extensive tissue-drug binding suggests that a tissue can act
as the storage site for drugs. Drugs that bind to both tissue
and plasma components result in competition between drug
binding sites.
• For majority of drugs that bind to extravascular tissues, the
order of binding is:
Liver > Kidney > Lung > Muscles

19. Several Examples Of Extravascular
Tissue-drug Binding Are:
1. Liver: Paracetamol bind irreversibly to liver
tissues resulting in hepatotoxicity.
2. Lungs: Basic drugs like imipramine,
chlorpromazine and antihistamines accumulate in
lungs.
3. Kidneys: Metallothionin, a protein present in
kidneys, binds to heavy metals such as lead,
mercury, and cadmium and results in their renal
accumulation and toxicity.

20. 4. Skin: Chloroquine and phenothiazines
accumulate in skin by interacting with melanin.
5. Eyes: The retinal pigments of the eye also
contain melanin. Binding of chloroquine and
phenothiazines to it is responsible for
retinopathy.
6. Hairs: Arsenicals, chloroquine and
phenothiazines are reported to deposit in hair
shafts.

21. 7. Bones: Tetracycline is a well-known example of a drug that
binds to bones and teeth. Administration of this antibiotic
to infants or children during odontogenesis results in
permanent brown-yellow discoloration of teeth.
8. Fats: Lipophilic drugs such as thiopental and the pesticide
DDT accumulate in adipose tissues by partitioning into it.
9. Nucleic Acids: Molecular components of cells such as
DNA interact strongly with drugs like chloroquine and
quinacrine resulting in distortion of its double helical
structure

22. References
• Shargel L. ,” Applied Biopharmaceutics &
Pharmacokinetics”, 7th Edition, 2005, Published by
McGraw Hill, New York, Page no – 267,276,277.
• Brahmankar D.M. , Jaiswal S.B. , “Biopharmaceutics
and Pharmacokinetics-A Treatise”, 1995, Published by
Vallabh Prakashan, New Delhi, Page no- 116-123.
• https://www.slideshare.net/azamushahiullahprottoy/effe
cts-of-proteinbinding

23. THANK
YOU