Lecture 2 Flashcards
Understanding Volume of Distribution (Vd)
_________ indicates the extent of drug distribution into body fluids.
It does not specify the exact tissue or fluid where the drug is found
Vd
____________: Suggests the drug distributes extensively throughout the body.
Large Vd
___________: Implies that the drug’s distribution into tissues is
limited.
Small Vd
Variability in Distribution
Two drugs might share the same Vd value, but their distribution patterns can differ. For instance, one drug might predominantly distribute into muscles, while another concentrates in adipose tissue.
Volume of Distribution(Vd)
Although Vd values sometimes correspond to real physiological volumes, many observed Vd values are clearly not equivalent to real physical volumes
When Vd is much greater than the subject physical volume, this implies sequestration of drug via binding to tissue proteins or concentration in fat
Significance of apparent volume of distribution
Typical Vd Values: Most drugs possess a Vd that’s __________ or ___________ to body mass.
less than or equal
Impact of Drug Binding:Binding to peripheral tissues or plasma proteins significantly influences Vd(apparent volume of distribution).
High Plasma Protein Binding: Leads to a higher initial concentration (Co) and, consequently, a ______ Vd.
smaller
High Peripheral Tissue Binding: Results in a lower initial concentration (Co) and a _________ Vd in turn.
larger
Vd Beyond Body Mass:
Some drugs might exhibit a Vd that exceeds body mass by multiple times.
Distribution Patterns:
Drugs with a substantial apparent Vd tend to be more concentrated in _____________ and less so within the vascular region
extravascular tissues
Significance of apparent volume of distribution
Dosing Regimens
Vd is a crucial parameter when establishing correct dosing regimens
Significance of apparent volume of distribution
Vd offers insights into the relative quantities of a drug in both vascular and extravascular tissues.
Significance of apparent volume of distribution
Physiological Significance:
While Vd doesn’t correspond directly to a specific physiological meaning, it’s essential in determining dosage requirements.
Significance of apparent volume of distribution
Dose Proportionality:
Typically, dosing corresponds to Vd. A larger Vd suggests that a _____________ is needed to attain the desired concentration.
more substantial dose
Significance of apparent volume of distribution
Foundation Knowledge:
To truly grasp drug distribution, one must first understand the basics of body fluids and tissues.
Intracellular water–> 27 Liters
Plasma–>3 Liters
Interstitial water–>12 Liters
Extracellular water–> 15 Liters
Total Body Weight= 40 Liters
Total body water of infants = 75 – 85 % of body weight
Total body water of adults = 60 – 55 % of body weight
For the body fluid compartments below, rank them from the lowest volume to the highest, in a
typical 70-kg person.
A. Plasma < ECF <ICF < total body water
B. ECF < ICF <plasma < total body water
C. ICF < ECF <plasma <total body water
D. Total body water < plasma < ICF < ECF
Volume of Distribution Interpretation
A drug has a Vd = 15-18 L, what that implies?
Its distribution is limited to __________ in a 70 kg
ECF
A drug has a Vd = 40 L, what that implies?
Drug distributing into ______________
all body water
If a drug has a Vd greater than 40-50 L, what
that implies?
Drug probably is being concentrated in tissues outside the plasma and interstitial fluid or there is ________________
protein/tissue binding
Drugs with no extensive distribution into extravascular tissues: well described by 1 compt model EX:
_____________
aminoglycosides
Extent of distribution is determined by ____________ of the drug
chemistry
Drugs extensively distributed in tissues (e.g., Benzodiazepines, very ___________) or with extensive intracellular uptake may be better described by more complex models
lipophilic
