药物分子的跨膜转运.pptVIP

School of Basic Medical Sciences 药物分子的跨膜转运 severe headache stiff neck sensitivity to light high fever and vomiting meningitis treated with gentamycin no improvement in vitro in vivo I.Clinical Sketch ╳ Filtration Simple Diffusion Facilitated Diffusion Active Transport Transport Across Membranes II. Simple Diffusion Diffuses across the membrane in the direction of drug’s concentration gradient No need of energy No carrier is involved Depends on the molecules lipid solubility Phospholipid Bilayer Cholesterol Phospholipid Molecule Protein Glycoprotein Cell Membrane Structure The membranes are primarily lipid in nature “Like Dissolves Like” H2O NaCl H2O oil Transport Across Membranes Lipid Membrane Lipid Soluble Drugs Polar Molecules Ions Gentamycin III. Effect of pH on Simple Diffusion Weak Acids HA H+ + A- (molecule) (charged) (cross membrane) Weak Bases B + H+ BH+ HA H+ + A- H+ HA OH- H+ HA Acidic Environment Basic Environment Effect of pH on Simple Diffusion weak acid acidic environment basic environment weak base weak acid basic environment weak base acidic environment Effect of pH on Simple Diffusion In the stomach (pH 2.0)，which drug will be better absorbed, a weak acid (pKa 6.8) or a weak base (pKa 7.1)? Effect of pH on simple diffusion plasma plasma weak acid weak acid weak base Question 1 Molecule Form Charged Form The drug will be trapped on one side of a membrane where the ionized form is predominant. IV.Ion Trapping IV.Ion Trapping Basic environment Acidic environment Weak Acid Weak Base Acidic drug’s accumulating in basic fluids Basic drug’s accumulating in acidic bodily fluids In the breast milk (pH 6.6)，which will be accumulated, a weak acid (pKa 6.2) or a weak base (pKa 7.6)? Question 2 Weak base Morphine (Basic Drug) Contraindicated in Lactation VI.pH Variation and Drug Kinetics Aspirin (acetylsalicylic acid, pKa 3.5) Stomach un-ionised→lipid-soluble →