MIT OpenCourseWare
http://ocw.mit.edu

SP.236 / ESG.SP236 Exploring Pharmacology
Spring 2009

Spring 2009 Class Blog

The Experimental Study Group is a learning community that exists at MIT. It offers freshman classes, taught in small groups, as well as spring seminars that are open to the entire MIT community.

SP.236, “Exploring Pharmacology,” is one of these experimental seminars, and it is currently in its third year.

Alcohol substitutes?
Funny and educational videos
The Action Potential
Research Scavanger Hunt
Please share your findings
Antidepressants
ESG Alumni Reunion Slides


  • Alcohol substitutes?
    What do you think about the idea of alcohol substitutes, drugs that mimic the feeling of alcohol with fewer negative side effects? Please write your thoughts in the comments below.

    The barbiturates have been used by some as alcohol substitutes for many decades, but these drugs have a nasty habit of causing fatal overdoses, especially when mixed with real alcohol. Many people say that barbiturates create a very convincing and complete facsimile of the effects of ethanol, but without the hangover and nausea. Some people say that certain barbiturates do cause a hangover, but this effect may be due to the long half-life of the drugs, which means that you are still half high on Monday morning. The lingering effects the next morning may be burdensome and no longer fun like they were the previous night when you were completely high.

    Various benzodiazepines have been proposed as alcohol substitutes, but they have never been commonly used for this purpose to my knowledge. Dr. David J. Nutt has written papers about the possible merits of the benzodiazepine partial agonist pagoclone as a new social drug to replace alcohol. The debate is mentioned in this article, but the article has many problems which are common in the popular press. The article might overplay the importance of GABA-A and NMDA receptors in ethanol’s normal effects. The mention of dizocilpine as an alcohol substitute seems pretty weird, for reasons I can discuss with anyone interested. Also, the article misspells “dizocilpine”.

    Benzodiazepines seem attractive because they are much safer than barbiturates and less addictive, but benzodiazepines are also less euphoric. Benzodiazepines almost never cause fatal side effects or overdoses on their own, although they can cause problems when combined with large doses of other drugs like opiates and alcohol. Dr. Nutt says that the partial agonist pagoclone will be even less addictive than the full benzodiazepine agonists like Xanax, Valium, Ativan, Rohypnol (roofies), Restoril, and Klonopin. He also says that it will cause fewer falls, less memory loss, and less aggression. He even suggests distributing the antidote to benzodiazepine sedation - the antagonist flumazenil.

    What do you think about alcohol substitutes? What do you think about distributing the antidote, so that people can pop a second pill and sober up instantly for the drive home? Will the free availability of antidotes make people safer, or engender false confidence? Debate. Don’t be timid, say what’s on your mind.

  • Funny and educational videos
    This is a Youtube video, but I strongly advise you not to look at the visuals because they are stupid. Just queue it up, turn up the volume, and then minimize your web browser: Paracetamoxyfrusebendroneomycin by The Amateur Transplants.

    In contrast, it is very helpful to watch the screen during this video: The Drugs Song by The Amateur Transplants.

    Extra credit: What drugs’ names do you see wrapped up in the name “paracetamoxyfrusebendroneomycin”? List as many drugs as you can that have contributed a piece of their name to this wonderdrug. Alternatively, what chemical functional groups do you expect this drug to have, based on the name?

    To receive this extra credit, please log in and add your answers as comments.

  • The Action Potential
    This is a neat link: http://www.cs.cmu.edu/~dst/HHsim/. There is a Matlab application on this website that will simulate a neuron’s membrane potential, including action potentials and the effects of select drugs.

    Wikipedia’s entry on action potentials is also a pretty good learning tool.

  • Research Scavanger Hunt
    Mel T. Disciplinary is taking a pharmacology seminar at college, and he is getting bored. The teacher spends every class just rattling off a laundry list of drugs, and Mel can’t seem to stay awake and focused without ingesting an even larger laundry list of drugs. He has tried caffeine, Adderall, Ritalin, modafinil, amantadine, pemoline, khat, cocaine, and meth, but nothing is strong enough to keep him awake during those interminable lectures.

    Mel T. Disciplinary has decided that drugs may not be the answer to his problem* - or more precisely, taking drugs isn’t the answer to his problem. He has to study drugs, and make them interesting by relating his lessons in pharmacology class to other topics in science and art. Can you help Mel by researching and answering the following questions? (Please post your answers as comments below, or email your answers to pharmacology-teachers@mit.edu and I will post your answers anonymously)

    1. Chemistry/Physics:
    What exactly is the difference between crack and powder cocaine?
    How do you make crack?
    What route(s) of administration are best suited for crack and powder cocaine, respectively?
    If you really want to inject crack, you have to mix it with lemon juice. Why? What else would work? Why would you want to inject crack anyways, isn’t smoking it just as fast? In what way is injecting better than smoking? (While answering this final question, please use the arguably flawed criteria of a drug addict)

    2. Chemistry:
    Jen K. is addicted to opioids, but she has a bad liver and the only drugs on hand are Vicodin tablets. Vicodin tablets contain a mix of hydrocodone (which will get her high) and acetaminophen (which will aggravate her liver). How can Jen K. separate out the good stuff and spare her poor liver?

    3. Home economics/Mathematics:
    Dilaudid tablets (hydromorphone) have only 20% oral bioavailability, but remember that the bioavailability by intravenous injection is 100% by definition. Opana tablets (oxymorphone) have only 10% oral bioavailability. Dr. Shopper is addicted to opioids - and his doctorate is in mathematics, so he can’t just write himself a prescription or steal some. If the cost of Dilaudid (in $/mg) is Cd, the cost of Opana is Co, the ORAL potency of Dilaudid (in mg/dose) is Pd, the oral potency of Opana is Po, and the rate at which Dr. Shopper ingests opioids (in doses/day, either oral or injected doses) is R, then how much money will Dr. Shopper have to spend on drugs (in $/day)?
    That was just an example question, I will answer it for you. The real question comes later. Here is the answer so far:

    For Dilaudid:
    TOTAL_COST_d = R*Cd*Pd*(0.2)

    For Opana:
    TOTAL_COST_o = R*Co*Po*(0.1)
    It seems that Dr. Shopper should take whichever drug is cheaper, and only that drug. Which drug is cheaper is determined by this formula:
    CHEAPER_DRUG = MINIMUM( 2*Cd*Pd, Co*Po )

    You don’t yet have enough information to find which of those expressions is smaller. So I will tell you: So far, all the numbers I have given you are accurate. The bioavailabilities of hydromorphone and oxymorphone really are 20% and 10% respectively. Opana is much more expensive, though. In the real world, doing all Dilaudid will be cheaper, even if you are injecting. One equivalent oral dose of Dilaudid (Pd) is 7.5mg, one equivalent oral dose of Opana (Po) is 10mg. These “equivalent doses” are relative to the standard equivalent dose of 10mg IV morphine, a relatively potent shot of opiate that would shut up most patients after a car accident.

    However, Dr. Shopper has a problem. His physician is only willing to give him G (given) doses per day, but he needs N doses per day to satisfy his addiction. N is much greater than G. How will Dr. Shopper get the N doses he needs if the doctor will only give him G doses? Remember, the doctor is only giving him G doses, but the doctor thinks he is taking all these doses orally and never injecting.

    Here is your assignment: Write some fancy equations based on the variables above. In the end, figure out how Dr. Shopper can save as much money as possible while still getting exactly N doses of opioid. The answer will require a mix of Dilaudid and Opana, it will depend on the unknown variables Cd and Co, but it will not depend on Pd or Po (I gave values for those) or R (R is actually the same as N, the needed number of doses).

    4. Medicine:
    Explain why Jen K. and Dr. Shopper are being incredibly stupid (despite their respective knowledge of chemistry and math), and what medical problems they are likely to have.

    5. Physics/Physiology:
    Potheads are very environmentally conscious and thrifty, so they try to get high off of as little weed as possible. How can a cannabis aficionado maximize the bioavailability of the active ingredients in smoked marijuana? Is it best to use a bong, a pipe, or a joint? There are valid arguments for all three methods. Why might a bong be best? What are the pros and cons of a pipe? What about a joint? I would love to see purely theoretical musings and thought experiments, but information about the boiling point of XXX chemical or real research studies with pot smokers and blood tests are also lovely.

    6. Art:
    What is your favorite book or movie about drugs? Do you think Mel T. Disciplinary would like it? Fiction and non-fiction are both acceptable.

    7. Stupid humor:
    Each of the characters’ names above is a stupid joke. To what does each name refer?

    8. Undefined:
    What is your favorite discipline? Can you come up with a question that ties your discipline to pharmacology? If you can’t, please state your favorite discipline and the rest of us will try to come up with something. (Hint: Almost any discipline can be related to drugs by finding one of the most famous thinkers from that field, and then noticing that they were addicted to drugs.)

    9. Undefined:
    Make a series of analogies between drugs and things in your discipline. “If programming languages were drugs, then Java would be caffeine because c’mon, it’s called Java”, and so on. Here is some inspiration: If programming languages were cars, and if programming languages were religions. Okay, this is probably really hard. You don’t have to be funny at all, does that take some pressure off? Also, feel free to email me and I will post them anonymously. Or I will not post them at all if you want, I will snicker at them, I will express my thanks, and then I will carry your secret to my grave.

    *I know, I know, he’s crazy. Drugs are always the answer. You have to finish reading the sentence before getting appalled.

  • Please share your findings
    Deepa uncovered a very nice site, it has fun flash animations and pretty good explanations in layman’s terms: here it is, scroll down to the “modules” section. Here is a link directly to the stimulants module, and this is the sedatives module. I am very impressed with this website, it is pretty accurate about the pharmacology, despite the spelling errors. This website is much less biased and more accurate than the 9.00 (Intro Psychology) textbook, which has a very misleading table of common drugs.

    Remember, your homework is to spend some time researching drugs on the internet. Please share your findings in the comments below, or ask questions, or suggest topics for your classmates to research. If you find a good lead, please tell your classmates so that they won’t have to wander the internet aimlessly.

  • Antidepressants

    Do you have any theories about why antidepressants take a few weeks to kick in?

    Have you found anything particularly interesting while surfing Wikipedia for info on your assigned antidepressant?

    Is it right for millions of Americans to mess with their minds by taking medication to cure what might be normal emotions? Will the overuse of antidepressants cause people to stay in unhappy marriages and unhappy jobs? Or should people part with this delusion that nature is perfect and must not be tampered with? If the mind is all just chemicals floating around in your brain, what does it matter whether your body synthesized those chemicals or you took them as a pill? Why should you be stuck with what nature has given you, especially if you have been dealt an inferior hand of cards with crippling anxiety and depression?

    Please share your theories, your findings, or any thoughts you might have as comments to this posting. Have a very nice week.

  • ESG Alumni Reunion Slides

    The Drugs Chart is here.