Orderly and clear summary of chapter 5 what is discussed during the medical pharmacology lectures. It is a summary from the book "Medical pharmacology which is written by the professors". With this summary you will save a lot of time. I passed this course with a 8. Good luck :)
Medical pharmacology – Chapter 5 – Distribution of drugs
When drug enter bloodstream after administration it will spread through rest of body
by passing through capillary endothelium. The endothelium barrier is more
permeable than epithelial barrier because intercellular spaces are larger
So, lipophilic or not it can pass barrier (in both ionised and unionised form)
Only too large molecules cannot pass barrier; endothelial barrier acts as ultrafilter
Apparent volume of distribution (Vd)
Major fluid compartments body (35L);
1. Blood plasma (3L)
2. Interstitial fluid volume (IFV; 12L)
3. Intracellular volume (ICV; 23L)
Apparent volume of distribution (Vd); liquid volume over which the
drugs seems to spread.
Vd= amount of drug in the body (dose) / concentration in the blood in
L or L/kg
Vd= intravascular administered dose A / concentration in the plasma
(A) at t=0 (trek de lijn van elimination door wat er dan op t=0 staat moet
je pakken zie evt. Lecture 7) in L or L/kg
As the Vd for drugs becomes greater a given dose will lead to lower
concentration in the plasma.
The Vd can vary due to age or certain diseases. Also consider that
drugs may be bound to plasma proteins. Only the free (non-bound)
drugs are able to distribute extravascular.
Cannot pass through capillary endothelium? Vd is 3L (blood plasma)
(e.g dextran)
Can pass through capillary endothelium but insufficiently
lipophilic to pass through cell membrane? Vd is 15 L
(blood plasma + interstitial fluid volume) (e.g insulin)
Can pass through capillary endothelium are sufficiently
lipophilic? Vd is 35 L (blood plasma + interstitial fluid +
intracellular volume)
Can pass through capillary endothelium are sufficiently
lipophilic? Vd is bigger than 35 L. This is the result of
storage (depot formation) in high concentration in tissues. Liphophilic drugs
accumulate in fat tissue. So, in this case the Vd no longer corresponds to actual
liquid volume.
Rate of distribution; partition equilibrium
Rate depends on:
1. Physcio-chemical properties of the drug
2. Tissue perfusion (doorstromen van vloeistof)
The distribution process continues until equilibrium is reached between concentration
in plasma and concentration in various tissues.
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