Factors influencing distribution Characteristics of drug binds to plasma protein Reversible A bound drug has no effect Nonspecific Competitive displacement:a drug with a higher affinity may displace a drug with weaker affinity. Renal failure,fasting,malnutrition can have effect on plasma protein binding. 21
Reversible A bound drug has no effect ! Nonspecific Factors influencing distribution Characteristics of drug binds to plasma protein 21 Competitive displacement: a drug with a higher affinity may displace a drug with weaker affinity. Renal failure, fasting, malnutrition can have effect on plasma protein binding
This binding will influence the drug's distribution:only the unbound(or free)drug diffuses through the capillary walls. Capillary Tissue Albumin molecule in solution Drug molecule Cell If high binding, drug 1 ml plasma "trapped"in plasma. 18 drug 2drug Drug strongly bound to plasma albumin If low binding,drug free 1 ml plasma to disperse→tissues 3drug 17 drug Drug strongly bound to tissue sites =cells D =albumin ■=drug molecule in solution 22
This binding will influence the drug’s distribution: only the unbound (or free) drug diffuses through the capillary walls. If high binding, drug “trapped” in plasma. 22 If low binding, drug free to disperse tissues
Factors influencing distribution 2.Physiological barriers to drug distribution ·Blood-Brain Barrier 。Placental Barrier 23
• Blood-Brain Barrier Factors influencing distribution 2. Physiological barriers to drug distribution 23 • Placental Barrier
Factors influencing distribution 2.Physiological barriers to drug distribution ·Blood-Brain Barrier 。Placental Barrier lonized,or polar drugs,and protein bound drug generally fail to enter the membrane barriers Inaccessible to many drugs unless high lipid solubility. 24
• Blood-Brain Barrier • Placental Barrier Factors influencing distribution 2. Physiological barriers to drug distribution 24 Ionized, or polar drugs, and protein bound drug generally fail to enter the membrane barriers ! Inaccessible to many drugs unless high lipid solubility
Factors influencing distribution 3.Blood flow Highly Poorly vascularized vascularized tissue tissue Blood flow to the liver,kidney,brain and heart is greater than that to the muscle,adipose tissue and skin. 25
Factors influencing distribution 3. Blood flow 25 Blood flow to the liver, kidney, brain and heart is greater than that to the muscle, adipose tissue and skin