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Drug Distribution

Drug Distribution. Dr. Prabhakar Adake Asst. Professor Department of Pharmacology Yenepoya Medical College. Set induction.

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Drug Distribution

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  1. Drug Distribution Dr. PrabhakarAdake Asst. Professor Department of Pharmacology Yenepoya Medical College

  2. Set induction Dear students, have you ever thought how drugs reaches site of action from site of administration? What factors affects the distribution? All these aspects we shall discuss today.

  3. FATE OF DRUG Drug Absorption Drug Distribution Drug Metabolism Drug Action Drug Elimination

  4. DISTRIBUTION OF DRUG Systemic Circulation Various organs Drug Action

  5. Factors for distribution Lipid Solubility Ionization at the physiological pH Plasma/Tissue Protein binding Regional blood flow

  6. APPARENT VOLUME OF DISTRIBUTION Volume that would accommodate all the drug in the body, if concentration throughout was same as in plasma. Dose administered V = Plasma Concentration Total Body Water = 42L Intracellular = 28L Extracellular =14L (10L Interstitial Fluid + 4 L Plasma Volume)

  7. Significance of aVd Lipid Insoluble drugs : Streptomycin : ECF :14L Highly plasma protein bound drugs : Warfarin: ECF :4L Congestive Heart Failure, Cirrhosis of liver, uraemia : Alter aVd

  8. Redistribution of drug Highly Lipid soluble drugs: Thiopentone sodium Organs with High blood flow: Brain, Kidney, Liver Less vascular & Bulky Tissue: Fat, Muscle Termination of Drug Action

  9. Penetration of drug into brain & CSF

  10. Significance of BBB • Only Lipid soluble drugs enter brain • Lipid insoluble drugs don’t enter brain: Streptomycin. • Presence of p-GP & OATP: Efflux transporters • Enzymatic BBB: MAO/Cholinesterase • BBB deficit in CTZ & Periventricular sites

  11. Passage across placenta • Lipoidal in nature • Presence of p-GP, MRP-3 • Site of drug metabolism • Entry of lipid insoluble drugs if concentration is very high • Incomplete barrier.

  12. Plasma Protein Binding • Acid drugs : Albumin • Basic drugs : α1 Acid Glycoprotein • Higher drug concentration : Saturate binding site

  13. Significance of Plasma Protein Binding • Highly plasma protein bound drugs : Small aVd • Bound drug + Free drug = Total Plasma Conc. • Bound drug = Free drug conc. • Free drug: Action/ Metabolism/ Excretion • Bound fraction of drug: Reservoir

  14. Significance of Plasma Protein Binding • More than one drug can bind to same site: Displacement • Acidic drugs displaces acidic drug in same site • Salicylates displace sulfonylureas • Indomethacin, phenytoin displace warfarin • Sulfonamide displaces Bilirubin

  15. Significance of Plasma Protein Binding • In hypoalbuminemia: High level of free drug: Phenytoin & furosemide. • In Pregnancy & Inflammatory disease: Low level of free drug: Propranolol.

  16. Tissue storage • Certain drugs accumulate in specific organs: • ↑ aVd & Toxicity • Tetracycline: Bone & teeth • Choroquine: Retina • Streptomycine: Vestibular apparatus

  17. Summary • Many factors affect drug distribution • Redistribution of drug mainly seen with highly lipid soluble drugs like thiopentone sodium • Plasma proteins act as drug reservoir. Many displacement reactions can occur at the same binding site.

  18. References 1. Tripathi K.D., Essentials of Medical Pharmacology 8th ed. Jaypee Brothers 2018 2. Satoskar R.S. & Bhandarkar S.D., Pharmacology and Pharmacotherapeutics, 25th ed. Elsevier 2017.

  19. THANK YOU

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