VP Joe Biden goes full VEEP

I changed by Time Warner deal and somehow landed HBO for a year.  I know how.  They want me to have it cheap for one year so that I won't be able to get rid of it next year when the deal ends and my bill skyrockets.  Anyways, I had wanted to watch VEEP with Julia Louis-Dreyfus playing a gaffe-prone vice president.  Other than the excessive use of expletives, the show is hilarious and I recommend it to anyone and everyone.  For the White House Correspondents dinner Julia Louis-Dreyfus got the real Vice President, Joe Biden to go on a full VEEPish trip through the White House.

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.

New Drug Update - Ibruvica (ibrutinib)

During our Hospital IPPE month, we had to give a presentation on a recently approved drug from the last year.  A lot of important medicines received approval including to oral treatments to Hepatitis C.  I also liked that each of these drugs had been discussed during our lecture classes.  I might not have remembered what they did, but I at least recognized some of the names.

I waited until the end of the sign up period, because I did not really care what I got.  In the end, I selected Imbruvica, the oral treatment for mantle cell lymphoma and chronic lymphocyctic leukemia.  We also had to find some way to actively engage the audience during our presentation.  It's almost like I have a Master's degree in that.  But really, I do.  I chose to impersonate a couple of our professors from the semester.  I had a pickle jar with everyone's name in it, a chemist hat, played pharmacy hangman, and wrote a short poem.  I also chose a punny subtitle for the lecture.  PO is the pharmacy abbreviation for ORAL - tablet, capsule, etc.

Ibrutinib Presentation by Adam Corey

TED Talk Tuesday: Derek Sivers

Derek Sivers has given several short, but great talks at TED conferences.  Concise and funny seems to fit his style.  In this one, Derek uses an odd example to explain leadership and how to start a movement.  Movements start with one person, a visionary, willing to step out and be different.  But until someone else joins them, he will be a lone nutcase.  Momentum cannot begin until the second person joins the movement.  There are two types of leadership in this example.  We need creative people to find new ways to do things, but we also need people to recognize the good ideas.  We always talk about great leadership.  Derek reminds us that great leadership is more about the idea or the group than the person.

PY1 Review - Pharmaceutics

As the keepers of tablets, capsules and suppositories, pharmacists must obviously understand how these products are manufactured and deliver medicines to the body.  That class is called pharmaceutics and is unique to the field of pharmacy.  We took two semesters worth of information for one of the most interesting classes we had during the PY1 year.

Determining the route of administration of a drug is just as important as choosing the right drug.  If a person has diabetes, as many people do, we want to give them insulin.  A lot of other medicines work as well, but insulin remains the standard.  So how do you get the insulin into the body?  Most people know about insulin injections - a subcutaneous administration of an endogenous protein.  But 3-4 injections a day adds up quickly to 21-28 a week or 1,095-1,460 injections per year.  What if we could devise a better way to deliver insulin without a needle?  That is pharmaceutics.

The most common method of taking medicines today are pills.  Pills, pills, pills.  Patients taking 30 or 40 per day.  Tablets can be different sizes and different shapes.  The type of oral medication depends on the aspects of the drug itself.  Some drugs degrade in low pH, like in the stomach.  In that case, you don't want the drug released until it gets into the small intestines.  Enteric coating can protect drug by not dissolving in the stomach.  A lot of science goes into designing the right pill.  A lot more goes into making the pill stable as some sit in boxes for 2 years from manufacture to your mouth.  We talked a lot about the excipients added to medications and the testing process each product must go through.

Unfortunately, great pills don't always deliver all of the medicine through the digestive system.  The amount that actually gets through to your body determines the bioavailability.  Some oral products have very low bioavailability, but the gold standard will always be intravenous injection.  If pills are complicated to make, IVs have their own problems.  Producing IV meds involves a lot of thought in stability and sterility.  Hospitals have giant clean rooms to prepare IVs to reduce the likelihood of contamination.  Even then, a drug in saline solution may only be stable for a few hours before precipitating into a useless cloudy mess.

I really liked both semesters of pharmaceutics.  The topics were interesting and the wide range of professors provided a lot of entertainment.  Pharmaceutics seems like one of the secrets kept by the pharmacists from the other health care professionals.  You can take this subject with you to counseling patients in the community, to preparing IV bags in a hospital, or to developing a new billion dollar drug in the industry.

Why we call Football Soccer

Lionel Messi (Argentina) scores in opener of the World Cup

I don't know about you, but I have been enjoying the World Cup.  Soccer isn't a sport I usually watch, but this is a major event.  Everyone else in the world calls it Football or Futbol, but Americans and Canadians call it Soccer.  I thought I should find out.

Even in other languages, the sport is referred to in some variation of Football.  The Spanish for foot is not fut, but pie.  So the sport must have begun in the English speaking world.  In fact, the modern game began in England during the 1860's (The origin of football in England is quite ironic as they royally suck during the World Cup).  They called it football for the obvious reasons.  Actually, the real name is Association Football.  FIFA is the  Fédération Internationale de Football Association.  The association part was meant to distinguish the sport from Rugby Football.  So where does soccer come from?

Since the 1880's, Oxford students had a habit of adding -er to common words.  Bonners for bonefires, Congratters for congratulations, even Eccer for exercise, and my favorite Brekkers for breakfast.  People got the -er treatment as well - Beckers for David Beckham, Cammers for David Cameron and Britters for Britney Spears.  Apparently Oxford students are a bit pretentious.

Remember that football is officially called Association Football.  That was abbreviated Assoc. Football, which then received the Oxford -er.  The -er added to the end of Assoc-er and then dropped the first As- to become Soccer.  In fact, they started by spelling it socker to get the hard cc sound which does not appear in association.  So lets recap:

FOOTBALL (Futbol)

Association Football

Assoc. Football

Assoc-cer

SOCCER

The name soccer really comes from the 3rd, 4th, and 5th letters from association.  While incredibly convoluted, the name soccer actually makes a little bit of sense.  Not really.

Irinotecan - Topoisomerase Poison

Easily the most stress of PY1 came from the Biochemistry Presentations.  Another group lab presentation, but instead of fun, herbal supplements, we talked about the way chemo and antiviral medications worked.  I greatly enjoyed the topic, but the level of difficulty increased dramatically.  My group was given irinotecan, a treatment for colorectal cancer.  Not a lot of jokes were going to be made in this one.

Irinotecan is a very interesting drug.  The molecule blocks the effects of Topoisomerase 1 and results in an accumulation of double strand breaks that leads to cell death.  Of the cancers, Topo1 increases the most in colorectal cancer, but it is being investigated for others as well.  Irinotecan acts as a prodrug for its active metabolite, SN-38, which undergoes glucuronidation and can become a part of enterohepatic recycling leading to extreme diarrhea.  The complexity of irinotecan showed up in every class during the spring semester.  Which was great, as I became an expert on the drug.

While other groups took the traditional lecture approach to the presentation, my group wanted to do something different.  We created a demonstration of Topoisomerase with rope, scissors and duct tape.  As DNA is copied for cell division, the unwinding of the helix increases the stress on the molecule upstream.  Topo1 releases that stress by cutting one strand of the DNA, allowing the molecule to unravel, and resealing the original cut.  Pretty simple idea, especially if you could have seen our demonstration.  We did do it, but due to snow delays only six people were in the room and I doubt anyone watched the video afterward.  However, it was a big hit with the professors and TAs as other people who weren't there came up and talked to me about it.

As I said, it was a group project with a great group of girls.  I do not want to take all the credit by posting it on her.  My job was the Mechanism of Action.  I chose it specifically because it generally received the most difficult questions from the feared professor.  Other than issues with the weather, our group nailed the presentation - possibly even the best of the semester.

PY1 Review - Biochemistry

Out of all the classes on our PY1 schedule, biochemistry frightened me the most.  While I have taken biology and I have taken chemistry, I had never been enrolled in a class that combined the two.  Other PharmD students had majored in biochemistry, and I had absolutely no idea what to think.  By the second class, my fears were realized as I sat through a 90 minute presentation without understanding a single word.  Biochem would be my downfall in pharmacy school.

Actually, biochemistry turned out to be one of my favorite classes.  Many of the topics had been covered in the high school bio courses I taught or at the very least extended from the same concepts.  If I had really known about biochemistry during my undergraduate years, I may have ended up majoring in it and began pharmacy school 10 years sooner!  In pharmacy school, biochemistry serves as the prerequisite to the medicinal chemistry on PY2.  Two semesters divide the topic into nucleic acids and not-nucleic acids.

Aspartate - structure with acidic side chain

The first semester began as a review of organic chemistry followed by the basics of proteins,
carbohydrates, and lipids.  From organic, you should know all of the functional groups names and relative pKas.  Under proteins, the course covers some about structure, but mostly enzymatic kinetics.  Michaelis-Menten mechanics drive every theory about enzymes and drugs.  For carbohydrates, you must memorize the catabolic processes of glycolysis, Krebs, and electron transport chain and the anabolic processes including gluconeogenesis.  Finally, lipids cover the basic structures of triglycerides and phospholipids.  If it sounds like a lot of information, it is.  Those that majored in biochem sailed easily through this part.  Others, like me, had to do a lot of work to keep up and it didn't get any easier next semester.

Irinotecan - mechanism of action.

In the second part of biochemistry, we studied anything and everything related to nucleic acids.  I was really interested in this part as many antibiotics target the DNA differences between us and them.
 Oncology also attacks the properties of our own DNA to kill rapidly growing cells.  This course began with the basics of DNA, similar to what I taught to my classes but again with a bit more detail.
Once through the discoveries of Watson and Crick, we went over the way cells use the DNA template for replication, transcription and translation.  Really, the order of topics should be familiar to anyone.  The difficulty came from the depth of information covered and the density of exam questions.  Compared to the first semester, we talked about all kinds of drugs affecting DNA, RNA, and ribosomes.  I know more about Topoisomerase 1 than I think I will ever use, but I understand the importance of irinotecan in the treatment of colorectal cancer.  Success in Biochem 2 required a lot of work, but it was worth it in the end.

I feel good about my understanding of biochemistry after this year.  I won't be earning a PhD in the topic, but I can hold my own.  Will it help my career as a pharmacist?  I think so.  That really determines which direction you go.  While you may not use gluconeogenesis, you do have to know that cortisol (and any other prescription steroid) stimulates the process.  Otherwise it varies.  Oncologists, yes.  Community, maybe not.  Overall, it broadens your knowledge base and provides more opportunities for you to pursue after pharmacy school ends.

TED Talk Tuesday: Mark Kendall

One of my favorite parts of the PY1 year was becoming certified to provide immunizations.  The vaccination program of modern science is one of our best methods to PREVENT disease.  Since beginning immunizations, we have practically eradicated diseases that used to ravage every society.  We are even at the point now to use vaccination to prevent cervical cancer caused by HPV.  Whether or not people understand it, vaccinations have made a huge impact on public health.

But there are still problems, especially in third world countries.  Getting vaccines to remote locations causes issues as these liquids must be kept refrigerated.  Also, a lot of people are afraid of needles.  Make Kendall, an Australian biomedical engineer, may have created the next answer.  His team created the nanopatch of about 400 invisible microneedles that deliver potent vaccines just under the surface of the skin.  It's easy, painless and effective.  This could be the future of world wide disease prevention.

History's Most Influential Person?

On Wikipedia, there is a rule that you can start at any innocent article and be fewer than 7 clicks away from Adolf Hitler.  The mass-murdering bastard played such an important role in the 20th century that eventually any object, place or person with a Wikipedia page is inevitably linked to him.  But is he the most influential person in history.  Clearly, the founders of modern religions have great influence on today's Wikipedia - Jesus, Abraham, Mohammad.  America's Founding Fathers must be important - Washington, Jefferson, Franklin.  But who tops the list?

Carolus Linnaeus: Most Influential Person

New Scientist featured an article about research by Young-Ho Eom, from France that attempted to answer just that.  He looked at Wikipedia links from 24 languages to determine the answer.  And at the top of the list sits:  Carolus Linnaeus!  The Swedish botanist that devised sciences modern system of species classification.  Any Wikipedia article about a living object must include its scientific name, and thus a link to Linnaeus.  That and of any person, Linnaeus has the most species named in his honor.  To round out the list of most influential people:

1. Carolus Linnaeus
2. Jesus
3. Aristotle
4. Napoleon
5. Hitler
6. Julius Caesar
7. Plato
8. Shakespeare
9. Einstein
10. Elizabeth II

Things were a little different in the English with Napoleon, Obama, and Linneaus taking the top three spots.  Interstingly, he also did a 2DRanking of Wikipedia that measures both incoming and outgoing links.  In this case, the extra layer produced this global result:

1. Hitler
2. Michael Jackson
3. Madonna
4. Jesus
5. Beethoven
6. Mozart
7. Pope Benedict XVI
8. Alexander the Great
9. Charles Darwin
10. Barack Obama

Again, the English version differed with Sinatra, Jackson, Pope Pius XII leading the way.  Does this prove anything?  Probably not.  But it always makes for a great debate!

Cake or Death - Disney Style

Eddie Izzard is funny.  Now he is animated with clips from Disney movies during one of his funniest bites.

Tigecycline - A New Weapon Against Antibacterial Resistance

As soon as Alexander Fleming accidentally discovered the medicinal benefit of antibiotics, bacteria began fighting back.  Penicillin appeared as the kind of “magic bullet” Paul Ehrlich envisioned, but the ability of microbes to evolve resistance mechanisms has led to an evolutionary and pharmacological arms race over the last century.  Antibiotics attack susceptible bacteria through specific mechanisms based on the cellular and metabolic differences between prokaryotes and eukaryotes.  One class of antibiotics, the tetracyclines, prevents the synthesis of new proteins by binding to the bacterial ribosomes.  Unfortunately, the bacteria responded by modifying their ribosomes and pumping the antibiotic out of the cell.¹  Tigecycline, a glycycline built of the tetracycline scaffold, possesses a unique functional group that allows it to block the bacterial ribosome and simultaneously evade bacterial resistance mechanisms.²  Developed under the name GAR-936 by Wyeth Pharmaceuticals in Philadelphia, tigecycline (brand name: Tygacil) provides a new weapon in the rapidly changing battle of antibacterial resistance.

As a new tetracycline, tigecycline uses the same mechanism of action of its tetracycline ancestors – preventing protein synthesis.  Invading bacteria require new proteins to survive, which are made by ribosomes.  A copy of the genetic information is transcribed into an RNA message that can be translated by a ribosome.  During the translational process, the mRNA feeds between the two subunits presenting the codon that determines the appropriate amino acid to be added to the growing peptide chain.  The transfer RNA (tRNA) with the correct anticodon enters into the A-site with the specified amino acid.  From here, the amino-acyl-tRNA pivots to the P-site for the peptidyl-transfer reaction.²  After attaching, the tRNA slides to the E-site and ejects from the ribosome as a new aminoacyl-tRNA enters to continue the elongation of the peptide chain.

Tetracyclines and tigecycline specifically target the 30S subunit of the bacterial ribosome by binding reversibly to the A-site, and preventing the accommodation of the tRNA.³  Within the 30S subunit, tetracylines interfere with the H34 helical region of the 16S rRNA through hydrogen bonds between the hydrophilic parts of the drug and the phosphate backbone.  The resulting steric hindrance prevents aminoacyl-tRNA from pivoting to the P-site and blocks the elongation of the peptide chain.  While tetracyclines bind to the subunit in one direction, tigecycline blocks the A-site although through a different orientation. This unique binding increases tigecycline’s affinity almost 5-fold giving the antibiotic its bacteriostatic properties and a method of circumventing the resistance proteins in some strains of bacteria.² 

All antibiotic products face the challenge of bacterial resistance.  Formerly susceptible bacterial strains employ two major resistance mechanisms against tetracycline antibiotics.  First, bacteria up-regulate efflux pumps to expel the harmful antibiotics from the cell before it can perform its inhibitory activity.  When Gram-negative bacteria encounter a tetracycline product, efflux genes known in sequence as TetA-E turn on to a decrease the concentration of drug within the cell.  Gram-positive bacteria remove tetracyclines through the same efflux process, but with the genes TetG-L.  These gram-positive bacteria also produce extra small proteins that block the location of tetracycline binding through the genes TetM or TetO.^1,4  The protective proteins compete with the tetracycline and reduce the effectiveness of the drug.  Researchers designed tigecycline with the intention of avoiding the Tet efflux pumps by including a bulky side chain that would stay in the cell to continue working, but they also found that it continued to work in the presence TetM proteins

During development in the early 1990’s, tigecycline became the main focus of a new antibiotic class of glycyclines that retained the ribosome blocking mechanisms of tetracycline but avoided the evolved Tet resistance.⁴  Starting with tetracycline’s four-ring structure, researchers developed new generations of antibiotics by attaching various functional groups to evade efflux and avoid TetM proteins.  For example, doxycycline moves a hydroxyl group from the C-ring to the B-Ring, while minocycline includes a dimethylamine to the 7-position on the D-ring.

Figure 1 Structures of Tetracycline, Doxycycline, Minocycline and Tigecycline Tetracycline, the original member of the family, provides a four-ring backbone which interacts with the 30S subunit of bacterial ribosomes.  The rings are identified A-D beginning with the amide-containing ring on the right side as A.  Notice that tetracycline contains a methyl and hydroxyl group attached to the C-ring.  Doxycycline moves the hydroxyl group from the C-ring to the B-ring, as a second-generation tetracycline.  Minocycline, also a second-generation tetracycline, removes the methyl and hydroxyl from the C-ring and includes a second dimethylamin in the C-7 position of the D-ring.  Tigecycline, a third-generation tetracycline or glycycline, builds on the minocycline backbone and includes the tert-butyl-glycylamido group to the C-9 position of the D-ring.  The long, bulky chain in the 9^th position produces the anti-resistance properties of tigecycline.

(Taken from Garrison M, Neumiller J, Setter S. Tigecycline: An investigational glycycline antimicrobial with activity against resistant gram-positive organisms. Clin Thera. 2005;27(1):12-22.)

Minocycline proved to be a strong antibiotic, but eventually succumbed to similar mechanisms of resistance.  Researchers attempted to improve minocycline by including a new functional group to C-9 position of the D-ring.  An early glycycline, dimethylglycylamido-minocycline (DMG-MINO) provided a hopeful avenue, but tigecycline showed the most promise against the more clinically relevant, multidrug resistant pathogens.^5,6  Structurally, tigecycline, a chemical descendant of minocycline, adds a tert-butyl-glycylamido group to the D-Ring, which provides the anti-resistance benefits while maintaining antibacterial properties with three main improvements.  First, the molecule became more lipophilic allowing for easier transport into the cell.  Because tetracyclines act on ribosomes, they must reach the cytosol to perform their inhibitory mechanisms.  The additional side chain increases tigecycline’s volume of distribution to 7-9 L/kg, showing that more of the drug resides tissues than in plasma.³  Secondly, the extra-long alkyl group creates enough steric hindrance to prevent efflux from the cell.  Where tetracyclines would be removed, the bulky tigecycline continues to work.  Thirdly, tigecycline shows five times more affinity to the 30S ribosome compared to tetracycline.²  The 9-tert-butyl-glycylamido group shifts the orientation of tigecycline within the 30S ribosome and generates more stable hydrogen bond stacking, shielding the molecule from TetM protective proteins.^7,8  The important glycylamido addition to the minocycline backbone provides the biochemical opportunity for the pharmacological improvements of tigecycline over minocycline and other tetracyclines.  Unfortunately, some anaerobic bacteria have displayed resistance to tigecycline through the upregulation of a different set of efflux pumps.  Enterobacter and Acinetobacter increase the number of RND pumps on their membranes, which are not blocked by the bulky side chain and remove tigecycline from the cell.² 

Interest in tigecycline led to worldwide testing process as many countries sponsored research into the effectiveness of tigecycline through the TEST Program (Tigecycline Evaluation and Surveillance Trial).  Tigecycline showed similar or improved results to treatment by minocycline (the closest relative), to a vancomycin-azetrenam combination, and to an imipenem-cilastatin combination.  Specifically, tigecycline provides hope to treat the various drug-resistant strains like vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphalococcus aureus (MRSA), penicillin-resistant Streptococcus pneumonia, and beta-lactamase producing E. coli.  However, the TEST program has shown regional variations in the activities of tigecycline against resistant bacteria and a growing resistance to tigecycline itself.  The FDA approved tigecycline for the treatment of complicated intra-abdominal infections, community-acquired bacterial pneumonia, and complicated skin infections against a wide range of species.^3,4,9 The FDA Black Box Warning suggests a 0.6% increase in morality risk and advises the use of tigecycline only when alternatives are not available.⁹

Unsusceptible to the normal methods of tetracycline resistance, tigecycline continues to inhibit the 30S ribosomal subunit despite Tet efflux transporters or TetM proteins that protect the accommodation site of the ribosome. Tigecycline demonstrates the creative ability biochemistry provides to overcome bacterial resistance by building on the structure of minocycline. Tigecycline’s bulky side chain generates the improved characteristics of tigecycline.  At this point, tigecycline remains the only FDA approved glycycline and offers a potent weapon against antibacterial resistance.

References

1. Projan S. Preclinical pharmacology of GAR-936, a novel glycycline antibacterial agent. Pharmacotherapy. 2000;20(9):219-223.

2.  Seputiene V, Povilonis J, Armalyte J, Suziedelis K, Pavilonis A, Suziedeliene E. Tigecycline - how powerful is it in the fight against antibiotic-resistant bacteria? Medicina (Kaunas). 2010;46(4):240-248.

3.     Doan T, Fung H, Mehta D, Riska P. Tigecycline: A glycylcyline antimicrobial agent. Clin Thera. 2006;28(8):1079-1106.

4.     Peterson L. A review of tigecycline - the first glycycline. International Journal of Antimicrobial Agents. 2008;32(S4):S215-S222.

5.     Garrison M, Neumiller J, Setter S. Tigecycline: An investigational glycycline antimicrobial with activity against resistant gram-positive organisms. Clin Thera. 2005;27(1):12-22.

6.     Loh E, Ellis-Grosse E, Petersen P, Sum P, Projan S. Tigecycline: A case study. Expert Opin Drug Discov. 2007;2(3):403-418. 

7.     Olson M, Ruzin A, Feyfant E, Rush T, O'Connell J, Bradford P. Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother. 2006;50(6):2156-2166.

8.     Jenner L, Starosta A, Terry D, et al. Sturctural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis. PNAS. 2013;110(10):3812-3816.

9.     Tygacil  [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; September 2013.

Changing How We Die

Over 110 years, medicine took huge strides to treat the major illnesses of the day.  A look at the major causes of death in the years 1900 and 2010 tell that story.

Infectious diseases ruled the world as the major cause of death.  But antibiotics and vaccinations have decreased there power.  Instead, we now live in a world with a long life span and abundant food.  The longer people the more that cancer and heart disease increase.  Even those numbers have changed.  There is a reason that medical forms ask if anyone in your family died of a heart attack before the age of 50.  Not much could be done in the 70's and 80's.  Now, people with heart disease live into their 70's and 80's.  Much work remains in treating cancers, but new treatments appear promising.

TED Talk Tuesday: Simon Sinek

Every level of education talks about leadership.  We talked about in high school sports and now again in the midst of pharmacy school.  There may be an intense debate between leadership and management, but the need for successful administrators remains high.  Simon Sinek is a management theorist and talked to TED - almost all leaders in their fields - about leadership.  The best leaders make us feel safe and make every individual feel as a part of the group and begins to work cooperatively.  I personally enjoyed the leadership style of Dean Smith who wrote very well about his process in The Carolina Way.  Good leaders care about the members of the group.  Sinek believes that if the members feel safe about their position in the group they will preform better.

PY1 Review - Physiology

Starting pharmacy school marked a major shift in my life.  No longer do I stand in front of the class talking about science and lighting things on fire.  Now I sit in the front row, taking notes and answering questions.  Before a couple years ago, pharmacy school was never an option that crossed my mind.  Not because I did not think that I could do it, but because I had never learned anything about it.  Teachers, counselors, nor professors ever presented pharmacy as a potential option.  I hope to change some of that.  Obviously, I am attempting to write on this website and twitter, but I also hope to talk to teachers and students about an exciting career path.

In attempt to help, I thought that I would review some of my experiences in the first year of pharmacy school.  My first topic will be Physiology.

Since I taught anatomy, I figured physiology would be one of my advantages this year.  But the way I taught the course was completely different from my first course.  In high school anatomy, most teachers begin with an overview of terms then on to cells, tissues, skin, bones, muscles, brain, endocrine, and whatever else can fit in before the final exam.  The pharmacy physiology class began with Cardiology.  It makes sense.  Heart attacks and congestive heart failure are among the biggest killers in the United States.  Next to pain, medicines to control blood pressure top the most prescribed and sold drugs each year.  HCTZ and other diuretics balance the accumulation of water while ACE inhibitors and statins affect the diameter of blood vessels.  Rather than primarily focusing on the structural anatomy, pharmacy physiology appropriately addresses the function of the body.

This particular course was set up differently from the others.  Before the unit, we read a document that reviewed the system and then took a quiz.  We answered the quiz questions individually and then as a group.  In the next class, the ever changing professors (clinicians in the specific field) taught through case studies.  Before exams, we faced cases that integrated several systems together.  Despite the strange course set up, I felt that I learned quite a lot.  My knowledge base as an anatomy teacher definitely helped, but would not have carried me through the course.  I really like learning anatomy through the lens of medications that alter or restore baselines.

For any teachers interested, I will list the order topics here.
Module 1 - Cardiology
Module 2 - Renal
Module 3 - Hematology
Module 4 - Gastrointestinal
Module 5 - Central Nervous System
Module 6 - Respiratory
Module 7 - Endocrine

Obviously, not much discussion about skin, bones and muscles.  Instead, the course featured the primary health care related systems.  Millions of people live on blood pressure medications and kidney problems drastically affect a patient's response to drugs.  How many people suffer from acid reflux or take mood stabilizing medications.  I like the idea of teaching the human body through clinical importance instead of easy memorization and textbook order.  If I had really thought about it when I was teaching, I would have strongly supported this curriculum.  Like 25% of the students take some sort of ADHD medication - Concerta, Adderall, Strattera.  Many kids suffer from asthma taking Proventil, Combivent, Advair.  Maybe more high school anatomy teachers can bring a clinical pharmacy perspective to the classroom.

The Daily Show on Vaccinations

After typing out the post about vaccines, I sat down to watch the Daily Show.  To my surprise, they tackled the exact same topic.  Their take was much more crass, but much funnier as well.

The Daily Show
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Measles On the Rise

Our greatest medical achievement is not open-heart surgery, not penicillin, but vaccination.  Everything else is a bandaid compared to the ability to actually prevent disease.  Smallpox ravaged communities until Edward Jenner developed a vaccine which has eradicated the disease and saved countless lives.  It became possible to immunize people from the deadliest pathogens on the planet.  Since that time, we can now prevent Small Pox, Chicken Pox, Tetnus, Diptheria, Whooping Cough, Pneumococcus, Hepatitis B, Measles, Mumps, Rubella, and even a vaccine against the cervical cancers caused by HPV.  Every year the number of deaths to preventable infectious diseases goes down.

Well, it did go down.  The CDC now reports that the number of cases of Measles has hit a 20 year high.  Ten years ago, measles was officially eradicated from the US (no transmission for 12 months).  Almost every case this year involves a person that was not vaccinated or without a vaccination history.  The same story happens for many of the diseases.  The high school I taught at was hit by Whooping Cough which is prevented by the P in the Tdap vaccination you should get every 10 years.  Thank fully the number of deaths stays low, because we do have the bandaids of modern medicine.  But eradicated diseases should not be making come backs.

I lay all of the blame on the Anti-Vax crowd.  Concerned that vaccinations, or the components within the vaccination, cause the cause of autism, Jenny McCarthy and others have led a crusade to scare people from vaccinating their children.  Somehow, it worked.  To some extent, their children are still protected from the worst diseases as smallpox and polio have been eradicated.  This is called herd immunity.  But some diseases still linger in the US from anti-vaxers and immigrants coming from places without vaccinations.  There is no evidence that vaccines cause autism.  None.  Well, there was one published paper, that the author had to retract as he admitted to cheating with the numbers.  So, we're back to none.

It is far better to prevent disease than to treat it.  From hand washing and sanitation, medical science finds ways to prevent diseases.  Vaccinations have been a successful part of that history.  More vaccines are introduced each year to prevent new diseases, to improve old vaccines, and to make administration easier without needles.  I know the anti-vaxers mean well, but they have been fed false information.  Which is the hardest kind to refute.