Orderly and clear summary of chapter 3 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 vu biomedical sciences biomedical sciences year 2
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Vrije Universiteit Amsterdam (VU)
Biomedical Sciences
Medical Pharmacology
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Medical pharmacology – chapter 3 – Resorption of drugs; passage
through biological membranes
Drug pass through biological membranes before arriving in the blood and from blood
into tissues or organs.
• Intestinal epithelium
• Capillary endothelium
Passage of drug molecules between cells (via intercellular spaces). Plays a
secondary role; when molecular size exceeds this form of passage is not possible -->
basis of ultrafiltration
Passage of drug molecules through cells (through cell
membranes).
• Diffusion through lipid; passive transport
• Diffusion through aqueous channel
• Carrier
Which form of passage depends on:
1. Nature of biological barrier; lipid double layers with phospholipids, cholesterol
and protein molecules
2. Chemical structure and physical properties of drug
3.1 passive transport
Drug; mostly are weak organic acid or bases.
Passive diffusion only includes the unionised form for transport, because unionized
form is more lipid
Degree of ionisation depends on:
1. The ambient (e.g. solution, cell/organ compartment) pH (pH is about the
environment) (body pH is bound to narrow extremes 7.2-7.4, in gastro-
intestinal tract pH levels can vary greatly due to administration of certain
substances (NaHCO3 or NH4Cl) which can have a significant effect on the
absorption of drugs. Urinary pH can also vary which has consequences for
the excretion of certain drugs)
2. The strength of acid or base (pK-value, it only tells how strong acid or base is!
High pK is weak acid and strong base and low pK is strong acid and weak
base) (pK is about the drug)
Rate of diffusion is determined by:
1. Concentration gradient of the unionised form across the membrane
2. Lipid-solubility of the unionised form
• Hydrophilic (e.g. ions) will not be able to pass by passive diffusion
• Lipophilic will be able to pass by passive diffusion
3. Available resorption surface (e.g. intestinal villi)
, 50% ionized and 50% unionized at pH=pK
Acid:
At higher pH values it becomes more ionised
At lower pH values it become more unionized
Base:
At higher pH values it becomes more unionized
At lower pH values it becomes more ionised
The rate of change of ionisation is greatest at pH values near
the pK (hier is de grafiek het meest stijl)
% unionised form:
pH-pK Of an acid Of an base
-4 99,99 0,01
-3 99,90 0,1
-2 99 1
-1 90,9 9,1
0 50 50
1 9,1 90,9
2 1 99
3 0,1 99,90
4 0,01 99,99
Acid; H+ donor. HA = A- (conjugated base) + H+
Base; H+ acceptor. BH+ = B (conjugated acid) + H+
General formula: acid = base + H+
If the drug is a weak acid (high pK) then base is in the ionised form
If the drug is a weak base (low pK) then the acid is in the ionised form
In theory; passive diffusion continues until equilibrium is reached
In practice; this balance is never reached because during resorption other processes
like distribution and elimination (excretion) also occur at the same time
Nevertheless, we can determine whether organs are beneficial to resorption of a drug
by paying attention to
• Nature of the drug (acid or base)
• pK-value (weak or strong acid/base)
• ambient pH
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