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DXM/Q

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Dextromethorphan-Quinidine

January 31st, 2018:  This page will be focusing on my journey with the cutting-edge experimental combination of non-prescription drug Dextromethorphan and prescription drug Quinidine for treatment-resistant neuropathic pain and central sensitization syndromes (including Fibromyalgia). This page will be written for the general public on my experiences with DXM/Q over the next month or so. As a philosophy of mind scholar, I will also be publishing a formal paper on Academia.edu, and I will be posting a link to that paper here for physicians and clinical researchers. This a purely self-guided study on my part (that’s right, I’m playing the part of the patient, doctor, researcher, and pharmacologist here) with the assistance of my exceptionally supportive neurologist, whom is prescribing the quinidine. My blood pressure has been monitored throughout this process by my in-home physical therapist, and my first EKG came back normal. I use my own oximeter to measure my heart-rate.

For those interested in pursuing this combination of medications for central sensitization syndromes, please ask for a referral to a neurologist or chronic pain specialist and print off this page to take with you to your appointment. Dosages will vary per patient.

Current Dose:

  • 75mg Dextromethorphan (DXM) Hydrobromide (HBr) – for its analgesic properties. 1xper day.
  • 300mg Quinidine Sulfate (Q) – to inhibit the metabolites Dextrorphan and 3-Hydroxymorphinan, in which result in the psychoactive properties of Dextromethorphan. 1x per day.
  • 2.5mg Cyclobenzaprine – To reduce the muscle tension and jaw clenching side effects of DXM.
  • 133mg Magnesium Glycinate – To reduce the muscle tension and jaw clenching side effects of DXM without increasing the cyclobenzaprine.

The dose for quinidine is approximately 4.5 times the dose of dextromethorphan within the first month. For the first month, the patient should take one dose in the morning and one dose before bed. Recommended 15mg increase of DXM per 1-2 weeks. After one month, only one dose may be required in the morning and the quinidine may be reduced to 4x the amount of dextromethorphan. Increasing beyond the 45/200mg at the 4.5x, for me at least, seems to lead to the quinidine side effects of increase muscle and joint pain.

UPDATE: Magnesium and tizanidine are not enough to counteract the long term muscle tension side effects of DXM. Switching back to low dose (2.5mg) cyclobrnzaprine resolves these side effects with a much longer half life without increasing the potency of the DXM.

UPDATE: 03.04.18: Magnesium supplements relieve some residual jaw clenching/tightness side effects.

UPDATE: 02.26.18: The DXM/Q seems to have successfully treated my Meniere’s disease. No vertigo or nausea at all.Also, increasing quinidine by at least 50mg decreases excessive yawning and related symptoms.

UPDATE: 02.19.18: I may be able to use other medications to increase the pain reliving effects of the DXM/Q without increasing those drugs specifically (example: the guaifenesin increases those effects but negatively impacts my muscle weakness, jaw clenching, excessive yawing, so other medications may increase the effects without these side effects, also any medication/supplement that increases the CYP3A4 enzymes may increase the analgesic effects). So, there are still options to take this further, but for now, my efforts will be on clearing up the brain fog caused by the anticholinergic effects.

UPDATE: 02.06.18: The guaifenesin addition appears to be leading to an increase in serotonin, whereby increasing the side effects of jaw clenching, excessive yawning, and teeth chattering. I will be removing the guaifenesin and readjusting the dextromethorphan and quinidine.

UPDATE: 02.04.18: Since coming off my flexeril 10mg at bedtime which increases the strength of DXM, I am re-establishing the DXM/Q balance. Since I am currently getting over the flu, it’s hard to do as of right now. But, the current amounts are 30mg, 20/400mg, 200mg.

Introduction

  • Experimental PrecedenceDextromethorphan and Quinidine in Adult Patients with Uncontrolled Painful Diabetic Peripheral Neuropathy
  • Dextromethorphan has been the only medication that has ever significantly targeted my pain.  I have known this since 1996. The higher the dose, the more my pain disappears. In fact, at very high dosages all of my pain is completely gone, all of it.  However, the side effects of high doses of Dextromethorphan alone were not tolerable. The addition of Quinidine Sulfate drastically reduces those side effects. The current dose is just the beginning, as only some of my worst pain has been successfully treated. My body will decide how high I can really go as there are limits to how much quinidine the body can handle.

History

Dextromethorphan & Its Metabolites

Dextromethorphan is a sigma-1 receptor agonist and an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Dextromethorphan and it’s metabolite 3-Methoxymorphinian produce analgesic effects. Dextromethorphan metabolites Dextrorphan and 3-Hydroxymorphinan produce the dissociative and hallucinogenic side effects of Dextromethorphan. For neuropathic and central sensitization pain reduction the therapeutic benefits of DXM/Q inhibit the dissociative and hallucinogenic side effects of Dextromethorphan, whereby allowing the analgesic effects of Dextromethorphan to remain.

Quinidine

Is a class I antiarrhythmic, acts as a blocker of voltage-gated sodium channels, blocks certain voltage-gated potassium channels, and acts as an antimuscarinic and alpha-1 blocker.

Cytochrome Enzymes

Quinidine increases plasma levels of Dextromethorphan by competitively inhibiting cytochrome P450 (CYP) 2D6, which catalyzes a major biotransformation pathway for Dextromethorphan. Quinidine also increases the systemic bioavailability of Dextromethorphan. Dextromethorphan exposure is increased by about 20-fold with quinidine, compared with dextromethorphan administered without quinidine. Quinidine also increases P450 (CYP) 3A4, which again increases the analgesic effect of dextromethorphan.

Prescription Alternatives to Quinidine

Finding The Effective Combination Dose

Quantitative Approach – I found that the balance of dextromethorphan and quinidine was strongly correlated with heart rate. Using a standard oximeter, I noticed that increased heart-rate was always present when the dextromethorphan side effects were still noticeable. However, heart-rate was normalized when the correct dosage was obtained. This normalization of heart-rate was measurable approximately 15 minutes after the dose was taken.

Qualitative Approach Closed-eye visual hallucinations at bedtime should be no stronger in quality than visual noise (specs of light). Moving auras or abstract designs suggest an increase of at least 50mg of quinidine may be required. Complex geometric hallucinations suggest upwards of 100mg of quinidine may be required. When the dextromethorphan dose is too high during the day, patients may describe visual hallucinations such as objects appearing more rounded than usual, some loss of color vividity,  and some loss of depth perception. Also, tunnel vision, apathy, zoning out, mind blanking, and a slightly altered perception of time may be reported. When the proper therapeutic dose is reached, the patient may use the word “comfortable” to describe the way they feel at rest. Dosage may need to be increased to reach comfort levels not at rest.

Initial pain may be increased over the course of several days for those who are sensitive to medications with vasodilation properties. The pain will be noticeable after the first dose begins to wear off. The vessels will adapt to this dilatation within about three days.

Increases in startle response during the day or at night (often noticeable by being woken up startled by sudden outside noises), are likely caused by too much of the guaifenesin. Alpha2-agonists have been found to increase the startle response.  Guaifenesin may be acting similar to an adrenic agonist, whereby increasing the startle response. In this case, eliminate or reduce the dose of the guaifenesin. Alternatively, try using an alpha-2 blocker with the guaifenesin.

Effective Dose Side Effects

Anticholinergic/Antimuscarinic effects – (Brain Fog)

Supplements being assessed currently.

  • Forskolin
  • L-carnitine

Supplements being considered.

  • Choline
  • Phosphatidylcholine
  • Phosphatidylserine
  • Docosahexaenoic acid (DHA)
  • Thiamine
  • Pantothenic acid
  • Vitamin B12
  • Taurine
  • Huperzine-A
  • Korean ginseng (may increase startle response).
  • Cessation of medications that increase these effects. (Full list)

Residual dissociative effects

Supplements being considered.

  • Glutamic acid

Stimulant effects

Supplements being considered.

  • Diphenhydramine (Benadryl) for sleep due to it’s sedative properties. It is also a 2D6 inhibitor so comfort levels are increased overnight. It also has no effect on 3A4 enzymes. Recommend 25-50mg when needed the first month of taking DXM/Q until a single daily dose can be taken in the morning only. Diphenhydramine also has anticholinergic effects.

Sedative effects

  • Reduce quinidine dose by about 25mg.

Excessive yawning effects

  • Increase the quinidine by at least 50mg.

Jaw clenching effects

  • Increase the quinidine by at least 50mg.
  • At least 2.5mg of cyclobenzaprine.

Contraindications

There are many medications that can increase or decrease the effectiveness of DXM/Q. I will be putting together a thorough list soon. In the meantime here is a short list of medications and supplements that can increase the potency of dextromethorphan: flexeril, melatonin, valerian root, and goldenseal (also inhibits 3A4).

SSRIs such as fluoxetine (prozac) should not be taken with DXM/Q unless the dose is very, very low. Caution should be used with using DXM/Q and MAOIs.

Guaifenesin increases serotonin, whereby increasing the side effects of jaw clenching, excessive yawning, and teeth chattering. It may also increase the startle response at night, reducing sleep quality, whereby leading to muscle weakness and fatigue during the day. L-theanine and caffeine increase the jaw clenching side effects, though magnesium supplements do seem to partially counter this effect.