Any detailed reference websites for physiological tolerance information?

[Aetherius Rimor]

I've found that sites like DrugBank and SuperCYP have greatly helped me in the process of learning pharmacology.

I've started getting to the point with my level of understanding that I'm having a hard time learning more due to not having access to academic journals or reference databases that contain the information I need to continue learning at a decent pace.

I have a copy of Goodman and Gilman's The Pharmacological Basis of Therapeutics, but I haven't had time to go through it thoroughly and use it primarily as a reference for concepts I don't understand.

What I'm trying to find is a data source that has breakdowns of tolerance with following information:

• Broken down into the independent effects that can be attributed to different physical mechanisms.
• Broken down between acute and persistent tolerance along with timelines for a return to base tolerance.
• Searchable by either the drugs that trigger it or the physical mechanism responsible for the effect (for cross-tolerance research)

While not required since I could do the research to find out if I have the information above, these would be nice too:

• Classification or break down of the physical mechanisms, is it metabolic, up/down regulation, g-protein channel decoupling based desensitization, etc; and any relevant information (CYP450 enzyme if metabolic for instance).
• Withdrawal effects also broken down and linked to the physical mechanism responsible for tolerance.
• Health related warnings when a drug's effects gain tolerance at different rates leading to increased toxicity.(Cocaine for instance)
• Health related warnings when a drug's withdrawal effects can be dangerous, so a tapered cessation is required (Benzos for instance).
• Any uncommon but possible tolerance/withdrawal related effects associated with a physical mechanism.

I really hope something like this exists.

 

[sekio]

You'll have more luck approaching this from a systems perspective than a compound-based one, I think. Tolerance and withdrawal is a response of the organism and is not necessarily linked to a specific drug - see also: opioid substitution.

Broken down between acute and persistent tolerance along with timelines for a return to base tolerance.

Don't we all wish there was such a thing. The fact of the matter is there are too many situational and personal factors that determine intensity and duration of withdrawal. Different people respond differently to drugs.

The best you're really going to manage is looking at the activity of the drugs in question and then seeing how human biology responds to disruptions in those systems. For instance, if you want to learn about morphine addiction, look at its pharmacokinetics, look at how it is typically used, look at how the opioid system in the brain maintains homeostasis, look at how it is related with reward, etc.

You'll not find a giant tome that says "Morphine is addictive under X, Y, Z, circumstances at a rate of W mg/day, and it lasts for V days...", or if you do, it won't be much more than generalization.

Perhaps you would want a pharmacopiea (doctor's prescribing guide) or at least the white papers for drugs in question (drug monographs). The Canadian one I know of is the Compendium of Pharmaceuticals and Specialties (CPS). This contains prescribing guides for narcotics, stimulants, etc, with "rule of thumb" dosing, taper stuff, etc. It's much less specialised into the addiction side of tings but it still is the closest thing I can think of.

 

[Aetherius Rimor]

This is disappointing.

I found this quote in a thread related to SSRI's and their reason for taking several weeks to become effective:

Actually this isn't entirely true, for the reason that Zalo posted above. 5-HT1A autoreceptors initially limit synaptic 5-HT. The first few doses of SSRI hardly increase 5-HT over baseline, maybe only 10-30%. Over the first few weeks of treatment the autoreceptors will desensitize. Synaptic 5-HT levels increase dramatically once that process is completed.

This is the type of information I'm looking for in a reference format. I want to more fully understand receptor tolerance/desensitization mechanics with regards to each specific type; so that when you have a pharmacological profile of drug A, you can deduce or at least have an educated guess as to the acute/chronic effects with regards to tolerance/withdrawal.

I suppose this is just a massive data collection and consolidation undertaking that hasn't been performed yet. The data is surely out there, just not in reference form I suppose.

 

[AlphaMethylPhenyl]

What drug type are you looking for in regards to tolerance specifically?