PY1 Review - Pharmacodynamics

To me, this class had the wrong name.  It was supposed to be an introduction to Pharmacodynamics, but became half about Pharmacokinetics.  It seemed much more like an overview of general pharmacology.  As an only 2nd semester course, pharmacodynamics incorporated a lot from the other courses.  Overall, this was a more daunting class than our others primarily due to the tests.  They were 90-minute tests crammed into 50-minute blocks.  On every exam, I wrote constantly to finish just before the time ended.  Luckily, the next thing was alway lunch so my hand cramps had a chance to relax.

As I said, the course wasn't really all of dynamics, but both dynamics and kinetics together.  We essentially traced the path of a drug from administration through to the effect and elimination.  So I will try to do a similar task.  We begin after the drug has been formulated and manufactured.  Let's assume a capsule of some kind.  Anything given orally is called PO (per oral, by mouth).  The patient takes the capsule and must pass from the GI tract into the blood stream.  This isn't easy.  Besides dissolution, the drug passes through the cells of the intestinal wall where it can be metabolized or it can be sent back to the GI or passed on into the blood.  Once in the blood system, the portal vein takes anything absorbed by the intestines directly to the liver to be detoxified.  A lot of drugs given orally to do make it past this step.  Called First Pass Metabolism, any PO drug must be able to sneak through.  After the liver the drug enters the systemic circulation and distributes throughout the body - hopefully to the site of action.

A drug must be absorbed and distributed to potential target.  In this case, the cancer cell is targeted by chemotherapy.  Metabolism and Elimination decrease the effectiveness of the drug as well as actions by the cancer cell itself to try to survive.  PK (pharmacokinetics) refers to the ADME properties and PD (pharmacodynamics) describes the biological effect.

Drug metabolism causes a lot of problems for drug manufactures.  Liver cells, hepatocytes, contain thousands of enzymes carefully designed for degrading potentially toxic substances.  Most notably, the cytochrome P450 family metabolizes the vast majority of medications.  CYP450 causes many problems when drugs are given in combinations.  One drug could inhibit CYP450, meaning that the other drug stays in the body longer and can accumulate to toxic levels (essentially a metabolic overdose).  On the other hand, the first drug could ramp up the CYP450 and decrease the amount of the other drug too fast for it to be effective.  Inhibitors and Inducers must be studied carefully and considered by the pharmacist when verifying and dispensing a prescription.

FDA approval is difficult and controversial.

If the drug avoids first pass metabolism, it must cause a desirable effect.  Specifically, more positive effects than negative effects.  FDA approval requires a consideration of the benefit versus the cost.  Chemotherapy drugs have a lot of side effects, but the benefits outweigh the potential problems.  Once
the drug reaches the site of action, the molecule binds to a cell receptor.  It could turn on an action or it could turn off an action.  All of these are important considerations when designing a new drug.  On average, a new potential drug takes more than 10 years to reach FDA approval.  99.9% of new molecules fail to become a marketed medication.

I enjoyed the pharmacodynamics course, even if I disagreed with the title.  The professors were amazing.  While the exams were difficult, you had to know what you were talking about to do well.  I think this course really seemed more like the introductory level of pharmacology that the other health professions take.  I went to a Starbucks the other day and a lady was reading from a pharmacology textbook.  During PY2, we take a pharmacokinetics course to go in much more detail.  I am ready for that.