Posted by CamW on September 16, 2005, at 19:27:53
In reply to Re: Low dose dexedrine contra. with nardil? » CamW, posted by Sarah T. on September 13, 2005, at 0:10:08
Hi Sarah - Thanks for the WB. Thanks for the info. As I said in the above posts, the MAOI/stimulant interaction isn't as deadly as the drug interaction resource references (eg. websites, texts, etc) all claim. Most of the deaths occurred in the 1960s and involved methamphetamine (aka "speed", "ice", "crank" methedrine, methylamphetamine, & various other street names, which elude me at the moment) with an MAOI (like Parnate™ - tranylcypromine & Nardil™ - phenelzine).
Most of the MAOI/stimulant deaths of the 1960s were due to cardiac arrest (heart stoppage) resulting from "hypertensive crisis". Basically, the clinical definition is a sudden drastic increase in blood pressure exceeding 210/120 mm Hg, where the "ideal" blood pressure for an adult is 120/80 mm Hg.
Characteristic symptoms of a hypertensive crisis begin may include severe headache, vertigo (dizziness), diplopia (double vision), tinnitus (ringing in the ears), nosebleed, muscle twitches, tachycardia (increase in heart rate), nausea, &/or vomiting. If treatment is not initiated fairly quickly, the afflicted may become confused, irritated, &/or stuporous (unresponsive); potentially followed by convulsions, coma, myocardial infarction, &/or renal (kidney) failure. If not treated by this point, cardiac arrest or stroke may occur; resulting in the afflicted person having a very bad day.
Street drugs, such as methamphetamine, are often are adulterated(ie. "cut") with inactive fillers or cheaper, readily available chemicals that superficially mimic the actions of the street drug, in order to increase profit. Methamphetamine is sometimes adulterated with legal decongestants (eg. pseudoephedrine - Sudafed™), that sorta mimic methamphetamine's pharmacologic action, but to a much lesser extent. The drugs share the same basic, underlying molecular structure, but have differing side groups attached, and it is this that determines which receptor sub-type and to where in the body each drug will act, and how potent each drug will be.
Amphetamines and decongestants are both sympathomimetic amines that indirectly activate alpha-adrenergic and beta-adrenergic receptors. The difference in activity between the two is that the methamphetamine has much greater activity at receptors in the central nervous system in the brain, while the pseudoephedrine preferentially binds to receptors in the nasal mucosa outside the brain.
The reason that methamphetamine adulterated with a decongestant (in the 1960s there were 2 other decongestants available - ephedrine & phenylpropanolamine - which have been since removed from the market) is more deadly than when added to an MAOI is that the decongestant inhibits the catabolism (metabolic breakdown) of amphetamine-like psychostimulants (eg. methamphetamine).
Ordinarily, when pseudoephedrine is added to methamphetamine to increase profit for the "crank dealer" nothing happens to the person buying and using the adulterated methamphetamine (except getting less "bang for their buck"). But, if that person is also taking an MAOI, the risk of hypertensive crisis is increased because both the pseudoephedrine and the methamphetamine both need the enzyme, monoamine oxidase (MAO), in order to be metabolized (& thus excreted - eliminated from the body). The monoamine oxidase inhbitor (MAOI - eg. Phenelzine™) binds to monoamine oxidase (MAO) making the enzyme inactive, thus "inhibiting" it's action (hence MAOI). Therefore, the little MAO that is available now has to metabolize both the methamphetamine and pseudoephedrine (as well as the neurotransmitters that MAO naturally metabolizes). The effects of both methamphetamine and pseudoephedrine are extended, since both retain activity and remain in the body until they are metabolized.
Also, since pseudoephedrine (as well as ephedrine) has the same basic molecular structure as methamphetamine, the decongestant can be changed into speed through a relatively simple chemical reduction reaction. The chemicals (&/or their reaction by-products) used to do this are toxic and moderately dangerous to handle, and depending upon which dosage form is being made (eg. injectible, smokeable, etc) for every 1 kg of methamphetamine "cooked" 5 kg of hazardous waste are produced (just a cool factoid I came across).
Another interesting tid-bit of information I came across is how to tell if a meth lab is close by (& thus be able to stay far enough away in case it blows up, and also allows you to try to keep clear of any of that hazardous waste. Apparently, a meth lab in production gives off a very strong odor of cat pee. And you thought that crazy old lady down the street just really like her pussy. ;^P
So, perhaps one reason that so many people died from the MAOI/methamphetamine combination in the 1960s may have been due to pseudoephedrine adulteration of the speed. This may have contributed to the perception that the MAOI/amphetamine drug-drug interaction is more dangerous and deadly than it really is.
Another possible explanation for the decrease in mortality over the past 40 years is the advances in the treatment of hypertensive crisis, both in efficacy and safety of the newer medications, as well as improvements in the delivery of emergency medicine.
I just thought I'd better clarify and update my last post. I hope that this is of some use to you. - Cam
poster:CamW
thread:554271
URL: http://www.dr-bob.org/babble/20050914/msgs/555795.html