Pharmacokinetics - Distribution Flashcards
Define Drug distribution:
The process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and then the cells of the tissues
in IV administration the first phase of pharmacokinetics is:
Distribution
instead of absorption, in case of Non Parenteral routes
Factors affecting Distribution:
a. Blood Flow
b. Capillary Permeability
c. Binding of drug to plasma and tissue protein
d. Volume of Distribution
e. Hydrophobicity of the drug
Which organs have greater blood flow as compared to Skeletal muscles.
- Liver
- Kidney
- Brain
Which regions of the body receive lowest blood flow
- Skin
- Viscera
- Adipose Tissue
Variance in blood flow partly explains the short duration of hypnosis produced by a bolus IV injection of ______
propofol
High blood flow, together with the high lipid solubility of _____, permits it to rapidly move into the CNS and produce anesthesia.
thiopental
How consciousness is regained, after Thiopental induced anesthesia?
A subsequent slower distribution to skeletal muscle and adipose tissue lowers the plasma
concentration sufficiently so that the higher concentrations within the CNS decrease, and, thus, consciousness is regained.
What factors determine capillary permeability ?
capillary structure ,
chemical nature of the drug
Capillary structure varies widely in terms of:
The fraction of the basement membrane that is exposed by slit junctions between endothelial cells
Why is capillary permeability better in Liver and Spleen?
In the liver and spleen, a large part of
the basement membrane is exposed due to large, discontinuous capillaries through which large plasma proteins can pass
Which way can drug molecules enter Brain?
- Drugs must pass through the endothelial cells of the capillaries of the CNS,
- Active Transportation
Which drugs can readily penetrate into CNS?
Lipid- Soluble Drugs
Name a drug that is actively transported into the brain.
Levodopa
Which drugs fail to enter CNS?
Ionized or polar drugs
What is blood brain barrier?
In Brain, the capillary structure is continuous,
and there are no slit junctions. These tightly juxtaposed cells form tight junctions that constitute the so-called blood-brain barrier.
Reversible binding to plasma proteins leave drugs in a:
Non-diffusible form
Which is the major drug binding protein?
Plasma Albumin
Plasma Protein Binding is relatively _______
Non-Selective
Binding takes place on the site of the protein where _____ compounds usually attach.
Endogenous Compound
e.g. Bilirubin
Plasma Albumin may act as a ________
Drug Reservoir
As the concentration of the free drug decreases due to elimination by metabolism or excretion, the bound drug: a. Strengthens it's bond to the site b. becomes more active c. dissociates from the protein
c. dissociates from the protein
What results in accumulation of drug in tissue?
- Drugs may accumulate as a result of
binding to lipids, proteins or nucleic acids. - Drug may be actively transported to the tissue.
What is the advantage and disadvantage of tissue drug reservoir?
Advantage: serve as a major source of the drug and prolong its actions.
Disadvantage: May cause local drug toxicity
Example of local toxicity:
ACROLEIN, the metabolite of CYCLOPHOSPHAMIDE is toxic to the kidney because of its accumulation in renal cells.
______ drugs readily move across most biologic membranes.
Hydrophobic
The major factor influencing the hydrophobic drug’s distribution is:
The blood flow to the area
What is apparent volume of Distribution?
The apparent volume of distribution, Vd, can be thought of as the fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma
Once a drug enters the body, from whatever route of administration, it has the potential to distribute into any one of _____ functionally distinct compartments of body water or to become sequestered in a cellular site.
Three
Name the body water compartments.
Plasma Compartment
Extracellular fluid
Total body water
When does a drug molecule stay in the plasma compartment?
- Drug has a very large molecular weight
2. Or binds extensively to plasma proteins
If a drug is trapped in plasma compartment, the drug distributes in a volume, that is about ____ % of the body weight
6%
Which drug show a plasma compartment distribution?
Heparin
What constitutes extracellular fluid?
The water of plasma and the interstitial fluid
Extracellular fluid is about ___ % of a person’s body weight.
20%
What kind of drugs distribute in extracellular fluid?
Hydrophilic with low molecular weight.
Example of extracellular fluid distributed drug?
Aminoglycoside Antibiotic.
What kind of drug distributes through total body water?
Hydrophobic and Low Molecular weight.
Give example of total body water distribution?
Ethanol
the drug, distributing through total body water, distributes into
a volume of about ____% of body weight.
60%
A constant fraction of the drug is eliminated per unit of time:
First order
Any factor that increases Vd can lead to an increase in the ____ and extend the duration of action of the drug
half-life
An _______ Vd indicates considerable sequestration of the drug in some tissues or compartments
exceptionally large
