L6: Drug Distribution Flashcards
the process by which a drug reversibly
leaves the bloodstream and enters the interstitium (extracellular fluid) and the tissues.
DRUG DISTRIBUTION
Factors affecting drug distribution
- Blood flow
- Capillary permeability
- Binding of drugs to plasma proteins and tissues 4. Lipophilicity
Capillary permeability is determined by:
- capillary structure
- chemical nature of the drug.
• The liver and spleen: Highly permeable
• The brain: lesser permeability (the blood–brain
barrier)
Variability of Capillary structure
Lipid-soluble drugs:
readily penetrate the CNS.
Ionized or polar drugs (Water soluble) :
fail to enter the CNS.
(act as a drug reservoir)
• sequesters drugs in a non-diffusible form
• slows their transfer out of the vascular compartment.
Binding of drugs to plasma proteins
and tissues
• hydrophilic drugs do not readily penetrate cell membranes
Lipophilicity
………………. ……….readily move across most biologic membranes.
Lipophilic drugs
the fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma.
Volume of distribution (Vd)
Plasma compartment:
TRAPPED IN THE BLOOD VESSELS
• Low Vd =plasma volume
• E.g. Heparin
b. Extracellular fluid:
• Drugs with low molecular weight but hydrophilic:
• Pass through the capillaries BUT, not across cell membrane
• Vd = plasma volume + interstitial fluid, (extracellular fluid)
• E.G. Aminoglycoside antibiotics
c. Total body water
• Drugs with low molecular weight and lipophilic
• Can move into the interstitium and into the intracellular fluid.
• Distribute to THE TOTAL BODY WATER • E.G. Ethanol
The percentage of an administered dose that reaches the systemic circulation.
Bioavailability
The duration taken to reduce the ………. …………. of the drug to
half
plasma concentration
