lecture 7.3 Flashcards
(51 cards)
Name an example of a drug that may be displaced by another drug in the plasma and subsequently increase its free drug conc and become fatal
displacement of dicumarol (an oralanticoagulant ) by phenylbutazone
*only 3% of dicumarol is free, additional displacement of 3% increases effects by 100%
What is dicumarol?
naturally occurring anticoagulant that depletes vitamin K
What is phenylbutazone?
non-steroidal antiinflammatory drug (NSAID) for the short-term treatment of pain and fever
What is full form of NSAID?
non-steroidal antiinflammatory drug
What is the characteristic of class 1 drugs in plasma?
high binding affinity to plasma protein
What is the characteristic of class 2 drugs in plasma?
lower affinity for plasma proteins and exist in a higher proportion as free, unbound drug in the bloodstream
How are class 1 and 2 administered simultaneously?
Class 1: dose less than available binding sites
class 2: dose greater than available binding sites
–> Displacement of Class I drug occurs when a Class II drug is administered simultaneously
At what sites can tissue localization occur? What drugs id accumulated at these sites?
- bone: accumulation of lithium or tetracycline through active transport
- thyroid gland: throglobulin responsible for
accumulation - liver: accumulation of antimalarial agent chloroquine
Does local blood flow play a role in the accumulation of tetracycline in bone? Why?
No, blood perfusion of the bone is not extensive.
Active transport and the presence of specific
binding proteins are responsible
Why does antimalarial agent chloroquine accumulate in the liver?
due to its interaction with hepatic DNA
–> intercalates adjacent pairs of the double helix
What is the extent of dsitribution of a drug known as?
volume of distribution (Vd)
What is the formula of Vd?
Amount of drug in body/
Concentration of drug in plasma
(units=liters)
For a 70kg individual, what is the total body water volume?
45L total body volume
–> 15L extracelluar
–10L interstitial
– 5L plasma volume
–> 30L intracellular
For the one-compartment model of distribution of drugs, what is the assumption?
that an administered drug is homogeneously distributed throughout the tissue fluids of the body
How does the two-compartment model of distribution differ from that of one compartment?
contains two or multiple central or
peripheral compartments
What does the central compartment include?
the blood and extracellular fluid volumes of the highly perfused organs (i.e., the brain, heart, liver, and kidney)
What does the peripheral compartment consist of?
relatively less perfused tissues such
as muscle, skin, and fat depots
What does the rate of distribution of a drug from the blood to a tissue depend on?
- extent of drug binding to plasma proteins
- ability of drug to diffuse through tissue membrane –> lipophilic able to diffuse
- degree of perfusion of tissue (blood/min/vol of tissue)
- properties of tissue membrane
What is distributive equilibrium?
the state where a drug has reached a balance between its movement into and out of tissues.
–> rate of drug transfer between blood (plasma) and tissues becomes equal.
The rate of distribution of a drug from the blood to a tissue also depends on ability of that drug to diffuse through tissue membrane. In general, lipophilic drugs are able to diffuse.
True or false
true
Rank the following in decreasing order of perfusion rate:
heart, brain, fat, lungs, muscle, lung
lung, kidney, heart, brain, muscle, and fat
Compare the diffusion of thiopental in muscle and brain.
Thiopental: lipophilic
–> can diffuse into brain and muscle
–> brain perfusion higher, thus diffuses more rapidly in brain
Compare the diffusion of penicillin in muscle and brain.
penicillin: polar
–> cannot diffuse into brain
–> muscle capillaries are porous, can diffuse into muscle
What would be the value of ‘apparent volume of distribution’ if the drug shows extensive tissue binding?
many times the total body size
