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KDM and sleep

Discussion in 'General ME/CFS News' started by heapsreal, Mar 15, 2013.

  1. overtrain

    overtrain Medical Mafia needs to die via this virus.

    Minipress, otherwise known as Prazosin, has helped me. It's off-label for PTSD & was 1st prescribed for veterans. Have been taking 1-2mg a night since last summer, but nightmares have recently returned.... psychiatrist said ppl take up to 6mg & that 1 or 2 mg "is nothing".

    One side effect- rather, effect, as "side" effects are just that, effects- is inability to remember any dreams at all, at least at first, though I slept for the 1st time ALL night since -when? Can't recall that far back. No hangover. Apparently, nightmares cause physiological stuff that awakens the body.... but Minipress lets ppl sleep an additional- can't rem., 82? 92? minutes a night... :angel:

    Agreed on the Klonopin (wow, friends have horror stories), & the benzo w/draw & rebound anxiety, etc. Am at 2mg Xanax a day. This @%*^ is addictive. Uncool. :eek:
    Mattman1 and heapsreal like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    interesting, thanks. i thought i recognised it and googling it, its commonly used for high blood pressure, it looks like it has a short half life so would be good to help reduce any next day sedation. i will ask my doc about it.
  3. Shoesies

    Shoesies Senior Member

    Minipress huh? I shall research. I just cannot handle anymore withdrawing like benzos. Perhaps some are more sensitive and have greater symptoms coming off. Me, color me Linda Blair when I stop that crap. UGH.
    overtrain likes this.
  4. overtrain

    overtrain Medical Mafia needs to die via this virus.

    Apologies for length; I lost the original post when my MAC lost charge. If I had more time I'd write a shorter post again. Overall ramifications for ME where CYP is concerned, I don't know. But, at least to me, there's some red flags below we're all familiar w, like NADPH, mito, lipid synthesis, etc.

    Along w the doctor, the psychiatrist may not understand the genes/enzymes of interest in your body which act on 1/4th or more presc. meds..... one doesn't need a framed diploma on an office wall to get it lack of knowl. is dangerous, esp. in a multiple script scenario.....

    I only know about the following because a shrink gave me serotonin syndrome. Thanks to Dr. Google, & the fact I felt my head was about to explode right off my body, & the fact I had the common sense to immediately cease ingesting citalopram, I figured out I have combined heterozygous genotypes of CYP2D6 and CYP2C19 that are funky. Naturally, the shrink gave me a blank look when I brought this to her attn.

    Apparently, it's imp. to know where you fall in these categories with which drugs on what alleles, because four phenotypes exist: poor metabolizers (PM), ultrarapid metablizers (UM), intermediate metabolizers (IM) and normal metabolizers (NM).

    "What is cytochrome P450 2D6/2C19?
    Cytochrome P450 (CYP) is a family of enzymes that are involved in metabolism – including drug metabolism. Two of the more common enzymes are cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19). DNA variations in the genes that code for these enzymes affect the rate and extent of drug metabolism.
    CYP2D6 (cytochrome P450 2D6) acts on one-fourth of all prescription drugs, including the selective serotonin reuptake inhibitors (SSRI), tricylic antidepressants (TCA), betablockers, opiates, neuroleptics, antiarrhythmics and a variety of toxic plant substances. Some 7-14% of the population has a slow acting form of this enzyme and 7% a super-fast acting form. Thirty-five percent are carriers of a non-functional CYP2D6 allele, especially elevating the risk of adverse drug reactions when these individuals are taking multiple drugs. Drugs that CYP2D6 metabolizes include Prozac, Zoloft, Paxil, Effexor, Hydrocodone, Amitriptyline, Claritin, Cyclobenzaprine, Haldol, Metoprolol, Rythmol, Tagamet, Tamoxifen, and the over-the-counter diphenylhydramine drugs, Allegra, Dytuss, and Tusstat. CYP2D6 is responsible for activating the prodrugs codeine and other opioids into their active forms. The analgesic activity of the drugs is therefore reduced or absent in CYP2D6 poor metabolizers. Refer to list for substrates, inhibitors and inducers of CYP2D6.
    Therapeutic drug monitoring is recommended in patients with metabolic variations. Keep in mind that subjects with metabolic deficiency will have decreased drug clearance and require additional time to achieve steady-state. In contrast, subjects with increased metabolic activity (UMs) have increased drug clearance and will achieve steady-state sooner that extensive metabolizers. CYP2D6 activity also is dependent upon hepatic and renal function status, as well as age. CYP2D6 activity does not appear to change with age; however, CYP2D6 activity may appear to be altered because of age-associated changes in hepatic blood flow or a decrease in renal elimination of metabolites.


    Tricyclic antidepressants, such as imipramine and amitriptyline, and phenothiazine antipsychotics, such as thioridazine, inhibit cardiac potassium channels. Individual risk for drug-induced prolongation of the QT interval was shown to be related to genetic variants in genes encoding cardiac K+-channels, such as the HERG gene encoding for a K+ channel subunit.

    If CYP2D6 converts a drug that has a strong effect into a substance that has a weaker effect, than poor metabolizers (weak CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects; conversely, if CYP2D6 converts a different drug into CYP2D6 and CYP2C19 genotype-based dose recommendations for ...a substance that has a greater effect than its parent chemical, then extensive metabolizers (strong CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects.

    Why would I test for variations in CYP2D6 and CYP2C19 when monitoring prescription drugs?

    Genetic variations in a patient’s CYP2D6 and CYP2C19 genes can help explain unusual results observed:

    * Some prescription medications are converted/metabolized to a more active form. If the patient is a poor metabolizer, he/she may not experience adequate pain relief.

    Most CYP is anchored to membranes of the microsomal portion of the cell. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum.

    Knowledge of the P-450 system is critical in understanding drug metabolism and drug interactions. Listed below are 3 links that will show 3 different tables: The first table shows what cytochrome system is involved in the metabolism of various drugs (substrates). The second table shows various drugs and the various cytochrome P-450 enzyme systems that either inhibit or induce that drugs metabolism. Lastly the third table shows the various cytochrome P-450 enzyme systems and shows what drugs induce or inhibit the various enzyme systems.

    Table 1 - Various Drugs and the P-450 Systems Responsible for Their Metabolism

    Table 2 - Various Drugs and the Variuos P-450 Enzymes that Inhibit or Induce their Metabolism

    Table 3 - Various P-450 systems and What Drugs Inhibit or Induce the Enzyme System

    Table 4 - Drugs / Foods that Induce or Inhibit Various Cytochrome P-450 Systems and the Drugs that are effected by this Induction or Inhibition.

    Tricyclic antidepressants, such as imipramine and amitriptyline, and phenothiazine antipsychotics, such as thioridazine, inhibit cardiac potassium channels.307 Individual risk for drug-induced prolongation of the QT interval was shown to be related to genetic variants in genes encoding cardiac K+-channels, such as the HERG gene encoding for a K+ channel subunit. If the patient is a nursing mother and an ultra-extensive metabolizer, codeine therapy should be carefully controlled to prevent neonatal morphine toxicity.
    Codeine is ineffective at typical doses in up to 10% of Caucasians carrying two nonfunctional CYP2D6 alleles.


    Asians, Pacific Inlanders, African and African Americans have higher percentages of reduced functional or non-functional CYP2D6 alleles (between 40% and 50%) than do Europeans (26%). Therefore the percentages of PMs in the former groups are most likely higher. Pacific Islanders have a high frequency (41%) of a reduced functional allele CYP2D6*10, indicating slower metabolism. Non-functional PMs and reduced function IMs represent about 50% of African populations (non functional CYP2D6*17 represents 35% of allele variation). African Americans show twice the allele frequency of PMs compared with Africans (14.5% vs 6.3%). CYP2D6 activity also is dependent upon hepatic and renal function status, as well as age.

    What is polymorphism?
    In different people and different populations, activity of CYP oxidases differs. Genetic variation in a population is termed 'polymorphism' when both gene variants exist with a frequency of at least one percent. Such differences in activity may have profound clinical consequences, especially when multiple drugs are given to a patient. There are profound racial differences in the distribution of various alleles - data on a drug that works in one way in one population group cannot necessarily be extrapolated to another group.


    Is enzyme induction of CYP important?
    Yes. Although most of the CYPs can be induced (the notable exception being 2D6), perhaps the most important in this regard is CYP3A4. 3A4 is the most prevalent CYP in the body, and metabolises many substrates. The most important inducers of 3A4 are antimicrobials such as rifampicin, and anticonvulsants like carbamazepine and phenytoin, but potent steroids such as dexamethasone may also induce 3A4. The long list of agents metabolised by the enzyme include opioids, benzodiazepines and local anaesthetics, as well as erythromycin, cyclosporine, haloperidol, calcium channel blockers, cisapride and pimozide. Oral contraceptives are also metabolised, and their efficacy may be impaired when an inducer such as rifampicin is taken.


    Function
    This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates.

    Even more important than the inducers of 3A4 are the inhibitors. There is a long list - azole antifungals, HIV protease inhibitors, calcium channel blockers, some macrolides like troleandromycin and erythromycin, and the commonly used 'SSRI' antidepressants. Lethal clinical consequences can result from combining 3A4 inhibitors with drugs that are metabolised by this cytochrome. Non-sedating antihistamines have resulted in fatal arrhythmias, as has occurred with cisapride administration in combination with an inhibitor. Erythromycin in combination with theophylline may cause toxicity due to the latter.

    The clinical consequences of CYP polymorphism, inhibition and inducibility have already been mentioned. Unfortunately, these are potentially so complex that whenever you give a drug you should ask whether it has an effect on a CYP isoform, and whether it is metabolised by CYP.

    David Flockhart has composed (and maintains) a superb table of interactions at Georgetown University. Visit it! You may also wish to wander by Ed Hayes' excellent CYP page.

    Also: http://snpedia.com/index.php/CYP2D6

    Is CYP important in cancer?
    There has been much speculation about the role of the various CYP proteins and polymorphisms as causes of cancer. Some CYPs may activate pro-carcinogens to carcinogens; many are probably involved in the removal of carcinogens from the body. In addition, several cancers are hormone sensitive, and those CYPs involved in, for example, steroid or retinoic acid metabolism may play a crucial role in suppression or promotion of malignancies through such metabolism.


    For specific dosages see charts and tables adapted from Julia Kirchheiner, et al Molecular Psychiatry Feature Review, 9 442-473 (2004), "Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response," a meta analysis of published research from 1970-2003 on the relevance of pharmacogenetic effects of CYP 2D6 and CYP 2C19 on 36 antidepressants and 38 antipsychotics.

    Cytochrome P450 chemistry is fascinating and challenging. Note that the bond between the two atoms in an oxygen molecule is rather strong. This implies that a substantial amount of energy is required to break the bond - energy that is supplied by addition of electrons to the iron atom of heme. These electrons in turn come from the last protein in an "electron transfer chain". There are two such chains in cells that end up at P450. The first is in the endoplasmic reticulum (ER), and the protein involved is called NADPH cytochrome P450 reductase - electrons pass from NADPH to FAD to FMN and thence to heme. The second chain lurks within mitochondria. A complex bucket brigade of proteins hands the electrons down to heme. NADPH passes electrons to ferredoxin reductase, thence to ferredoxin (which itself has an iron-sulphur cluster), and from there to CYP. }

    o Cytochrome P450 Drug Table

    "To the Editor: There have been a number of reports that combination therapy with tramadol and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine +(1), paroxetine +(2), and sertraline +(3) can lead to serotonin syndrome. Citalopram monotherapy has also been described as leading to serotonin syndrome +(4), but we believe this has not yet been observed under coadministration with tramadol."
    (Yeah? TRY ME. I got chur "anecdotal" right here. The above is eerily akin to physician attitude toward ME.... "Anecdotal" needs dictionary revision to include "Hasn't experienced it him/herself".) I figured out I'm a heterozygous carrier of deficient alleles for both enzymes, bc metabolizing capacity of both pathways was reduced, hence the weirdest sensation I've ever had in my head..... Last, a friend was on NINETEEN diff. prescriptions & morphing into Jack Nicholson in The Shining.... Asked if his docs knew his CYP genotyping.... he asked & they didn't even know what he was referring to.


    And.... careful with herbs like St. Johns Wort.. teas, etc.... I take a lot of herbs & triple-check interactions now. :cautious:
    Last edited by a moderator: Oct 29, 2013
  5. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    overtrain

    I'd like to read your post but the font is too small for me!

    Would you mind clicking on edit at the bottom of your post and raising the size to 3?

    Thanks,
    Sushi
  6. barbc56

    barbc56 Senior Member

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    I'm not sure about other countries but when I was on an SSRI and Tramadol, my psychiatrist, the pharmacist were aware of this precaution. My psychiatrist looked up the dosage of each to make sure this would not happen. My neurologist already knew which dosages would be therapeutic without serotonin sickness which can be life threatening.

    Possible interactions are red flagged by the pharmacy.

    Barb
  7. overtrain

    overtrain Medical Mafia needs to die via this virus.

    I think you mean to write, "Ideally, possible interactions are red flagged by the pharmacy." I actually did ask the pharmacist and the shrink specifically about SS and both said no worries..... Was Walmart, & the pharmacist called my shrink to double-check. Maybe that's routine, but I was surprised my permission wasn't solicited prior to the call.

    I have no neurologist. Could have used one after that. Also, while taking Tram, I had some St. John's Wort tea, a few sips, just to see..... this was long before the SSRI debacle. Same reaction, only minor. And yes, SS has killed people.
    My system is quite sensitive to anything put in it- always has been- but meds like coedine do nothing whatsoever for me. This is why I start with 1/4 to 1/2 of any new med to see how I react. I'd only taken 1/2 the citalopram.

    Ahh, to live in an ideal world. :thumbsup:
  8. barbc56

    barbc56 Senior Member

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    When did this happen? Every pharmacy I have been to, at least the last five years have red flagged drug interactions. I believe it's in the computer system. One was only a week ago at Walgreens, not my usual pharmacy as I was prescribed a muscle relaxer for a torn muscle in my arm. Maybe, this is recent development? Possibly only serious interactions but then serotonin sickness is a serious reaction. Huh.

    I don't fool around with most herbs. I had two students whose parents took them off antidepressants and substituted St. John's Wort. One attempted suicide and barely made it. The other ended up in the hospital. These students had emotional disabilities so don't know if that made a difference.

    But remember these are my anecdotal experiences.

    Barb
  9. overtrain

    overtrain Medical Mafia needs to die via this virus.

    Anecdotal is valid.

    Maybe there wasn't a long enough window between going off the SSRIs and taking the Wort. There needs to be enough time.

    This was last spring. Same Walmart that attempted to hijack a prescription recently. I'd gone in & asked for the price only. Not a refill. Just price quote. She said it would be 20 mins. before she'd know. When I went back, they had FILLED IT. And attempted to charge me- can't recall- but out of my budget. When I reminded them they were to price check the med ONLY, the pharmacist said too late, we've filled it. I said so what. Give me back the prescription. He said he couldn't because he "wrote on it already." I said no, you can't just take a prescription and it makes no difference you wrote something on it. Took me 3 strong attempts (with a lot of attitude) but I did get it back, then promptly went to a supermarket & filled it for far less.

    Walmart? Nope. I'm over it.

    Herbs are far safer than BigPharma, but it helps to study them a bit.

    1. The Untold Story of Psychotropic Drugging


      Containing more than 175 interviews with lawyers, mental health experts, the ...... statistics like “psychotropic drugs kill twice as many people as homicides.Annually, psychotropic drugs are estimated to kill more than 2 1/2 times more people than are killed by homicide. And who is entrusted with protecting the public ...



      Careful out there.....:aghhh:
  10. barbc56

    barbc56 Senior Member

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    Oops!! I read Walmart as Walgreens. I'll go with Big Pharma:) Herbs and supplements are not regulated in the US and the only supplements I use are where I have a deficiency or has scientific backing.​

    Do you have a site for your reference? Remember statistics can be manipulated in terms of how you interpret them.​
    Thanks. Barb​

    ETA I just found that this is a movie backed by one of the sponsors of Scientology. I have heard these memes over and over and as someone who has worked in the field of psychology I take them with a grain of salt. Yes drugs can have side effects and psychiatrist who are not professional exist. But is it the drug that kills the person or depression ?
    YIKES!!!!!!!!​

  11. Misfit Toy

    Misfit Toy Senior Member

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    Whoever wrote about Flexoril is right on. I was on it a few years ago and it got me into a super deep sleep and I felt great the next day. Flexoril was originally an antidepressant that they realized was really good with pain and so that took it off of the shelves as an antidepressant and made it a muscle relaxer. I had a great vacation due to Flexoril back in 2007. Problem is, I became a nutjob on it after about a year. I became super hyper constantly.

    Remeron put 27 pounds on me.

    Klonopin....24 years of being on. No way am I going off of it. I know it would kill me and it does calm me down and help me to sleep. I take 1 mg at bedtime.

    Trazadone makes me beyond sick to my stomach and I can't sleep a wink on it.

    5HTP gives me the worst dreams ever. I have dreams of horror on it.

    I agree with Heaps, I am sticking to staying on Klonopin. Too sick to go through withdraw and it helps.
    Xandoff and heapsreal like this.
  12. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    I chose Xanax because it is a little less difficult to withdraw from than Klonopin. I have no intention of stopping it until and unless I recover from the ME. As long as it is helping, I will take it.
    Xandoff and heapsreal like this.
  13. jimells

    jimells Senior Member

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    My biggest fear about addictive medication is, what if I can't get it anymore? This could happen due to supply chain problems, lack of cash, doctors refusing (or threatening) to renew the prescription, or cancellation of medical benefits. So far I have experienced all but the first. Fortunately I'm not on any meds that are likely to cause big withdrawal problems.

    I had one doctor threaten to withhold access to migraine medication (Imitrex) if I didn't "get the blood pressure under control". Of course I only have high blood pressure at the doctor's office, but most doctors I've seen refuse to accept that could be possible.

    The state is constantly trying to cancel my Medicaid coverage. My disability check is $14 a month over the limit to receive Medicaid, so I will have no access to medical care after April 1, until Medicare starts on June 1. The fact that I am disabled due to a severe chronic illness is irrelevant. The Rules (which change nearly every month) say I make too much money, that's all that matters. After all *nothing* is more important the The Rules.
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  14. sandgroper

    sandgroper

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    thats interesting....i take it and i do not get any stage 3 or 4 sleep.....I thought one of the side effects was reduced stage 3/4 sleep and it was one of the reasons i was concerned about taking it....perhaps someone else can shed light on this as i know it is frequently prescribed
  15. sandgroper

    sandgroper

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    a cardio told me i was suffering from white coat hypertension - which is to say that my blood pressure was influenced by seeing him...i actually have a form of orthostatic intolerance where my HR and BP go up and sometimes (down) if yours is up when you go to dr it might not be white coat it might be a form of OI

    like you i don't like being on such a med but i also can't do without sleeping, and so far I have only had problems with one dr refusing to treat me if i was on it ......it does seem readily available and price seems to have come down but i hear you about the concern
    ahimsa likes this.
  16. overtrain

    overtrain Medical Mafia needs to die via this virus.

    The Spitfire likes this.
  17. overtrain

    overtrain Medical Mafia needs to die via this virus.

    What about filming yourself
    What about cellphone-filming yourself taking your own BP a few days in a row? Mine goes thru the roof- well, or DID a year ago when I attempted to get medical care for EBV?MONO-turned-CFS.

    Some ppl have 2 psychiatrists in the states.... & also stockpile in case of cut-offs or shortages. ER sees ppl going thru w/drawl all the time off various substances....
  18. overtrain

    overtrain Medical Mafia needs to die via this virus.

    I'm not interested in debating herbs vs BigPharma beyond what I have here, but it sounds like you're interested in learning more. Good for you! Google.

    Part of CFS for me is a direct result of overdoing everything. And needing that everything to be as perfect as possible. And doing for others what they can do for themselves. The days I have a brain, I use it for me, not that I can't share on this site my own observations, research, resources. The limited time I have left alive I reserve for my own genuine engagement on my own path.

    Re Scientology- sure, wouldn't surprise me. Nothing surprises me anymore.
    maryb likes this.
  19. jimells

    jimells Senior Member

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    Interesting idea. My current GP was fussing about my BP last week, suggesting the monitor may be out of calibration, which I suppose is possible, but seems unlikely. If she keeps fussing about it, I'll insist on a 24 hour BP monitor, and grit my teeth when the thing wakes me up every hour.
  20. Old Salt

    Old Salt Rowing the boat

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    I was being violently awakened between the hours of 2 and 4 am by a nightmare, with tachycardia and stomach cramps then chills for an hour. The md's had no clue. A naturopath found I was reacting to wheat and citric acid consumed during the day. He used an electric dermal device. Taking digestive enzymes alleviated that problem, as I believe they attacked my Candida gut issue but the die off results in no sleep and urinating every hour during the night but not so during the day. For us, sleep issues are probably due to gut dysbiosis! The more I deal with the gut bugs, the less I sleep!

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