Last Blog

Hello all - now all of you (I hope) entering Term 3 in January 2013. As I had explained - I could not manage to create any of the promised blog entries in the fall of 2012. And now I also have to tell you that I will not be coming back to Trinity.

So this is the end of this blog - and I hope that overall it was a good thing that is coming to this end...You are, however, welcome to ask me any questions on subjects we had covered or beyond!

All the very best to all of you!

Hans Baer

Welcome Fall 2012 Term!

I think I managed to figure out the problem of inserting an image when using this new tablet of mine, and so I am sending you this shot taken some 15 m away, by a friend of mine back in Canada. The reason he was not eaten, I think, is that the animal saw that he was old (82) and thus would not taste so good...in time you, too, will learn to recognize your patient,s features just by looking at them...

Another Topol digital medicine idea

The FDA (following European licensing authorities) has approved ingestible sensors to be used for monitoring compliance with drug use and also relaying other vital sign data such has heart rate in the course of therapy. I do not fully understand, beyond the general principle, all the aspects of this new approach and form of "digital medicine" and have no idea about the cost. You can read up on this here.

New beta-adrenergic drug

The FDA just approved a new drug, Mirabegron, for the treatment of overactive bladder: This drug is a selective beta-3 agonist, and it looks like these receptors are prominent in the bladder and cause relaxation when stimulated. So, maybe we have to add this to the list of items to cover in my ANS lectures. To date I have not talked about beta-3 recptors. They are present in brown fat cells that is very rich in mitochondria and contribute to heat generation in the body (such as in babies), and it is now news to me that they are also in other parts of the body and can be "exploited" now in this scenario of bladder related dysfunction. The classical treatment of overactive bladder is with anticholinergic drugs, as you may recall.
What adverse effects would you expect with this new drug mirabegron?? Make a comment below!

An interesting question:

Which is the leading cause of death worldwide among boys 5 to 14 years of age?

In the United States, this cause of death is the second leading cause of injury-related death among children 1 to 4 years of age, with a death rate of 3 per 100,000, and in some countries, such as Thailand, the death rate among 2-year-old children is 107 per 100,000. In many countries in Africa and in Central America, the incidence of this cause of death is 10 to 20 times as high as the incidence in the United States. Key risk factors for this cause of death are male sex, age of less than 14 years,alcohol use, low income, poor education,  rural residency, risky behavior and lack of supervision. For people with epilepsy, the risk of this cause of death is 15 to 19 times as high as the risk for those who do not have epilepsy. For every person who dies from this cause of death, another four persons receive care in the emergency department for nonfatal incidences of this cause of death.

Give us your answer or guess in the Comments!

Missing slide: Indirect i.v. effect of ACh

Somehow, a slide seems to have disappeared from one of my lectures, dealing with the i.v. effect of acetylcholine. I inserted it into the ANS2 lecture and it says this:

• Injecting ACh i.v., interaction with vascular smooth muscle should cause contraction and rise in BP.
• BUT: Muscarinic receptors on endothelial cells, when stimulated, will cause Ca-mediated activation of nitric oxide synthase and formation of nitric oxide: This will overcome the contractile s.m. effect and lead to vasodilation and fall in BP/shock.
• This is referred to as an "indirect" action of ACh.

HB

Read after the exam: A rare dysautonomia

Shely sent an interesting reference to me that you might enjoy reading after the exam: A very rare disease that may first present right after birth, namely, when the newborn does not open its eyes for several days and later will cause the affected to have frequent orthostatic hypotension-like events all the way to short term coma... Actually this deficiency disease caught my eye when I looked at the list of dysautonomias in my ANS3 lecture today, slide #57, where it is listed - and I thought to myself that I should look up sometime what it entails!

Thanks, Shely!
HB

Success in Life

Many people will give you advice on how to become successful in life - beginning with your parents and now maybe continuing with your professors....
The formula below, however, is all I can tell you and promise you it will be highly effective!

Agonists, inverse, partial and full

Let's see whether you understand inverse antagonists etc:

1. I you combine an agonist with a competitive antagonist you will
   A) never obtain a maximal response
   B) get a negative response like with an inverse agonist alone.
   C) eventually will obtain a maximal effect when increasing the agonist concentration.
   D) get no or only a very small effect.

2. If you combine an antagonist with an inverse agonist you will
   A) get a positive response instead of a negative one as you would in the absence of the inverse agonist.
   B) get no response when increasing the antagonist concentration.
   C) will get an increased negative effect.
   D) will form a black hole.

3. If you combine a partial agonist with an inverse agonist you will get
   A) a maximal effect.
   B) a negative effect if you keep increasing the inverse agonist concentration.
   C) a negative effect if you keep increasing the partial agonist concentration.
   D) will precipitate a Big Bang.

Goods luck: I want to see responses by each of you in the comment section!

Inverse agonist

I found a very nice and clear description of what an inverse agonist is - right in the Wikipedia (just one example of how things are described there sometimes clearer and better than anywhere else.... Go ahead and google "inverse agonist"! Here is a nice graphic and the descriptive text"

"....an inverse agonist is an agent that binds to the same receptor as anagonist but induces a pharmacological response opposite to that agonist.

A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level activity in the absence of any ligand. An agonist increases the activity of a receptor above its basal level while an inverse agonist decreases the activity below the basal level. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.

The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0%, while an inverse agonist has < 0% (i.e., negative) efficacy...."

NB" I noted with some pleasure that the first author quoted in the references is a Terry Kenakin: he was student in my department at the U. of Alberta back in 1970/72 or so and has made a big name for himself when it comes to classical analysis of dose response curves (although coming up with hypothesis most have trouble following or seeing the relevance of with respect to medicine...).

A dosing question

You are giving some one a drug, say, penicillin G, and you inject i.v. and you inject a total of 1 g. What would you think the plasma concentration is going to (make it in terms of g/L). Give me your thoughts as a Comment below.

Whatever you guestimate, would it be the same answer if you gave the drug orally?

Don't be afraid to give a wrong answer - I won't remember within a day who said what!

Too much acid - acidosis

When someone takes an overdose of a drug that is a carboxylic acid, then its buildup in the plasma can contribute to a borderline acidotic metabolic problem (due to whatever derangement of metabolism) and contribute to the overall metabolic acid build up in plasma and precipitate an acute metabolic acidosis (characterized diagnostically by a large anion gap - in case you know what this is).

Can you think of a way to accelerate the excretion of the acid drug and save the patient from serious trouble?

A rectal question for you

A very young patient is treated with an antibiotic at 2 mg every 4 hours, but the kid does not like the taste and rejects taking his drug, causing a "compliance" problem and a flare-up of his infection. His doctor decides to make use on a rectal preparation of the same drug and thus prescribes the same dose for this formulation and frequency of administration.

Do you see a problem with this or would you have done the same or what information would you require before proceeding in any way? 

Please explain via a comment below!

Don't forget to recreate!

Here in this vacation paradise of St. Vincent and the Grenadines you are supposed to lay the foundations for becoming a great physician...but you are also supposed to be a bit of a tourist and enjoy some of the outdoors, the beaches, the jungle and whatever: Here are links to some videos you might enjoy and maybe they will animate you to go and do some of that live:

http://youtu.be/hUHlWQKtEUA

http://youtu.be/p-PzLpfcV_M

http://youtu.be/spSSlzdMe8A

Welcome to Spring 2012 Class

Hello eager students:

On the side bar of this blog you will find places to

• sign on to this blog
• register your email for notifications on new entries
• get some background information on your new lecturer

Once we are underway in this course, it will make sense for you to scan through the archive all the way - there will be lots of entries that will have relevance to what we are doing in this course and your education in general. There is a bit entertainment as well. I know you have lots of things to do - but I still expect that you will "participate" in this blog dialogue by entering comments (such as lousy entry, excellent information or whatever) and enter questions - that way we can share the answers and the issues that may arise! Also, it would be terrific if you could provide some material for this blog to share with the class! Just send me the info by email, I will enter it.
Below is a shot from just across the border - Mt. Shuksan in the Mt. Baker Park of just some 3 weeks ago - but now I am happy to join you for some sunny and warm days in the Caribbean....

Smart phone for lectures?

I wonder whether any of you has a smartphone and has knowledge or experience with connecting this to the LCD projector for big screen display. I recently learned about the Samsung Galaxy Note phone and am told that (a) it runs ppt files and (b) it can connect to a projector via a USB-to-VGA cable. Do earlier versions of this phone (Nexus or earlier) allow for this also?. I feel that the Note would be absolutely great because of its tablet and screen writing (with a stylus) capability. In fact if it works like that, and flawlessly, it might become the traveling lecturer's preferred device for lecture delivery. What do you think and what experiences do you have? Your comments will be important to me and my possible decision to plunge head first into the smartphone user pool. This dive of course is not cheap - in Canada the Note costs 200.- up front plus three years of monthly 50.- for a minimal plan.
Please use the Comment section for communication on this.

I am not at the forefront of app users (as I don't have (as yet) the needed device) - but this add by Medscape caught my attention. It loads to both i-devices and androids or some ibooks. Is anyone using it, would you want to share your views or experiences with whatever you are routinely using in your studies? Let us  all know by adding a comment!

Make practical sense of terms and definitions

How about these problems:


If the drug concentration is 5 mg/L, then how many  milligrams of drug would you have in each litre?
If the infusion rate is 10 ng per hour, then how many nanograms does the patient get each hour?
If your initial salary as a resident is 40 K/year, how many dollars will you receive each year?
(Please see answers below!)


Well, maybe the above questions are more complicated than you think. Look at the following video - I believe the lady in there is a former student of mine...! She eventually got her MD by marrying one!
 http://www.youtube.com/watch?v=Qhm7-LEBznk#!


Answers to problems:
(1) 5
(2) 10
(3) Zero (i.e. after taxes and paying off loans).


Have a good day!

Ingenious New Method of Exam Grading

Writing good exam questions and grading exams is an art - not a science. Some of my colleagues think they can write 100 questions and come up with a scientific analysis of the results that gives you an absolute and fair grade. Nonsense: there is no intrinsically absolute value in a question, or in 100 questions, and in the end everything is relative! For the most part this then is fair and good enough - but maybe we could do one better by adopting Mr. D's ingenious and intuitive method, as shown in this video:

Dimensions - what do they mean to you?

Numbers usually have some associated dimensions, so when doing dosing calculations it is important to not forget about the associated physical dimensions. Sometimes the dimensions make easy sense: Plasma concentration, for example has the dimension of something like mg/L. Makes sense? Sure. But how about AUC - the famous "area under the curve": mg/L x h Unless you are a numbers and mathematics genius, that dimension makes less sense at first site....

How about speed, say, 80 miles/h? When you see this number and I ask you "How long would it take you to go 80 miles?" - can you easily answer that? If not - here is how a former student of mine deals with this complex task:
http://www.youtube.com/watch?v=Qhm7-LEBznk#

Are you still a nicotine addict? Read this, maybe....

FDA release today: "Tobacco use is the leading cause of preventable death in our nation. And until we dramatically decrease the access and appeal of tobacco products to youth, it will remain one of America's most pressing health problems. Today’s ground-breaking report by the Surgeon General not only documents the devastating consequences of tobacco use for our nation’s youth, but also represents a clarion call for bold action at every level of government to implement proven strategies to keep kids off tobacco."

Full press release

Surgeon General's Report

Medication error risks

I just saw a report on Medscape that lists the 12 most common instrument-related errors occurring in medical practice/hospitals. Among those are medication/dosing errors when using infusion pumps. This is the text from the slideshow relating to this problem: make sure that you don't get into this sort of mess - ever!

Medication Administration Errors When Using Infusion Pumps

Mistyping information, entering it into the wrong field, and other data-entry mistakes can be dangerous or even fatal. Doctors, nurses, pharmacists, and others can contribute to errors. Medication orders may be illegible, drugs and solutions may be incorrectly prepared, and a medication may be given to the wrong patient.

"One way to avoid errors is to use a dose-error-reduction system," says Keller. "It has built-in limits, or guardrails. If a nurse enters a dose that exceeds the limit, an alert will occur to catch the error before it can happen."

It's crucial to determine the compatibility of the pumps with your safety systems. Get the names of other sites that have integrated the pump with information systems from the major providers. For staff who will be using the system, emphasize the importance of safeguards, and be aware of any resistance to new workflows and safety compliance issues. 

Muscle cramping

This post is outside my teaching program this term, but it should be a useful reminder for all the athletes out there:

Yesterday, after a soccer game in Kingstown, I talked to a student re. muscle cramping and later revived my understanding of the underlying causes – here is my summary:

Muscle cramping during exercise seems to have two major causes (and 100 suspected causes): (1) a nerve muscle fatigue syndrome (“sick muscle”) where you have to stretch against the contraction but won't be able to control the situation such as to continue exercising and (2) inappropriate systemic fluid and sodium levels, precipitated by inadequate pre-hydration, sodium intake or intermittent fluid intake during prolonged exercise. Forget about calcium, potassium and magnesium. Sweating looses a lot of water and sodium. Just taking water or juices may suffice but could not overcome the cramping risk if too much sodium has been lost: it is better then to take salt containing sports drinks or home-made fluid (½ tsp of salt/0.5 L). Definitely do not use pop drinks containing caffeine/theophylline: these methylxanthines cause diuresis and fluid and sodium loss, exactly the opposite of what you need.

When biking around the island I noted once that I precipitated some leg cramps within minutes after taking some fresh water from roadside taps. When repeating the exercise later and taking along some Gatorade, I had no problems. Unfortunately, the roadside rum shops carry no water or sparkling water – just pops.

Happy running, biking, playing!

Some spelling humor for you

Here is a record of a real email exchange between Professor Hans and a student:

Student: Someone left a stethescope in the van coming back from the hospital - maybe
you could send a message to the class about that?

Prof: OK, I just did. But for my benefit, what is a "stethescope"?

Student: A stethescope is used by doctors to listen to ones heart and lung sounds!

Prof: Oh, that would be a stethoscope, I know about that. But you said you found a
stethescope - and I still don't know what that would be!

Student: Haha, I see my spelling error! Sorry!

Prof: Ok, all clear. But just to be picky it should be "one's" instead of "ones".

Student: OK, thanks! If we had to go through all our mails and texts with a spellchecker
we would have little time for study!

Prof: (to himself): "Spellcheckers - alright, those are for typos. But how about knowing
some English, Hair Doctor?"

(Of course, it is a standing yoke that docters do not wright and spel good. If KMC had
continewd to eccist, we mite have stahted an englisch cuarse!)

They eye: closed angle glaucoma

I am sorry we did not have time to cover that. But you should be aware of the various drugs useful in treating, symtomatically by reducing intraocular pressure, close angle glaucoma. In the end it is quite easy, though initially looking complex: You have to just remember the anatomy of the anterior eye structures and where the receptors are located.

• Circular muscle has M receptors.  
• Radial muscle has alpha1 receptors. 
• Cilial muscle has M-receptors. 
• Cilial epithelium has beta-2 receptors (and these control aqueous humor production). 
• Alpha-2 receptors are located - where? No idea. but stimulating them with agonist opens alternative uveoscleral fluid outflow. 

Contracting the iris re-establishes some Canal of Schlemm outflow. All of this ism like an autonomic clearing house!
Additionally to using ANS drugs, one can reduce aqueous humor outflow by using (a) a carbonic anhydrase inhibitor, like  aceazolamide, or (b) one can draw fluid from the eye osmotically by increasing plasma osmolality with glycerol  (just by drinking a cup of it) or injected mannitol.

In reality, 2-3 of these approaches are employed!

New pharm learning site??

I love this title I just found on the Internet (although maybe it should be re-titles as "...by Dummies):

I did some clicking but found, unfortunately, that it is a dental pharm course....

Autonomic drug puzzle

We normally conclude the discusssion of ANS drugs with a "puzzle". I have no idea where this came from, and certainly it is not a fully realistic scenario that would be observed exactly like this in a real animal experiment. But the puzzle serves to review and thus gain additional understanding about tyhe functionalities of the ANS and ANS drugs. The recorded file now has been forwarded to your class rep. It is 20 MB and some emails cannot handle this - I am sure you will be colleagually (a new word?) interactive within your class and each student will be able to get it and listen to it.

Wine & Cheese parties

These are a no-no for persons who take MAO inhibitors like selegeline against depression. Reason: Tyramine can be taken up into adrenergic nerve terminals or varicosities and then replace norepinephrine. The outpour of norepinephrine then precipitates a hypertensive crisis and accelerates the heart beat. The outcome can be death from stroke or maybe arrhythmia and cardiac arrest. Wine and cheese are foods that contain significant amounts of tyramine - this normally is rapidly metaboized by MAOs and remains inconsquential, except when the enzymes are inhibited.

Preceding dosing problem - no response

A small reminder: Nobody seems to have bothered trying out the preceding dosing problem. You better reconsider!

A dosing problem for your entertainment

A  patient is maintained on  an oral drug, given 4-hourly, but develops some adverse effects too frequently during periods of peak plasma concentrations.  Measurements show that his plasma concentration fluctuates between 120 and 60 microgram/L.

The physician decides he would rather place him on a continuous infusion.

What maintenance dose rate would you suggest then?

Parameters for the drug are:

Bioavailability 25%

Volume of distribution:  2.4 L/kg

Pt. Weight: 80 Kg

Plasma Half-life: 4 hours

Look for previous entries re. pharmacokinetics

Make sure you scan through ALL entries in this blog - you will find some that are relevant to what we have covered or will cover in this course. For example, there is a useful module telling you how to deal with the determination of AUC....search for "AUC" or scan through all previous entries...

Pharmakokinetics course online

I mentioned to you the boomer.org website by David Bourne.

For those who like to play games on their computers, here, for once, is a useful "game": Display time curves using a Java module provided by Bourne:

The link  to the course contents page is this:    http://www.boomer.org/c/p1       Here is the example where you to vary inputs and show resulting PC-versus-Time curves for oral drug administration, as follows: http://www.boomer.org/c/p1/Ch15/Fig57/Fig57.html

In some cases the formula section is f ollowed by links to Java graphics modules where you can play around by changing parameters! 

Have fun!

Welcome to Spring 2012 Class

So, here we go:

• Sign up for email notifications and/or as a member.
• Participate in this blog by commenting (always indicate whether you find an entry informative, interesting, useful or boring) and
• Consider sometimes to provide an entry - referring to something you read, saw or wonder about (you would send your entry to me, and I will enter it).
• Ask for content: more questions or more of what?
• When asked a question, always try for an answer.
• Had an experience with a drug reaction or issue you wish to share?

There are plenty of ways to make this interesting for us all....

Clonidine details

In class we talked about clonidine only very briefly. Here is a recent summary of comments from an article shown in eMedicine/Medscape, just so you can see how little we scratched the surface...and if you were to look at the entire article you will see how many considerations need to be made to treat a patient who may suffer from serious adverse effects.
Summary of clinical uses and adverse effects:

Clonidine is a central alpha-agonist that is used as an antihypertensive agent. Other reported clinical uses include treatment of opiate and alcohol withdrawal and control of atrial fibrillation with a rapid ventricular rate. It is also used as a pediatric preanesthetic, for pediatric postoperative pain management, treatment of migraine headaches, nicotine addiction, menopausal flushing, attention deficit disorder, Tourette syndrome, and pediatric panic and anxiety disorders.

At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses, it can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults.