Distribution Of Drugs Flashcards
Distribution of drugs is determined by what 4 things?
1) size of organ
2) blood flow
3) capillary permeability (large plasma proteins cross liver and spleen capillaries; BBB prevents proteins from crossing)
4) hydrophobic vs hydrophilic nature of the drug
What is the primary binding protein to plasma proteins?
Plasma albumin
What will happen to drug concentration in a compartment where the drug is binding to plasma proteins in the blood or tissue?
It will increase the drug concentration in that compartment
Also can cause competition for binding
If you have a drug that is more hydrophilic (water soluble), does it need to bind to plasma proteins?
No; it doesn’t need a carrier
What are the requirements for drugs to get past the permeability of brain capillary?
Must be lipid-soluble and/or use carrier-mediated transport
What type of drug can not breach the brain capillaries?
Charged (ionized) drugs
A hypothetical volume of fluid in which a drug is disseminated?
Volume of distribution (Vd)
How much water is in the plasma compartment of the body?
6% of body weight, or 4 L in a 70 kg individual (154 lbs)
How much water is in the extracellular fluid compartment of the body?
20% of body weight, 14 L in 70 kg individual = 154 lbs
=plasma water plus interstitial fluid
How much water makes up the total body water?
60% of body weight, 42 L in 70 kg individual = 154 lbs
How many liters make up the total body water?
42 liters
How many liters of water make up the intracellular volume?
28 liters
How many liters of water make up the extracellular volume?
14 liters
How many liters of water make up the interstitial volume?
10 liters
How many liters of water make up the plasma volume?
4 liters
What does Vd (volume of distribution) relate?
The amount of drug in the body to the plasma concentration of the drug
Equation for finding the volume of distribution (Vd) of a drug
Vd (volume of distribution) = (amount of drug in the body)/(concentration in the blood)
When talking about volume distribution, if the plasma concentration (in blood) is high, then volume distribution (in tissue) is what?
Low
When talking about volume distribution, if the plasma concentration (in blood) is low, then volume distribution (in tissue) is what?
High
Example
If the amount of drug in the body is 20 units, and the concentration in the blood is 2 units, what is the volume of distribution (in the tissues)?
Vd = 20/2 = 10 (low)
Example
If the amount of drug in the body is 200 units, and the concentration in the blood is 2 units, what is the volume of distribution (in the tissues)?
Vd = 200/2 = 100 (high)
Can Vd (volume of distribution) be larger than the total volume in the body? If so, when?
Yes, if a drug is given in large doses and rapidly leaves the vascular compartment
If Vd does not necessarily refer to an identifiable physiological volume, what does it refer to?
The volume that would be required to contain all of the drug in the body at the same concentration as in the plasma
Because Vd refers to the volume that would be required to contain all of the drug in the body at the same concentration as in the plasma, what is it referred to?
Apparent Vd
What is apparent Vd?
It refers to the volume that would be required to contain all of the drug in the body at the same concentration as in the plasma
What is the distribution phase?
The initial phase after drug administration where a drug is distributed to the various compartments
What is the elimination phase?
The much slower phase after administration of a drug, after the distribution phase, and represents the drug leaving the plasma and being lost from the body
If the serum concentration starts close to 4 (the high peak) upon rapid injection of the drug, then this drug had to have been administered through what technique?
IV (intravenous); slope only decreases from here due to distribution and elimination
You can use Vd to calculate what?
The amount of drug needed to achieve a desired plasma concentration
What does a large Vd tell you?
Most of the drug is in the extraplasmic space
Example:
A drug has a Vd of 25 L and you desire a plasma concentration of 1 mg/L; what is the amount of drug you would give the pt?
25 L x 1 mg/L = 25 mg
Units for the answer if he asks for the amount?
Mg
Units for the answer if he asks for the concentration?
mg/L
Example:
A cardiac patient with arrhythmia is not well controlled due to inadequate levels of digoxin; suppose plasma concentration is 1 ug/L (C1) and the desired level of digoxin is 3 ug/L (C2); the clinical needs to know how much additional drug to give to bring the circulating level of digoxin from C1 to C2.
Vd x C1 = amount of drug initially in body
Vd x C2 = amount of drug in the body needed to achieve the desired plasma level
Vd(C2-C1) = difference between the 2 values is how much is needed
Vd for digoxin is 440L, so 440L(3ug/L-1ug/L) = 880 ug
Where are drugs that are not being delivered to the organs of elimination (liver, kidney)?
Extraplasmic space
A factor that increases Vd does what to the drug’s half life?
Increase the half-life and extends the duration of action of the drug (because it’s not being eliminated from the body)
What is used well for drugs with low Vd, meaning the drug is in the blood, not the tissue?
Hemodialysis
Why is placental transfer of drugs important?
Drugs can cause congenital abnormalities
How do drugs cross the placenta?
Primarily by simple diffusion
What type of drugs readily enter the fetal blood from the maternal circulation?
Lipid-soluble, non-ionized drugs
Is the placenta a barrier to drugs?
NO
If a drug can get into the CNS, it can definitely get past what?
The placenta
