Showing posts with label Pharmacy. Show all posts
Showing posts with label Pharmacy. Show all posts

Wednesday, September 24, 2014

Compounding in Pharmacy School

One of the more stressful parts of Pharmacy School so far has been compounding.  Compounding prepares a specific product for a specific patient.  As opposed to manufacturing that provides a more generalized approach.  You can remove excipients that might cause allergic reactions or you can simply change one formulation for another.  A lot of this is done for pediatrics turning a large tablet into a liquid.  So far in three semesters, we have made creams, sticks, solutions, and suppositories.

The actual compounding can be fun.  Manipulating ingredients to help a patient.  The stress comes from rest of the process.  We have a quiz on the various formulations in the form of questions written by the man who wrote the textbook regarding compounding.  We must complete a compounding record that includes the manufacturer, lot number, and exact amounts of every ingredient.  We counsel our TA as if s/he were the patient, so we memorize the major counseling points.  And every product is tested to make sure it is within 10% for the stated strength.  If your products falls outside of 10%, you have to come back and remake it.  If you are too far outside, especially too high, you have "killed the patient" and receive a zero without the option to remake it.

But I learned last week that not every pharmacy student goes through this.  In fact, only half of the pharmacy schools do any compounding at all!!!  For some, compounding is little more than an elective course that students take for a semester.  Few compound as regularly as we do.  Of those, very few routinely test the products for accuracy.  And we seem to be the only school that tests every product that gets made.  That means that they just go through the motions and hope that the products are good.

Much of this comes from budgeting concerns.  Compounding is expensive.  I know.  I bought lab supplies for my classroom.  It's not easy.  Checking the products takes more money and time.  Things that can be rare in a pharmacy school.

But compounding is important.  A study randomly checked some compounded products from some pharmacies and found a wide range of accuracy, from drastically underdosing (essentially a placebo) to dramatically overdosing (more than 400%).   A lot of the range comes from technique.  We hear a lot about quantitative transfer.  We routinely make 10% extra product to account for loss.  But in all, compounding is an important skill.  A licensed pharmacist may never, ever compound during there career.  But all pharmacists should know how to do it.  It's like parallel parking.  I avoid parking that way, but to get my driver's license I had to display enough control of a car to complete the task.  Maybe compounding should become an essential part of a PharmD degree.

Thursday, September 4, 2014

Measuring Medicine

Just a spoonful of sugar can help the medicine go down.  But how much medicine are you taking.  Most of the time, that is an easy question.  The tablets come presized with 200 mg or 25 mg.  They might be scored for turning into half-sized tablets.  But what about liquids?  And more importantly, what about kids?

NPR published a story on the dangers of ineffective measurements.  Pediatric medicines require specific doses.  This is because kids come in all different sizes and side effects can cause serious problems.  But because kids don't like to swallow pills (even mixed up in apple sauce), many medicines are give as liquids.  Cough syrup, Tylenol, and Vancomycin all have versions as oral solutions.  So how much are you supposed to give the kid?  A teaspoon?  Tablespoon?  This can be a very important detail that leads to drastically different outcomes.  Studies show that neither teaspoon nor table spoon should be the best answer.  They are unreliable can mess up a child's therapy.

Instead, we turn to the more structured metric system.  You don't give the kid a teaspoon, but rather 5 mL.  You can give a syringe or graduated cylinder to help measure.  It's easier to measure, visualize and gives the right dose.  No matter what Mary Poppins says, the answer is not a spoonful.

Thursday, August 28, 2014

National Immunization Awareness Month

As August comes to a close, so does National Immunization Awareness Month.
Unfortunately, I was unaware that vaccines received a whole month of education until the last week.  One of our Pharmacy Organizations has us posting Immunization Facts each day on Facebook and/or Twitter.  I support it.  Mostly because I believe in the proper education of patients about vaccines.  But also because I am allowed to immunize people as a PharmD student - which will be doing either at the Student Union or hopefully at the NC State Fair!

I stand by my claim that vaccines are the most important breakthrough in medical history.  We can actually prevent disease by taking the buggers, stripping them of their nastiness, and putting into a person.  Then the patient's own immune system can develop the defenses to fight off any attacks.  We have eradicated polio and small pox and made it so people don't die from the common infectious diseases of our past.  If you don't care about that, realize that kids don't have to get chicken pox anymore!  There a lots of other facts swarming Facebook, like Women should get a flu shots and a Tdap while pregnant to protect their babies.  If you want anymore factual information about vaccinations go to this CDC site.  It is a great resource.

Sadly there is still a thread of people who became convinced that vaccines give children autism.  There are even some Facebook threads spreading their "information" as well during NIAM.  Thankfully, Penn and Teller devoted an entire show to proving why their claims are "Bullsh!t".

Please go out and get vaccinated and help teach others about immunizations.

Wednesday, August 27, 2014

How Are You Still Alive?

The Universe is conspiring to kill you.  You body is under constant attack.  But most days, you don't die.  You don't even get sick.  This is thanks to your enormously complex immune system.  Full of B cells, T cells and antibodies, your immune system fights off invading armies of bacteria and viruses.

This video by Kurzgesagt explains the basics of keeping you alive.  I could have used this during PY1.

Monday, August 18, 2014

Your Skin Through UV

In our therapy class, we are talking about dermatology.  Our first SOAP note, due Wednesday, is about skin care and sunburns.  Most of the damage caused to our skin comes from Ultraviolet Radiation.  UV rays come in three flavors - UVA (aging), UVB (burning), and UVC (blocked by ozone layer).  To protect yourself from burning, aging, and potential skin cancer, everyone should use sunscreen.  The fairer your skin, the higher the Sunburn Protection Factor (SPF) should be.

The video below will show you why.  We have ultraviolet cameras now which can show you what your skin actually looks like.  Thomas Leverit took a UV camera into a park to show people their skin.  The more freckles that appear the more damage had been done.  Look at the kid's skin compared to everyone else.  BUT most importantly, stay until the end and see the effect of sunscreen on the camera.  You will not be disappointed.

Friday, August 8, 2014

Last Day of Summer

My summer break has reached its final day.  This weekend I go to work at the Hospital before a CAPS meeting on Monday and the first day of classes on Tuesday.  Surprisingly, I accomplished a lot during this unexpected break.  The plan was to work at the hospital during the weekdays during the months of June and July, but too many new full time technicians were starting that they moved me to my weekend schedule.  That meant a lot of free time for the entirety of July.

Chivalry returned to BBC America on Sunday Nights
I know that I shouldn't complain, but I was worried that I would go a little crazy.  Usually my summers are filled with football practices and planning for the next year.  Not anymore.  I have no control over the requirements for this year.   I really did not want to revert to a month of TV watching, so I turned to more constructive ideas.  The closet under the stairs got shelves for better organization.  The guest bathroom was quarterrounded and the master bathroom received two shelves in a completed wasted space.  Our screened in porch now has carpet and a dinner table.  The cats litter box was concealed inside a table looking box.  I also kept the house very clean - which I think my wife will miss the most.

There was some TV watching though - Under the Dome, The Musketeers, Orange is the New Black,
and the World Cup.  I went to seen Dawn of the Planet of the Apes and read The Patriot Games and Allegiant.  The Hobbit was on HBO yesterday.  While I did a lot of work, I did get plenty of relaxation in.  Of course some relaxation isn't so relaxing.  I took the dogs on a lot of walks and Charlie, the black lab, pulls incessantly.  I tried to train them without going to someone.  It helped a little, but he can still be annoying.  Running also fits into the relaxing but not so much category.

But all that is behind me now.  It might have been better not to have worked at the hospital so I could get more done at home.  Then again, I could have used the experience.  Next Tuesday begins Pharmaceutical Year #2.  I met several PY1s at the social led by CAPS leaders at McAllister's.  The all seemed excited about starting their journey, like I was last year.  While I began the semester with a combination eagerness, anxiety and worry that I made a life-altering mistake for my family, PY2 begins with confidence and yet more excitement.  They say PY2 is the hardest year of pharmacy school - tons of material and an exam every week.  Clearly they weren't a high school football coach with an "exam" every week.  I am not worried about this semester, but I might feel differently in a month.  We do have a quiz on the first day of lab and an assignment has already been completed.  Before I know it, it will be December.  I will try to keep writing throughout the semester but I might miss a day here or there.  I should have plenty of material for a weekly update on PY2.  Here is a look at our classes for the Fall Semester:

  1. Drug Literature
  2. Medicinal Chemistry
  3. Pharmacokinetics
  4. Pharmacotherapy - GI, Respiratory, Dermatology
  5. Pharmaceutical Care Lab #3

Thursday, August 7, 2014

Getting a Cavity Filled

Anesthetic injection to the Trigeminal Nerve
So, I had to get a cavity filled yesterday.  Not too much fun, but I did figure out that I can learn from it.  If I asked you what drug they give you to numb you up, I am sure that you would all know the answer - Novocaine.  Right?  Nope.  Apparently, dentists have not used Novocaine for about 30 years.  The answer that we all seem to know is wrong.  Novocaine is the brand name for procaine a synthetic cocaine from 100 years ago.  Unfortunately, a lot of people had allergic reactions to the drug and dentists search for a new choice.

This post started because I asked the technician what the drug was that I would be injected with.  Of course, I then told her that I was in pharmacy school.  I have learned that whenever a nurse or technician learns that you are in pharmacy school, the very next thing they will say is how much they hated their pharmacology class.  Every time, guaranteed.  Moving on.

Articaine - Dental Amide
The dental assistant said that it wasn't novocaine but instead Sceptocaine.  Unfamiliar with the name, I figured it was just a specific brand of Novocaine (which I later learned is itself a brand name).  Sceptocaine is a combination of 4% articaine and 1:100,000 epinephrine that was approved by the FDA in 2000.  For the nerve block to perform a tooth filling, the dentist injects 0.5 to 3.4 mL under the mucous in the back of your mouth near the trigeminal nerve.  The articaine blocks our pain receptors by altering the action potential threshold for the nerves in the area.  A much greater stimulus is needed for a response, which doesn't come.  The epinephrine constricts the surrounding blood vessels to prevent the absorption of articaine into the blood stream and keeps the tissue concentration high.

There aren't a lot of problems with articaine, but allergies to sulfites can be an issue.  This is only for submucousal injects as accidental intravenous injection could lead to serious problems.  As the dentist tells you, you will lose all sensation in the area for several hours.  It will come back.  It took over four hours before I regained all my senses in the area.  The dentist also tells you not to eat anything while drug is working because you might bite your lip, check or tongue.   So when you go to get that next cavity filled, remember that you are not getting Novocaine anymore.  Dentists now give articaine in the form of Sceptocaine or Orabloc.

Thursday, July 31, 2014

Saving Money at the Drug Store

Looking for a simple way to save some money.  Stop buying brand name drugs.  The generic versions required by law to be identical to the more famous names.  Why spend extra money just on a name?  Hospitals save money by only providing generics, unless they have to.  Medicaid and Medicare save money by requiring generics if possible. If they can do it, so can you.  This is a not-so-secret strategy employed by doctors, pharmacists and nurses when they go to the drug store.

Let's look at an example from the Walgreen's website.  Pain is the number one reason people buy medicines.  They head to Walgreen's for some Advil.  You can buy a bottle of 200 Advil tablets for $15.99.  That comes out to about 8 cents per tablet.  Not a bad price if you think about it.

But Advil is just the brand name that Pfizer gives to the drug ibuprofen.  The pain reliever and fever reducer was developed in 1961 as an alternative to aspirin.  McNeil Consumer Healthcare also produces a version of ibuprofen known as Motrin.  All three names work the same, because all three are the same thing - ibuprofen.  As a non-steroidal anti-inflammatory drug (NSAID), ibuprofen interrupts the inflammation process (by blocking the COX enzyme) which reduces swelling and pain.  Any tablet that contains ibuprofen works exactly the same way.

So let's head back to the pain aisle of Walgreens.  They sell a bottle of Walgreen's ibuprofen in the generic form as well.  It's the same thing and works the same way, so how much.  A bottle of 1000 generic tablets costs $19.99 or 2 cents per tablet.  Advil (8 cents) is literally 4x more expensive that a product that does the exact same thing.  So why do people by the Advil instead of generic ibuprofen?  Mostly advertising and not understanding drug names.  I think there maybe some kind of placebo effect as well.  If I pay more for this name brand it should work better.  But it doesn't and Pfizer counts on the majority of people not to know such things.

This can save you a lot of money in the long run.  Assume you took 12 ibuprofen everyday for one year- which you shouldn't because you will probably end up with an ulcer.  Buying Advil will cost you $350 over that year.  The generic tables will come to an astounding total of $88.  It really adds up fast.  So save some money, buy generics!

Wednesday, July 9, 2014

IPPE Yippies

During the entire month of May, I interned at the University of North Carolina Hospital.  The coveted Chapel Hill placement gave me a ton of opportunities that other PY1s may not have experienced.  The first thing you need to know is that UNC Health Care is huge.  The campus covers the entirety of South Campus and houses the Memorial Hospital, Children's Hospital, Women's Hospital, Neurosciences and Cancer Center.  There are three amazing places to eat and the world's largest Starbucks (24/7 and a 20% discount).

My internship was called the Introductory Pharmacy Practice Experience (IPPE).  Working with a preceptor, we are expected to learn the ins and outs of being a hospital pharmacist.  Almost every other pharmacy school sends their first year students into the community first, but we do things a bit differently.  You definitely start off feeling out of place on a content level and lost on a physical level.  My goal at the beginning was simple - find out if there was any area of hospital pharmacy that I could not see myself doing.  In the end, I felt comfortable throughout and could not find anything to mark off the list of possible future careers.

I and my 14 fellow IPPEs experienced many different areas of hospital pharmacy during our rotation in May.  I feel that we probably received a broader education than IPPEs that went off to other hospitals, especially the smaller ones.  While spending more than one day in an area would give depth to the experience, I would not trade the breadth.  I will be writing about each of the different areas that we went in much more detail throughout the month.  I have a lot to say about each of them and maybe they help some other people.

One major difference to mention now would be the set up.  Instead of a single pharmacist in charge of us, UNC delegates the IPPE education to two outgoing PGY2-Administration residents.  The Pharmacy Administration Residency is a two year program and they do a lot regarding management and leadership.  As a former coach, I have great respect for those particular aspects of the pharmacy world.  Our 15 students were divided into two groups for a challenge to have a pizza lunch with the Director of Pharmacy at the hospital.  My team, the IPPE Yippies, took on the Conformational Floppies through several tasks.

  1. We wrote on Wiki site through the School of Pharmacy about pretty much anything.  Whoever wrote the most received the most points for their team.  I hadn't planned on doing, but a another student pounced on it early.  I soon made my goal to catch her, but she had such a huge lead that I could only achieve second place.  
  2. One day we debated the merits of the 340B program that UNC Hospitals use for cheaper medications.  Our team won that by having the pro-340B side with all of the judges being hospital pharmacy residents.  I will write more about 340B later.
  3. We wrote SBAR memos to the director to make suggestions about improving the hospital.  SBAR is a common method of communication in the hospital to deliver ideas or information quickly and efficiently.  The Conformational Floppies dominated us in this one.  They wrote 7 suggestions while my team only wrote 3 (and I had 2 of them).  At this point, it did not seem like my team was interested in winning the competition.
  4. Finally, we mapped out the flow of medication through the hospital from order, verification, dispensation and administration.  Each team had to make one in a group effort to understand the hospital.  The Conformational Floppies apparently met for several hours on a Sunday to do theirs.  The IPPE Yippies put it off until the last second.  I tried to organize a lunch meeting to work on it, but it was a no go.  We really did not want to win apparently.  On the last day, we knew that we had to turn something in, so someone put it together quickly.  We looked it over on Google Docs and submitted it with no color and very little effort.  Whichever team won the map would win for the month.  
By a vote of 2-1, the IPPE Yippies prepared the most accurate medication map for the hospital.  Theirs was prettier, but ours was better.  You could say that we were shocked at the announcement.  We did not expect to win, nor did we really try.  Oops.  In the end, I suggested that everyone should be invited to the lunch with the Director.  And on the last day, after evaluations, we ate pizza and said our anticlimactic goodbyes for the rest of the summer.  It was weird leaving the hospital that last day.  Our badges had been taken and we had nothing left to do.  Classes wouldn't start for 2 months and all the stress and anxiety of our first pharmacy rotation had come to an end.  I am grateful for the opportunity to experience each of the areas at the UNC Hospital.  I have much more to say about everything that happened for my own reflection and for those interested as well.

Monday, July 7, 2014

Hobby Lobby and the Supreme Court Misjudge Emergency Contraceptives

This past week, the US Supreme Court decided that "closely held" companies can opt out of covering particular forms of birth control for their employee insurance based on a "sincere" religious objection.  The sincerely-religious owners of Hobby Lobby objected to the Obamacare requirement of insurance plans to cover birth control for their employees.  To be fair, they did not object to all forms of birth control, just the ones that they felt were the same as causing abortions.  Unfortunately, many people continue to believe that the morning after pill, emergency contraceptive, Plan B, or levonorgestrel is an abortion-causing pill.  The ruling also applied to Inter-Uterine Devices (IUDs) for the same reason.

One problem - these pills do not cause abortions.  An abortion refers to the medical termination of a pregnancy.  Levonorgestrel and IUDs prevent a pregnancy from occurring in the first place.  Thus preventing the potential for an employee to seek an abortion due to an unwanted pregnancy.  Hobby Lobby, and the other conservative companies that will soon be refusing to pay of emergency contraceptives, do provide health insurance plans that cover most of the other forms of oral contraception.  Normal contraceptives must be taken daily and generally at the same time everyday.  Missing a dose can prevent the hormonal control "the pill" is attempting to maintain.  This is were Plan B comes in.  If a woman forgets to take her normal birth control pill, levonorgestrel can help.  And a lot of people forget to take their pills.

So how does Plan B work?  Levonorgestrel is a synthetic version of progestin.  Progestin prevents ovulation.  Pregnancy actually only occurs during a very small window of about 4 or 5 days, sort of.  The sperm can survive for a while waiting for an egg to be released, but the egg lasts for less than a day.  Oral contraceptives prevent the release on an egg over the course of the month.  An emergency contraceptive like levonorgestrel serves as a surge of progestin than prevents ovulation about 72 hours.  To work best, Plan B should be taken as soon as possible after unprotected sex, but it doesn't always work.  Levonorgestrel does not work after ovulation.  So if the egg is out, pregnancy is possible whether you take the pill or not.  If fertilization has already occurred, levonorgestrel will not help either.  Some thought that it could prevent implantation of a fertilized egg, but no evidence supports that mechanism of action.  And one thing that it definitely does not do is terminate a pregnancy.

So here's where I am concerned about the Hobby Lobby ruling.  Forcing employers to cover abortions is controversial, so I am okay with taking that out as a compromise.  But allowing them to object to certain forms of birth control because they believe that they cause an abortion is wrong.  Plan B does not cause abortions (period).  We study the mechanism of action.  We know how it works.  It prevents pregnancy.  This is not about a belief system.  This is an education problem.  They can believe that it causes an abortion, but they are flat out wrong.

Friday, July 4, 2014

John Oliver Takes Down Dr. Oz

Corespondent John Oliver left the Daily Show for his own show on HBO called Last Week Tonight.  On the episode from June 22nd, Oliver went after Dr. Oz who had appeared before Congress the previous week.  Dr. Oz has made a ton of money teaching people to be healthy.  He wrote You - The Owners Manuel and has a daily television show.  On that show he often promotes products to help you lose weight.  More recently, Oz hawked Green Coffee Extract to shed pounds describing the product a a magic cure.  Under oath, Oz admitted that there is no such thing as a magic cure, despite his use of the phrase over and over again.

The real problem is nutritional supplements that suggest they offer cures for numerous maladies.  Dr. Oz got caught filling time with hype and taking money from a $32-billion business.  FDA has very little control over nutritional supplements despite their label as "food".  Some products are no better than placebos and some cause health problems rather than cure them.  When the FDA sought to establish control over the market, the supplement lobby responded to squashed such laws by scaring the public and buying congressmen.

John Oliver details the long story of fake cures and FDA oversight in this excellent commentary.  It goes a little off the rails at the end, but he is a comedian.  Enjoy.

Wednesday, July 2, 2014

Self-Care - Vitamin C

In first semester lab, each group of 3-4 students delivered a 20 minute presentation on an herbal remedy.  Self-care refers to the items that customers by at the front of the store and routinely forget to inform their doctors and pharmacists about.  Herbal supplements are big business making huge profits as a trendy alternative to a prescription without the risky part of actually testing the product through clinical trials.  Labeled as dietary supplements, herbals do not have to actually provide data about whether or not the product works.  Then again, they cannot say that the product does work either.  A lot of these products rely on anecdotal evidence and the mythos of ancient, traditional or alternative medicine.

To be fair some of the products worked.  A little.  Most were inconclusive.  And one big one - St. John's Wort - interacts with almost every pharmaceutical drug out there and can be dangerous in combinations.  My group's topic was no different.  We had Vitamin C.
Molecular structure of
Vitamin C (ascorbic acid)

Vitamin C, you know, occurs naturally in citrus fruits.  Our body needs it and a lack of the vitamin results in Scurvy.  Sailors and pirates would return from see emaciated and losing their teeth.  It was determined that they lacked Vitamin C and prescribed oranges, lemons and limes.  Vitamin C works great as a treatment for scurvy.  But the makers of EmergenC are targeting sailors.  Rather, they trick people into thinking that large amounts of Vitamin C could prevent the common cold.  They even had a two-time Nobel laureate on their side.  Linus Pauling loved Vitamin C taking over a 1000 mg a day or about 1667% greater than the recommended allowance.  He claimed it kept him from getting sick, even when he obviously suffered from a cold.  Later he claimed that it prevented cancer, even though he and his wife both died of cancer.  In short the Pauling promotion of Vitamin C lingers into confusion today.  Despite the assertions of the eminent scientist, no evidence ever supported him.  

In our group, I landed the introductory role.  My job was to get everything started and get people interested.  I only presented the first five slides, but I researched and wrote one of the slides at the end (about the Cochrane Review).  While I am posting this on here, I do not want to take credit on the interwebs for the entire project.  Vitamin C deeply interested me and I enjoyed the history of this great confusion.  My group did a great job and they should receive the credit they deserve.

Wednesday, June 25, 2014

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.

Thursday, June 19, 2014

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.

Tuesday, June 17, 2014

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.

Thursday, June 12, 2014

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 9th 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.

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.

Monday, June 9, 2014

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.