1 / 21

PASSAGE OF DRUGS ACROSS MEMBRANES

PASSAGE OF DRUGS ACROSS MEMBRANES. A drug must cross one or more biologic membranes to reach its site of action (absorption later distribution, interaction with the receptor and finally elimination).

shay
Download Presentation

PASSAGE OF DRUGS ACROSS MEMBRANES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PASSAGE OF DRUGS ACROSS MEMBRANES

  2. A drug must cross one or more biologic membranes to reach its site of action (absorption later distribution, interaction with the receptor and finally elimination)

  3. In addition to the transcellular pathway of drugs, an aqueous paracellular pathway formed by 10 nm-15 nm clefts between the endothelial cells permits passage of water soluble drugs even small proteins Facilitated diffusion water, small electrolytes hydrophilic molecules move readily –transmembrane proteins facilitate diffusion, can be saturated at high drug concentrations example GLUT family of glucose transporters

  4. ~ 2000 genes -7% of the total human genome code for transporters ABC and SLC ~ 49 ABC transporters hydrolyze ATP to provide the energy needed for molecular transport →primary active transporters P-glycoprotein (P for altered permeability) MDR-1 is given the designation ABCB1 (some anticancer drugs, antivirals, CCBs, digoxin, antibiotics, antifungals, hormones, immonosuppressants are transported) a few substances are so large or impermeant → can enter only by endocytosis →substance is bound at a cell surface receptor engulfed by the cell membrane, and carried into the cell by pinching off ofthe newly formed vesicle inside the membrane, substance can then be released inside the cytosol by breakdown of the vesicle membrane Vit B12 iron

  5. PHARMACOKINETICS Pharmacokinetics is concerned with the relationship between the dose of a drug and the concentration of that drug in the body fluids and tissues over times: absorption distribution metabolisation elimination

  6. ABSORPTION • Drug absorption refers to the passage of a drug from its site of administration into the circulation • Absorption requires the passage of drugs across one or more layer of cells

  7. Drug faces a greater barrier to absorption after oral administration than after parenteral administration

  8. Pharmacologic effect Clinical response Toxicity Effectiveness Dose of drug administered

  9. DRUG EFFECT AND THERAPEUTIC WINDOW

  10. The majority of drugs are either weak acids, such as aspirin, or weak bases, such as propranolol • The presence of an ionisable group(s) is essential for the mechanism of action of most drugs, because ionic forces represent a key part of ligand-receptor interactions • Drug receptors are formed by the three-dimensional arrangement of a protein, and drug binding requires both lipid- and water-soluble sites within the drug molecule; the latter are usually produced by an ionisable functional group.

  11. WEAK ELECTROLYTES AND INFLUENCE OF pH

  12. HANDERSON-HASSELBALCH EQUATION Log(protonated form/unprotonated form) = pKa-pH

  13. C8H7O2COOH ↔ C8H7O2COO- + H+ Neutral aspirin Aspirin anion Proton C12H11ClN3NH3+↔ C12H11ClN3NH2 + H+ Pyrimethamine Neutral Proton cation Pyrimethamine

  14. Weak acids (HA) donate a proton (H+) to form anions (A-), whereas weak bases (B) accept a proton to form cations (HB+) Only the nonionized form of a drug can readily penetrate cell membranes

  15. ION TRAPPING • Body fluids where a pH difference from blood pH will favor trapping : stomach contents small intestine breast milk aqueous humor (eye) vaginal secretions prostatic secretions

  16. ION TRAPPING-2 Kidney: • Nearly all drugs filtered at the glomerulus: • Most drugs in a lipid-soluble form will be absorbed by passive diffusion. • To increase excretion: change the urinary pH to favor the charged form of the drug: Weak acids: excreted faster in alkaline pH (anion form favored) Weak bases: excreted faster in acidic pH (cation form favored)

More Related