The End...?

I am not certain of the final day for the internship. Needless to say I am now in the last week or so of actual time. My vote is to end fairly soon. I will be traveling out of town in about a week's time - I will be going to Japan of all places - so I won't really be focusing on the internship during that time. If it continues, the 3 weeks that I am gone is going to make for a lot of lost time.
I do still have fliers that I didn't hand out though, I keep thinking that I am going to hit the neighbors up one of these afternoons when I find myself with time to work on this thing.

I honestly don't know what to say this week. I find myself wishing that I had saved some sort of, 'best for last' type of thing. Honestly I was giving all I had during the length of the internship itself, so I don't have much left.
It is not as though there are no more meds to discuss; but most of my focus is now centered on doing the final analysis. All of the information might be interesting, but without a summary statement of some kind...all other effort would be sort of lacking.

This week I am going to skip doing a feature. Until I get an email telling me when the program is going to officially be over this could very well be my last post.
Over the last 4 months I have noticed several things; in previous posts I have made brief mention of some of these things, but I think now would be a good time to list them in greater detail. Also, doing this will help me to write out some ideas for a final analysis.

After all of the research and work I have put into this the most I think I have learned is about people. There is so much of social construct in what we do. Whenever I approached someone about their medications they were quick to inform me that they did not take medications, or drugs, of any kind and they tried to be as natural and healthy as possible. That is what prompted me to make the paper surveys in boring old OTC medications, because then I could talk people into doing surveys. There is not a single person from the western world who has never taken an over-the-counter anti-inflammatory drug; I am sorry, but to say you have never taken Tylenol or Ibuprofen ever is just laughable. We even have a version that is made for kids that they can chew and is supposed to have a bubble gum flavor or something.
The other thing that is funny is this idea that somehow introducing a 'foreign substance' like Tylenol into your body is a bad thing. Yet another thing that seems to have happened to us in the western world is this idea that older cultures somehow knew what they were doing and we are just a bunch of fools putting toxic things into ourselves. Not all natural things are good; if the body were left to it's own devices - as it often was in older times - to sort out a fever or broken bone etc. then the person either didn't live long, or walked with a limp and so on. One of the ancient codes of law known as Hammurabi's Code talks about there being a punishment affixed for botched surgery, and it affixes the payment. There are futher instances of surgical codes, but I have chosen to quote the two that are most relevant to our discussion.

If a surgeon has operated with the bronze lancet on a patrician for a serious injury, and has cured him, or has removed with a bronze lancet a cataract for a patrician, and has cured his eye, he shall take ten shekels of silver.

If a surgeon has operated with the bronze lancet on a patrician for a serious injury, and has caused death, or has removed a cataract for a patrician, with the bronze lancet, and has made him lose his eye, his hands shall be cut off. (http://www.commonlaw.com/Hammurabi.html)

If the age of something makes it better or more 'natural' then why are we currently using surgical stainless steel in place of bronze lancets?

I have also learned that there is no pharmaceutical treatment of the hydrochephalic child. That seems a shame to me. There are treatments for adults, but not children. In one of my earliest blog posts I mentioned a drug called Diamox which is being used for treatments of this kind, and may one day be used for treatments for children as well. More research is needed before any solid answers can be given. I have been thinking about this for a long time now, over the course of this internship all the way back to when I had occasion to speak with a man who is doing research on hydrocephalic rats - who happens to be a good friend of one of our neurosurgeons. This researcher talked about there being possibilities for pharmaceutical interventions, but also told us that the medications have been known to turn the patients' teeth yellow so they would not be considered in pediatric populations (I ask you, what is better? To have to have a shunt and potential revisions and ALL of the complications that go with that, or to have yellow teeth? Seems a no-brainer, in my opinion).

Though, despite all of these concerns and complaints I am better off for having this experience. I find that there are ideas rattling around my brain in relation to what I should write my final analysis on, but when I see the raw data I think I will have things narrowed down considerably.

Until I know the nature of things better, these are my thoughts today, I will hopefully post at least one more time, but who knows?

Continuity

If you are reading this for the first time, and you got a card in your door, then you have come here for more information. My last post talked about that stuff too, but I figured maybe some people were still checking this place out to know what exactly is going on. If you would be so kind please look at the top banner. I have taken the liberty of explaining the basics of my blog and internship there as well as some basic instructions as to how to fill out surveys and give me credit. If you have further questions please give me an email at tristanbennett@radpprep.com and I will get back to you as soon as I can.
If you are interested in learning more about my personal work then read on good friend! And don't forget to post comments on what you have found.

This is to be the day when I continue all of my old posts. After searching for some time I found that I really only had one that I had not finished completely; my post of Fosphenytoin. I feel as though I did a thorough job of explaining the med - at least as far as the confines of this blog go - but I did not do a good job of explaining possible side effects.
Discussion of side-effects seems somewhat relevant to me right now because I spent most of my day on Thursday keeping an eye on a patient who had come into the ED (Emergency Department) for a 3+ hour long seizure.
I am not certain about this, but would be rather surprised if the patient was not given Fosphenytoin in an attempt to stop the seizure and restore normal function as quickly as possible. I had to sit with this patient as a consequence of being so loaded up with anti-seizure medication that they did not no what they were doing most of the time and needed someone to make sure the didn't hurt themselves.
The chart that I posted in the original Fosphenytoin post that compared seizure length to mortality rate should be a compelling enough reason for my thought-process.

Without further ado, the 'Drug of the Week' feature is (drum-roll please): FOSPHENYTOIN - PART 2!

As I have already discussed the basics of this med and shown the organic molecule, I will skip right to the continuation.
I did not give adequate time to side-effects. In fact, not much time has been spent talking about the secondary effects of the meds that have been featured. However - especially due to my experience this last week at the hospital, and the fact that I MUST finish the 'to be contined...' - I will now give a description of Fosphenytoins side effects.
This link: http://version2-6.blogspot.com/2009/05/well-we-are-nearing-end-of-our-journey.html will put you at the original post so that any questions as to the mechanism and etc. will be answered. I won't re-post it because of length, time and laziness.

Like all medicines Fosphenytoin has both common and uncommon side effects (actually it is quite funny to list off the less-common side effects to someone who is taking that medicine; they kind of freak out now that they know all of the things that 'could go wrong' but most likely will not). Common side-effects of Fosphenytoin are: confusion, dizziness, drowsiness, vomiting, nausea. The less common list is a bit longer, so I am going to block quote it:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal muscle movements; back and forth eye movements; blurred or double vision; chest pain; clumsiness or unsteadiness; fever or sore throat; irregular heartbeat; joint pain; pain, swelling, or tenderness of the lymph nodes; rash; severe burning, itching, or numbness of the skin; severe stomach pain; shaky movements; slurred speech; staggering walk; swollen or tender gums; unusual bruising or bleeding; yellowing of the skin or eyes.
(http://www.drugs.com/sfx/fosphenytoin-side-effects.html)

www.rateadrug.com (this link will send you straight to the survey for Fosphenytoin Sodium if you doubt that www.rateadrug.com has a more extensive list) has a good list of side-effects associated with all meds. They list the common and less-common side-effects of Fosphenytoin as being: abdominal cramping, allergic reaction, anemia, blurred-vision, coordination/ balance problems, depression, concentration/ focus problems and lastly: diziness, drowsiness, fatigue and nausea. The less common side effects are as follows: mood swings, apathy/ indifference, hair growth, sore/ swollen gums, impaired thinking/ judgment, lethargy, osteoporosis/ loss of bone mass, infection, liver failure, skin rash, fever, aplastic anemia, bleeding, blistering, decrease in platlet count, decrease in white blood cell count, sore, thinning/ loss of hair, liver damage, mouth sores and pancreas problems.
If I was on a med and knew all of that stuff could go wrong, I might kind of freak out too.

http://www.drugs.com/sfx/fosphenytoin-side-effects.html has some statistics that help explain what percentage of people experience side-effects; and what percentage of the time that they experience them. I am trying to get some interviews at local neurological clinics so I can get some serious survey work and questions answered about side effects and etc. The information is found on two different tables.

TABLE 2. Treatment-Emergent Adverse Event Incidence Following IV Administration at the Maximum Dose and Rate to Patients With Epilepsy or Neurosurgical Patients

(Events in at Least 2% of Patients Treated with Fosphenytoin Sodium Injection, USP)
BODY SYSTEM Adverse Event	IV Fosphenytoin Sodium Injection, USP N = 90	IV Phenytoin N = 22
BODY AS A WHOLE
Pelvic Pain	4.4	0.0
Asthenia	2.2	0.0
Back Pain	2.2	0.0
Headache	2.2	4.5
CARDIOVASCULAR
Hypotension	7.7	9.1
Vasodilatation	5.6	4.5
Tachycardia	2.2	0.0
DIGESTIVE
Nausea	8.9	13.6
Tongue Disorder	4.4	0.0
Dry Mouth	4.4	4.5
Vomiting	2.2	9.1
NERVOUS
Nystagmus	44.4	59.1
Dizziness	31.1	27.3
Somnolence	20.0	27.3
Ataxia	11.1	18.2
Stupor	7.7	4.5
Incoordination	4.4	4.5
Paresthesia	4.4	0.0
Extrapyramidal Syndrome	4.4	0.0
Tremor	3.3	9.1
Agitation	3.3	0.0
Hypesthesia	2.2	9.1
Dysarthria	2.2	0.0
Vertigo	2.2	0.0
Brain Edema	2.2	4.5
SKIN AND APPENDAGES
Pruritus	48.9	4.5
SPECIAL SENSES
Tinnitus	8.9	9.1
Diplopia	3.3	0.0
Taste Perversion	3.3	0.0
Amblyopia	2.2	9.1
Deafness	2.2	0.0

TABLE 3. Treatment-Emergent Adverse Event Incidence Following Substitution of IM Fosphenytoin Sodium Injection, USP for Oral Dilantin in Patients With Epilepsy

(Events in at Least 2% of Patients Treated with Fosphenytoin Sodium Injection, USP)
BODY SYSTEM Adverse Event	IM Fosphenytoin Sodium Injection, USP N = 179	Oral Dilantin N = 61
BODY AS A WHOLE
Headache	8.9	4.9
Asthenia	3.9	3.3
Accidental Injury	3.4	6.6
DIGESTIVE
Nausea	4.5	0.0
Vomiting	2.8	0.0
HEMATOLOGIC AND LYMPHATIC
Ecchymosis	7.3	4.9
NERVOUS
Nystagmus	15.1	8.2
Tremor	9.5	13.1
Ataxia	8.4	8.2
Incoordination	7.8	4.9
Somnolence	6.7	9.8
Dizziness	5.0	3.3
Paresthesia	3.9	3.3
Reflexes Decreased	2.8	4.9
SKIN AND APPENDAGES
Pruritus	2.8	0.0

As you can no doubt see this table has the side-effect and the body system seperated into different categories. Fosphenytoin - like all drugs - has different effects on different parts of the body. http://www.drugs.com/sfx/fosphenytoin-side-effects.html#system_7389 explains the commonly associated side effects and the relevant body systems in more detail. I was going to write the information as part of this post, but decided it might be a bit redundant with the two tables explaining the information already.

All medicines have side-effects. It is impossible to introduce a foreign body into the human anatomy and not have it cause several different consequences. Generally the medicines that we commonly use or have prescribed to us are those that have been found to be safe. There are of course the extreme examples. The television screen often blares messages about users of medications and the latest class-action lawsuit taking place against the makers thereof (don't even get me started on tort law and the necessary reforms).
Clinical trials and studies have been done and done and redone to find out the long and short term effects on medicines. Those studies are effective, interesting and helpful. However, they are under controlled circumstances that do not always catch all problems. Thus, www.rateadrug.com has come along. Now there is a database where people can check on their meds or see what others have to say about them.
Drug surveys for the drug user is what I always say.

Be sure to tune in next time, as we are nearing the end of our run, as I discuss yet another interesting and compelling medication!
Until then faithful readers!

For more info.

Hello,
My name is Tristan Bennett and I am a premed student at the University of Utah. If you are checking this out then you should have recieved a flier on your door talking about www.rateadrug.com telling you to do some surveys and check out this blog for more info, but no matter all are welcome!
Surveys range from anything you have ever taken - you can do as many as you like - and from hard prescription stuff to over-the-counter supplements.

If you choose to do a survey please go to www.rateadrug.com, type in the name of the medication you want to survey, click the link that says 'take the survey' and fill it out. If you are not comfortable entering your personal email you can enter tristanbennett@radpprep.com; that is my email and will work just fine.
At the end of the survey - after you have pressed submit for the first time - the survey will ask how you heard about www.rateadrug.com; please enter premedprogram/TB927 in the two drop down menus so I can get credit for having talked to you.

Thanks for your interest! Be sure to read other posts on this blog so you can see more about what we are all about; and post comments about your thoughts and questions!
Tristan

Free squishy brain

I want to begin this blog with whining a little. I should not do that though as I am doing quite well, at least that is what Cathleen - the person in charge of answering my silly questions and keeping me motivated - keeps telling me. I am just sort of frustrated because one of the doctors I attempted to speak to is not interested in working with www.rateadrug.com. To be honest I don't think the guy even looked at the materials that I dropped off for him, but I guess it doesn't really matter. Above all I wish I could have gotten some feedback so I would know what to do to alter my approach when speaking to other physicians.

Instead of complaining, though, I will choose to focus on happier things. I am nearing the end of the 'Drug of the Week' features. That will be a sad day. It has been cool to learn things on my own about the medications that surround me daily.

There are, of course, cool things that are going on in the hospital. The unit I work with is going to be allowed to use ICP monitors soon - I actually got a free promotional squish brain as part of the training. Discussion of ICP monitors is outside of the scope of this blog, but if you are interested in learing more, click the spot I linked and click on the picture, it gives a basic definition. That will be kind of cool to have those around, before only the PICU (Pediatric Intensive Care Unit) was allowed to take care of those patients. We are getting them now on sort of a trial period.

Anyway, the squishy brain got me thinking about promotional stuff. I see a lot of promotional stuff working in a hospital - duh - but one thing I hear about a lot intrigues me, it is a medication called Keppra.
As far as I know Keppra is another anti-seizure medication.
However, this is the point of this blog! To learn more about medications and drugs that surround us daily! Let's learn together shall we?

Here is Keppra as an organic molecule:



And here is a space filling molecule:

Both images tell us the same thing, but I like the pretty colored one.
Keppra's brand-x name is: Levetiracetam, but I usually know stuff by the brand name, so that is what we are going to call it.

KEPPRA is an antiepileptic drug available as 250 mg (blue), 500 mg (yellow), 750 mg (orange), and 1000 mg (white) tablets and as a clear, colorless, grape-flavored liquid (100 mg/mL) for oral administration.
(http://www.rxlist.com/keppra-drug.htm)

Keppra is used in the treatment of different types of seizures based upon the age of the patient. The types of seizures include: Tonic-clonic, parital onset, and myoclonic. This page has a great deal more information, including charts that relate the side-effects and the dosages. I have tried to get a picture posted here, but I can't seem to find the link. So, here is the link for the webpage for those of you who are interested in learning more.

I like pictures, in case you can't tell, so here are some more pictures!
These pictures are actually rather compelling, they show the efficacy rates of several different AEDs medications or anti-epileptic drugs:
Due to the fact that there is no way to illustrate the effectiveness of one AED medication over another, basically some statistical math was used to show the rate at which one medication would cause a 50% reduction in seizure activity versus a placebo.
(http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=epi&part=ch12)

Keppra works according to this model:
The Keppra molecule can be seen binding to the SV2A synaptic vesicle site (I got this image from a webpage that discussed how an AED medication can be used as a mood stabilizing agent, which shows that Keppra is not just a one-trick pony).
The Keppra molecule is the one that looks like this:






The shortest definition I could find to explain just what the SV2A vesicle protein site is is this defintion:

SV2, an integral membrane protein present on all synaptic vesicles, is a small gene family consisting of three isoforms, designated SV2A, SV2B, and SV2C. SV2A is the most widely distributed isoform, being nearly ubiquitous in the CNS, as well as being present in endocrine cells
(http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=470764)

Further reading from this page demonstrates that the exact mechanism of Keppra is under investigation, but that the protein binding of SV2A is involved and will most likely lead to further understanding of seizures via pre-synaptic response.

I am always amazed when I come across a medication where the exact mechanism is not known. I am also amazed when I come across a medication where they DO know the exact mechanism. Some of the science and study involved in this stuff is so detailed and minute that it is mind-blowing.
Medicinal chemistry would be kind of cool, but there are so many years of finding and fixing nothing for that one second of discovery. Tedious work if you ask me.

That concludes our discussion of Keppra. Be sure to tune in next time as I attempt to explain and make good on all of my 'to be continued...' posts from this internship. You don't wanna miss it!

Shaken not stirred

Well, we are nearing the end of our journey. I feel as though I have made good progress. I should be somewhere near 180 surveys (I have some paper surveys that I still need to enter from the last week). In the next 3 weeks I hope to not only hit the required 200 surveys, but to surpass it.

This has been a good experience. I feel like I know much more about the medications that I am constantly around, and I feel like I have gained a lot of insight into research in general. I am glad I got to do this thing.

As far as the matter of 'Drug of the Week' features go there has been some straying off the chosen topic. Mostly because of things I have wanted to learn more about that were issues that I was personally dealing with or issues that the world at large was dealing with (see last weeks post about Tamiflu and the Swine Flu Virus). We will, however, be getting back on schedule. Especially because I have had occasion to speak with a large amount of Neurologists in the last week trying to get their support so that I can get some more information about anti-epilepsy medications.

With this in mind I am going to post today on a med that is relative new to me: Fosphenytoin. The brand name of this drug is Cerebyx, but we will just call it Fosphenytoin.
So - drum roll please - let us begin with...! THE ORGANIC MOLECULE!
And, here is the 3D model. The 3D model doesn't really help us understand anything about the drug itself; it just looks cool.
'The colors children! The colors!'

Fosphenytoin was approved by the FDA for use in treating epilepsy on August 5, 1996.
Fosphenytoin is used for treating certain types of seizures ie: status epilepticus (I have often heard this term at the hospital when referring to children who have come out of a seizure but are still a little loopy. Basically after a major seizure the brain needs time to sort itself out. That time varies depending on the length of the seizure, a lot of children just fall asleep after a prolonged seizure due the exertion on their bodies)

According to the Epilepsy Foundation Status Epilepticus referrs to any seizure activity that lasts longer than 30 minutes. Other defintions exist, but that was the most succint I could find. Typically neurologists at work have a standing order to be paged when seizure activity lasts longer than 5 minutes and to administer Atavan (It is easiest to think of Atavan as like mega Valium, it mellows you out in a hurry. I will probably post on Atavan in the next few 'DotW' features).
This graph illustrates the damaging effects of continued Status Epilepticus activity. After viewing this graph it is not hard to see why a drug like Fosphenytoin is administered for 'status-type' seizure activity.

Fosphenytoin is also used to prevent potential seizure activity after brain or nervous system surgery. (http://www.drugs.com/cdi/fosphenytoin.html)
This would likely explain why I seem to hear of it's use fairly frequently because we work with neurosurgeons in addition to neurologists. Fosphenytoin is administered as a subcutaneous injection - read needle.

Seizure activity is usually measured via a procedure known as an EEG or Electro Encephalograph. This device measures electrical activity in the brain. Here is an example of what the read out looks like:
Despite having seen countless patients having this procedure done, I still can't read the thing worth a darn. The EEG techs and neurologists can; all I ever know is if the leads are connected properly.
This image was actually taken from an EEG where a patient had been treated with Fosphenytoin which altered the electrical activity, but did not help the patient clinically.

The next image is one comparing the relative concentrations of Fosphenytoin and the length of time that was required for a seizure to stop. Administration in this case was for a Status Epliepticus type seizure:
Phenytoin is essentially the same thing as Fosphenytoin; they act in the same way.
The primary anticonvulsant mechanism is modulation of sodium channels.
(http://www.medlink.com/medlinkcontent.asp)

Well, I am trying to think of some way to some up my research and interest in this med. Personally I like to see when things are administered for preventative measures. It will be interesting to see the results of the paper surveys that I am giving out to local neurologist offices. I will be in a better position to understand what, if any, problems and complications are associated with this med and I will get it from those who have tried it.

So, I think I will have to say, to be continued....

H1N1 vs. Tamiflu

Let's talk about some news. I have done my first trial with paper surveys, so far things are going well. I need to clean up some of the language and try to make it a little more clear, and to try and make the font smaller or maybe print both sided. Right now the paper surveys work out to about 5 pages, which is a deterrent for some people I have talked to. It is funny how it is hard to talk people into doing surveys for even simple OTC anti-inflammatory meds. I don't personally take many drugs, but if I need to pound some Ibuprofen - like when I had Strep Throat around Valentines Day (see previous blog post on Ibuprofen) - I don't really have a problem telling people about it. I need to work on how I present the survey maybe; better explanation is always a useful thing.

We are nearing the end of the internship. This has been a lot of hard work, but I am glad that I did it. I have learned a lot of stuff about medications, a lot of stuff about research and a lot of stuff about communication.

Since we are so near the end - and since every blog deserves one REALLY long post - I think that this week I will be featuring a drug that has come to the forefront of a lot of people's minds right now: Tamiflu.
The Swine Flu, or H1N1 has received a lot of press lately. Inevitebly we as people will find something to panic about. This 'new' flu virus has caused a lot of uproar. Recently at work I was talking with the man who is in charge of education on my unit and he asked what I thought of the Swing Flu. Working in healthcare we are poised to be taking care of the children who are diagnosed with Swine Flu, this is especially true of the fact that we give very specialized care at my hospital. I told him that I thought that we might see a few cases - half-a-dozen at best - but that would be the extent of it. I could be wrong, but I doubt it.
According to: http://www.theblogofrecord.com/tag/jama-influenza-flu-death-mortality-studies/ nearly 36,000 Americans die every year from the 'normal' influenza virus and cnn.com reports that 615 people are currently infected with Swine Flu worldwide and out of all the the worldwide infections, 16 persons have died.
While the loss of human-life is not good on any scale, the number of deaths is not consistent with the panic. At least, not in my opinon.

So, what is Swine Flu? The Swine Flu, or H1N1 is a type A flu virus that is usually transmitted to individuals who spend a lot of time around pigs, but it can be transmitted from person to person. The symptoms are usually the same as the 'normal' flu, but in children there have been some reports of dirhea and vomitting associated with the virus. Like any other influenza virus the H1N1 Swine Flu virus any underlying medical conditions are exacerbated by the virus.

The news is, of course, not all bad. It seems that the Swine Flu virus is susceptible to the standard anti-viral medications. One such medication that is important in this fight is Tamiflu.
(http://www.cdc.gov/h1n1flu/eua/pdf/tamiflu-patients.pdf)

There are A LOT of online resources about Tamiflu. I am not going to take the time to look it up, but I bet the number of hits is pretty high right now.

So, let's begin the discussion with an' old favorite; the organic molecule:

I also found an image that details all of the steps required to convert Shikimic Acid - the botanical starting product that is eventually converted to Tamiflu - into Tamiflu. This is obviously a multi-step synthesis. The diagram is probably a bit too complicated for the casual reader - myself included! - but it was too cool to pass up the picture of how the make the stuff.

For best result Tamiflu must be taken within the first 48 hours of symptoms.

Tamiflu acts as a neuraminidase inhibitor meaning, among other things, that it inhibits infected cells from transmitting virions to other parts of the body. Neuraminidase is used to cleave the bond between an infected cell and a virion, when that process is inhibited by introduction of Tamiflu, the infection is slowed or even halted totally allowing the body to fight the infection.
(http://www.fluwikie.com/index.php?n=Consequences.NeuraminidaseInhibitors)

Time will tell if I am wrong, or if I am right. But, if you think of the times when people have been agitated or panicky about some worldwide problem - think of Y2K here - it has proved to be minor and in some cases nonexistent.