Runner wrote:
As with overdose, you might be right, and a lot of people don't reach the threshhold point, but IMHO the rapid increase in heart rate after a meth hit is a clear example where the body has failed to stabilise itself/detox
This is not really the case and yet in a strangely paradoxical way it is. What needs to be understood here is what represents acute toxicity.
All drugs are toxins. Any substance which significantly alters homeostasis can be considered toxic. The dose is as mentioned, a deciding factor, but so is the integrity of the specific target system and degree of expected response. If the action of the drug helps to restore homeostasis or “normal state conditions” within non-metabolism dependant dosages, it is reasonable to say a subject suffering a condition for which the medication is designed to help may tolerate higher doses before toxic levels are reached.
The opposite of course also applies. Should someone with high blood pressure and arteriosclerosis take an alpha and Beta1 agonist, the lethal dose may be very low as these receptors control arterial constriction and heart rate. (But someone with low blood pressure and a healthy heart could perhaps tolerate several times this dose)
This is a rather simplistic representation, and many other factors can of course contribute towards and affect an outcome.
In brief, relative to cardiovascular actions:
Alpha 1 and 2 adrenoreceptor agonists => Vascular constriction
Beta 1 adrenoreceptor agonists => Heart rate increase
Beta 2 adreno receptors agonists => Vascular dilation
The natural body (endogenous) chemicals which affect these systems are noradrenaline (NA or norepinephrine) and adrenaline (epinephrine)
Amphetamine has strong CNS and peripheral actions. Primarily, amphetamine is a noradrenaline releaser. It does this by mimicking NA, and so is taken up by presynaptic receptors (known as uptake 1) after binding to the carrier molecule.
Once inside the cell it moves into the vesicle (storing NA) via another carrier molecule. Vesicle migration of amphetamine causes previously stored NA to be released. Amphetamine also reduces NA reuptake (the NA release control system) and inhibits mono amine oxidase (required to break down endogenous and other sympathomimetic amines). Extracellular levels of NA then markedly increase. It is this NA which mostly affects the heart rate, and BP.
Amphetamine also causes release of serotonin and dopamine from respective nerve terminals, and all three are involved in CNS responses. This is added to by probable increase in the biosynthesis of dopamine from the amphetamine released precursor noradrenaline.
At different dosages amphetamine and methamphetamine differ considerably in their peripheral and CNS actions. Methamphetamine is considered the more potent of the two in regards to CNS activity.
From Goodman and Gillman's The Pharmacological Basis of Therapeutics
Methamphetamine is closely related to amphetamine and ephedrine. Its pharmacological actions are similar to those of amphetamine, but it [meth] exhibits a different ratio between central and peripheral actions. Small doses have prominent CNS effects without significant peripheral actions; somewhat larger doses produce a sustained rise in systolic and diastolic blood pressure due in man mainly to cardiac stimulation. Cardiac output is increased although the heart maybe reflexly slowed.
Methamphetamine is principally used for its CENTRAL EFFECTS which are more pronounced than those of amphetamine and are accompanied by less prominent peripheral actions…..
What this is basically saying is that meth at low doses causes CNS effects and little cardiac effect involving peripheral circulation.
High doses can actually cause depression of the heart muscle. Amphetamine on the other hand increases both cardiac and CNS effects at low doses, with higher doses increasing heart rate further.
A possible reason for users experiencing a sudden increase in heart rate after a lower dose of street meth (5-15mg) could be explained by the level of unreacted pseudoephedrine in the speed. Ephedrine causes systolic and diastolic pressure increases and may or may not result in a higher heart rate. I believe this is often the thumping heart feeling experienced after a line of supposed meth.
Runner, this is in line with what you mentioned regarding purity. Many people claim to take a half point or more of base, crystal whatever. However, I believe most street whiz base is way less than 50% purity, with most of the contaminant being unreacted pseudoephedrine. It’s not always the case mind you. Anyone with half a brain and a conscience to go with it would be able to get around a 90% conversion with normal techniques, and be able to separate the rubbish.
If we were to examine each of the pharmacological properties of any drug, particularly sympathomimetic amines, we could draw up separate response curves to measure specific changes in BP, heart rate etc. and we would find each would have different dose level characteristics. This is because the binding affinity/ efficacy is different between types of receptor. This is also affected by the body’s efforts to maintain homeostasis, which may increase detoxification by increasing enzyme availability, reduce availability of the receptor through down regulation (more chronic use related), or even prevent activity through preferential binding from a natural antagonist - as seen in the case of some opiates.