2 - Distribution Flashcards
What % of body weight does total body water constitute?
60%
What % of body weight does intracellular fluid constitute?
40%
What % of body weight does extracellular fluid constitute?
20%
What % of body weight does plasma fluid constitute?
4%
What % of body weight does blood volume constitute?
7%
What is included in blood volume but NOT in plasma?
Red blood cells, which make up about 3% of body weight
Why is it important to know if a drug enters RBCs or not?
- If it enters RBCs, drug [ ] in plasma will be the same as drug [ ] in blood
- If it doesn’t enter RBCs, drug [ ] in plasma > drug [ ] in blood
What happens if a drug has a very large volume of distribution, ex: 2000 L?
It will go into tissues and less will be in plasma
Following absorption, the pattern of drug distribution is governed by ______
Rate of blood flow (perfusion) to each tissue and affinity of drug to accumulate in the tissue
What is important to note about tissues that are highly perfused?
Will rapidly equilibrate w/ the drug
What does low blood flow to a tissue mean?
Low amount of drug entering the tissue
Blood flow is an important factor in determining the ________ of drugs
Initial distribution
Which tissues are highly perfused?
- Adrenals
- Kidneys
- Thyroid
- Liver
- Portal-drained viscera
- Heart
- Brain
Which tissues are poorly perfused?
- Skin
- Muscle
- Connective tissue
- Fat
Drug accumulation into tissues is dependent upon ______
Blood flow and tissue affinity for the drug
What will happen to the tissue [ ] of drugs w/ low tissue affinity?
- Will equilibrate rapidly w/ plasma drug [ ]
- Will decline rapidly as the drug is eliminated from plasma
What happens to drugs w/ high tissue affinity?
Tend to accumulate or concentrate in the tissue, so will remain in tissues long after it is depleted in plasma or whole blood
Highly lipophilic drugs are extracted by ____ organs, so drug accumulation is _____
- Poorly perfused (ex: fat)
- Slow
Removal from fat tissue is _____
Extremely slow
Can chemicals remain in fat tissue for years?
Yes
What is the formula for volume of distribution?
Amount of drug added (mg) / drug concentration (mg/L)
What does albumin do?
Binds lipophilic compounds and acidic drugs
What does AAG do?
Binds basic drugs
Where are albumin and AAG found?
In blood
What is important about a drugs affinity for albumin or AAG?
Determines how the drug will be transported
What is the relationship btwn drug concentration in water and volume of distribution?
Inverse relationship
What is the relationship btwn volume of cells and volume of distribution?
Direct relationship
What causes albumin concentration in plasma to decrease? Why?
- Renal failure b/c will be leaky
- Cirrhosis b/c liver produces albumin
- Severe burns b/c will leak fluid containing albumin
- Pregnancy b/c mother is sharing blood supply w/ fetus
What causes AAG concentration in plasma to increase?
- Renal failure
- Severe burns
- Stress/trauma
- Obesity
- MI
AAG is a ____ protein
Stress
What is the difference btwn the rate of change of albumin concentration and AAG concentration?
- AAG can change concentration w/in hours
- Albumin takes days to change concentration
When is a change in protein binding clinically important?
When drug is highly protein bound and has a narrow therapeutic window
What is the relationship btwn % protein bound and half life? Why?
- Half life increase as protein binding increases (direct relationship)
- B/c when a drug is protein bound, it is unavailable for distribution b/c it is stuck in vasculature
What is the difference btwn compound 1 w/ VD = 10000 L and compound 2 w/ VD = 2000 L?
Compound 1 will have greater intracellular bonding than compound 2
What happens when 2 drugs are fighting for the same protein binding site?
One will lose, so need to adjust the dose of that drug to get same effects
What is lowest possible apparent Vd for a healthy 70 kg male?
2.8 L (plasma)
What effect can phenybutazone have on warfarin?
Phenybutazone can displace warfarin and affect bleeding time
