Introduction to Pharmacology

Pharmacology is like a foreign language. You have to start in the beginning with a foundation and then just learn, learn, learn. There will be a lot of rote memorization that takes place and also some concepts.  The information in these articles are probably simple relative to your pharmacology textbook and not a replacement for it.  If you want to understand something in greater detail, refer to your textbook.

When drug names are given, you’ll see the generic name, trade name in parenthesis and also the routes of administration (p.o., iv, etc).  You must be able to recognize every drug, what it’s used for, the drug class (and subclass) and side effects.

Mnemonics: It’s very helpful to come up with mnemonics, no matter how silly they may seem, to help you remember certain things.  For example, for barbiturates, three out of the four we go over are easy to recognize because they end in -barbital.  For some drug classes there are no tricks/mnemonics to memorize and you have to get very creative.

For example, flurazepam is a hypnotic (meaning its for inducing sleep) benzodiazepine and the brand name is Dalmane.   I couldn’t remember this with flashcards so I had to come up with something silly.  Okay so I said, FLURA(zepam) sounds like fluoride… And fluoride is often purported on the internet to put people to make people passive (like to put them to sleep, hence its a hypnotic benzo), so I said “Damn the man!” (Dalmane!) for putting fluoride in our water supply.

Sounds stupid?  SURE DOES!  Do I remember that Flurazepam is a hypnotic benzo and the brand name is Dalmane? YEP!  So I don’t care how stupid it sounds.

DEFINITIONS

Pharmacology: The science of chemicals that effect a living process.

Toxicology: Adverse effects of these chemicals.

Drug Therapy: “Management” of disease with a medication.

It’s rare that we could use a better word than management for most drug classes such as “cure.” We could cure bacterial infections with antibiotics and there are a few other minor exceptions but it’s overall management that drugs are doing.

Drug: Alters an effect that already exists but makes that change in a quantitative manner.

You all have a heart rate, it’s beating. If I give your epinephrine, it speeds up. Did I make anything new? No. I just sped it up. The beating already took place and we just made it faster.  Something not as straight forward: I give a person a laxative. What is the quantitative change? There is an increase in peristalsis.

Federal laws that govern medications

1938 Food and Drug Cosmetic Act

One of the first major laws that Congress passed that said in order to market a product, you had to prove that it was safe. Before this, people were selling “cures” and “tonics” and people were dying.

What was missing in this law that took 24 more years to create?  The efficacy portion!  As long as the product didn’t kill the person, it was okay to use, but they didn’t have to prove EFFICACY! The drug could have been a fake!

1962 Kefaver-Harris Amendment

This added that the drug must prove efficacy. There was a little collusion going on though as there was a “grandfather clause” built into this law that said that any drug that existed before this law, could continue to be used without proving efficacy.

It took another 20 years before the FDA put legislation in that required these grandfathered-drugs to show that the were effective.  There are still grandfathered drugs such as cold medications.

This leads us to another topic, a category of products you could buy at a pharmacy or supermarket.

Natural Herbal supplements/products

These are not regulated by the FDA.  Find a problem with an herbal? It takes an act of Congress to do something about it. The herbals walk a fine line. Yes they are natural, but so are some drugs. The difference is the claim.

An herbal cannot make a claim that it’s indicated to treat something.  St. John Worts for example, is often thought to be good for depression.  On the label it is stated that it’s “for your mental health” and not one word is mentioned about depression or treating something.  Valerian root, known to be a sedative, doesn’t have one word about that.  The label would, again, say “for your mental health.”

We have an example of a diet-aid that was a herbal, called Ephedra, that a lot of people died from due to heart attacks.   The FDA could not touch it until one day a baseball player died from it during a game. Not only is there a lack of testing of efficacy, but also no testing of PURITY for them.  Pharmaceutical drugs on the other hand can be recalled and pulled from the market even after they have been marketed for years.

Investigational New Drug (IND) Procedure

This procedure is required for…

1. A chemical or substance not used in a human being before.

2. A new combination not used in combination before.

Tylenol+codeine required a new IND procedure.

Remember fen-phen? These were two, separately-approved drugs for weight loss by the FDA, fenfluramine and phentermine that were not approved to work together.  Doctors prescribed them together though and some patients died or got serious cardiac disease as a result of the misuse.  Could the doctors have told their patients this was safe? No because this combination was never tested and if you look at the labeling it says you shouldn’t be on another diet drug if you were on one already.

3. A new use for a previously issued drug.

Ibuprofen, for example, was approved in the late 1970’s only for arthritis by prescription only. If you were a bright physician who realized that ibuprofen could be used for many other things in the 1970’s, you COULD legally prescribe the drug for non-approved use. The drug companies, on the other hand, cannot promote it for just any reason though.

4. New dosage form

If a tablet form came out, they can’t just make the IV or suppository form without being tested for it.

Investigational phases

Research in some places used to be a joke.  Nowadays, we live in a much better world.  When the researchers today are oing to give major speeches, they have to disclose who has paid them and under whose salary they were so you could see if they have a conflict of interest.

If we’re talking about a brand new drug, animal studies are being done before we even get to Phase 1. If it’s safe in animals, then we try to see if we could do it in humans.

Phase 1: These are the very first few humans to ever put this drug in their body.  We are not giving this drug to a person who has the disease we are trying to treat.  These are also very well paid volunteers.  They determine the safety and tolerated dose in a few “healthy” volunteers.

Phase 2: Then, we determine the safety, efficacy and phamacokinetics in selected “diseased” individuals.

Phase 3: Determine safety and efficacy in a wider group and probably a more prolonged period of time. What’s the advantage of phase 3? Side effects. The more numbers you have, the better chance that you’re going to pick something up. This could go on for years unless it’s a fast-track drug like for AIDS.

Phase 4: The drug is approved and marketed with surveillance and this is the phase the drug companies are hoping for. Up until this point they have been paying out billions of dollars.

Then the drug is out on the market and they start price gouging you. But why?

A drug company patents every chemical they come up with.  Out of every one hundred patented chemicals, how many make it to Phase 4? About 1%. There are 99 failures.  So while it seems like price gouging to us, it’s not because the successful drug is paying for the 99 failures and the limited patent life.

What does “with surveillance” mean?

Instead of tens of thousands of patients, we are now going to have millions of patients. More side effects or dangerous things can pop up during this period. Vioxx for example, was a very good arthritic drug but they found out patients might be getting heart attacks from this and the drug was pulled from the market. The FDA is surveilling while the doctors are providing the data.

Types of Studies

Double blind studies eliminate the bias.

The physician doesn’t know what the patient is getting. The patient doesn’t know what they’re getting. All they know is that they are on a study. They are either getting a drug A or drug B or drug C but nobody knows what they’re on.

Here’s the dilemma: The patient gets ill and goes into the emergency room. They are asked if they are on any medications. The patient says yes but I can’t tell you which one I’m on. Who knows? The pharmacist where the drug is administered has a code-list in a safe that can be opened only in case of emergency.

More Definitions

Generic name: Chemical name for a medication.

Trade name: A manufacturer’s name for the generic product.

So for example, ibuprofen is a generic name. It’s not exactly the chemical name but for the general purposes of this article, it’s the generic name. The trade names for these are Motrin and Advil and they are registered trademarks and are always capitalized, unlike generic names.

Over the counter: Non-prescriptive drug/agent.

Legend drug: prescriptive drug/agent. In this situation, the only way you could get it, is for a doctor to prescribe it.

Behind the counter drug: Does not require a prescription but you need to show some document for it.

For example Sudafed (pseudoephedrine) requires an ID because people can convert it to methamphetamine.

The morning-after-pill also, requires that you’re over the age of 17 before someone can get the pill.

Insulin can be bought behind the counter but we need proof that you’re a diabetic otherwise it can be dangerous.

Controlled substance: Prescriptive agent that has the potential for abuse. Every controlled substance requires a prescription but not everything that requires a prescription, is a controlled substance.

Bioequivalent: This leads to the generic drugs. When a drug company patents a drug, they own that drug for roughly ~19 years. Drug companies had a problem with this because testing for the drug may as long as the patent period. Congress added a law that says, a drug company has a minimum of 5 years sole-rights.

If a drug-company takes 12 years to test a drug, they get 7 years to recoup their costs. If they take 18 years to test the drug, they get 5 years to recoup their costs.

Generics are overall very clean nowadays but in the 1980’s they had a bad name due to companies that are out of business now because they switched manufacturers due to cost.  Due to different binders and fillers, the absorption won’t be exactly the same as the brand name but it will be very close.

Until recently, all these drugs had to be made in the US or Puerto Rico. Now we are finding drugs made outside the US and now the FDA has to put branches of the FDA in foreign countries to monitor the drugs that are coming into the country. So far it’s been clean. If you take a look at brand name drugs, even they are being manufactured outside the country as well.

If the drug companies do pediatric studies on the drug, they can get an extra half year on the patent. But here’s the joke that takes place: So 19.5 years pass and the branding company files a lawsuit against the generic company that just started making it and they will say they are infringing on the process on how we are making the tablet. The courts create an injunction that makes the generic company stop the manufacture of that drug. Until the actual law suit is complete, 2 years can be passed and that’s billions of dollars in revenue for the brand name company. They can repeat this process again and get an extra 6-8 years like this. The unofficial saying goes, each brand name company is entitled to one frivolous law suit per drug.

The Joint Commission or JCAHO

The Joint Commission (TJC), formerly the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), comes out to survey your health care facility and give it accreditation or not and that dictates whether you get federal money (Medicare, Medical, etc).

They walk in on any given day and one of the things they look at are adverse drug reactions. They may ask how many adverse drug reactions have you gotten in the past 2 years? Why? Because 10% of all patients in a hospital bed are there due to an adverse drug reaction. They’re interested in this because they want to see if you’re making improvements.

Something that happened at the VA one time: A patient had an allergy to a medication and they were prescribed a Sulfa-drug they were allergic to. The pharmacist filled the prescription and the patient came back with an allergic reaction. This happened because the computer crashed that day and didn’t alert them. Their solution?  Next time the system crashes, they’re going to ask the patient if they have any allergies. And it worked.  TJC wants you to admit you have a problem, and how you fixed that problem.

The requirements for the FDA in terms of adverse reactions is this: If the drug has been out for less than 2 years, ANY reaction must be reported. If the drug has been out for longer than 2 years, they want to know of anything that hasn’t been seen before and anything that’s life threatening.

Controlled Substances

In 1970, Congress created the Comprehensive Drug Abuse and Prevention Act which divided the drugs of abuse into 5 roman numerals.

Schedule I: High abuse potential with little medicinal benefit. These are called illegal drugs.  If you are caught with any of these, you will get arrested.

Examples include: heroin, LSD, PCP, marijuana, cocaine.

California allows medicinal marijuana, which conflicts with federal law. There is a medical use for marijuana and that is why they have created FDA approved drugs that mimic it for this purpose (Marinol).

Schedule II: Have a high potential for abuse but have medicinal benefits. Examples…

Narcotics: morphine, meperidine, methadone
Stimulants: dextroamphetamine, metyhlphenidate (Ritalin)
Barbiturates: secobarbital, pentobarbital

What are the laws or rules about these? Schedule II’s have to be on paper. There is no verbal prescription allowed. We’re waiting on approval for electronic prescribing. Schedule II will probably not be allowed electronic prescribing anyway.

What do pharmacies do with these drugs? A triplicate-form (pharmacy keeps one, and two are sent to the wholesaler, one copy is sent to the Department of Justice) is created to act as a red-flag if a pharmacy is buying too many of these drugs. They also take a look at doctors because we’ve had a lot of high-profile celebrities die from these drugs.

Schedule III: Lower abuse potential with medicinal benefits.  Examples…

Combinations with narcotics: acetaminophen with codeine. Codeine is schedule II.  If you add tylenol to that, it becomes schedule III, which doesn’t really make sense.  Vicodin/norco (hydrocodone/acetaminophen) is being overly abused and they are OD-ing on the acetaminophen portion.

Testosterones. Why is a male sex hormone a controlled substance? These are your performance enhancing drugs used by athletes!

Schedule IV: Lower abuse potential with medicinal benefits.  Examples…

Benzodiazepines: diazepam, alprazolam
Long acting barbiturate: phenobarbital (because you can’t get high immediately from it)
Propoxyphene was pulled from the market in 2011. The drug has been around for 50 years but people realized it had no effect on pain but people loved abusing it.

Schedule V: Low Abuse Potential with medicinal benefits.  Examples…

Cough syrups with narcotics. You have to drink a lot of cough syrup to get high from it.
Diphenoxylate with atropine (antidiarrheal agent). The diphenoxylate is nice, but the atropine makes the high atrocious.