Monday, October 31, 2011
QT Lengthening or Long QT Syndrome
Please take a look at an earlier blog on QT lengthening. I think it is important you know about this unique adverse effects that is based, apparently, on a number of possible "Channelopathies", i.e. mutations in ion channel proteins!
Alpha-2 Receptors etc.
In the lecture I was a bit short on explaining issues regarding these receptors: The classification of such receptors of course is based on struture-activity studies, eventually confirmed by molecular biology/cloning. Initially these were seen to function as pre-synaptic receptors whose stimulation by norepinephrine (NE) reduced NE discharge and thus represented a self-regulatory process. Later it was found that agonists of alpha-2 receptors were present in many tissues and functioned sometimes independent of innervation/neurotransmission pathways, both in the periphery and centrally. You just should be aware of this in principle, and you don't have to memorize the long list of individual functions I copied from theWikipedia:
- decrease release of acetylcholine
- decrease release of norepinephrine
- Inhibit norepinephrine system in brain
- inhibition of lipolsis in adipose tissue
- inhibition of insulin release in pancreas
- induction of glucagon release from pancreas
- platelet aggregation
- contraction of sphincters of the gastrointestinal tract
- ↓ Secretion from salivary gland
- relax gastrointestinal tract (presynaptic effect)
- decreased aqueous humor fluid production from the ciliary body
Friday, October 21, 2011
What is the TI re. alcohol lethality?
You may recall that in today's lecture I was asked what the TI for alcohol is and that I recommended to the student (James) to go and look it up. He did and sent me this (you will see that my general idea that a TI of 4 is not good enough for comfort is shared by the author of the site):
Dr. Baer, here is a link to some forums with information regarding thetherapeutic index of alcohol:
http://www.drugs-forum.com/forum/showthread.php?t=34430
Below is the direct quote from the website:
"From Pharmako/Poeia, a book I find myself often quoting these days:
Quote:
Ethanol, drinking alcohol, is far from harmless. Alcohol is a
protoplasmic poison. It kills bacteria, animals, and plants, even the
plant that produces it to begin with. The most effective concentration
for germicides is 140 proof, or 70 percent alcohol. This is the
concentration used in doctors offices as a disinfectant. Pure alcohol
is less effective, evidently because it gelatinizes the cellular walls
of the targeted microbes.
The toxicity of medicines and poisons is commonly expressed as the
LD50, the "lethal dose for 50 percent." Usually measured in grams per
kilogram of body weight, it signifies the amount of the substance
necessary to result in death for one-half of the unfortunate test
subjects. The relative safety or danger of a drug is denoted by its
therapeutic index, its margin of safety. The therapeutic index is the
ratio of the drug's LD50 to its effective dose, the dose necessary to
produce the desired effects. Since both the effective dose and the
LD50 are in grams per kilogram, the therapeutic index is a pure
number. The larger the therapeutic index, the safer the drug.
The therapeutic index of alcohol is only about five. That is, five
times the amount needed to get high can kill you. This puts alcohol,
as recreational drugs go, into the "highly dangerous" category. To
illustrate: if your child were going to overdose on a drug as part of
some rite of passage, say, turning twenty-one, would you rather he or
she overdose on alcohol or on marijuana? Either/or is not the point of
course. The point is that merely by drinking too much alcohol too
quickly, even once, you can die. Even cigarettes are safer than that."
Dr. Baer, here is a link to some forums with information regarding thetherapeutic index of alcohol:
http://www.drugs-forum.com/forum/showthread.php?t=34430
Below is the direct quote from the website:
"From Pharmako/Poeia, a book I find myself often quoting these days:
Quote:
Ethanol, drinking alcohol, is far from harmless. Alcohol is a
protoplasmic poison. It kills bacteria, animals, and plants, even the
plant that produces it to begin with. The most effective concentration
for germicides is 140 proof, or 70 percent alcohol. This is the
concentration used in doctors offices as a disinfectant. Pure alcohol
is less effective, evidently because it gelatinizes the cellular walls
of the targeted microbes.
The toxicity of medicines and poisons is commonly expressed as the
LD50, the "lethal dose for 50 percent." Usually measured in grams per
kilogram of body weight, it signifies the amount of the substance
necessary to result in death for one-half of the unfortunate test
subjects. The relative safety or danger of a drug is denoted by its
therapeutic index, its margin of safety. The therapeutic index is the
ratio of the drug's LD50 to its effective dose, the dose necessary to
produce the desired effects. Since both the effective dose and the
LD50 are in grams per kilogram, the therapeutic index is a pure
number. The larger the therapeutic index, the safer the drug.
The therapeutic index of alcohol is only about five. That is, five
times the amount needed to get high can kill you. This puts alcohol,
as recreational drugs go, into the "highly dangerous" category. To
illustrate: if your child were going to overdose on a drug as part of
some rite of passage, say, turning twenty-one, would you rather he or
she overdose on alcohol or on marijuana? Either/or is not the point of
course. The point is that merely by drinking too much alcohol too
quickly, even once, you can die. Even cigarettes are safer than that."
Special Kinetics 2: Zoledronic acid
Wednesday, October 19, 2011
A dosing problem
This dosing problem we will come back to after having discussed dosing issues in general - it follows from the previous blog on appropriate pain management in a pain crisis.
Say that the time to maximum effect for morphine is 8 min (I hope I remember correctly...) and that you needed to double the dose (as per the recommendations in the reference in the preceding blog) successively, thus giving 2+4+8+16 mg to have the patient pain free. Now, what would be the maintenance dose for this patient? How often would you have to repeat your administration, and how much would you give each time? For that you need some parameters. Which one or which ones?
Lets assume the following, and you then pick:
Volume of distribution: 82 L
Half-life: 4 hours (if you needed to (do you) you can calculate from this the clearance or the rate constant of elimination, of course).
1,2,3 go!
Say that the time to maximum effect for morphine is 8 min (I hope I remember correctly...) and that you needed to double the dose (as per the recommendations in the reference in the preceding blog) successively, thus giving 2+4+8+16 mg to have the patient pain free. Now, what would be the maintenance dose for this patient? How often would you have to repeat your administration, and how much would you give each time? For that you need some parameters. Which one or which ones?
Lets assume the following, and you then pick:
Volume of distribution: 82 L
Half-life: 4 hours (if you needed to (do you) you can calculate from this the clearance or the rate constant of elimination, of course).
1,2,3 go!
Special kinetics: Pain Control
In our discussions on drug kinetics we could not cover all therapeutic situations. For example, I will not say anything or much on the parameter "time to maximal effect". But this seems to be a major concern when dealing with a pain crisis - as you can see by listening to the following recording. Make a note of it - this is of importance to any of you and something you can throw into discussions on the subject anywhere. here is the link:
http://www.medscape.com/viewarticle/747777?src=mp&spon=17
Now, you may need a user account and password to view Medscape files (I will alert you often to new and interesting ones). Registration is free - so go and get it in any case!
http://www.medscape.com/viewarticle/747777?src=mp&spon=17
Now, you may need a user account and password to view Medscape files (I will alert you often to new and interesting ones). Registration is free - so go and get it in any case!
Monday, October 17, 2011
How about rowing instead!
Who knows, one or the other of you may need a break from studying. And since you are down here in the Caribbean, how about an interlude described in this link: http://theadventureblog.blogspot.com/2011/10/want-to-row-across-caribbean-in-2012.html.
But watch it: yesterday we came back from Bequia in a speed boat - and a lunar tide threw up waves that even surprised me!
Good luck
But watch it: yesterday we came back from Bequia in a speed boat - and a lunar tide threw up waves that even surprised me!
Good luck
Welcome to Fall 2011 Class
OK: here we go! You might enjoy looking at some of the previous term's blogs, and from here on we will deal with your class - "Fall 2011".
Remember, if you sign up you would get email notifications of new entries, and you can make this blog lively by asking both stupid and intelligent or challenging questions (actually, both types could be challenging, right?) - just don't be afraid to ask and comment!
As I said already in one or the other of the preceding blogs, I will sometimes insert some stupid exam questions - knowing that this always attracts students magically...and then we can argue about things!
Welcome again!
Remember, if you sign up you would get email notifications of new entries, and you can make this blog lively by asking both stupid and intelligent or challenging questions (actually, both types could be challenging, right?) - just don't be afraid to ask and comment!
As I said already in one or the other of the preceding blogs, I will sometimes insert some stupid exam questions - knowing that this always attracts students magically...and then we can argue about things!
Welcome again!
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