Lecture-3 - Dependence of drug absorption on pH and drug...

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Dependence of drug absorption on pH and drug protonation Almost all drugs can be classified as: (1) uncharged molecules; (2) organic acids; or (3) organic amines. For example, an amine type of drug can take two forms as shown to the right; protonation decreases absorption in the stomach. In the case of an organic acid, it can also take two forms; protonation increases absorption in the stomach. This is why ASA absorption is higher in the stomach.
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K a is the equilibrium constant for the dissociation that yields H + Increasing the pH of the fluid in which the drug is dissolved increases the ionization of acidic drugs (less absorption) and decreases the ionization of basic drugs (more absorption). Basic drugs tend to accept protons and give them up only when the H + concentration falls; their K a values are low. Acidic drugs readily give up their protons, so their K a values are high. pK a = -log (K a ) = the pH at which 50% ionization of drug occurs.
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Putting it simply: organic acids are better absorbed in acidic environments (stomach) while organic amines (bases) are better absorbed in basic environments (intestine)
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Effect of surface area on absorption Small intestine has a MUCH greater surface area than stomach. This more than compensates for the effect of ionization of organic acids by high pH, which would tend to decrease absorption. The single most important variable affecting rate of g.i. absorption of drugs is the rate of stomach emptying.
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Active transport of drugs Although most drug permeation occurs passively, there are many examples of active transport of drugs across cell membranes (eg. penicillin, digital glycosides). What is meant by active transport? Occurs when the cell needs to bring in large molecules (> 1000 Da) or drugs tightly bound to plasma proteins. Eg. proteins, bacterial toxins, antigens. Pinocytosis of drugs
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of Drugs Passive diffusion down a transmembrane concentration gradient can be facilitated by relatively selective carrier molecules in the membrane. These carriers combine with substances, forming complexes that can diffuse across cell membranes more rapidly than the free substances themselves. Once inside the cell, the substances dissociate from carriers and are released into the cell. Examples:
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This note was uploaded on 11/04/2009 for the course BIO 365D taught by Professor Mihic during the Spring '08 term at University of Texas at Austin.

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Lecture-3 - Dependence of drug absorption on pH and drug...

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