protein binding.pptx

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

1. SIGNIFICANCE OF PROTEIN BINDING Presented By- Vivek Kumbhar Pharmacology M Pharm. First Year Roll No. 06 1

2. Contents What is protein binding..? Mechanism of protein binding. Classes of protein drug binding. Significance of protein binding. Summary. References. 2

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. 3

4. Mechanism of Protein Drug Binding. Binding of drugs to proteins is generally reversible or irreversible . Reversible generally Involves Weak chemical bond Such as: Hydrogen bond Hydrophobic bond Ionic bond 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. 4

5. Classes of Protein Binding. Binding of drugs to blood components. A. Plasma protein drug binding- B. Binding of drug to blood cells. Binding of drugs to extravascular blood cells. 5

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 6

7. 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- Site1: warfarin Binding site Site2: Diazepam binding site Site3: Digitoxin binding site Site4: Tamoxifen binding site. 7

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. 8

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. Acidic- Diclofenac Neutral- Cyclosporin A Basic- Chlorpromazine. 9

10. 4. Binding Of drugs to Globulins. Globulin Synonym Binds To Alpha1 globulin Alpha2 globulin Βeta1 globulin Beta2 globulin Gamma globulin Transcortine ceruloplasmine Transferin _______ _______ Steroidal drugs, Thyroxin and cynocobalamine . Vitamin A D E K. Ferrous ions Carotinoids Antigens. . 10

11. B. Binding of Drugs to Blood C ells . The rate and extent of entry into RBC is more for lipophilic drugs. The RBC comprises of 3 components- Haemoglobin: phenytoin, phenobarbital. Carbonic anhydrase: Acetazolamide and Chlorthalidone. Cell membrane: Imipramine, Chlorpromazine. 11

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 12

13. Significance of Protein Binding of Drug. 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. 13

14. Continue.... 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 . 14

15. Continue… 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. 15

16. Continue.... 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. 16

17. Continue… 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. 17

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. 18

19. References K. D. Tripathi , essential of medical pharmacology, 6 th edition Page no. 20-23 Bhramankar D. M. And Jaiswal S. B. : Biopharmaceutics and pharmacokinetics p. No. 116-136 19

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