Carvedilol and ed

Symptoms: constant muscle weakness, constant muscle fatigue, low appetite, low sex drive, heart area weakness, ED, lethargy
A1C 4.4
Male 22, type 1 diabetic of 13 years. African American. 6’4 225LB. For the last 5-6 years I have intense heartburn experienced constant extreme muscle fatigue. Not only in functionality, but the inside of my muscles constantly feel weak as well. The only way I can best describe the sensation I feel in my muscles at nearly all times would be high blood sugar. It feels as if something is constantly eating away at my muscles. When this all started I felt intense heartburn and fatigue. I assumed that my insulin was no longer working, because my body would feel as though I was at least in the 300-400s. Unfortunately every time I checked my glucose it would never be high. If it was high it would be low 200s. Definitely nothing to warrant the way I was feeling. I was a high school senior when this began in 2018. I was an athlete back then, in quite good shape. I loved running and lifting, however I never pushed myself too far. Now it’s as if every time I attempt lift weight or gain muscle in my arms I experience the unpleasant sensation mentioned above only stronger. I feel it all hours of the day, even when I attempt to flex my arms. It’s like something “eats” away at my progress. if I was instructed to do 10 pushups, I could do them (with a little difficulty considering I’m not as spry as I once was haha). Within the next few minutes the sensation intensifies in mainly my biceps and upper arms, numb and trembling. it doesn’t seem to affect my deltoid strangely. After only 10 pushups, it feels like I’ve tried to do 60 pushups in a row. Same concept with any arm exercise. My legs don’t feel nearly as bad as my arms, but they still feel weak as well. I am able to walk, run, and jump. However I’ve noticed that anytime I do workout my legs, not only do they feel somewhat like my arms but I never get sore like I used to. No matter the exercise, it’s like I never even worked out. Frequent need to urinate. I’m quite tired all the time. I’m exhausted no matter how much sleep I get. I could sleep through an entire day if I tried. In early 2020 I was given a Transthoracic echocardiogram the to summarize these are the results posted on MYMERCY: “There is mild concentric left ventricular hypertrophy, most likely athlete's heart. No significant valvular dysfunction.”
They just assumed it was mild Cardiomyopathy. At first I was relieved to finally receive a diagnosis, but even after being prescribed 2 medications (carvedilol and lisinopril) my symptoms did not improve. I still felt the constant muscle fatigue, the heart burn, and the chest weakness. In January of this year I was asked to do another echocardiogram. Keep in mind, none of my symptoms have improved in any way. These are the results: “Mitral Valve: Normal Leaflets. Trace regurgitation. No stenosis. Tricuspid Valve: Normal. No regurgitation. No stenosis. Pulmonic Valve: Normal. No regurgitation. No stenosis. No findings consistent with cardiomyopathy or athlete's heart.”
I won’t lie, seeing that bummed me out. I just want to know why I feel like this all the time. I’ve tried everything. Altering my diet, taking a truck load of vitamins, I’ve tried positive thinking…but nothing works. I feel terrible no matter how good my glucose is. I lost my scholarship because of this and not to sound dramatic, but I can’t enjoy life feeling like this. I just want to feel good again….or as good as you can feel with Diabetes… you know what I mean. I don’t even care what illness I have. I just want to know so I can get treated and be free of the pain. Thank you all for your help.
Medical procedures done in the last 3 years.
Multiple Metabolic: panels all levels within normal range.
Emg: no signs of Delayed nerve response
Gastric emptying: Normal gastric imaging time
Upper endoscopy: no signs of damage of any kind
Checked for parasites as well, stool samples proved negative.
2x Muscle biopsy 1 in each thigh
Genetic blood testing, negative for ALS and MS.
Urinalysis: PH UA= 8.5 WBC UA= 6-10
Negative for Rhabdomyolysis
Negative for Addisons disease
Negative for any thyroid disorders.
Negative for Sickle Cell
Not sexual active (….unfortunately)
Suspected diabetic ED (…equally unfortunate)
Duodenal biopsy Gastric biopsy Esophagus biopsy
CTA CHEST ABD PELVIS

I feel like attendings always correct me or even if they don't correct, they just throw in comments, which make me feel like it's personal. Maybe it's the medical knowledge part, but I don't think I'm stupid or anything compared to my co-residents.
1) A patient comes in for uncontrolled HTN. He is already maxed on Lisinopril and amlodipine. He is also on clonidine. He tried HCTZ in the past but stopped due to side effects of ED... And he states he was on spironolactone but I couldn't find anything. So anyways I said let's discontinue clonidine and restart/start on spironolactone. And the attending is like nowadays I've seen cardiologist using carvedilol more than spironolactone for HTN. This guy doesn't have any cardiac history, not tachy, I didn't think carvedilol would lower BP as much as spironolactone. So she looked on up-to-date and didn't see much that says carvedilol was better than spironolactone for BP control, but was like switch spironolactone to carvedilol at the next visit..
2) A patient comes in with headache that is more consistent with tension headache than migraine. I typically start on amitriptyline (CGRP not covered well in my area), but then the attending says amitrptyline is off-label and it should be topamax. I looked up on uptodate and they are both off-label, but it looked like uptodate says amitriptyline is most frequently used than topamax for prevention? The attending then goes "oh well but still we use topamax".
3) A 65+ patient comes in for COPD exacerbation. No risk factor for Pseudomonas. Followed uptodate algorithm and prescribed augmentin. And was told that is not the right antibiotics and should be doxycycline (if not azithro or cephalosporin). Again, I showed uptodate, and was brushed off.
I understand that maybe I followed uptodate straight up, but I don't think my medication choices were wrong. So was this attending being an asshole or was there something that I'm missing in terms of knowledge?
Edit: 1) got deleted and some spelling for typing over the phone

Hi I’m 22 and I was recently diagnosed with hEDS and I’m getting diagnostics done next month to diagnose POTS (although I am fairly certain that I do have POTS). I’ve always had issues with sleep. When I was really young I would have nightmares most nights so I wouldn’t sleep well, then in middle school I was sleeping too much. Then in Highschool I had PTSD so I would keep myself up to not have nightmares and end up falling asleep in classes. After Highschool I started over-sleeping again and was still falling asleep in classes. And in college I started having some issues being tired while driving. I would often sleep through alarms for work or classes in the morning. I’ve been in veterinary medicine for a little over 3 years now which is physically and emotionally very demanding which I’m sure hasn’t helped. I’ve been working swing shifts and overnight in ERs for about the past 2 years. Initially I felt significantly better, and I wasn’t late frequently from sleeping through alarms and it was easier to stay awake on the drive to and from work. I’ve been struggling with chronic fatigue for a long time but lately everything has been worse. I am constantly tired. If I’m sitting down, especially if I am leaning on something there is a very good chance I will fall asleep and if I lay down I will fall asleep. My husband has been getting very frustrated because I can’t even hardly stay awake to watch a show with him. One of the really frustrating things for me is that the chronic pain feels like is getting worse too (mainly back and hips), so I just want to sit or lay down and be comfortable, but I can’t without falling asleep. And it doesn’t help that I have practically no motivation or energy to do anything. I’ve also noticed that the past few weeks I’ve been really cold when I’ve never been the kind of person to always be cold. I’ve also had urinary issues (frequency and urgency) for a while which I feel have been worse too. Although I will admit that I have been drinking more water which I’m sure contributes. I feel like I have a fairly solid sleep schedule. I generally get home about 7:30-8:30am, and I’ll eat enough to take my many meds (currently- Venlafaxine, Lo Loestrin, Rosuvastatin, Carvedilol, and vitamin D3 & B12 supplements), then sleep from 9am until about 2pm. Around this time I’ll eat a snack and fall back asleep from about 2pm until 5pm when my husband gets home. I avoid caffeine because of my hypertension and tachycardia so I only drink a soda (no energy drinks) on my way home from work and sometimes during my shift to stay awake. I’m not entirely sure why I’m writing this, I just feel like everything is getting worse. I am under the care of a PCP, a Gynecologist for endometriosis, 2 Cardiologists (1 for hypertension and 1 for Familial Hyperlipidemia), a psychiatrist for depression, and I have autonomic testing next month.

My dad is a 66 male (relatively healthy, no smoking, no alcohol. Only medications are amlodipine 5 & carvedilol 6.25 bid) just had chest pains and taken to the ED. Found to have 99% blockage in the OM2 with 70% blockage in the LAD & D1 in a bifurcated fashion. Here are the pictures of the heart cath: https://imgur.com/a/eTu6APJ
He received a stent to the OM2, but now is needing to decide between CABG vs stents for the 70% blocked LAD/D1. I understand the CABG is a major surgery, but he is better equipped to handle it now rather than if he was older. I also understand that stents could get blocked and would need restenting in the future. I was just wondering if you were in his position, would you pick CABG or stents? Any advice is appreciated.

I had posted awhile ago that I was having random rocketing BP. For reference, I am 65F; BMI -25. My Cardio Dr let me choose which BP med to try...with the proviso that he really preferred that I stay on my current meds- Carvedilol 6.25mg 2x; Clonidine .1mg 1x (this helps with pain management as well as evening BP issues) and just add on. So, I went with Amlodipine for 2 reasons: Lisinipril makes me feel like death warmed over (so I am assuming that an ARB may be just as bad, but its still on the table) and in researching, Calcium Channel Blockers seem to generally be advised for older folks. I was Rx-ed 5mg, but I cut in half (cleared this with dr) after first day. I am a slow metabilizer of every thing, so the 2.5mg is working GREAT. My BP in the mornings has been 110/65 to 125/75. I have not had the "spiking BP" to crises levels all week! I had been suspecting I may be on too much Levothyroxin for hypothyroidism, so I reduced my dose. This was helping "some", but the LOW dose Amlodipine along with my other bp meds is really helping alot. Virtually no side effects at this dosage. It all seems too good to be true. :-)

BIO - 37M, 5'10, 200 lbs, caucasian, Non smoker, non drinker, no recreational drugs, duration of symptoms -
Duration: This seems to have steadily gotten worse over 20-25 years
Medications:

1. Fenofibrate 54mg 1 time a day
2. Xyzal 24 hr 1 time a day
3. Tizandine HCL 4mg 1 at night
4. QUETIAPINE Fumarate 50MG (Seroquel) 1 at night
5. Pramipexole 1MG 1 at night
6. Carvedilol 80mg 1 in the morning
7. Ketamine Troche 300mg 3 x week
8. Prilosec 24 hour 1 x day

Existing medical issues:

1. Chronic feeling of tightness on the left side of my face. It started with a feeling of pressure behind my left eye. I think it's a nerve thats inflamed or something. Ongoing for 20 years.
2. Almost completely numb left side of throat. I don't feel food much going down that side of my throat but a swallow study shows it does in fact. Also chronically stiff feeling left side of tongue.
3. Chronic really bad acid reflux, Famotidine did almost nothing, prilosec helps a bunch though.
4. Intermittent high blood pressure. It ranges mostly from the high 130s/80s to 155/90s.
5. Max heart rate is low Maybe not an issue but i seem to have autonomic problems, Heart rate doesn't climb to a normal rate when working out hard. It's almost impossible to get it to the 90% range, and personal trainers and my last PCP both thought it was weird. (personal trainer commented on how they've never had this issue with any clients and I was working out to near muscle failure)
6. Intermittent loss of sensation on skin of left side of body.
7. Insomnia - I think this is due to being unable to relax
8. Stiff joints, especially on left side of body, physical therapists of different kinds have all said they think I have some neurological issue
9. Myoclonic Jerks - I'm getting an eeg to see whats causing it in a few days
10. Severe irritability- I developed this out of the blue a year and a half ago. Small things all of a sudden make me really mad.
11. ED and inability to orgasm - Started having issues with the latter at 21 same time as #12. ED came later. ED meds don't seem to do anything.
12. Left side of urinary tract numb - I had to relearn how to tell when I needed to go pee as I barely feel it. Started when I was 21
13. Evidence of brain issues - Recently had a PET scan done following a MRI. The scan showed a pattern matching primary and secondary parkinsons as well as early onset Alzheimers. I've been told my Seroquel could cause this as well as hypometabolism. The MRI showed nothing of note.
14. Possible visual hallucinations a couple times upon waking up. Both within the last few months.
15. Trouble feeling like bladder is empty when peeing, and emptying bowels. My body seems to switch between mild constipation and mild diarrhea all the time. Meds for urinary issues seem to do nothing.
16. I sweat an unusual amount when working out, as in I'm a spectacle at the gym. I think that may have been SSRI's though which I have stopped taking.
17. Restless leg Syndrome
18. Right eye randomly tears up, this is. a new issue and I'm planning to see an ophtamolgist soon

Primary Complaint- I want to be able to relax. I wonder if its possible if my Parasympathetic nervous system could be messed up or blocked or something due to neurological issues. If you skimmed through my health problems you may have noticed many of these could be part of an underlying neurological issue.
I've been tested for a host of autoimmune diseases and everything has come up negative. MRI looks normal, my FDG PET scan was abnormal though specifically, the scan showed a pattern matching primary and secondary parkinsons as well as early onset Alzheimers. I've been told my Seroquel could cause this result on the PET scan as well as hypometabolism. I've probably had 15 doctors tell me I have something neurological going on. And 3 neurologist in all say they don't think I have MS.
But the worst thing of all my symptoms is my Anxiety and inability to truly relax. By relax I mean my mind won't calm down. I've been in this state virtually chronic for many years. There are a couple instances where this changed though.
The first was after an intense Ketamine infusion (about 160mg over 90 minutes) for a day or two I felt normal, it felt like a miracle. I had literally forgotten how it felt for my mind to be relaxed until that day. Then I was back to my normal tense state. The second instance this happened it was even more pronounced. I felt like I might be able to sleep for once without medication. I was seeing a holistic doctor and I went into a hyperbaric chamber for 2 hours followed by cold laser therapy on my brain. I thought one of these was the solution, but after about 20 repeated attempts over 2 months, this affect was only achieved one time. There where a few times a felt a little more relaxed but it seemed hopeless to get that relaxed state back. Maybe that one time was a weird fluke?
Anyways could my parasympathetic nervous system be messed up or something due to neurological issues? Any suggestions for types of doctors I should see or therapies I might ask my doctor about to treat this "relaxation" issue? I'm almost in tears here. I feel like the issue is getting more pronounced the more time goes on. It's crippling, and makes it really hard to get anything done. I spend almost all of my free time trying to relieve this anxiety/tension, or to try and numb myself to it. I've tried a million medications under the Sun, as well as TMS.
​

1. Edit: removed typo on medical issue 16

​

Age 39
Sex F
Height 5’2
Weight 250lb
Race white
Duration of complaint several weeks
Location Ohio USA
Any existing relevant medical issues
s/p total nephrectomy 2017 due to renal cell carcinoma/ s/p parathyroidectomey 2018 due to parathyroid hyperplasia/Chronic kidney stones/Rheumatoid arthritis/Fibromyalgia/Metabolic syndrome/Interstitial cystitis/IBS
Current medications
Current: * Zoloft * Metformin * Imuran * Carvedilol * Avapro * Prilosec * Myrbetriq Recently weaned: * Wellbutrin * Tramadol
Include a photo if relevant
A couple weeks ago, my husband found me sitting up on the couch with my hands/arms clutched up to my chest, having a seizure. I was cyanotic and unresponsive. I had foam around my mouth. This lasted around 8 minutes. I did not lose bowel/bladder control. I did bite my tongue quite badly.
This is the first seizure I’ve ever had, and I have no family history of seizures.
I remember coming to when the paramedics were entering the house. I was very confused and couldn’t remember what happened at least 10 minutes prior to my husband finding me. I was pretty post ictal, but was pretty oriented by the time we got to the ED.
I had a negative head ct in the ED, and some wonky labs. However I was allowed to go home with strict return precautions.
I had a normal brain MRI yesterday and have an EEG scheduled for tomorrow.
In the meantime I have weaned off of Tramadol and Wellbutrin, which I have been told can cause a lower seizure threshold.
I’m wondering if anyone can explain the theory of seizure thresholds? I understand that certain things (like medications) could raise the likelihood of a seizure.
But what causes the seizure? I’m not sure if this makes any sense and it’s just something that has no cause?

HX: long term lower GI bleed. Told by doctors for several years that there would be no way this issue would ever cause enough blood loss to be an issue. Fast forward... my H&H work their way down to 5.2/16.8. I become symptomatic, visit pcp few times over 10 days. We adjust htn meds to no avail. I force their hand to draw blood. Got the call later in same day to head to ER due to low H&H. Get 3 units emergent blood (1 month ago) and an uppelower gi scope along with a 4 night admission. Scope was inconclusive other than this one issue in the lower which they still swear I couldn’t be losing this much blood from this. The three units got my hgb up to 6.9, I trended up to 7.2 on my own before DC. As a side note I have disagreed with all the doctors on the source for years, def think it’s from this lower GI source. I got a referral to see someone to have this lower bleeding fixed ASAP. I am 2 weeks removed from have the bleeding stopped. My hgb has trended up to 8.8. Outward signs of bleeding have in fact stopped.
My info: 36 y/o Caucasian male in the US. Mildly fit and very active 6’5” 230lb (195.5cm 104.5kg) All standard drawn blood labs outside hgb are normal at this point
Occasional afib RVR (like less than once/year and no longer than a couple hours after taking my PRN flecainide)
Current meds:
Carvedilol 6.25 BID -htn
Flintstone vitamins for the iron
Gabapentin 300mg PRN @ bedtime -RLS
Aspirin 81mg - prophylacticly for AFib - currently paused
Flecainide - prn for afib
I am a full time Public servant/first responder as well as an RN working in the ED in a pretty busy area. 17 years in emergency medicine.
My question: How long should I expect it to take for my HGB to return to above 13?
Edit to say: Thanks for any input!! And add height/weight
Second edit: non smoke no recreational drug use. Alcohol only socially. Should’ve read the “about” before posting.
Third edit: realized formatting didn’t show up how I intended.

i am 48 years old. had a heart attack 3 months ago. had a blockage in artery and sten put in. feel good now, no issues but I am on 6 meds.
carvedilol, entresto, brilinta, baby aspirin, spironolactone, crestor
cholesterol was good and in rang, all my blood work was good, doctr said they were surprised at my good #s
just having a lot of side effects and I feel I am over medicated. sides
tired, weak, sluggish, no sex drive, ED, wired sweating, hot flashes, feet ache, hands go num, brain fog, just dont feel right
​
two questions
is a statin necessary when my cholesterol is good? two doctors told me sleep apena could be the biggest factor for the blockage that cause the heart attack. statin scare me
is it common to be put on this much meds after a heart attack?

I am a 40 year old male, white and of Cajun descent, 5'9", 165 lbs. Living in Boston. Currently non-drinker, never smoked, very occasional marijuana use in the past.
Over the course of the last 15 or so years, I have experienced what may be best described as a progression of a subset of "fight or flight" type symptoms, with notable jumps in severity during periods of extended stress (the first couple years of graduate school, work crunch times, etc):
The symptoms I have noticed (when unmedicated) so far are as follows, with most of them following a circadian rhythm, being at their lowest (although still significant) around 5:00-6:00 AM and at their highest around midnight.

• Increased muscle tension over the whole body, although worst in the jaw, sufficient by 2010 to start causing spontaneous subluxations in several locations including my knee, TMJ (when my mouth was at rest, slightly open and my teeth not clenched), metatarsals, and (possibly) ribs (my physicians have had strong opinions on whether or not this was possible, see also possible EDS below).
• Increased HR and BP (Both systolic and diastolic), notably following the circadian rhythm mentioned above, which is the inverse of the normal human rhythm.
• A sense of urgency/danger with all sensory inputs, as though in the moments before impact in a car crash or when someone takes a swing at you. But elicited by say, a box of cereal or a golden retriever puppy. Severe enough since about 2011 to elicit constant involuntary attentional orienting responses.
• Exacerbation of normal fight or flight responses, such as an increased change in heart rate from rest to exercise, or a very strong physical response to a minor surprise.
• Impaired working memory, cognition, and long term memory formation (possibly due to attentional issues)
• Insomnia, including difficulty falling asleep and being woken from sleep when the other symptoms get bad enough.
• A "restless limb" feeling, like a building pressure to move, present in in arms/legs/neck/torso.
• Dryness and audible "creakyness" in both eyes
• Reduced gut motility (noticed in a number of circumstances, but actually measured in terms of transit time when I accidentally swallowed the crown of a dental implant that came loose)

Other, possibly unrelated chronic conditions include

• GERD (treated with tums/rolaids)
• Reynaud's Syndrome
• ADD (diagnosed at age 12, currently treated with 10mg IR Adderall daily, although I have tried going unmedicated for this for multiple years, with no noticeable impact on the above symptoms)
• Asymptomatic celiac disease, diagnosed in 2009, treated with a gluten free diet
• Mild exercise induced asthma, treated with albuterol
• A family history of Ehler's-Danlos Syndrome, which I suspect I may have but of a type where I have been told there is no reliable test.

Notably, there is not increased sweating. Sleep deprivation reduces the intensity of the symptoms (leading to oscillating intensities with a period of about six days if I am not medicated, as insomnia builds up exhaustion until I can sleep, then sleep restores symptom intensity and corresponding insomnia). Intense aerobic exercise also provides partial short-term relief, with a noticeable reduction in symptom severity for maybe 2 or 3 hours per hour of strenuous exercise.
When these symptoms first became noticeable, the immediate thought was "Anxiety. Talk to my psychiatrist." I had either no response or a paradoxical response to every anxiety medication I was placed on (I can provide a list if requested), but gabapentin helped me sleep through the night.
After a couple years of effort and CBT, combined with the fruits of a lifetime of meditation practice (my parents were hippies), I was able to keep the elevated heart rate and sense of urgency attached to sensory inputs from triggering anxious thinking. I was and am able to live my life without intrusive thoughts, pathological worrying, or other hallmarks of anxiety. However, the listed symptoms not only remained following this process, but were growing more severe. When unmedicated, I can be meditating with a tranquil mind for hours on end, but my body still feels like it is bracing for impact right before a car crash. These symptoms can certainly impact my state of mind if I am not careful, but my state of mind seems to have little or no impact on the symptoms. I have seen three psychiatrists and multiple therapists regarding this, and the conclusion from them all has been that these symptoms are not a psychological or psychiatric problem, and I need to talk to a physician. I then spoke to several physicians, but was immediately told that it was anxiety and I needed to see a psychiatrist.
So with neither side willing to engage, I began looking into this myself, applying my background in computational biology. Based on existing theory, experimental studies, and my own modeling work, my current working hypothesis is that this is something like a stress-triggered, adult-onset Monoamine Oxidase A (MAOA) deficiency or hypofunction, which would (among other things) lead to elevated intracellular norepinephrine levels primarily in neurons of the sympathetic ganglia, which do not express COMT and lack the usual redundant metabolic pathway for breaking down MAOA. This would in turn multiply the effect of the standard activity of these neurons, increasing the norepinephrine released with each action potential. If anyone would like a detailed explanation of the reasoning that led to this hypothesis (including citations if desired), please let me know.
Unfortunately, both modeling work and experimental data from other labs suggest a lack of proportional change between enzyme efficacy, substrate concentration, and metabolite formation when dealing with these sorts of systems. Experimental publications show that even an order of magnitude increase in intracellular norepinephrine produces less than a 10% reduction in the rate of DOPEG(AL) production, and no commonly available metabolite panel would be able to detect that. (Most reference ranges are one-sided anyway, and only designed to detect increases, as in the case of a pheochromocytoma.)
With no tests available, I simulated various interventions and saw promising results with α2 agonism and/or with a blockade of postsynaptic α1, β1, and β3 receptors. Taking my simulation results, reasoning, and a ton of citations (omitted here for brevity, but all available upon request) around to physicians and psychiatrists, I convinced one psychiatrist to try Carvedilol as an α1/nonselective β blocker. It was immediately and stunningly effective, providing complete relief of literally all of the listed symptoms. Management of this prescription was then transferred to my GP, as it is not a psychiatric medication and he was uncomfortable overseeing it. With extended release doses twice a day, I had complete relief from my symptoms for the first time in over a decade. It was life changing.
I also arranged a blinded test with Carvedilol/sugar pills in capsules, to rule out this being placebo relief of conversion. The return of my symptoms predicted with 100% accuracy which ones were sugar pills. Even now, if I forget a dose, I am reminded when the symptoms return, right on schedule even if I am distracted or asleep.
The condition appears to be worsening, however. Increasing the dose of Carvedilol has reliably relieved all symptoms, but over the past few years it has needed to be increased several times, seemingly correlated to periods of stress in my life. Unfortunately, a lack of stress does not seem to restore the symptoms to their previous level. I have little memory of the last time I was off medication, but I am told I was minimally functional, slept rarely, and spent most of my time either exercising to exhaustion or in hours-long meditation and breathing exercises while I sat there twitching and trying not to scream.
I am currently on 100mg of extended release daily (40 in the morning and 60 at night), and seeing as I am beyond the maximum listed dose, my physicians are (understandably) unwilling to increase it further. At the moment all my hopes seems to lie in a better understanding of what this condition actually is. Unfortunately, my GP feels it is beyond her training to attempt to diagnose, and I have yet to see any specialists who are willing to attempt a diagnosis either...I am generally left in a limbo between departments with each one insisting it is the others' area.
I have managed two small victories so far. The first is that I found a geneticist who warned me that he does not expect any of the commonly tested mutations to account for my symptoms, but agreed to advise me in analysis of my own whole exome sequencing data if I got sequenced (which I am paying for out of pocket and having done early next month). This is a longer-term project, however, as it basically involves me doing a second PhD in my spare time.
The second is that my GP has agreed to do is oversee weaning myself off the medication for a week or so in order to schedule as many evaluations and tests as possible, adding as much data as possible to my medical records in the hopes that something will convince a specialist to see me and engage. She said she does not know which tests would be helpful, however.
In the meantime, I am seeking help from whatever online communities I can locate, in the hopes that someone will have an idea, or will have dealt with something similar. If anyone has heard of anything similar, has a curious question, a guess, or a notion of a test that might help narrow down possibilities or test my working hypothesis, please don't hesitate.

I am a 40 year old male of Cajun descent. Living in Boston.
Over the course of the last 15 or so years, I have experienced what may be best described as a progression of "fight or flight" type symptoms, with notable jumps in severity during periods of extended stress (the first couple years of graduate school, work crunch times, navigating a Title IX witness situation with retaliation, etc):
The symptoms I have noticed so far are as follows, with most of them following a circadian rhythm, being at their lowest (although still significant) around 5:00-6:00 AM and at their highest around midnight.

• Increased muscle tension over the whole body, although worst in the jaw, sufficient by 2010 to start causing spontaneous subluxations in several locations including my knee, TMJ (when my mouth was at rest, slightly open and my teeth not clenched), metatarsals, and (possibly) ribs (my physicians have had strong opinions on whether or not this was possible, see also possible EDS below).
• Increased HR and BP (Both systolic and diastolic), notably following the circadian rhythm mentioned above, which is the inverse of the normal human rhythm.
• A sense of urgency/danger with all sensory inputs, as though in the moments before impact in a car crash or when someone takes a swing at you. But elicited by say, a box of cereal or a golden retriever puppy. Severe enough since about 2011 to elicit constant attentional orienting responses.
• Exacerbation of normal fight or flight responses, such as an increased change in heart rate from rest to exercise, or a very strong physical response to a minor surprise.
• Impaired working memory, cognition, and long term memory formation (possibly due to attentional issues)
• Insomnia, including difficulty falling asleep and being woken from sleep when the other symptoms get bad enough.
• A "restless limb" feeling, like a building pressure to move my limbs, in both arms and both legs.
• Dryness and audible "creakyness" in both eyes

Other, possibly unrelated chronic conditions include

• GERD (treated with tums/rolaids)
• Reynaud's Syndrome
• ADD (diagnosed at age 12, currently treated with 10mg IR Adderall daily, although I have tried going unmedicated for this for multiple years, with no noticeable impact on the above symptoms)
• Asymptomatic celiac disease, diagnosed in 2009, treated with a gluten free diet
• Mild exercise induced asthma, treated with albuterol
• A family history of Ehler's-Danlos Syndrome, which I suspect I may have but of a type where I have been told there is no reliable test.

Notably, there is not increased sweating. Sleep deprivation reduces the intensity of the symptoms (leading to oscillating intensities with a period of about six days if I am not medicated, as insomnia builds up exhaustion until I can sleep, then sleep restores symptom intensity and corresponding insomnia). Intense aerobic exercise also provides partial short-term relief, with a noticeable reduction in symptom severity for about eight or nine hours following three hours of strenuous exercise.
When these symptoms first became noticeable, the immediate thought was "Anxiety. Talk to my psychiatrist." I had either no response or a paradoxical response to every single anxiety medication I was placed on (I can provide an extensive list if requested), but gabapentin helped me sleep through the night.
After a couple years of effort and CBT, combined with the fruits of a lifetime of meditation practice (my parents were hippies), I was able to keep the elevated heart rate and sense of urgency attached to sensory inputs from triggering anxious thinking. I was and am able to live my life without intrusive thoughts, pathological worrying, or other hallmarks of anxiety. However, the listed symptoms not only remained following this process, but were growing more severe. When unmedicated, I can be meditating with a tranquil mind for hours on end, but my body still feels like it is bracing for impact right before a car crash. These symptoms can certainly impact my state of mind if I am not careful, but my state of mind seems to have little or no impact on the symptoms. I have seen three psychiatrists and multiple therapists regarding this, and the conclusion from them all has been that these symptoms are not a psychological or psychiatric problem, and I need to talk to a physician.
I spoke to several physicians, but was immediately told that it was anxiety and I needed to see a psychiatrist.
So with neither side willing to engage, I began looking into this myself, applying my background in computational biology. Based on modeling work, my current working hypothesis is that this is something like a sort of stress-triggered, adult-onset Monoamine Oxidase A (MAOA) deficiency or hypofunction, which would (among other things) lead to elevated norepinephrine levels primarily in neurons of the sympathetic ganglia, which do not express COMT and lack the usual redundant metabolic pathway for breaking down MAOA. This would in turn multiply the effect of the activity of these neurons, increasing the norepinephrine released with each action potential.
Unfortunately, both modeling work and experimental data from other labs suggest a lack of proportional change between enzyme efficacy, substrate concentration, and metabolite formation when dealing with these sorts of systems. Experimental publications show that even an order of magnitude increase in intracellular norepinephrine produces less than a 10% reduction in the rate of DOPEG(AL) production, and no commonly available metabolite panel would be able to detect that. (Most reference ranges are one-sided anyway, and only designed to detect increases, as in the case of a pheochromocytoma.)
With no tests available, I simulated various interventions and saw promising results with α2 agonism and/or with a blockade of postsynaptic α1, β1, and β3 receptors. Taking my simulation results, reasoning, and a ton of citations (omitted here for brevity, but all available upon request) around to physicians and psychiatrists, I convinced one psychiatrist to try Carvedilol as an α1/nonselective β blocker. It was immediately and stunningly effective, providing complete relief of literally all of the listed symptoms. Management of this prescription was then transferred to my GP, as it is not a psychiatric medication and he was uncomfortable overseeing it. With extended release doses twice a day, I had complete relief from my symptoms for the first time in over a decade. It was life changing.
I also arranged a blinded test with Carvedilol/sugar pills in capsules, to rule out this being placebo relief of conversion. I was able to state with 100% accuracy which ones were sugar pills, because my symptoms returned during those periods. Even now, if I forget a dose, I am reminded as the symptoms return right on schedule, even if I am distracted or asleep.
The condition appears to be worsening, however. Increasing the dose of Carvedilol has reliably relieved all symptoms, but over the past few years it has needed to be increased several times, seemingly correlated to periods of stress in my life. Unfortunately, a lack of stress does not seem to restore the symptoms to their previous level. I have little memory of the last time I was off medication, but I am told I was minimally functional, and spent most of my time either exercising to exhaustion or in hours-long meditation and breathing exercises, trying not to scream while I sat there twitching.
I am currently on 100mg of extended release daily (40 in the morning and 60 at night), and seeing as I am beyond the maximum listed dose, my physicians are (understandably) unwilling to increase it further. At the moment all my hopes seems to lie in a better understanding of what this condition actually is. Unfortunately, my GP feels it is beyond her training to attempt to diagnose, and I have yet to see any specialists who are willing to attempt a diagnosis either...I am generally left in a limbo between departments with each one insisting it is the others' area.
I have managed two small victories so far. The first is that I found a geneticist who warned me that he does not expect any of the commonly tested mutations to account for my symptoms, but agreed to advise me in analysis of my own whole exome sequencing data if I got sequenced (which I am paying for out of pocket and having done early next month). This is a longer-term project, however, as it basically involves me doing a second PhD in my spare time.
The second is that my GP has agreed to do is oversee weaning myself off the medication for a week or so in order to schedule as many evaluations and tests as possible, adding as much data as possible to my medical records in the hopes that something will convince a specialist to see me and engage. She said she does not know which tests would be helpful, however.
In the meantime, I am seeking help from whatever online communities I can locate, in the hopes that someone will have an idea, or will have dealt with something similar. If anyone has heard of anything similar, has a curious question, a guess, or a notion of a test that might help narrow down possibilities or test my working hypothesis, please don't hesitate.

I am a 40 year old cis male, white, of Cajun descent. Living in Boston.
Over the course of the last 15 or so years, I have experienced what may be best described as a progression of "fight or flight" type symptoms, with notable jumps in severity during periods of extended stress (the first couple years of graduate school, navigating a Title IX witness situation with retaliation, etc):
The symptoms I have noticed so far are as follows, with most of them following a circadian rhythm, being at their lowest (although still significant) around 5:00-6:00 AM and at their highest around midnight.

• Increased muscle tension over the whole body, although worst in the jaw, sufficient by 2010 to start causing spontaneous subluxations in several locations including my knee, TMJ (when my mouth was at rest, slightly open and my teeth not clenched), metatarsals, and (possibly) ribs (my physicians have had strong opinions on whether or not this was possible, see also possible EDS below).
• Increased HR and BP (Both systolic and diastolic), notably following the circadian rhythm mentioned above, which is the inverse of the normal human rhythm.
• A sense of urgency/danger with all sensory inputs, as though in the moments before impact in a car crash or when someone takes a swing at you. But elicited by say, a box of cereal or a golden retriever puppy. Severe enough since about 2011 to elicit constant attentional orienting responses.
• Exacerbation of normal fight or flight responses, such as an increased change in heart rate from rest to exercise, or a very strong physical response to a minor surprise.
• Impaired working memory, cognition, and long term memory formation (possibly due to attentional issues)
• Insomnia, including difficulty falling asleep and being woken from sleep when the other symptoms get bad enough.
• A "restless limb" feeling, like a building pressure to move my limbs, in both arms and both legs.
• Dryness and audible "creakyness" in both eyes

Other, possibly unrelated chronic conditions include

• GERD (treated with tums/rolaids)
• Reynaud's Syndrome
• ADD (diagnosed at age 12, currently treated with 10mg IR Adderall daily, although I have tried going unmedicated for this for multiple years, with no noticeable impact on the above symptoms)
• Asymptomatic celiac disease, diagnosed in 2009, treated with a gluten free diet
• Mild exercise induced asthma, treated with albuterol
• A family history of Ehler's-Danlos Syndrome, which I suspect I may have but of a type where I have been told there is no reliable test.

Notably, there is not increased sweating. Sleep deprivation reduces the intensity of the symptoms (leading to oscillating intensities with a period of about six days if I am not medicated, as insomnia builds up exhaustion until I can sleep, then sleep restores symptom intensity and corresponding insomnia). Intense aerobic exercise also provides partial short-term relief, with a noticeable reduction in symptom severity for about eight or nine hours following three hours of strenuous exercise.
When these symptoms first became noticeable, the immediate thought was "Anxiety. Talk to my psychiatrist." I had either no response or a paradoxical response to every single anxiety medication I was placed on (I can provide an extensive list if requested), but gabapentin helped me sleep through the night.
After a couple years of effort and CBT, combined with the fruits of a lifetime of meditation practice (my parents were hippies), I was able to keep the elevated heart rate and sense of urgency attached to sensory inputs from triggering anxious thinking. I was and am able to live my life without intrusive thoughts, pathological worrying, or other hallmarks of anxiety. However, the listed symptoms not only remained following this process, but were growing more severe. When unmedicated, I can be meditating with a tranquil mind for hours on end, but my body still feels like it is bracing for impact right before a car crash. These symptoms can certainly impact my state of mind if I am not careful, but my state of mind seems to have little or no impact on the symptoms. I have seen three psychiatrists and multiple therapists regarding this, and the conclusion from them all has been that these symptoms are not a psychological or psychiatric problem, and I need to talk to a physician.
I spoke to several physicians, but was immediately told that it was anxiety and I needed to see a psychiatrist.
So with neither side willing to engage, I began looking into this myself, applying my background in computational biology. Based on modeling work, my current working hypothesis is that this is something like a sort of stress-triggered, adult-onset Monoamine Oxidase A (MAOA) deficiency or hypofunction, which would (among other things) lead to elevated norepinephrine levels primarily in neurons of the sympathetic ganglia, which do not express COMT and lack the usual redundant metabolic pathway for breaking down MAOA. This would in turn multiply the effect of the activity of these neurons, increasing the norepinephrine released with each action potential.
Unfortunately, both modeling work and experimental data from other labs suggest a lack of proportional change between enzyme efficacy, substrate concentration, and metabolite formation when dealing with these sorts of systems. Experimental publications show that even an order of magnitude increase in intracellular norepinephrine produces less than a 10% reduction in the rate of DOPEG(AL) production, and no commonly available metabolite panel would be able to detect that. (Most reference ranges are one-sided anyway, and only designed to detect increases, as in the case of a pheochromocytoma.)
With no tests available, I simulated various interventions and saw promising results with α2 agonism and/or with a blockade of postsynaptic α1, β1, and β3 receptors. Taking my simulation results, reasoning, and a ton of citations (omitted here for brevity, but all available upon request) around to physicians and psychiatrists, I convinced one psychiatrist to try Carvedilol as an α1/nonselective β blocker. It was immediately and stunningly effective, providing complete relief of literally all of the listed symptoms. Management of this prescription was then transferred to my GP, as it is not a psychiatric medication and he was uncomfortable overseeing it. With extended release doses twice a day, I had complete relief from my symptoms for the first time in over a decade. It was life changing.
I also arranged a blinded test with Carvedilol/sugar pills in capsules, to rule out this being placebo relief of conversion. I was able to state with 100% accuracy which ones were sugar pills, because my symptoms returned during those periods. Even now, if I forget a dose, I am reminded as the symptoms return right on schedule, even if I am distracted or asleep.
The condition appears to be worsening, however. Increasing the dose of Carvedilol has reliably relieved all symptoms, but over the past few years it has needed to be increased several times, seemingly correlated to periods of stress in my life. Unfortunately, a lack of stress does not seem to restore the symptoms to their previous level. I have little memory of the last time I was off medication, but I am told I was minimally functional, and spent most of my time either exercising to exhaustion or in hours-long meditation and breathing exercises, trying not to scream while I sat there twitching.
I am currently on 100mg of extended release daily (40 in the morning and 60 at night), and seeing as I am beyond the maximum listed dose, my physicians are (understandably) unwilling to increase it further. At the moment all my hopes seems to lie in a better understanding of what this condition actually is. Unfortunately, my GP feels it is beyond her training to attempt to diagnose, and I have yet to see any specialists who are willing to attempt a diagnosis either...I am generally left in a limbo between departments with each one insisting it is the others' area.
I have managed two small victories so far. The first is that I found a geneticist who warned me that he does not expect any of the commonly tested mutations to account for my symptoms, but agreed to advise me in analysis of my own whole exome sequencing data if I got sequenced (which I am paying for out of pocket and having done early next month). This is a longer-term project, however, as it basically involves me doing a second PhD in my spare time.
The second is that my GP has agreed to do is oversee weaning myself off the medication for a week or so in order to schedule as many evaluations and tests as possible, adding as much data as possible to my medical records in the hopes that something will convince a specialist to see me and engage. She said she does not know which tests would be helpful, however.
In the meantime, I am seeking help from whatever online communities I can locate, in the hopes that someone will have an idea, or will have dealt with something similar. If anyone has heard of anything similar, has a curious question, a guess, or a notion of a test that might help narrow down possibilities or test my working hypothesis, please don't hesitate.

Hope this is allowed. I tried to look on my own, but really didn't get anywhere.
I'm on a cardio rotation right now and I've noticed a lot of doctors prescribe things without any knowledge of pricing difference. A lot of the patients in the community I'm in are on disability, homeless, addicts, etc and while non-compliance is obviously an issue everywhere, I noticed in talking to patients that a decent number are actually compliant with heart related medication up until they run out or have to wait to get paid, etc. Some also have no insurance or just can't afford their medication to the point that they end up just coming into the ED repeatedly with CHF exacerbation or HTN emergency bc they ran out of carvedilol/metoprolol and are waiting to get paid, etc.
I'd really like to be able to suggest alternatives or alternative formulations or other tricks to help bring down cost. My attending mentioned to a patient in such a situation that she could purchase a regimen for about $4 a month, but that was the extent of what he could tell me.