DRUG DISTRIBUTION

Administration of drugs:

1. IV: in hospitals and emergencies, drugs are often given intravenously

2. Oral: most common

3. Pulmonary: via inhalation of the drugs, ie. In asthma, one inhales the drugs

4. Other: an ointment, or nitroglycerine absorbed through the skin

The limiting factor in drug distribution is absorption. The drug’s pK, polarity, etc. makes some difference in how fast the drug is absorbed. If given via an IV, for example, a drug is absorbed immediately into the systemic circulation. When in the systemic circulation, this is the ‘active’ concentration of the drug—although some of the drug is buffered by protein (plasma components) and is not active. Slowly the drug is released from the proteins, making these proteins true buffers. Some drugs are stored or partitioned in tissues (eg. Adipose tissues) and can be released at some point under all kinds of circumstances. Finally the drug goes to the site of action, which is generally referred to as the receptor… although we’ll see that receptors include different modalities, which in our case extend from our old definition of straight receptors.

Some of the drug is metabolized in the liver.

This is important because the ability of the liver to metabolize drugs will interfere with the activity of the drugs. There is a complex adaptation—

eg. Aspirin will upregulate the expression of enzymes that are hydroxylating drugs. If a patient who takes Heparin to keep blood clotting at a certain level decides to take Aspirin every day for a week for pain, the aspirin will increase the hydroxylating enzyme so that some of the chronic meds that the pt was taking will metabolize faster and not be as effective as they normally would… this is an important point!

Drugs are finally eliminated in the kidney where there is a balance between excretion and reabsorption. The entire subject of drug distribution is important.

In biology and medicine the 50% measure of something is a recurrent theme. In pharmacology, if you measure the drug level in blood as a function of time, you’ll see that after you give the drug by IV it will decrease exponentially.

To see how fast the drug level will decrease, take the 50% level and extrapolate the amount of time that it takes the drug to be reduced by 50% in the blood.

For example, if the time is 6 hours and you want to keep a constant dosage throughout the day, you’ve got to give 4 dosages during 24 hours. For each drug in the PDR, the half-time is listed.

…the 50% rule will be important in other areas also, for example in how much of a drug it takes to kill an animal. Extrapolate the Lethal Dose which kills 50% of the mice (called the LD₅₀) and this is a criteria for toxicity.

Category: Pharmacology Notes