70mg hydrocodone, 5mg alprazolam, 50mg diphenhydramine, and 500mg cipro as a potentiator, feeling nice again, was getting in an unpleasant mind-state earlier.
Good. Just got 2 scripts for OC80s, 1 for OC40s and 1 for oc20's. Also for bromazepam and lorazepam. Omw to fill those scripts now and then I'll be golden.
/edit: I'm on 160mg oxycontin, 1.25mg lorazepam and 12mg bromazepam. Also chainsmoking cigarettes, I'm pretty damn buzzed. Quite the contrast to this morning when I felt horrible.
Cigs seem to potentiate opiates for a short while. I think I read somewhere that there's a real explanation for that, but I forgot what it was since it was quite long ago, I definitely feel a short boost in effects when I smoke cigarettes on opioids. When I have weed I don't have the urge to chainsmoke, mainly because weed+(good) opiates/oids send me off to nodland really quick, weed is a very strong opiate potentiator (it's actually a synergy rather than potentiator IIRC, but let's not get caught up on the details, I'll refer to it as potentiator). For opiates, IMO, weed is the king of potentiators (at least from all the potentiators I've tried on opiates) without making the high 'dirty' (think DXM or the like). Benzos are also awesome, but can be dangerous for the untolerant. Not advised unless you're experienced enough and have a high enough tolerance. Ket is a nice one too to use in small doses while on opis. But I
very rarely use it for that purpose, since it's too nice of a drug to use just for potentiation.
An excellent potentiator of hydrocodone is ketoconazole - it drastically increases the amount of hydrocodone converted to hydromorphone and increases the half-life of hydromorphone from what I remember of the mechanism of action and I do not know if it increases plasma levels of hydrocodone or not, but this is one of if not the best potentiator of hydrocodone and some other opiates you can get - but it may not be as effective for other opiates that do not have a stronger metabolite increased in level from this mechanism. I know it is great for hydrocodone and works maybe to a lesser extent with other opiates. Perhaps it would cause a similar thing with oxycodone, converting to oxymorphone, not looking that up.
But what it is even better at is potentiating alprazolam/Xanax and some other benzos. Erowid states in the alprazolam FAQ that it increases AUC (Area Under the Curve, a measure of total systemic exposure to the drug) 3.98 fold.
Here is a list of interesting drugs that should be potentiated by ketoconazole, a potent CYP450-3A4 inhibitor:
opioids (mainly analgesics)
alfentanil[32][34]
buprenorphine[37] (analgesic, anti-addictive)
codeine[32] (analgesic, antitussive, antidiarrheal)
fentanyl[32]
hydrocodone (partial involvement, not the bioactivation factor)[38]
methadone[32] (analgesic, anti-addictive)
levacetylmethadol[32]
tramadol (to inactive metabolites, do not confuse with metabolism via CYP2D6)
benzodiazepines
alprazolam[32][34]
midazolam[32][34]
triazolam[32][34]
diazepam[32] (bioactivation to desmethyldiazepam)
some hypnotics
zopiclone[34]
zaleplon[32]
zolpidem[32]
Others
Methoxetamine
Cocaine
DXM
Oxycodone (does not say how ketoconazole affects it, but it is going to do something probably not too different from itraconazole if the effects on it are similar to what ketoconazole does to alprazolam
MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of oxycodone, which is substantially metabolized by the isoenzyme. Increased oxycodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. According to some manufacturers, oxycodone systemic exposure (AUC) was, on average, approximately 2.4-times higher (range 1.5 to 3.4) during coadministration with itraconazole (200 mg orally for 5 days); 1.8 times higher (range 1.3 to 2.3) during coadministration with telithromycin (800 mg orally for 4 days); 3.6 times higher (range 2.7 to 5.6) during coadministration with voriconazole (200 mg twice daily for 4 days); and 1.7 times higher (range 1.1 - 2.1) during coadministration with grapefruit juice (200 mL three times daily for 5 days). Because oxycodone is also partially metabolized by CYP450 2D6, the magnitude of interaction may be even greater with concomitant use of a CYP450 3A4 and a CYP450 2D6 inhibitor, or concomitant use of a drug that is a dual inhibitor of both isoenzymes.
Grapefruit juice can really potentiate this one significantly but for some very little. And the degree of potentiation widely variable among individuals so be sure to start with a much lower dose.
Alprazolam
From the drug interaction checker, it seems it may be even better (although with alprazolam it looks like it is more an increase in the duration of effects without the maximum blood concentration not affected too much). Oxycodone, the one you asked about, is dramatically potentiated by ketoconazole,
In pharmacokinetic studies, itraconazole (200 mg/day) and ketoconazole (400 mg/day) individually increased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and elimination half-life (T1/2) of a single 0.25 mg oral dose of triazolam by more than 3-, 22- and 6-fold, respectively, compared to placebo. Similarly, Cmax, AUC and T1/2 of a single 7.5 mg oral dose of midazolam were more than 3,- 10- and 3-fold higher, respectively, during coadministration of itraconazole or ketoconazole relative to placebo. The AUC of a single 2 mg IV dose of midazolam increased 5-fold after pretreatment with ketoconazole. The results for alprazolam have been less dramatic, presumably due to limited first-pass metabolism in the intestine. In separate studies, itraconazole and ketoconazole increased the AUC of alprazolam (0.8 and 1 mg single oral dose) by 2.5- and 4-fold, respectively, compared to placebo, while Cmax was not significantly affected. Pharmacodynamic changes associated with the interaction include increased and prolonged sedation, enhanced benzodiazepine-related EEG effects, and increased impairment of psychomotor performance. The interaction is subject to a high degree of interpatient variability.
Hydrocodone
MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of hydrocodone, which is substantially metabolized by the isoenzyme. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Because hydrocodone is also partially metabolized by CYP450 2D6, the magnitude of interaction may be even greater with concomitant use of a CYP450 3A4 and a CYP450 2D6 inhibitor, or concomitant use of a drug that is a dual inhibitor of both isoenzymes.
One thing to keep in mind is that CYP450 2D6 inhibitors reduce the amount of hydrocodone converted to hydromorphone and with the wide variation among individuals (from poor metabolizers to ultra-rapid metabolizers), inhibiting 2D6 may make it stronger or weaker, you just have to find out for yourself.
Also, using ketoconazole for very long can have serious health effects and there may be short term problems I don't know about. But I was doing this for quite some time without negative effects that I could detect. Try at your own risk, it is a powerful potentiator but it can have side effects. Don't forget to add diphenhydramine or doxylamine succinate (or better yet, hydroxyzine). Adding a low amount of DXM (maybe 60-180mg or something like that) may be helpful but you can experiment with that yourself.
Do not use cimetidine as a potentiator with ketoconazole as it reduces ketoconazole levels as much as 75%.
