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Pharm Lect 5

QuestionAnswer
Effects of Lipid solubility on drug distribution Inc lipid solubility increases the drug's rate of crossing capillary membranes and reach their target tissue (this rate is limited only by the rate of perfusion). Lipid solubility allows it to diffuse out of capillaries as fast as it can get there.
Effects of Ionization on drug distribution allows them to be more water soluble which means they escape from the capillaries at a much slower rate. **Flow freely in BL but have trouble crossing capillary membrane.
Drug distribution into the CNS Very difficult due to BBB (tight junctions around the capillaries formed by glial cells). Highly lipid soluble drugs enter. Polar/ionized/water soluble drugs do not cross at all (intrathecal route).
How can meningitis or injury alter drug distribution into the CNS? by making the BBB leaky which can then allow drugs entry that normal wouldn't be able to cross the BBB. **This could cause toxicity
Functions of ABC transporters like P-glycoproteins in the CNS Rapidly transport drugs out of the CNS back into systemic circulation
Placental Barrier has no protective barrier, meaning most drugs can easily cross. Lipid solubility is most important. **Metabolites may accumulate in the fetus b/c they may be more ionized and rate of diffusion back into maternal circulation is much slower.
Volume of Distribution equation Vd = D/Cpo. D:dose. Cpo:plasma concentration. The larger the Vd, the longer the drug stays in the body. **Vd reflects the balance b/w drug in blood or the tissue.
Volumes of physiological compartments that drugs are limited to 1.Plasma: 3L. 2.Extracellular water: 12L. 3.Intracellular water: 28L. 4.Total body water: 40L. **if a drug is concen outside of plasma, the Vd will exceed total body water
How does plasma protein binding affect drug distribution It will slow the rate at which the drug can cross the membrane/ biological barriers (move out of the capillaries or be eliminated by kidneys).
Plasma proteins involved in drug binding 1.Albumin (prefers ACIDIC drugs, binding is reversible). 2.Alpha 1-acid glycoproteins AAG (prefers BASIC drugs, binding is reversible). **Saturation and competition can occur for binding sites.
How would an increase in AAG due injury would affect drug distribution? Decreased drug intensity and prolonged drug duration.
Plasma protein binding's effect on Vd Free and bound drug are not distinguishable in the Vd.
Hypoalbuminemia alters the intensity and duration of drug aciton. **Albumin levels decrease with age
Binding interactions are clinically significant when: 1.>90% of drug is bound. 2.Drug has a low TI. 3.Drug has low hepatic extraction. 4.Drug is given IV
Redistribution since some tissues perfuse rapidly to reach equilibrium and other tissue perfuse slowly to reach equilibrium, a drug from a rapidly perfused tissue may be redistributed to a slowly perfusion tissue where the drug action will terminate. **Thiopental
Created by: WeeG
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