Viagra/Sildenafil + Nitrates = Potentially Fatal Reaction

I just missed  a question on this topic in the USMLE World QBank.

If a patient has taken sildenafil, at least 6 hours should pass before taking nitrates.  The sildenafil, obviously, is used to treat erectile dysfunction or pulmonary arterial hypertension, while nitrates are used to treat angina or pulmonary edema.  When used during an MI, nitrates can decrease the size of the infarct and decrease mortality.

Why should sildenafil and nitrates not be combined?  Because they affect the same NO/cGMP pathway and have additive effects which can cause severe hypotention and possibly an MI.

Sildenafil MOA:  It is a PDE5 (cGMP phosphodiesterase 5) inhibitor, so it prevents the degradation of cGMP by PDE5.  More cGMP results in vasodilation, and thus more blood flow to the penis.

Nitrates MOA: Examples of nitrates include nitroglycerin and isosorbide dinitrate.  They release NO in smooth muscles, thus activating the cGMP pathway.  NO activates guanylate cyclase, which makes cGMP.  cGMP then causes the dephosphorylation myosin light chain phosphate so that it can no longer interact with actin.  This results in smooth muscle relaxation and vasodilation (veins more than arteries).

When I read about the drug interaction, it did sound a wee bit familiar.  Here is a clip from "Something's Gotta Give" to help you remember this drug interaction and a potential case presentation.

Entertaining Memorization Strategies

My Pharmacology NBME percentile score is back and that verified what I already knew.  I suck at Pharm.  Not only do I suck at Pharm, I also dislike it.  (Yes, I am using rationalization, an immature ego defense.)  Why do I dislike it?  Because it is just memorizing a bunch of strange-sounding names and apparently random drug interactions and side effects.  Of course there is also the mechanism of action (which I find somewhat interesting).  It is tough to attach meaning to what seems like an unimportant pile of facts.  But I know Pharmacology is HUGELY important.  It is integral to the practice of medicine.  I know it is essential to understand which drugs are the first-line approach for each disease.  It is also important to be able to counsel your patient on how to take the medication and what to expect while taking the medication in order to help the patient adhere to using the drug and to enhance the physician-patient relationship.  And there are all kinds of other reasons Pharmacology is important, but that would make this post way too long.  Because of my concern for my future patients, and because of the approaching USMLE STEP 1, I will be spending a lot of time focusing on Pharmacology in this blog. 

I finally figured out how I can make myself learn Pharmacology.  Unfortunately, I did not hone in to these techniques until after most of the Pharmacology class was over.  I taught high school Biology for three years before I started medical school, so I learned several methods to enhance memory formation.  I should have put them to use earlier, but I was afraid it would take too much time.  It turns out that these techniques are actually kind of fun and do not take that long.  In fact, the time I put into this method is much higher yield than going over flash cards over and over again.    So, the idea is to INTERACT creatively or personally with the material in some way—repetition is NOT enough.  And I’ll explain the specifics of what I mean by INTERACT in a little bit.  Through this interaction, you make the material personal to you.  I also think when you interact with the material you use several different parts of your brain, so you are probably branding that information into many synapses in various areas.

How do you interact with your learning?  For Pharmacology, I made up rhymes and imagined ridiculous drug advertisements and jingles.  I made up stories or fake patients that serve as mnemonics for me.  Some of these things start to sound like the ravings of a schizophrenic patient, but I’ll share lots of them here in case they help you as well.  You can also draw cartoons or pictures.  Writing lyrics and putting them to a well known tune would be extremely helpful, but I have not tried that.  It is also helpful to share this stuff with your friends because talking about it reinforces it.  If you make up a mnemonic for the cephalosporins, share it and explain it to your friends.  It’s better if it is funny or rhymes.  And…things that are disgusting, vulgar or offensive…are easier to remember.  For example, I will NEVER forget that trazodone can cause priapism.  Trazodone?  Tragic bone.  I learned that when my husband was in med school.  He just mentioned it once when he was studying Pharmacology, but it stuck.  When I am old(er) and have vascular dementia and cannot remember the names of my children, if you say “trazodone” questioningly, I will still answer “tragic bone”.

I call or text friends and family members with various diseases and ask them what drugs they take.  When I study the sleep aid drugs, I think about my friend Jim (a fake example).  He told me he experiences some day time sleepiness on Trazodone. I tell Jim he should watch out for priapism.  If that ever becomes a problem, he can switch to Zolpidem or a benzodiazepine.   And when I learn new information about insomnia or sleep aids, I think about it in the context of Jim and how it will affect him.  If I learn something useful to Jim, then I text him about it.  Making it personal really helps it to stick. 

I only use this method for things that I just do NOT know, even after finishing classes.  I am not wasting my time doing this for things I already have down pat.

I took my First Aid to Kinkos, had it hole-punched and put into a 3-ring binder.  I put tabs on all of the different sections (obviously all of this is not my idea—lots of people are doing this).  Whenever I read First Aid, I annotate it, highlight things, underline and put boxes around important words using various colored markers and highlighters.  Humans are really visual and we LOVE color and graphics.  We also love looking at our own handwriting and our own work, so you are going to pour over your First Aid even more if you personalize it.  Write all over it, spray your perfume on it, kiss on it, paste in your personal photos (obviously exaggerating a bit, but certainly do make out with your First Aid if you think that could boost your Step 1 score) and make it yours even if that isn’t usually your style.  Nobody is going to want to buy your used First Aid anyway.  They will want the new, improved 2012 edition.  Anyway, if you can think of how something would be better understood with a diagram or chart, make one yourself by hand on a piece of paper and put it in your First Aid.  Use lots of colors and images where appropriate.  If you make up a list of mnemonics (or come across them), or a cartoon or poem or whatever else, then write it down neatly and put it in an appropriate section in First Aid.  Cut or photocopy useful images out of Netter’s (or another useful reference) and put them in your First Aid. 

An example of a chart to help me compare the types of arthritis in one spot.  Good for self-quizzing.  Notice how my complete inability to draw stuff did not stop me from making this neat illustration of an edematous hand with scary, wrinkly, monster witch fingers.

How I annotate and highlight and write all over everything in First Aid.

Clearly, I am a bossy and uptight ex-teacher.  I’m sure you use lots of these ideas or have thought of them already.   You know what works the best for you, so stick to what works or try some of my suggestions if you are in need of changing things up.  

A MEAN old guy called Aminoglycoside

Hey Fellow Med Schoolers.

Just to let you know, “The Plan” has been a big fat flop so far.  I have been mentally overwhelmed by the prospect of 5 enormous tests in two weeks, plus life in general, plus recovering from the giant storm last week.  I have been meeting various repair folk at my home to get estimates for the removal of 2 giant fallen trees from our back yard (which apparently warrants a crane to lift the root balls OVER my home since my back yard access space is essentially nil), the fence repair (from said trees), stone patio repair (tree root ball took some stone patio with it), as well as sewage line repair (tree root ball took the sewage line with it, as well).  Oh yeah, and we had a roof leak. 

So, we have a porta-potty in our front yard.  That is on account of the very small back yard access space, and the ruined sewage drainage line.  Imagine…it is raining and chilly, and nature calls late at night.  Yes, I have to get dressed, grab a roll of TP, get an umbrella and turn on my front porch light so that I can see my way to our Johnny on the Spot.  The front porch light also serves to make sure all of my nearby neighbors know that I need to use the restroom.  They can watch me make my approach, dressed in mismatched clothing and probably slippers, a TP roll shoved under my arm and juggling an enormous umbrella while trying to open the door to our new half-bath. 

It’s better than nothing.

I hope everyone else has had a better studying experience so far.

In honor of the upcoming MICRO/IMMUNO NBME, I thought I would share how I remember things about the AMINOGLYCOSIDES.  First, read the info on p187 of the 2011 First Aid.  Remember, “buy AT 30, CELLS at 50” to determine how various antibiotics target bacteria.  A = aminoglycosides, which target the 30S ribosome.

My name is Bacteroides fragilis, and I just wanted to tell you about my new friend, AMINOGLYCOSIDE.

At first, I thought he was A MEAN OLD GUY (aminoglycoside), but it turns out he is one of those new (neomycin), amicable (amikacin) type of gents (gentamicin).  He gave me a Toblerone (tobramycin) and when I was cold, he stripped (streptomycin) off his jacket and put it over my shoulders.

I told him I was surprised that he was so nice to me, and he said he has nothing against obligate anaerobes (ineffective against them—requires O2 for cellular admission) like myself, although he usually does kill any other gram-negative rod that he sees. 

He said, “I also hate babies (teratogenic).  They are loud.  And I hate kidneys (nephrotoxic).  I don’t know why people eat fried chicken kidneys.  That’s disgusting.  I hate ears (ototoxic), too.  They stick out and they look weird.  But you, Bacteroides, you are my buddy.”

The Plan

The last school-issuedl test is over!  I am now facing a 2 week block of 5 NMBEs.  Then?  The hard core Step 1 studying begins.  My test date is June 28^th, which is kind of late, but I feel like I need the extra time.  I feel like I have a lot of making-up to do because I have not really just hit the books hard since my son was born during winter break of my M1 year.  Also—who knows what could come up!  My son could get sick for a week—he could do that 2 separate times!  He was sick for 6 solid weeks at the beginning of the M2 year (first real time at day care!!).  Who knows!  So…I feel like I need a time-buffer for that.

I don’t have a set-in-stone specific study schedule as of yet, but my general weekday plan is:

5:00 AM:  get to work in the study at home.  I know—it’s early!! The sun isn’t even up yet!!!  But my brain is on this early.  It’s just a matter of prying my eyelids off of my eyeballs and getting out of bed. When my son wakes up, my husband has kindly volunteered to take over the get-child-fed-and-dressed routine.  At least until Step 1 is over.

7:30:  take my boy to day care and head to the library myself. 

9:00 AM: meet with my study group and trudge along until we hit our goals for the day.  I will study on my own after that.

2:30PM:  My big hope is to hit the gym and actually get a regular workout into my schedule for once.  I think I’ll listen to a Goljen lecture while I work out. 

3:30PM:  leave school and pick up my boy and spend some quality time with him!!  Nowadays, that means play outside…constantly. That is the ONLY place he wants to be!!

5:30PM:  dinner, followed by some family time.  Also: laundry, dishes, house cleaning.

7:30PM:  The kiddo goes to bed.  Make lunch for tomorrow, more housework.  Hang out with my hubby!  I will probably sweet talk him into quizzing me over something or doing some Q-bank questions with me for a little bit. 

10:00PM:  Step 1 Subjugater goes to bed.

I don’t know when I will implement this plan.  I should probably start Monday, actually.  My Pharmacology NBME is Tuesday!!  The study group stuff isn’t starting until after the NBMEs. 

Anyway, I plan to post some general STEP studying experiences here, as well as some mnemonics and charts that I make.  I hope it helps you!!