present study indicates the mechanism, classes and mainly significance of protein binding.

1. SIGNIFICANCE OF PROTEIN
BINDING
Pharmacology M Pharm. First Year
RollNo. 06
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2. Contents
1. What is protein binding..?
2. Mechanism of protein binding.
3. Classes of protein drug binding.
4. Significance of protein binding.
5. Summary.
6. References.
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3. What is Protein Binding..?
• The phenomenon of complex formation of drug With protein is called
as a protein binding of drug.
Protein + drug ⇌ protein-Drug complex
• As a protein bound drugs is Neither Metabolised nor excreted hence
it is pharmacologically inactive due to its pharmacokinetic and
pharmacodynamic inertness.
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4. Mechanism of Protein Drug Binding.
• Binding of drugs to proteins is generally reversible or irreversible.
• Reversible generally Involves Weak chemical bond Such as:
1. Hydrogen bond
2. Hydrophobic bond
3. Ionic bond
4. Van der wall forces
• Irreversible drug binding is rare, arises as a result of Covalent binding
and is often a reason for carcinogenicity or tissue toxicity of drug.
Eg. Chloroform and paracetamol metabolites.
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5. Classes of Protein Binding.
1. Binding of drugs to blood components.
A. Plasma protein drug binding-
B. Binding of drug to blood cells.
2. Binding of drugs to extravascular blood cells.
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6. A. Plasma Protein Drug Binding.
• The binding of drugs to plasma protein is reversible.
• The order of binding of drugs to plasma proteins is :
Albumin > α1-acid glycoprotein > Lipoprotein > Globulins
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7. 1. Binding of drugs to Human Serum Albumin
• It is most abundant plasma protein (59%) having molecular weight of
66.5 KDa with large binding capacity.
• Four different sites on HSA for drug binding-
1. Site1: warfarin Binding site
2. Site2: Diazepam binding site
3. Site3: Digitoxin binding site
4. Site4: Tamoxifen binding site.
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8. 2.Binding of drugs to α1-acid Glycoprotein.
• It has plasma conc. Range of 0.6 to 1.2 g/dL
• It binds to no. Of basic drugs like imipramine, lidocaine, propranolol,
Quinidine.
• The binding is often reversible and bind with weak chemical bonds
such as – hydrophobic interactions, Electrostatic interactions and van
der walls forces.
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9. 3. Binding of drugs to Lipoprotein:
• Binding by – Hydrophobic bonds, Non competitive.
• Lipid core composed of:
Inside- Triglycerides and cholesteryl esters.
Outside- Apoproteins.
• Eg.
1. Acidic- Diclofenac
2. Neutral- Cyclosporin A
3. Basic- Chlorpromazine.
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10. 4. Binding Of drugs to Globulins.
Globulin Synonym Binds To
1. Alpha1 globulin
2. Alpha2 globulin
3. Βeta1 globulin
4. Beta2 globulin
5. Gamma globulin
Transcortine
ceruloplasmine
Transferin
_______
_______
Steroidal drugs, Thyroxin and
cynocobalamine.
Vitamin A D E K.
Ferrous ions
Carotinoids
Antigens.
.
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11. B. Binding of Drugs to Blood Cells.
• The rate and extent of entry into RBC is more for lipophilic drugs.
• The RBC comprises of 3 components-
1. Haemoglobin: phenytoin, phenobarbital.
2. Carbonic anhydrase: Acetazolamide and Chlorthalidone.
3. Cell membrane: Imipramine, Chlorpromazine.
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12. 2.Binding Of drugs to extravascular Tissue
protein.
• Importance: 1. It increase the apparent volume of distribution of
drug.
2. Localisation of drug at specific Site in body.
• Binding order-
Liver > kidney > lung > muscle
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13. Significance of Protein Binding of Drug.
1. Absorption:
• Absorption is a transfer of free drug from Site of administration into
the systemic circulation.
• Absorption equilibrium is attained when concentration between two
compartments is equal when equilibrium is attained the process may
stop.
• Binding of absorbed drug to plasma protein decreases the free drug
concentration in systemic circulation and disturbs the equilibrium
which results in Conc. Gradient re-establishment and act as driving
force for further absorption.
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2. Distribution:
• Protein-bound drugs can distribute into tissues with a high protein
content, such as muscles and organs, more effectively.
• Distribution helps drugs reach their intended sites of action.
3. Metabolism:
• protein binding decreases the Metabolism of drug and enhances the
biological half life.
• Only unbound fraction get metabolised.
• Eg. Phenylbutazone, sulfonamide.
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4. Elimination:
• Only the unbound drug gets eliminated.
• Protein binding prevent the entry of drug to the metabolising
organ(liver) & to glomerulus filtration.
• Eg. Tetracycline 65% bound to plasma proteins, elimination half life is
8.5 hrs.
• Eg. Doxycycline 93% bound to Plasma proteins, elimination half life is
15.1 hrs.
5. Systemic solubility of drug:
• lipoprotein act as a vehicle for hydrophobic drugs like Steroid, heparin
and oil soluble vitamins.
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6. Drug targeting:
• Protein binding can help achieve target specificity by allowing the
drug to interact selectively with carrier proteins that are present in or
around the desired target.
• This ensures that the drug is delivered to the intended site of action.
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7. Drug storage:
• The bound fraction of drug is not available for action.
• When the concentration of free drug is reduced due to elimination the
bound drug gets dissociated from proteins.
• The complex of drug protein in the blood acts as a reservoir and
continuously supply free drug
8. Diagnosis:
• The chlorine atom of chloroquine Replaced with radiolabelled I-131
Can used to visualize melanomas of eye and disorders of thyroid gland.
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18. Summary:
• All Pharmacokinetics parameters can be influenced by protein binding
of a drug.
• Understand the concept of pharmacodynamics & pharmacokinetics
of a protein binding of a drug.
• Role of a drug protein complexation in a blood it acts as a reservoir
and continuously supply of a free drug.
• To have known the mechanism & classes of whole scenario of protein
binding of drug.
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19. References
1. K. D. Tripathi, essential of medical pharmacology, 6th edition Page
no. 20-23
2. Bhramankar D. M. And Jaiswal S. B. : Biopharmaceutics and
pharmacokinetics p. No. 116-136
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