Drug Distribution and Protein Binding: Impact on Drug Activity and Elimination - Prof. Dou, Study notes of Pharmacology

Download Drug Distribution and Protein Binding: Impact on Drug Activity and Elimination - Prof. Dou and more Study notes Pharmacology in PDF only on Docsity! 30 January Drug Distribution Back diffusion would oppose drug distribution Lipophilic drug can passively diffuse through membrane, but could do the same in the opposite direction Serum albumin binding sites for drugs 119 positive charges 96 negative charges Many lipophilic sites Many other serum proteins Bound drug is not available to act – inactive Equilibrium between bound and unbound Buffering system Drug binding prevents back diffusion Lipophilic drugs have low solubility in water, but can piggyback on serum proteins – faster Consequences of Protein Binding Protein-bound drug is generally inactive Only free drug is active Protein binding provides a drug reservoir and buffers against drug elimination Drug-drug competition Dicoumarol (anticoagulant) 97% bound Aspirin compete for binding Free drug increased from 3% to 6% Greater tendency to bleed, less coagulation Drug-metabolite competition Thiopental (anesthetic) 75% bound Free fatty-acids elevated in diabetes Displace bound thiopental Free active thiopental increased Increased depth of anesthesia Elevated FFA: diabetes, fasting, anorexia, bacterial infections Protein-bilirubin (heme product) binding Sulfonamides (antibiotics) compete Free active bilirubin levels are increased May cause kernicterus in newborn Bilirubin enters brain Encephalopathy Seizures Potentially fatal Protein binding reduces rate of biotransformation and rate of removal from body through kidneys Effect on biotransformation at liver 80 Å pores Binding generally slows biotransformation Depends on how tightly bound the protein is, how rapid dissociation is Effect on glomerular filtration and excretion 80 Å pores Generally slows filtration and excretion But penicillin, for example, rapidly dissociates so is quickly eliminated