pKa

Elimination

Kidney Excretion

The average pH of urine is 6.0 and the average pH of blood is 7.4.
We show a base in its neutral, unprotonated state (B), which passes freely across the membrane.
We show an acid in its neutral, protonated state (HA), which passes freely, as well.

Excretion of Toxic Substances

As a simple rule:

Rationale

Our goal is to keep a toxic molecule in the urine and prevent it from diffusing across the lipid membrane back into the blood (ie, we want it out of the body (excreted)). Charged molecules are lipid-INSOLUBLE. Thus, the more of a drug that is in its charged state, the less the amount of drug that can diffuse through the lipid membrane.

Toxic Base

For toxic bases:

Again, we show that the neutral, unprotonated base (B) passes freely across the membrane.
To trap it, we add protons (we can acidify the urine using ammonium chloride), which protonates the base, making it ionized and thus trapping it within the urine, so it can be excreted.

Toxic Acid

For toxic acids:

Again, show that the neutral, protonated acid (HA) passes across the membrane easily.
To trap it, we add a base (we can alkalinize the urine using sodium bicarbonate), which causes the acid to deprotonate, making it ionized and thus trapping within the urine, so it can be excreted.

Summary

For weak acids, we alkalinize the urine, which will cause the acid to donate its proton and become charged and lipid-insoluble.
For weak bases, we acidify the urine, which will cause the base to accept a proton and become charged and lipid-insoluble.

Elimination Kinetics

Overview

Finally, let's address elimination kinetics, which is the study of the rate at which drugs clear from the body in relation to their plasma concentration.

First-Order Elimination

In first-order kinetics, the rate of elimination is proportional to the concentration of the drug: the higher the concentration, the greater the relative elimination rate.

Draw a graph and show Drug Plasma Concentration on the Y-axis and Time on the X-axis.
Show that the rate of elimination decreases in exponentially with time.

Example

Assume, for instance that the half life of a drug is 1 hour, meaning 50% of the drug is eliminated every hour, and the starting concentration is 20.

Zero-Order Elimination

In zero-order kinetics, the rate of elimination is constant regardless of concentration.

This occurs when a drug saturates its elimination mechanisms, so regardless of the reduction in concentration, the rate of elimination remains unchanged.
The elimination rate curve is linear.

Draw a graph and show Drug Plasma Concentration on the Y-axis and Time on the X-axis.
Show that the rate of elimination decreases is a constant, linear fashion.

Example

If the concentration was 20 and 5 units were removed every hour, then in 1 hour, the concentration would be 15; in 2 hours it would be 10; in 3 hours it would be 5.
Key examples of drugs with zero-order kinetics are phenytoin, ethanol, and aspirin.
As well, if it is a controlled release medication or a medication that is rate limited by gastric emptying, the drug may demonstrate zero-order kinetics.