Protein Binding and Drug Distribution PDF

PROTEIN BINDING CYRUSCHAD TUTOR, RPH, MBA  DRUG DISTRIBUTION After a drug is absorbed in the systemic circulation, molecules of the drug are distributed throughout the body. Drug molecules are...

PROTEIN BINDING CYRUSCHAD TUTOR, RPH, MBA  DRUG DISTRIBUTION After a drug is absorbed in the systemic circulation, molecules of the drug are distributed throughout the body. Drug molecules are carried by the blood to the target site and to other tissues. CCTUTOR2024  DRUG DISTRIBUTION Drug distribution is generally rapid, and most small drug molecules permeate capillary membranes easily. The passage of drug molecules across a cell membrane depends on the physicochemical nature of both the drug and the cell membrane. CCTUTOR2024  DRUG DISTRIBUTION If the drug is bound to a plasma protein such as albumin, the drug–protein complex becomes too large for easy diffusion across the cell or even capillary membranes CCTUTOR2024  PROTEIN BINDING protein binding normally refers to the reversible association of a drug with the proteins of the plasma compartment of blood, and this binding is due to electrostatic and hydrophobic forces between drug and protein CCTUTOR2024  PROTEIN BINDING Drug- protein binding may either be a reversible or irreversible process. However, most drugs bind to proteins by a reversible process. CCTUTOR2024  Reversible drug–protein binding implies that the drug binds the protein with weaker chemical bonds, such as hydrogen bonds or van der Waals forces. The amino acids that compose the protein chain have hydroxyl, carboxyl, or other sites available for reversible drug interactions. CCTUTOR2024  The protein-bound drug is a large complex that cannot easily transverse the capillary wall and therefore has a restricted distribution. Protein- bound drugs are pharmacologically inactive. Proteins include albumin, alpha1-acid glycoprotein, and lipoproteins. CCTUTOR2024  ALBUMIN The major component of plasma proteins responsible for drug- protein binding. Distributed in the plasma, extracellular, and interstitial fluids. Forms complexes with FFA, bilirubin, and hormones. Weak acidic/anionic drugs bind to albumin by electrostatic and hydrophobic bonds. CCTUTOR2024  ALPHA-1-ACID GLYCOPROTEIN also known as orosomucoid binds primarily to basic/cationic drugs CCTUTOR2024  LIPOPROTEINS macromolecular complexes of lipids and proteins classified as VLDL, LDL, and HDL responsible for transport of lipids to liver responsible for the binding of drugs if the albumin sites become saturated. CCTUTOR2024  EFFECTS OF PROTEIN BINDING inactivates the drug reduce overall clearance of drug decrease Write down apparent volume of all the advantages distribution of drug CCTUTOR2024  Drugs with Extensive Protein Binding CCTUTOR2024  Pathophysiological Conditions affecting Protein Level Decreased HA burns chronic liver disease cystic fibrosis ESRD pregnancy Increased HA hypothyroidism, hypovolemia Increased AAG MI RA CCTUTOR2024 Crohn's disease HIV  END OF PRELIM CCTUTOR2024