#its also the muscle pain and the nerve pain and the GI pain and the headaches and the angina and and and

[peachykcqt]

Do you have bendy ligaments or some other fresh hell?

I can't imagine how exhausting chronic pain is. Gentle hugs 💚

i sure do 😭 but ive also the "some other fresh hell" too lol, idk what exactly the cause of my chronic pain is i just know theres a lot of it :s ty for the gentle hugs tho 💚

[duality-disability]

on the 17th, I see GI & Genetics; and on the 18th, I see our new neurologist.

i'm.. So fucking anxious.

GI is a follow up to discuss test results to see if there's anything causing the issues we've had with our mouth and throat muscles.. which have gotten better as of the past week?

Genetics is new, is an inital intake, and is for some more private stuff, but then i'm also gonna ask to see if they can look more widely at possible genetic causes or predispositions we have that may be causeing our mystery illness

then.. Neurology is the one i'm really worried about.

We want to get MS ruled out, and honestly anything else that he can test for and be able to discount as not a cause of our issues.

So far with the notes we've been making; It's something that causes widespread pain, fatigue, messes with vision, blood pressure issues, issues regulating temperature & heart rate; Causes problems with weakness, numbness, dizziness, balance, maybe even our spacial awareness stuff - Pain with moving body limbs, our eyes, and difficulty with bathroom habits; both joints and muscles also affected. Headaches/migraines..

It's also something that, flares up and then gets better. In a very repeating cycle - But each time it flares, it gets worse. So it's a slowly descending downwards spiral.

it's. All of this shit is pointing to somethng with our nerves. That is the nerve specialty doctor.

I.. i dont want to be told its all in my head again. I'm not imagining my knees buckling from under me or staying up until 6am with imagined pains. Something is wrong and i need it to be found out before it kills me.

Edit: If you've never been in my notes before or interacted with me, please stop attempting to diagnose us based off of 1 post. Thanks.

[myrawjcsmicasereports]

 Schwannoma: A C Sigmoid Colonase Report & Review of Literature by Muneerah Khalid Aljadidi in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

Colorectal schwannoma is a rare neoplastic growth originating from the myenteric plexus of the GI tract, which was described for the first time in 1962. It is an extremely rare presentation, with around 95 reported cases with only 28 reported cases in the sigmoid colon. This paper presents a case report of a 55-year-old male patient with complaints of constipation, per rectal bleeding, and on-and-off abdominal pain. He was worked up coloscopically and radiologically and found to have a sigmoid colon mass with ulceration and lumen narrowing leading to colonic intussusception. Preoperative biopsy was inconclusive. The patient underwent open sigmoid resection after proper preoperative preparation, with his postoperative histopathology reported as sigmoid colon schwannoma.

Background/Introduction

Verocay, in 1910, was the first to describe a benign rare neoplasm of ectodermic origin growing from the neural sheath and characterized by the presence of Verocay corpuscles (Baig et al., 2019). This growth, later known as schwannoma, is a tumor originating from the Schwann cells of the nerve sheath of the peripheral nervous system.

The presence of schwannoma in the gastrointestinal tract -from the myenteric plexus- is not a common occurrence. It is commonly found in the stomach (80%), followed by the small intestine (10-15%), while colorectal schwannoma is extremely rare (Uhr et al., 2016).

Due to its risk of malignant transformation, resection of schwannoma is the recommended treatment (Qi et al., 2021).

Case Report

A 55-year-old male known to have diabetes, hypertension, and end-stage renal disease on hemodialysis was referred to our hospital complaining of constipation secondary to colon mass. A physical exam showed a middle-aged, vitally stable man with a soft and lax abdomen. The patient's per rectal exam was unremarkable for masses or blood. Colonoscopy was done for him, and it showed a fungating ulcerating mass 40 cm from the anal verge, and the scope could not pass. Histopathologic examination of the colonic biopsy was non-diagnostic, with only fibrin and ulcer debris present in the sample. CT chest, abdomen, and pelvis with triple contrast showed the findings of mid-sigmoid colon mass with significant lumen narrowing with no high-grade bowel obstruction, with few mildly enlarged suspicious regional mesocolic lymph nodes suspicious for malignancy. FDG PET/CT scan was also done FDG avid rounded mass at the upper sigmoid colon in keeping with known colon cancer-causing colo-colic intussusception with no evidence of obstruction and no PET evidence of nodal or distant metastasis. The patient, after this, was taken to the theater for laparoscopic anterior resection with end colostomy and mucus fistula as primary anastomosis was not feasible due to poor nutritional status and co-morbidities. Post-operatively, the patient developed pseudomembranous colitis, for which he started oral and rectal vancomycin. He stayed stable throughout the postoperative recovery period and was discharged home in good condition. The sigmoid resection specimen demonstrated a 5 x 4.5 x 3.0 cm mass associated with mucosal ulceration. Histologic sections of the colonic mass revealed spindle cellular proliferation with alternating hypocellular and hypercellular areas (Wang et al., 2016). There are occasional thickened and hyalinized blood vessels seen throughout the mass. The tumor cells show eosinophilic cytoplasm and contain elongated wavy nuclei with fine open chromatin and indistinct nucleoli. There is no evidence of increased mitotic activity, necrosis, or marked cytological atypia. Immunohistochemical stains show that the neoplastic cells are diffusely positive for S100 and negative for DOG-1, CD117, desmin, and smooth muscle actin. The overall morphologic and immunophenotypic findings support the diagnosis of colonic schwannoma (Hsu et al., 2007; Wang et al., 2010; Chayanupatkul et al., 2018; Ferreira Cardoso et al., 2019).

Discussion

According to Bohlok et al. (2018), 95 cases of colorectal schwannomas have been reported distributed from the most common location to the least; cecum and right colon (30.5%), sigmoid (28.1%), rectum (21.1%), left colon (8.3%) the transverse colon (5.3%) and the appendix (1.15) with slight female predominance (58%) and a median age of 61.2 years.

The presentation of colorectal schwannoma varies on its presentation. It can be incidentally diagnosed in an asymptomatic patient during screening colonoscopy or with a wide range of symptomatic presentations, including abdominal pain, change in bowel habit - constipation, diarrhea or change in stool diameter, per rectal bleeding, tenesmus, decrease in appetite or weight loss (Zippi et al., 2013; Pansari et al., 2020). It can also present with a mass effect complication, e.g., intestinal obstruction or intussusception. Two reported cases where schwannoma was diagnosed during workup with a synchronous colorectal adenocarcinoma (world journal of surgical oncology page 97 & Page 77)

Due to its wide range of presentation, the workup of colorectal schwannoma follows a seemingly similar route to the workup of any colorectal mass. On colonoscopy, schwannoma varies in its gross appearance as a polypoidal lesion or a submucosal mass with normal overlying mucosa, which might mandate the use of endoscopic ultrasound and deeper biopsy or FNA to reach an accurate diagnosis (Wilde et al., 2010). However, the mucosal covering might be ulcerating with bleeding/sloughing/lumen compromisation mimicking malignancy.

The initial biopsy specimens were non-diagnostic, most likely due to the superficial nature of submitted tissue material and the submucosal nature of this neoplasm, like in any other mesenchymal tumors of the gastrointestinal tract where a deeper and targeted sampling approach results in a higher yield diagnostic neoplastic tissue. Schwannomas are characterized by biphasic growth patterns of hypercellular areas (Antoni A) of spindled tumors containing elongated and wavy nuclei admixed with loose/myxoid regions (Antoni B). However, some of the classic findings of Schwannoma described in soft tissue and central nervous system counterparts may be absent in the gastrointestinal tract tumors. The presence of lymphoid aggregates at the periphery of the tumor is a helpful diagnostic clue but not identified in our case. The gastrointestinal stromal tumors (GIST) are the most common mesenchymal gastrointestinal tumor and occasionally can share morphological similarities with Schwannoma; thus, the immunohistochemical staining panel should include GIST markers (CD117 and DOG1 stains). The diagnosis can be confirmed by diffuse positivity for S100 and SOX10 and after the exclusion of other more frequent mesenchymal tumors (such as GIST and smooth muscle neoplasms).

Radiological studies such as enhanced CT or MRI to characterize the colorectal mass with the use of contrast to delineate the tumor and lumen patency better are recommended as part of the workup, especially when malignancy is suspected with the need to rule out metastasis (Fotiadis, 2005; Cak et al., 2015). Findings on CT scans were mentioned differently among the reported cases, including a mural-originating colorectal mass with low attenuation with either smooth margins or suspicious edges, compromised lumens, thickened wall, fat stranding, and the presence of enlarged adjacent lymph nodes. All these variations add more challenges to the diagnosis of this pathology.

Moreover, a preoperative FDG-PET CT scan has been done for 5 reported cases, including our patient. Despite that, all of them were labeled as benign. Four of these cases were FDG avid lesions making it more difficult to rule out malignancy without a pathological diagnosis.

Whether colorectal schwannoma was diagnosed pre- or post-operatively, the standard treatment is radical colorectal resection depending on the tumor location, without any clear recommendations for neoadjuvant or adjuvant treatment (Kojima et al., 2020). Despite this, there have been several cases that were diagnosed preoperatively and found to have benign schwannoma treated more conservatively by endoscopic resection (page 12), cecal wedge resection (page 84), and trans-anal with no reported recurrence, yet small sample size is very limiting.

Postoperative histopathology is the final accurate way to diagnose schwannoma. Grossly it tends to be lobulated well-defined tumors, sometimes ulcerating into the mucosa with rich staining of S-100. Histologically, there are two recognized patterns, Antoni A, with a dense growth of fusiform cells compactly arranged in palisades to form Verocay bodies, and Antoni B, in which the fusiform cells are distributed more loosely with rounded and elongated nuclei, myxoid stroma and xanthomatous histiocytes (Nonose et al., 2009).

Miettinen et al. (2001), divided colorectal schwannoma into three clinicopathological types; spindle cell, epithelioid and plexiform. All three types are positive for S-100 protein and GFAP but lack CD117 (KIT), differentiating it from GIST tumors.

Despite these histological features and types, judging a colorectal schwannoma as benign or malignant depends pathologically on its mitosis rate, atypical mitotic figures, and nuclear hyperpigmentation, Ki-67 index with a value of more than 10% considered malignant. Clinically, long-term local recurrence or distant metastasis have also been used to judge the malignant state of a colorectal schwannoma, with only 3 cases reported in the literature.

Conclusions

Colorectal schwannoma is a rare disease with a wide range of presentations but mostly benign courses. Differentiating it from other mimickers is the biggest challenge, yet excision seems to be the main treatment approach.

Conflict of interest:

There was no conflict of interest in making this case report.

Declaration:

Ethics approval and consent to participate & Consent for publication:

Patient has been consented

Availability of data and materials: Available through citation, literature review, imaging and pathology pictures

Competing interests: No competing interests

Funding: By the author

Authors' contributions: Both authors participated in writing the manuscript and revision of data

Acknowledgements: Dr. Mohammed Alsomali for his participation in the pathology related data.

[diabetesreversalprograminindia]

10 Health Conditions Often Found with Diabetes

This article is originally published on Freedom from Diabetes website, available here. Unhealthy diets combined with lack of physical exercise and high-stress levels are known to trigger a phenomenon known as insulin resistance. The big issue of diabetes is a damage to organs. Without treatment, it worsens and causes many health issues.

10 Common Conditions That Follow Diabetes:

Heart disease Atleast 50% diabetics are suffering from the heart disease. It has some common risk. Smoking, obesity, lack of exercise, high-fat diets, and alcohol overconsumption are commonly seen in both these conditions. That also means that the measures that work to manage blood sugar levels (BSL) are equally effective in lowering the risk of heart damage. In this condition your first priority should be take care of your diabetes, and try to maintain normal blood sugar levels. So try to follow proper diet inlcuding healthy eating, low GI fruits, carbs, fiber, protein, and micronutrients like antioxidants are considered good for both the heart and BSL. Including your dialy routine exercise, meditation can help reduce stress and lower the risk of heart disease.

Joint Pain

Uncontrolled BSL can cause significant damage to the musculoskeletal system leading to compromised mobility and pain. Almost half of all adults with diabetes end up with arthritis as well. This is a result of high BSL that damages nerves and blood vessels, which goes on to erode the cartilage that cushions joints.

Muscle mass loss Everyone wants to build muscle, but it's especially important for diabetics. While walking used to be the main exercise recommended, doctors now recognize that muscle mass is crucial. Muscles burn glucose, so having more muscle helps burn more calories.

Slow-healing wounds

This is the most common symptoms of mismanaged diabetes is slow-healing wounds. Lack of sensitivity—caused by nerve damage—most often seen in the lower extremities means that cuts, blisters, and small sores can go unnoticed, becoming a breeding ground for harmful bacteria. This leads to open wounds, which the body is unable to quickly fight off owing to its compromised immunity, due to high BSL.

5.Hypertension (High BP)- Like diabetes, hypertension does not noticed easily. Many diabetics also have high blood pressure, often due to insulin resistance. Regularly check your blood pressure; if it's over 120/80, you may be at risk for hypertension. One of the primary causes of diabetic hypertension is plaque build-up on arterial walls, which is caused by high LDL cholesterol (aka, “bad” cholesterol). Losing weight is the first step in reducing risk and preventing complications. And this means, switching to a healthy diet, getting regular exercise, managing stress, stopping smoking, and reducing alcohol consumption.

Do you want to know more about, Skin Problems, High Cholesterol, Cancer, Memory loss, Fragile bones, and joint problems, visit our Article. To read more about this, please visit our Article. Also please connect with me on my website, Facebook page, and YouTube if you want to stay in touch or give me any feedback!

[redrobin-detective]

Side Effects of ghost powers

Hey all! I’m writing a DP fic called Side Effects exploring the physical and later mental/emotional impact of Danny initially getting his ghost powers. As an ICU stepdown nurse for 3 years, I wanted to view Danny’s accident through a slightly more realistic, medical lens. 

Note: I had to fudge a good amount because Danny really should have fucking died and there’s no getting around that.

I do recommend you read the fic first before reading this as there’s some spoilers. Or if you don’t care you can read on. So! The two factors we are looking at regarding the accident are: ecto-contamination secondary to electrocution. 

Electrocution

I was forced to downplay a lot of the severe symptoms of electrocution because, again, a bad enough shock will kill someone. My hand-wavey explanation is simply that the portal didn’t activate at a deadly voltage so he got a good shock but not enough to be fatal. I guess.

Muscle weakness/spasms: intermittent muscle spasms are common from shocks, muscles being activated by electricity and reacting to the lingering impulses. Danny’s is transient but quite annoying for a time. But his muscles are gonna be weak and achy af for days if not weeks after from the massive contractions caused by the shock and the after effects. Sensory issues: lots of things can cause nerve damage, including electrocution so Danny is experiencing some pretty severe neuropathy primarily manifesting with numbness and tingling throughout his body. His entire skin and peripheral nervous system got fried so while its mostly numb it’s also super sensitive for a bit of time causing massive pain and discomfort from your body tingling like a thousand bee stings. It’s worst in the hours after the accident but is something that never quite really goes back to normal both from the electrocution and his ghost half taking over and generally dulling his sense of touch.

Hearing/Vision loss: Like skin/nerves, your sensory organs in your eyes and ears would be affected by such a severe and allover electric shock. Danny has some blurred and occasionally double vision from his eyes not properly receiving/understanding input. Hearing loss is common following electricity given how delicate the inner ear is but I just give Danny some nasty tinnitus (ear ringing) for a bit. This inner ear problem also massively throws off his balance when he’s trying to move post accident. These factors are exacerbated by the ecto-contamination and mostly fade in the days following the accident before going away as his superhuman healing kicks in.

Heart Arrhythmia: an irregular heartbeat caused by the electrical impulses that control basal heartrate not coordinating they they should for a variety of reasons, in this case, massive electric shock. Danny would be somewhat aware of it, its not exactly painful exactly but you can just feel that your heart isn’t beating right. Secondary side effects are dizziness, chest pain, fatigue and shortness of breath. This resolves almost entirely when Danny stabilizes

Cognitive issues: Danny got his brains a little scrambled in addition to his molecules being rearranged. The first third of the story Danny is very clearly NOT thinking straight and Tucker/Sam should not have left him alone. Shocks can cause things like irrational emotional behaviors from hormone release along with memory loss and depression. He constantly waxes and wanes in mood and opinions on what to do in the story and never comes to a true decision that, damn lucky for him, worked out on its own.

Ecto-Contamination

Alright so Danny got massively shocked, sucks right but people live through that all the time. Ecto-contamination is more tricky (not only cause its made up and I had to think about what symptoms it would theoretically produce) but because the effects are more life threatening. It’s also irreversible, once he was contaminated it was only something that could be survived not cured. 

So I theorized that Danny got shocked by the accident and was slowly dying of ecto-contamination and was pretty much clinically dead for a brief moment there, the death was enough for the large quantity of ectoplasm in him to immediately coalesce into a ghost (Phantom). So Danny was mostly dead but not quite, I’ve coded and brought back enough people to know it can be reversed somewhat. Danny becomes Phantom but the sudden stable formation of the ectoplasm into what its supposed to be, a ghost, caused his body to stop fighting the ectoplasm as a foreign invader and become part of the self. His core finished forming in his chest and his body started back up again, his ghost safely nestled in his once again living body as he slowly comes to grips with his actual death experience. 

Nausea/Vomiting: I likened the idea of ecto-contamination to radiation poisoning, something that is essentially the antithesis to life. One of the first symptoms of radiation is n/v which is also why it’s one of the first overt symptoms Danny has. He was heavily electrocuted/irradiated and his body wants to expunge it all. As for the ectoplasm/blood he vomits, that’s the next section. 

Gastrointestinal (GI) Bleed: So I was a little mean here. When one vomits up blood (or in this case ectoplasm/blood mix) it has to come from somewhere and a lot of the times it’s a GI Bleed. These are nasty, they need to be either cauterized or surgically repaired not to mention replenishing the blood lost. Fanon says that ectoplasm is at least mildly corrosive to humans so it is here, as it’s bonding to him, it’s literally eating him very slowly from the inside out which is causing a great deal of his internal pain. It’s not enough to be immediately life threatening but would kill him eventually. He developed some nasty bleeding ulcers in his stomach which let in blood and ectoplasm which were expunged. Danny’s core formed overnight and began healing the damage it had previously been causing but Dan is still gonna be vomiting excess blood/ectoplasm not to mention having black, tarry stools for at least a few days afterwards.

Hypothermia/Tremors: Hypothermia is when the body hits 95F/35C which Danny is just above at the start of the chapter. Danny initially starts shaking really bad (rigors) but as his body temperature cools further his shaking slows and eventually stops, a sure sign that the body is rapidly losing the fight to hypothermia and will likely die soon without immediate intervention. This is caused not only by the ectoplasm but his ice core shakily starting to form inside of him. Once he fully turns half ghost his hypothermia doesn’t change but it just no longer negatively affects him (I say Danny hovers naturally around 96-95F/35-33C getting much colder as Phantom at baseline. His body still can be damaged by going too cold but that’s a whole other post.) 

Incoherency/Hallucinations: I mentioned in the electrocution section that Danny is more than a little addled and the contamination didn’t help in that regard. Not only is he not thinking clearly but he’s also getting a little delirious and seeing things. Common hallucinations I see are: someone in the room watching you, things crawling on the walls, creeping shadows, you’re in the wrong place. I think its a solid 50/50 as far as Danny straight up hallucinating but also becoming more aware of natural ectoplasm that hangs around in the atmosphere. (And before anyone asks, yes Clockwork did come and visit, Danny just doesn’t remember)

Pain: Being electrocuted, irradiated, being dissolved slowly on the inside is enough to cause massive amounts of pain. Danny is 14, he doesn’t understand true pain and probably underestimated how much it would hurt. Once it got bad, it was almost paralyzing so it got to the point where even when he wanted to call for help, he couldn’t move or think past the horrible pain of his every molecule slowly dying and rearranging itself.

Weakness/Fatigue: I don’t really have anything much to add for this section that hasn’t been said in the others. Just the combination of all of the above meant Danny is so incredibly weak and fatigued, this will be problematic in the days and weeks following the accident as his body heals from the stress put on it. Poor boy was probably just getting past the worst of his symptoms by the time of the Lunch lady attack one month in.

Ghost instinct: Going off the medical rant for a minute to go into another aspect of the contamination present in the story, the idea of ectoplasm adding inherent ghostiness to Danny. Its common fanon that all ghosts (through ectoplasm) have their own unique code and language that is just omnipresent and instinctive. Such a massive, body altering dose of ectoplasm saw those things start to leech into Danny even before he became half ghost. The biggest is his fear of being seen, majority of ghosts are completely invisible and don’t want to be seen by the living. As Danny’s suffering and literally dying, he can’t bring himself to confess to his loved ones for very understandable reasons but also this ghostly instinct in the back of his head telling him to hide and get away. Other instincts are a strong attraction to the portal/Ghost Zone, lowkey being able to sense living people around him and a bit of an emotional dampener when Phantom. 

[war-torn-and-collateral-damage]

So I have a new medical update for everyone!! As many of you know I have had a very hard time finding a decent doctor and getting answers to my medical problems. Since 2017 when I was diagnosed with "Functional Neurological Disorder" my medical issues have only gotten worse, I have been subject to abuse, maltreatment and dismissal by the healthcare system time and time again. BUT!!! Finally, over 4 years later I have a doctor who is AMAZING who actually tested me for things, actually looked into my history, actually actively listened to me and my concerns and CORRECTED my diagnosis and gave us some answers.

Apparently, I have a rare genetic connective tissue disorder called Hypermobile Ehlers Danlos Syndrome, he was able to diagnose this based off of a 30 minute physical evaluation and my medical history, that is literally all it would have taken for another doctor to figure it out, hEDS itself explains why I have been dislocating/subluxing joints hyperextending/spraining and tearing muscles and ligaments for literally as long as I can remember. But you don't just have connective tissue in your joints, there is connective tissue in the entire body!!!!! In your head (this is why I am so prone to concussions) in your organs (which causes them to sag and makes things like digesting food difficult) etc.

hEDS alone does not explain everything but when it was confirmed today that it was paired with Autonomic Dysfunction we finally got some insight into what is going on!!!!

First off, we learned recently that my seizure/paralysis episodes are triggered by cardiac events. That is, I go tachycardic prior to an episode, my heart rate jumps from resting to 170 in about 3 seconds.

This is because the Autonomic Nervous System (which controls involuntary body functions i.e:

dizziness and fainting upon standing up, or orthostatic hypotension

an inability to alter heart rate with exercise, or exercise intolerance

sweating abnormalities, which could alternate between sweating too much and not sweating enough

digestive difficulties, such as a loss of appetite, bloating, diarrhea, constipation, or difficulty swallowing

urinary problems, such as difficulty starting urination, incontinence, and incomplete emptying of the bladder, bladder retention

vision problems, such as blurry vision or an inability of the pupils to react to light quickly)

You can experience any or all of these symptoms depending on the cause, and the effects may be mild to severe. Symptoms such as tremors, shaking, and muscle weakness may occur due to certain types of autonomic dysfunction as well.

We also learned today that tranquilizers and nerve relaxers amplify these episodes of paralysis and shaking because it over relaxes the autonomic nervous system which explains why my episodes would last so long and become so severe because in the past doctors were treating me for "psychogenic Neurological symptoms" with anxiety meds, nerve relaxers and tranquilizers.

I was continously sent to PT and OT with no results and worsening symptoms, we learned this is because my body cannot regulate its temperature so I have an exercise intolerance, I work out, do strengthening exercises etc and get hot (as you do in a work out) but my body cant cool itself down so then the ANS freaks out and i have episodes. (We now have a recommendation and referral for hydro-therapy)

We also learned that I have NOT been having seizures this entire time, I have been having "shaking episodes" which is another more severe symptom of autonomic dysfunction.

Autonomic dysfunction is now also being investigated for the cause of my GI problems. My doctor believes I have autonomic esoughagial dysfunction with an R wave meaning my esoughagus is working in the wrong direction!!!! Testing for this has now also been recommended and ordered!!!!

Unfortunately we did also learn that there is not a cure BUT now that we know the problem we can work at preventing episodes and symptom management (trying to keep me cooled of for example) we also learned ways to get me out of an episode of paralysis by "shocking the nervous system" by using ice baths, smelling salts, pain stimulation etc.

We have in no way fixxed the issues at this point but today we actually got answers and validation and I consider that alone a blessing.

In an effort yo manage symptoms there are some things I need, ai get what I am able to when I have the money but I do not make much on disability so if anyone wants to help ojt woth items on my home health wishlist zi would very much appreciate it. I will link the list here. Thanks everyone for the continues support and encouragement.

[vtforpedro]

medical/life stuff - TWs in tags

hnnnnn this is long sorry I've got a lot of stuff going on and none of it is good lol beyond getting my third covid dose and flu vaccine, I guess. did those three days ago and only had mild fatigue and arm soreness this go around worried about actually getting covid from the pharmacy tho cause they didn't require masks and it was really busy hahahaha and so many people were coughing and sneezing and no one was social distancing hahahaha I am always scared of going anywhere, even to see my PCP, because of covid. it's my life now and has been since covid got to the US. I've only been this scared after going to the ER, truly hope I don't get sick. but looking forward to another year of fear either way anyway. have some abdominal stuff going on and there could be benign reasons but it hurts a lot. luckily I finally have my appt with an actual GI in two days. he's the same doc who did my colonoscopy/endoscopy. sooo we know I'm good from that procedure but when he presses on my guts and I react in Pain™ I'm a little afraid of what he might suggest lol 😩 also have some lady stuff going on that started a couple of weeks ago. I actually had an appt with an OBGYN scheduled so I could talk about getting off birth control since it's a leading (potentially) contributing factor to literally everything that's wrong with me. I canceled it because delta has gotten so bad and then of course my lady parts are now being weird. so I am going to reschedule in a few weeks once the vaccine is at its best cause I am also 1.5yrs behind on a pap also thanks to covid s i g h also! my leg muscles are atrophying. so that's really fun and exciting and I guess I get to set up an appointment with my pcp to figure out 🙃 what 🙃 I fucking do about it 🙃 because I can't do PT!!!! I can hardly do any physical movement which I assume is causing the problem because of my neuro shit, which is also not fixed and probably never will be idek how to process seeing my muscles shrinking in my legs. I'm trying not to think about it too much before I see my doctor but it's scary. it just is I don't know what else to say about it still in a weight plateau. trying to be kind to myself with reminders that I am stretched as thin as I can go and have new, awful stressors every fucking week (which makes me snack when I'm in breakdown mode and not on the good stuff, even if I'm sticking to my calorie budget) so it's not shocking weight isn't coming off. it still is, but at the most glacial pace. it's taken three months to get 9.7lbs down. should be at 15+. still really hoping I hit my big goal (just 10lbs away!!!!!!) before the end of the year I don't know if upping the dosage of nerve pain meds has helped or not because my IIH stuff is episodic now. my new neuro was actually willing to put me on the med no one else wants to without a lumbar puncture cause I am describing obvious elevated pressure in the brain which is causing expected IIH symptoms and he's not a moron. which is nice of him but I also don't want to be on it because it's not without moderate to severe risks? most people end up getting off it within a few weeks or months but hey at least he fucking believes me and said yeah it's prolly IIH but I can't diagnose you without the LP but let's cautiously treat it as IIH I've had two appointments with my psychologist now and I ...... like him....??? but also I don't??? he's fine personally, I think, but I have my doubts already about how he's going to be able to help me professionally. thinking of just calling it quits now and finding someone who takes my insurance so it'll be one less worry. I want to work on trauma and I feel like $150 was completely wasted last week so that's a red flag, right? lol finding a decent therapist is so fucking hard and I wish it wasn't my lease is up in mid-february so I will get a renewal offer no later than early-mid december. it's gonna go up over $400 lol four people have moved out in my building in the last month because of the increase. I paid $680 for this exact same apartment (before renovations but I barely

count them because they're cheap af) when I moved in and it's on the market for $1650-1720 now. makes me feel physically ill my mom can't afford it. she tells me she can, but I truly do not believe it. she says it would make her crazy trying to find somewhere else because I can't move in with her while my brother lives there, because I'm so disabled living there wouldn't be feasible for so many reasons, because I absolutely cannot stress Isis out (who had to go to the emergency vet again. but she's ok) or introduce my two cats to my mom's three cats, one of whom has FeLV. either way tho it's the disability!!!! I am trapped in my own apartment by my disability lmao my mom's friend wants to put me in his rental house but that's just too much. I can't have this giant upheaval in my life both physically and mentally. but I live and suffer in agonizing guilt every single day of my life because my mom pays for this apartment, which wasn't awful when I stopped working, but they've raised rent from $900ish to $1720 in *three years* it's insanity. I cry about this often because I can't move, my mom keeps telling me we can't, and not to worry about money but she's only saying that because it's impossible to leave I am so beyond stressed. this isn't counting what I went through with two (2) pen tablet companies to try to get a working fucking tablet so I could continue my commission. took 15 days but now I can work on art again. it was a nightmare september and october have been nightmarish months in every possible way actually lol rent wouldn't be *as* terrible if my disability claim got approved, but I would be shocked if not only it finished before early/mid-december, but if I get approved at all. and even if I do, every dollar would be going to rent and it wouldn't even be HALF OF RENT. I hate it here I hate this country I hate how it treats disabled and poor people I hate it hate it hate it hate my life too. I can't help it. I hate all of this and it feels like every time I'm begging the universe for a break it keeps throwing more shit at me instead. idk how to have hope anymore but that's been true for a long time now I suppose I have to be careful about how much/how hard I cry. a good hard cry no longer eases the tension but builds up insane pressure in my skull. I can't even cry for a release anymore like come on. it's a joke guys my life is just a joke now I had realllllllly hoped by the end of this year, after starting to lose weight in january, I would be telling you all that my IIH was cured. I shouldn't have hoped for anything at all p.s. I went back a couple of posts and realized I already talked about my neuro and the meds, sorry for saying the same stuff. I can't remember anything and I don't know what time is anymore

[eds-zebra-warrior]

2021 Ehlers Danlos Society Awareness Month (Day 8 Prompt: Movement and Activity

Movement and Activity can be very limited for those with EDS, especially those who have more severe symptoms and comorbidities. You may think of exercising as a run around the block or taking a trip to the gym. Others may think of exercise like going to physical therapy and peddling on a stationary bike slowly walking on a treadmill or working with elastic band. Exercise isn't always something that gets you out of breathe or your heart rate way up. For someone with EDS and some other conditions, exercise can take on a totally different meaning. Exercise can be some movements or positions that those who are healthy take for granted and do effortlessly without thinking twice about.

Exercise for us could be as simple as sitting up for a certain amount of time, remembering to change positions more often so we don't get blood clots, one of my exercises was rocking. Sitting on the couch and rocking back and forth or side to side just to get my bones moving a little bit to try to relieve some of my pain. doing light stretches or putting on AFO leg braces and sitting with our legs straight out on the couch to give them a little stretch to prevent furthering of spasticity I am one in a handful of EDS patients who cannot walk at all and is paralyzed from the waist down.

Though many EDS patients may have exercise plans such as walking to the mailbox and back each day, or bouncing on a balance ball, I do not have that ability do such activities and with my spinal issues which insurance will not cover the repair of it can be extremely dangerous for me to do things like this. For me sometimes it just a matter of lying on the couch on my back and trying to slide my foot up so my knee is bent and the bottom of my foot is flat on the couch with as little use of my hands as I can then extend it out straight again pushing with what little I still have in my legs, using my hands as little as possible to get it back straight out on the couch. I will also try this up by sliding it on the couch and trying to extend it by pressing my leg out, using a little help from my hands as possible to pull it back up which is much harder than doing so lying down. Many who are paralyzed or have paralysis have some movement in their legs, especially with a partial spinal cord injury but the movement usually isn't enough to do much with.

I cannot stand or support my own body weight on my legs but on my good days and in socks or shoes without clingy soles I can sometimes slide my foot back on my footplate if I go over a bump or something and my foot slides forward or off. This too is exercise by using what little I have to the best of my ability. I may not be able to lift my leg or move it well but sometimes I can slide it which is better than nothing. My doctors do not like me doing this anymore due to Osteoporosis however I still occasionally will put my KAFO leg braces on which have locks on them to lock my leg straight so my knee cannot bend and simply stand up in them. My legs cant do much as without them my knees would go out and I would go straight onto the floor but they do allow my body weight to distribute into my legs and my circulatory system to get some practice circulating blood in an upright position.

Another issue with EDS is movement disorders which is something I struggle with, sometimes worse than other times, especially in the evenings and when I have done too much. As mentioned in previous posts, the compression of my spinal cord. With so many nerves going through the spinal cord and brain, putting pressure and stress on those nerves result in them misfiring. I actually had this issue as a kid before we knew what it was but at the time it was only in my hand. My wrist would jerk so my hand, on the side of my thumb would jerk up towards my inner arm.

As an adult sometimes my legs will involuntarily kick or I will go spats so my legs won't bend and will hover several inches in front of my chair with my feet twisting inward and upward. I’ll have full body jerks kind of like what sometimes happens when you have those dreams of falling and your body jerks upon waking up but it will happen several times in a row and then several times in a row a few minutes later where my spine goes very straight then flaccid. I will also have facial ticks or full body ticks where the small muscles in my body will start twitching. When this happens in my GI system and respiratory system, it can get really scary because it can make me vomit, unable to swallow anything, give me blurry vision when my eyes start twitching or make it hard to breathe as I cannot control these smaller muscles. Some light stretches can reduce speciosity and stretch these muscles which doesn't reduce the neurological issues but reduces the muscular responses to those.

Movement and activity plans for someone like me may seem too easy or simple but until I can get a surgery to repair some of my neurological, brain and spine manifestations simple is about as good as it gets. The biggest goal of my movement activities is to prevent further sparsity, blood clots and to try to make it so that my heart and autonomic nervous system don't get to a point of no return if we can ever get my surgery approved or another treatment is found. You use it or you lose it so we are trying to prevent me from loosing any more function without going the other way and decreasing my movement through further damage to my spinal cord. It can be quite the fine line between not enough and too much so maintaining that balance is the current goal when it comes to movement and activity and its play in my daily life.

[makeetelich92]

A Quick Guide to Getting Enough Vitamin D

A Quick Guide to Getting Enough Vitamin D

If you are like many of my patients, you may be wondering, "Am I getting enough vitamin D?" This is a valid concern, because vitamin D plays a very important role in overall health and, in fact, many people do not get enough. The Centers for Disease Control and Prevention estimates that about one-third of Americans have insufficient levels. The good news is that sources of this vitamin are easily accessible.

Why Is Vitamin D Important?

Vitamin D helps the body absorb calcium from the gut, as well as maintain normal blood levels of calcium and phosphate. These minerals are essential for healthy, strong bones. Bones are constantly being built up and broken down, like a building continuously under construction to maintain its integrity; in medicine we call it "remodeling." Vitamin D supports both the growth and maintenance of the bone. This essential natures blend multivitamin also aids the regulation of cells throughout the body, and helps our nerves, muscles, and immune system function properly. New research is finding that it is also involved in reducing inflammation.

When You Don't Get Enough

A lack of vitamin D can weaken bones, leading to rickets in children and osteoporosis in adults. this is often why older people, who tend to possess lower viosterol levels, often need supplements to stop brittle or dilution bones. Symptoms of a deficiency might embody generalized fatigue, muscle weakness, bone pain, or a foggy feeling.

How a lot of does one Need?

Vitamin D is measured in international units (IU). The  National Institutes of Health recommends that the general public get 600 IU of vitamin D per day, or, if you're over seventy years old, 800 IU. A vitamin D biopsy is that the best thanks to establish your baseline level and see whether or not you are obtaining enough. it's especially vital for those at exaggerated risk of deficiency to urge their viosterol checked. This includes folks with dark skin; those that get very little sun exposure; older people; vegetarians; people with gi illness or who have had internal organ bypass surgery; and people on bound anti-seizure medications, like purple heart and phenytoin.

Sources of aliment D

Sources of vitamin D are restricted to a couple of natural foods, some fortified foods, dietary supplements, and sun exposure:

Sun Exposure. The body makes its own vitamin D once the skin is exposed to ultraviolet B (UVB) rays from the sun. it's laborious to offer clear recommendations for adequate sun exposure, as several factors play into UVB absorption, as well as skin tone, age, geographical location, time of day, environmental factors like fog and smog, and sun blocker application.

That said, attempt to get ten to fifteen minutes of exposure a minimum of once or doubly a week, counting on skin tone, with honest skin requiring less time within the sun. Sunscreen--a very important tool in willcer|carcinoma} prevention--does block UVB rays. However, since its application is typically imperfect, folks can absorb adequate daylight even whereas sporting sunscreen.

Fortunately, your body stores viosterol in liver and fat cells. If you get enough sunlight during the summer, your body will stockpile a number of the {vitamin d|vitamin D|calciferol|viosterol|ergocalciferol|cholecarciferol|D|fat-soluble aliment} it makes to use later within the year once you might not get enough either through the sun or diet.

Natural Foods. it's continually best to urge vitamin D from natural sources when you can. important amounts are found in fleshy fish like salmon, swordfish, and tuna, yet as some forms of mushrooms. for many people, canned tuna or cod liver oil are straightforward fixes. Eggs, liver, beef, and sardines also contain vitamin D, however at lower levels. you'll realize it useful to stay a one-day food diary to ascertain if you're ingesting an adequate quantity through a natural diet.

Fortified Foods. to create up for the dearth of natural sources, within the us some foods are fortified with aliment D, notably milk and orange juice. several cereals are fortified, too. The us Department of Agriculture web site provides a information of nutritionary content, wherever you'll realize the simplest sources of vitamin D for each natural and fortified foods.

Dietary Supplements. For those that want additional vitamin D, rock bottom supplementation usually suggested is 1,000 IU orally per day. For extremely deficient patients, we are going to offer a 50,000 IU pill once a week. it's nearly not possible to require noxious levels of {vitamin d|vitamin D|calciferol|viosterol|ergocalciferol|cholecarciferol|D|fat-soluble aliment}.

Work along with your Physician

I encourage patients to possess a operating relationship with their medical care medico and obtain an annual medical exam to observe their overall health. If you're not feeling well and suspect that your vitamin D level may be a cause, it is best to ascertain your doctor to see if supplementation is necessary. the proper tools and support from a knowledgeable and sympathetic primary care doctor are a vital key to a healthy, active life.

[mcatmemoranda]

What I recall from the OnlineMedEd video on Pyruvate Dehydrogenase:

Thiamine (vit B1) is necessary for pyruvate dehydrogenase to function. If thiamine level is low, you can't convert pyruvate to acetyl CoA, which means you can't do the TCA cycle. Your cells can run out of energy. When that happens in the heart, you get wet beri beri-> CHF.

Thiamine deficiency occurs in alcoholics who aren't getting vit B1 because they're drinking alcohol and not really eating. Wernicke's encephalopathy presents as ataxia, dysarthria, and other signs of intoxication, although the pt isn't intoxicated. There's no structural brain lesion, so it's reversible if you give vit B1.

Korsakoff syndrome is Wernicke's encephalopathy plus confabulation and memory loss (amnesia). It results from structural lesions in the brain and is irreversible.

From Wikipedia:

Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1).[1] A severe and chronic form is known as beriberi.[1][5] There are two main types in adults: wet beriberi, and dry beriberi.[1] Wet beriberi affects the cardiovascular system resulting in a fast heart rate, shortness of breath, and leg swelling.[1] Dry beriberi affects the nervous system resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain.[1] A form with loss of appetite and constipation may also occur.[3] Another type, acute beriberi, is found mostly in babies and presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.[6]

Risk factors include a diet of mostly white rice, as well as alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics.[1][4] Rarely it may be due to a genetic condition that results in difficulties absorbing thiamine found in food.[1] Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi.[4] Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with treatment.[7]

Treatment is by thiamine supplementation, either by mouth or by injection.

[1] With treatment, symptoms generally resolve in a couple of weeks.[7] The disease may be prevented at the population level through the fortification of food.[1] Thiamine deficiency is rare in the United States.[8] It remains relatively common in sub-Saharan Africa.

Ok, so dry berberi is basically Wernicke's encephalopathy and Korsakoff syndrome. Wet beriberi = HF due to thiamine deficiency.

Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death.

Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.

Beriberi is divided into four categories as follows. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:

Dry beriberi especially affects the peripheral nervous system.

Wet beriberi especially affects the cardiovascular system and other bodily systems.

Infantile beriberi affects the babies of malnourished mothers.

Gastrointestinal beriberi affects the digestive system and other bodily systems.

Dry beriberi

Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:

Difficulty in walking Tingling or loss of sensation (numbness) in hands and feet Loss of tendon reflexes[10] Loss of muscle function or paralysis of the lower legs Mental confusion/speech difficulties Pain Involuntary eye movements (nystagmus) Vomiting A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.[11]

Brain disease

Wernicke's encephalopathy (WE), Korsakoff syndrome (alcohol amnestic disorder), Wernicke–Korsakoff syndrome are forms of dry beriberi.[4]

Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society,[12][13] though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease,[12] those with HIV/AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation.[14] This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.[15]

Korsakoff syndrome is, in general, considered to occur with deterioration of brain function in patients initially diagnosed with WE.[16] This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.[17]

Alcoholics may have thiamine deficiency because of the following:

Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.

Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.

Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.[18]

Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.

Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).[19] Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage. (See delirium tremens.)

Wet beriberi Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:

Increased heart rate

Vasodilation leading to decreased systemic vascular resistance, and high output heart failure[20]

Elevated jugular venous pressure[21]

Dyspnea (shortness of breath) on exertion

Paroxysmal nocturnal dyspnea

Peripheral edema[21] (swelling of lower legs)

Dilated cardiomyopathy

Gastrointestinal beriberi

Gastrointestinal beriberi causes abdominal pain. Gastrointestinal beriberi is characterized by:

Abdominal pain

Nausea

Vomiting

Lactic acidosis[22][23]

Infants

Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.[2]

In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure.

Beriberi may also be caused by shortcomings other than inadequate intake: diseases or operations on the digestive tract, alcoholism,[21] dialysis, genetic deficiencies, etc. All these causes mainly affect the central nervous system, and provoke the development of what is known as Wernicke's disease or Wernicke's encephalopathy.

[thecbdproductss-blog]

Why Are Many Senior Citizens Are Requesting CBD Oil?

Concern worrying negative impacts of narcotics in addition to interest in additional lawful professional options are triggering even more senior citizens checking out cannabis options.

According to the National Study of Drug Use and Health, in between 2011-14 in Washington state, the variety of individuals that have actually used cannabis over the age of 65 boosted from 0.9 percent to 2.4 percent.

Elders are choosing to utilize cannabis for medical problems, like pain, as opposed to prescription medicines. With the raised appeal as well as the decreased stigma of the plant, seniors are additional open than ever before to try cannabis.

A 2018 research study of elders discovered 93.7 percent of clients actually felt renovation from indicators like discomfort after taking marijuana for six months. What's more, 18 percent of individuals gave up or decreased, taking opioids by utilizing marijuana.

The opioid epidemic has struck senior citizens in addition to other age demographics. In 2013, 55 percent of opioid prescriptions more than likely to senior citizens, although they only accounted for 13 percent of the population. Opioids can be extra dangerous for senior citizens as a result of the fact that they increase the hazard of falling, mental complication, and also dependancy, according to the World as well as Mail.

Want to suggest marijuana as a various treatment for your moms and dads or grandparents? Look at our listing of the prominent aspects elders are using marijuana. Even Better CBD Oil

LEADING Factors seniors depend on CBD Oil.

1. Consistent Discomfort

From fibromyalgia to joint swelling as well as likewise nerve pain, consistent discomfort cripples great deals of senior citizens. Nonetheless, cannabis for senior citizens is changing that. Marijuana can help deal with neuropathic discomfort as well as discomfort prompted by joint inflammation in addition to inflammation because of the body's endocannabinoid system. When cannabis is taken in, its compounds, including THC as well as also CBD, impede pro-inflammatory bits in the body and likewise get in touch with different other all-natural pain-killing systems, like the body's endogenous opioid system.

Elders don't require to smoke a joint for pain reduction. If you're not seeking the psychedelic effects of cannabis, you can select a hemp-derived CBD product for all the medical benefits of marijuana without the high. Try providing CBD oil or CBD pills to your grandparent and also see specifically just how they feel. And additionally, hemp-derived CBD items can be delivered to all 50 states.

2. Glaucoma

Glaucoma is the leading root cause of loss of sight for people over 60. Glaucoma is a problem of increased pressure in the eye caused by liquid buildup that harms the nerves. To fight Glaucoma, individuals call for to soothe that stress, which is generally finished with prescription eye lowers. However, this eye goes down can be costly and also need to be utilized sometimes throughout the day.

This is an additional method marijuana for senior citizens is a video game-changer: cannabis naturally reduces that stress as well as likewise the results last for hours. Among the most significant advocates of marijuana for glaucoma is Whoopi Goldberg. She made up a short write-up for the Cannabist called, "My vape pen and I, a love story" where she explains precisely how vaping cannabis help with her glaucoma and the migraine headaches it produces. Keep in mind that you do not need the THC for health and wellness as well as health effects. We recommend HemPiDiol and also it can be delighted in through a vape pen if so wanted.

3. Alzheimer's Illness

Cannabis has actually shown phenomenal capacity for both the therapy as well as also avoidance of Alzheimer's and psychological degeneration.

Added research is seriously required, yet that's the catch in the U.S. As a result of the government's "Prepare I" category of the plant, executing professional studies as well as examinations is essentially difficult. In the meanwhile, nonetheless, several seniors are complying with the slogan: "A decrease a day maintains psychological damage away." So why not call our group of specialists as well as see what our company is doing in this department. We go to the center of HPD oil research along with would certainly enjoy talking to you concerning what would certainly fit your demands or the demands of your suched as one.

4. Parkinson's Health problem

Parkinson's Problem is a degenerative condition that creates dopamine-producing mind cells to pass away. Because dopamine helps the body control muscle mass in addition to action successfully, Parkinson's is defined by irrepressible tremblings, drinking, and also muscular tissue mass convulsions. Dopamine lacks, in addition, produce signs like:

Vertigo

Stringent muscles that are tough to relocate

Relax troubles

Loss of cognitive functions

Amnesia as well as additionally mental wear and tear

The certain origin of dopamine-producing cells to pass away is still unidentified as well as there is no effective treatment for Parkinson's, just medication to aid lower indicators.

Nonetheless, a research study in Israel on the impacts of cannabis on Parkinson's found indicators like drinks and also stamina was considerably reduced after people smoked cannabis. Evaluation Herb's full protection of marijuana and also Parkinson's health problem right below.

5. Cancer cells

Among the main factors clinical cannabis regulations you're on The golden state in the '90s was the plant's capacity to help cancer cells clients. At first, marijuana plainly assisted adverse impacts cancer cells treatment, like radiation therapy, activated, including pain and additionally queasiness.

But, an additional study has actually likewise shown that marijuana eliminates cancer cells. Plus, the plant's substances have actually been revealed to reduce the expansion of various sort of cancer cells, consisting of bust, prostate, as well as lung cancers cells. What's even more, scientists from Vanderbilt University School of Medication situated cannabis to avoid "metastasis," which is the spreading of cancer cells to healthy and balanced and well-balanced cells.

Although we wouldn't advise replacing your mama or gran's cancer cells treatment totally with marijuana, it can be a beneficial enhancement to their regular. It's simply an added method we would like to recommend HemPidiol a risk-free as well as reliable enhancement to deal with signs and also for senior citizens this non THC alternative is changing healthcare.

6. Rest

Countless senior citizens locate their restless than they did when they were much younger. What's more, the senior handle sleeping problems along with issue remaining asleep. Nevertheless remainder is essential to living a healthy and balanced life and for recuperating from sickness as well as injury. That's where marijuana for seniors plays a part.

Certain type of marijuana, like indica-dominant stress, are identified to sit back the body along with making individuals sleepy. Even "highness" cannabis things, like CBD oil, have sleep-inducing properties. Lots of people are counting on cannabis to help them sleep, young people along with seniors alike.

As a matter of fact, according to one of the most recent Eaze State of Marijuana Record, 95 percent of resting tablet customers surveyed in The gold state have in fact reduced their resting tablet usage by using CBD oil. Unlike resting tablets, cannabis is all-natural in addition to does not leave people feeling dazed in the morning.

8. Crohn's Illness

Essentially 800,000 Americans deal with Crohn's Illness, an inflammatory bowel condition that activates belly pain, bloody diarrhea, along with weight administration. It's a hard problem to handle as well as additionally does not have a cure. Really, it seriously influences victims' quality of life. Yet marijuana assistance for senior citizens and additionally more youthful grownups alike. Cannabis helps to take care of Crohn's disease symptoms and signs and give much-needed alleviation throughout flare-ups.

What's a lot more, there is some preliminary evidence to suggest marijuana can, in fact, aid send Crohn's Health problem right into remission. That's due to the fact that Crohn's is generally a puffy digestive (GI) tract as well as additionally marijuana battles that with its anti-inflammatory household or industrial homes. In fact, there are cannabinoid receptors throughout the GI tract. And likewise, according to a 2014 research study, Crohn's individuals that used marijuana had no negative side effects along with elevated cravings. Marijuana such as CBD oil/ HemPidiol for elders is absolutely worth considering for Crohn's.

9. Clinical depression

Anxiety among elders dominates. According to the Facility for Illness Control (CDC), concerning 7 million Americans over the age of 65 ended up being depressed every year. Regrettably, according to the very same record, senior citizens made up for 16 percent of self-destruction deaths in 2004. However, once again, that's one more use of marijuana for elders. Cannabis is known to boost mood as well as decrease anxiousness.

Cannabis oil is a quicker option for antidepressants. It sets off the endocannabinoid system and increases the development as well as growth of nervous tissue with little to no negative effects. It is dealing with depression with HemPiDiol a natural solution that offers customers assurance.

[paleorecipecookbook]

9 Nutrient Deficiencies Making You Crave Junk — What Your Body Really Wants Instead

We seem to always crave food that is high in sugar and fat, yet we never find ourselves craving a huge bowl of broccoli. What gives?

Craving certain foods is a multifaceted experience. There’s a cognitive component and an emotional component – aka “I am having a terrible day so I want to go home and eat my bodyweight in fro-yo.” And there’s even a physiological factor: you literally feel good after you eat certain foods.

It turns out cravings aren’t totally our fault. In fact, research suggests that many cravings are often a cry from our body, letting us know that it is seriously lacking in several key vitamins, nutrients, and minerals. These things help to regulate appetite, mood, hunger levels and cravings.

It’s not that our body desperately needs a piece of chocolate cake, we just misinterpret what our body is crying out for. Cravings, poor mood and stubborn weight issues can indicate psychological roots, specific nutrient needs, and/or vitamin deficiencies.

For every gram of sugar you consume, your body uses between 28-53 molecules of magnesium.

Certain food cravings can be triggered by specific moods. We all crave comfort foods when we are stressed out, lonely or sad. This has been linked to alterations in our gut microbiome, dysregulated cortisol levels and a low level of serotonin. (4) Research even found that highly stressed individuals report having more cravings than non-stressed individuals. (5)

The next time a craving strikes, pay attention to what the actual craving is. Do you notice that every time you have a bad day at work you rush home to eat ice cream? Do you have emotional triggers that cause you to overindulge? This self-reflection will help you control your cravings and make healthier choices on tough days.

Here are nine common nutrient deficiencies that might be at the root of your cravings:

Calcium

The Nutrient: We need calcium for more than strong bones; we need the mineral for nerve impulses, blood clotting, and for our heart to pump blood. Every cell in the body requires calcium and our body has very tight control of how much calcium is in the blood at any time. Our body will actually pull calcium from our bones when our blood levels drop or we experience pH changes in the body.

While many people think milk is a great source of calcium, it’s difficult to absorb calcium from dairy. Up to 75 percent of the population experiences lactose intolerance, meaning they lack the enzyme necessary to digest lactose. Stress, intense exercise, and too much sugar can all deplete your calcium stores.

Signs of a Deficiency: If you find yourself craving sodas, carbonated drinks and even dairy this could be a sign you need more calcium.

What To Eat:

Increase your intake of plant-based calcium sources such as 6):

Dark leafy greens

Turnip greens

Broccoli

Kale,

Celery.

Pumpkin seeds

Brazil nuts

Almonds

Asparagus

Coconut meat.

For non-plant sources, try:

Sardines

Salmon

Tuna

Magnesium

The Nutrient: Known as our relaxation mineral, magnesium contributes to nearly 700 enzyme and biochemical processes in the body. Our body has roughly 3,500 different binding sites for magnesium in our cells.

Up to 80 percent of the population is deficient in magnesium. It’s easily depleted in times of chronic stress, extreme exercise, during menstruation and when we consume sugar. In fact, for every gram of sugar you consume, your body uses between 28-53 molecules of magnesium.

Magnesium acts like a gate keeper for calcium, as it allows calcium to be excreted from our cells in response to various stressors. Calcium acts as an excitatory molecule, while magnesium acts as a calming molecule. Having imbalances in these minerals can lead to issues with our mood.

Signs of a Deficiency: If you find yourself having intense cravings for sugar and feel fatigued and sore, you may need more magnesium. This is true as well if you experience muscle twitches and cramps, depressed mood, and anxiety.

What To Eat (7, 8):

Dark chocolate (be sure it is organic with at least 70% cocoa content and no added sugar)

Avocados

Raw cacao

Cashews

Almonds

Pumpkin seeds

Sesame seeds

Dark leafy greens such as spinach, kale and broccoli.

Zinc

The Nutrient: Zinc is a part of at least 3,000 different proteins in your body and is involved in more than 200 different enzymes. In fact, zinc is involved in more enzymatic reactions in your body than any other mineral. Its highest concentrations are in your hippocampus, which deals with memory and mood.

This key mineral is important for our immune system, cellular growth, sleep, skin, insulin regulation, hormone balance and mood support. The body has no special storage capacity for zinc, so it is important to consume zinc-rich foods on a regular basis.

Zinc plays a role in modulating the brain and body’s response to stress and has been linked to depression. Under times of extreme stress, we get rid of zinc at higher rates through our urine, sweat and saliva. (9, 10)

The Signs of a Deficiency: If you suffer from GI distress, experience low moods, have extreme PMS, have high stress or take antacids and OTCs you likely could benefit from more zinc.

What To Eat:

Oysters

Shellfish

Salmon

Grass-fed meat

Pasture-raised chicken

Unsweetened dark chocolate

Pumpkin seeds

Spinach

Almonds

Omega-3

The Nutrient: Omega-3 fatty acids are known as essential fatty acids. Our bodies cannot make them on their own, so they must either be obtained through our diet or through supplements.

Signs of a Deficiency: Cravings for sweet, fatty foods, cheese and carbohydrates can be a sign of omega-3 deficiencies, as well as having poor mood and brain fog. (11)

What To Eat:

Essential fatty acids can be divided into three types: ALA, EPA and DHA, all of which can be found in:

Wild caught fish, such as tuna, salmon, and sardines.

Walnuts

Flax seeds

Hemp seeds

Chia seeds

Some algae such as spirulina.

Vitamin B12

The Nutrient: Roughly one in four Americans are deficient in Vitamin B12, a vitamin associated with memory, mood, energy and red blood cell health. Vitamin B12 is our largest vitamin and requires a good amount of stomach acid and a protein, called intrinsic factor, to break it down and absorb it. This is likely why so many people have suboptimal levels of this key vitamin.

Vitamin B12 can only be obtained from animal sources, as plant sources of B12 are in the analog form, which cannot be absorbed by the body. Methylcobalamin is the active form of B12 that the body can use, which can be found in methyl B-12 supplements or animal sources of B12. (12)

Signs of a Deficiency: If you have low energy, find yourself craving meat, suffer from anemia, or find yourself bruising easily, you likely could benefit from getting more B12 in your diet.

What To Eat:

This is a case where you want to eat what you crave. Increase your intake of:

Organic grass-fed meat

Venison

Veal

Bison

Pasture-raised chicken, turkey and eggs

Folate

The Nutrient: Also known as Vitamin B9, folate is the active form of folic acid that is necessary to support cardiovascular health, cellular health and cognitive health. With up to 40 to 60 percent of the population having the genetic variant for the MTHFR gene, consuming folate-rich foods, as opposed to synthetic folic acid, is necessary for overall health.

Methyl Folate is the biologically active form of Vitamin B9. It is also the form that is transported across membranes into peripheral tissues, particularly across the blood brain barrier. Methyl folate is used in the methylation process, which contributes to DNA health, detoxification pathways, and cell health.

Signs of a Deficiency: Natural dietary folate is found in food, while Folic acid is the synthetic form of B9 required to be added into processed grains. (13) If you crave processed grains, you may need more folate. This is also true if you have a history of cardiovascular disease, miscarriages, or experience fatigue, low energy, loss of appetite, anemia and have changes in mood and irritability.

What To Eat:

Dark leafy greens such as spinach and arugula

Beets

Bell peppers

Cauliflower

Asparagus

Broccoli

Lentils

Avocados

Okra

Brussels sprouts.

Vitamin D

The Nutrient: Also known as the sunshine vitamin, Vitamin D acts as a pro-regulatory hormone in the body, influencing over 2,000 genes. When our skin is exposed to the sun, Vitamin D produces compounds that support healthy moods.

With up to 70 percent of the population being deficient in Vitamin D, it is no surprise that our mood, cravings and even our immune health can be affected by having low levels of this vital vitamin. Scientists found that people with low vitamin D symptoms are 11 times more prone to be depressed than those who had normal levels. (14)

Signs of a Deficiency: If you find yourself getting sick a lot, having poor mood, bone loss, back pain and feel tired and fatigued you likely have low vitamin D levels.

What To Eat:

Fatty fish, such as tuna, mackerel and salmon,

Beef liver

Egg yolks

Note: Getting outside and playing in the sun can be a great way to increase your Vitamin D levels, but be sure to expose roughly 70 percent of your skin as close to solar noon as possible.

Selenium

The Nutrient: Selenium is an antioxidant-rich essential trace mineral that works in conjunction with other enzymes and proteins in the body. Selenoprotein S in particular is involved in the protection against cellular stress and regulating the release of pro-inflammatory cytokine release.

Adequate selenium levels are essential for not only proper immune function, but also for regulating excessive immune response (found at the root cause of several autoimmune diseases), chronic inflammation and protecting cells against free radical damage. (15)

Signs of a Deficiency: A decline in cognitive health, thyroid functioning and immune health, as well as heart disease and infertility may be signs of a selenium deficiency. If you find yourself excessively tired, as well as craving salty foods you could benefit from increasing your selenium intake.

What To Eat:

Brazil nuts

Garlic

Tuna

Nori

Seaweed

Sunflower seeds

Turkey

Lentils

Spinach.

Antioxidants

The Nutrient: Antioxidants are categorized as either fat soluble or water soluble. However, your body needs both to protect your cells from oxidative damage and free radical damage.

Antioxidants help rid the body of dangerous oxidative products by converting them into hydrogen peroxide, then into water. This is done through a multi-step process that requires a variety of trace minerals, such as zinc, copper, manganese, and iron, which are found in foods that are rich in antioxidants.

Signs of a Deficiency: If you have low energy levels, crave sweets, seem irritable and have general low immune function you can benefit from getting more antioxidants into your diet.

What To Eat:

Organic fruits and berries

Chlorophyll-rich vegetables

Lemons and limes

Grapefruits

Tart cherries

Sulfur-rich veggies like onions, garlic, broccoli, cauliflower, and broccoli sprouts.

CoQ10-rich foods, such as grass-fed beef, liver, sardines and mackerel.

(Read this Next: 9 Leaky Gut Symptoms and How to Start Healing Now)

The post 9 Nutrient Deficiencies Making You Crave Junk — What Your Body Really Wants Instead appeared first on PaleoPlan.

Source: https://ift.tt/10qRbxJ

[lowfodmapfoods]

How To Test for IBS: Symptoms & Causes

About 15% of the worldwide population has IBS, which affects women twice as frequently as it does males. Usually, symptoms don't appear until a person is in their 20s or 30s and most people don't visit their doctors to diagnose and confirm if they have IBS.

Almost 2,000 patients with IBS confirmed that they never get tested and diagnosed with IBS during the onset of the symptoms. According to a survey, it took patients 6.6 years before going to a healthcare provider to confirm their IBS.

In this article, we will be talking about how IBS is diagnosed. Additionally, you will also learn the possible medical procedures that you have to expect when you visit your GI doctor.

IBS Symptoms

IBS symptoms can vary from one person to another. Ruling out your symptoms can help your doctors identify what interventions and symptom management would work best for you.

It is important to know the most common symptoms that may happen to you and how to manage them effectively.

Common Symptoms of IBS:

Cramping

Sharp abdominal pain

Bloating

Distention

Fullness

Flatulence

Changes in bowel movements

Other Symptoms:

Lethargy (lack of energy)

Heartburn

Always feeling sick

Muscle pains

Dizziness

Painful menstruation

IBS Causes

The causes of IBS remain unknown but studies are still ongoing to learn more about the exact reasons behind the development of IBS in people.

On a positive note, experts have confirmed some of the probable causes of IBS. This may be a combination of different factors and digestive issues such as:

Stress during the early stages of life

Stressful childhood experiences cause the protein known as a nerve growth factor to communicate abnormally, starting a chain of events that eventually results in the development of irritable bowel syndrome (IBS).

IBS was most strongly predicted by emotional abuse. After adjusting for the existence of psychological and other non-gastrointestinal symptoms, the correlation between early trauma and IBS was also less strong.

Small Intestinal Bacterial Overgrowth (SIBO)

The increase in the number of bacteria in your small intestine can irritate your digestive system.

Studies provide evidence that SIBO might be an underlying factor in IBS. The first is that several studies have discovered that IBS patients are substantially more likely than unaffected individuals to have a positive Hydrogen Breath Test (HBT), suggesting that SIBO may be a problem.

Additionally, the study's discovery confirmed that many people see a considerable reduction in IBS symptoms after trying particular antibiotics.

These antibiotics are accessible to combat any bacteria that might be hiding in the small intestine because they are not absorbed in the stomach.

Mental health issues

IBS sufferers may be more sensitive to emotional issues, even though psychological issues like worry may not cause digestive illness.

Stress, anxiety, and depression can set off chemicals in the brain that activate pain signals in the gut, which could cause your colon to react.

Genetics

Genetics have been linked to the onset of IBS, according to research. You are also more prone to get the symptoms as an adult if your family has a history of IBS.

If some of your family members have been diagnosed with irritable bowel syndrome, and you have been noticing some of its signs, reach out to your doctor as soon as possible.

Food intolerance

Some people who have sensitive colons are prone to certain food intolerances, which can also be a cause of IBS.

According to a study, 20–65% of IBS patients are attributing their symptoms to food hypersensitivity.

It appears that the prevalence of food hypersensitivity in the IBS population is higher than in the general population. In fact, many IBS sufferers claim that certain meals make their symptoms worse.

Intestinal Muscle Contractions

Layers of muscle that contract as they carry food through your digestive tract line the inside of your intestines.

Gas, bloating, and diarrhea might result in stronger and longer than typical contractions. Weak contractions might hinder the passage of food and result in dry, firm stools.

Severe infection

After a severe case of diarrhea brought on by germs or a virus, IBS may appear. It is known as gastroenteritis.

There may be a connection between IBS and an overabundance of bacteria in the intestines (bacterial overgrowth).

Changes in the gut microbiome

According to research, those with IBS may have different microorganisms than those without the condition.

IBS Diagnosis and Testing

How is IBS diagnosed?

IBS can be accurately diagnosed with a thorough grasp of the symptoms, a thorough medical history, a physical exam, and the lack of any alarming symptoms. To eliminate other illnesses as probable sources of symptoms, minimal testing may be necessary.

A group of medical professionals developed the initial criteria for assessing irritable bowel syndrome in the 1990s (IBS).

The "gold standard" for the diagnosis of IBS in clinical research studies is the set of criteria known as the Rome Criteria.

According to the Rome IV diagnostic criteria for IBS, some symptoms must have started at least six months prior to and been present for the preceding three (3) months in order to qualify as IBS.

Also, the Rome IV criteria qualify IBS patients if they have two or more of the following symptoms related to abdominal pain:

Abdominal pain is related to defecation

Abdominal pain is associated with changes in the frequency of bowel movement

Abdominal pain is associated with changes in the appearance of stool

To clarify these symptoms further, the following reviews and examinations would also be conducted by your GI physician:

Review of Symptoms

To diagnose IBS, your doctor will interview you about your symptoms and search for a specific pattern in them. This will include the above-mentioned criteria to further verify if you have IBS.

Additionally, your physician will ask you about the duration of your symptoms. You will more likely to be diagnosed with irritable bowel syndrome if:

Symptoms occur at least once a week for the past 3 months; and

Onset of symptoms started at least 6 months ago

However, your physician may diagnose IBS even if you've had the symptoms for shorter periods of time. This can be further assessed by medical procedures.

Other symptoms may also be asked to check for other conditions like inflammatory bowel disease or other health conditions. The symptoms that could be a sign of other medical conditions are the following:

Rectal bleeding

Severe weight loss

Anemia

Bloody stool

Medical Procedures Done to Check for IBS:

Diagnosing Irritable Bowel Syndrome (IBS) requires various tests to rule out other conditions. This medical condition mimics other diseases and gut conditions.

Thus, your healthcare provider would recommend you take one or more of these tests:

Stool Tests

A stool test is performed to check your stools for any presence of internal parasites, blood, or bacterial infections.

The test can also be used to detect other conditions like inflammatory bowel disease and malabsorption syndromes.

Blood Tests

Your healthcare professional will conduct a complete blood screening in a laboratory. This screening is usually done to check for other medical conditions that you might have, such as digestive diseases, inflammatory bowel disease, anemia, tissue damage, or celiac disease.

Two blood tests are available to help in the diagnosis of IBS which are IBSchek and IBS-Smart

Both blood tests are intended to help diagnose adults with irritable bowel syndrome with diarrhea as the predominant symptom (IBS-D) or irritable bowel syndrome with mixed bowel habits (IBS-M).

Doctors would also check for specific antibodies known to be connected to IBS that were produced after a GI infection (post-infectious IBS).

In comparison to healthy individuals, patients with IBS-D or IBS-M had higher positive rates for these antibodies.

On the contrary, the amount of antibodies present in your body is not always a basis for being diagnosed with IBS. Having a negative test for these antibodies does not also conclude that you do not have IBS.

Further testing and medical procedures will be done to get an accurate diagnosis.

Colonoscopy

A colonoscopy is a medical procedure in which a doctor uses a long, flexible tube with a light and camera attached to it to examine the inside of the large intestine (colon) and rectum. This procedure can also be used to look for signs of colon cancer or other irregularities in your GI tract.

Upper endoscopy

The esophagus, the tube that connects your mouth and stomach, is entered through your throat with a long, flexible tube. Your healthcare professional can see your upper digestive tract thanks to a camera on the end of the tube. A tissue sample (biopsy) may be taken during an endoscopy. It is possible to take a sample of the fluid to check for bacterial overgrowth. If celiac disease is suspected, an endoscopy may be suggested.

Breath Test

A hydrogen breath test is also one of the most common tests to check for Irritable Bowel Syndrome.

The hydrogen breath test is a quick medical procedure that checks the amount of hydrogen gas (H02) in your breath when you exhale. It is employed to aid in the diagnosis of common digestive issues like SIBO, IBS, and lactose intolerance. The test's various iterations gauge how you digest various sugars.

Psychological Tests

Stress, anxiety, depression, and other mental health conditions are major triggers of IBS flare-ups. A psychological assessment may be ordered by your GI physician to effectively manage your emotional stressors and IBS symptoms.

Anorectal Manometry

Anorectal manometry is a test that measures muscle tone and sensation in the rectum and anus. It is used to diagnose problems with the anal sphincter muscles or nerves.

Lactose Intolerance Test

Individuals with lactose intolerance do not produce enough lactase. Lactase is an enzyme used to digest the sugar from dairy products.

This intolerance can lead to abdominal pain, excessive gas, and diarrhea which are the same symptoms of Irritable Bowel Syndrome (IBS).

The Next Step After Being Diagnosed With Irritable bowel Syndrome (IBS)

After being diagnosed with irritable bowel syndrome, your next goal should be to give your body what it needs - healing and a major transformation in your lifestyle.

[war-torn-and-collateral-damage]

So updates,

My most recent episode was 18 days long of bo mobility, limited speech, increased seizure activity etc. I am doing better-ish, I have mobility back but it is limited. Working on fine motor skills in OT as that has been a difficult come back, cognitive issues do seem a titch worse probably due to the seizure activity but with movement after a long time of no movement, not surprisingly came what always does, severe pain and spasms.

My muscle spasms on top of hyperflexibility get pretty intense and its almost comical cuz then I get muscle injuries in the most off the wall ways. So currently I am sporting a 2 inch soft neck collar after a severe spasm in my neck caused a sprain and damage to the nerve root, I have never had the duspleasure of being in a collar till now but I imagine it is what a dog feels like in a cone.

I am still bed ridden or stuck on my couch most of the time these days, although for the first time since before Christmas I did muster up enough energy to do some papercrafting, but my fiancé had inteoduced me to Minecraft, its a neat way to explore and adventure and be creative without have to leave and push my body as I am unable. Yesterday we built an automatic bee hive collection unit that harvests my honey and honeycomb. I am gonna use it to make blocks to build a bee sanctuary so my little bumble bitches will stop catching themselves on fire.

GI issues are terrible, I have been diagnosed with gastroparesis which we knew so they want me on this special diet but everything they want me to eat is stuff I can't eat due to my dysphagia. They did a swallow study, I gagged, choked and coughed on every swallow but got through it. They are changing ny reflux medication to get the acid in my stomach under control and then I will have a G tube placed, moving forward for the mean time until we can get things managed or controled the G tube will be my primary source of nutrition.

This month I go in for my cardiac event monitor. So they can track my tachycardic episodes and maybe find triggers or answers for my heart. problems.

So alot going on still but my doctor seems like he is definitely doing what he can.

My Physical Therapist recommended to my social worker to see if my waiver could cover, a set of orthopedic pillows to help alleviate bed sores and pain since I am mostly bed ridden these days, I only really get out and moving much for appointments or to get to my bedside cammode.

I am after a few medical supply items at the moment that I am unable to afford on my own right now. I am super low on my pull on style incontinence protection, and I am in need of wipes and a heated blanket as due to my autonomic dysfunction I have an inability to regulate my own body temperature, I live in Minnesota and it is very cold here. So a heated blanky could be very helpful and could also help with my muscle pain.

Any help would be much appreciated, I have an amazon wishlist and every bit helps, even just a reblog. Thankyou all for your continued encouragement and support.

[your-dietician]

The Overlooked Drugs to Reconsider When Prescribing for Pain

New Post has been published on https://depression-md.com/the-overlooked-drugs-to-reconsider-when-prescribing-for-pain/

The Overlooked Drugs to Reconsider When Prescribing for Pain

A review of pain medications of the past and how they may help to optimize the treatments of today.

Pain-treating clinicians are constantly searching for medications that improve patient outcomes and/or that can minimize the use of opioids. Perhaps, older treatment modalities just need to be reconsidered.

  Background

The management of pain – whether acute or chronic – is one of the most difficult medical conditions to treat and when treatment options are limited, the patient is the one left to suffer while the clinician bears the burden of trying to help the patient. The current opioid crisis in the US has significantly shifted the pendulum of opioid prescribing practices due to various restrictive guidelines, laws, regulations, and policies at both the federal and state level. Clinicians are challenged and quite possibly hesitant with managing complex pain syndromes in individuals with medical comorbidities.

Not all pharmacologic treatment options are viable for every case due to patient-specific factors, compelling medical indications and comorbidities, drug interactions, and even pharmacogenetics. Over time, some pharmacologic options are withdrawn from the market by the manufacturer, forgotten, or underutilized due to a lack of clinician knowledge or familiarity.

Here, we revisit this “land of lost analgesics” with the goal of refamiliarizing pain-treating clinicians – whether in specialty or primary care – with alternative treatment options that are worth consideration when initial first and second-line pain therapies have been optimized or are contraindicated. Potential uses, clinical considerations, and US availability are noted for each.

Not all pharmacologic treatment options are viable for every patient. Here, we revisit the “land of lost analgesics” with the goal of refamiliarizing pain-treating clinicians – whether in specialty or primary care – with alternative treatment options. (Image: iStock)

  Skeletal Muscle Relaxants

Skeletal muscle relaxants are a broad category of medications consisting of a wide spectrum of drugs with different indications and mechanisms of action. Muscle relaxants can be divided into two main categories: antispasmodic and antispasticity medications. Antispasmodics are used to reduce muscle spasms resulting from a painful condition whereas antispasticity medications are used to decrease spasticity that hinders functionality.1                   

Orphenadrine citrate

Orphenadrine citrate is classified as an antispasmodic with the mechanism of action being unclear, but is a derivative of diphenhydramine and its activity is believed to be related to its sedative effects. In four placebo-controlled trials, orphenadrine was found to be fairly effective in some musculoskeletal conditions (acute low back pain, neck pain, nocturnal leg cramps) as well as symptoms of pain intensity, stiffness, and functionality.2

However, given orphenadrine’s chemical nature, it consequently possesses anticholinergic activity and thus patients may experience dry mouth, blurry vision, constipation, urinary retention, and cognitive dysfunction.1 Orphenadrine citrate is indicated for mild to moderate pain of acute MSK disorders and as an adjunct to rest, PT, and other measures for relief of discomfort associated with acute painful MSK conditions. In 2020, FDA granted a supplemental ANDA for a combination formulation of orphenadrine citrate with aspirin and caffeine in 2020.

Brand names: Norflex, Norgesic, Orphenesic Forte

Formulations: oral, injectable

Potential targets: acute low back pain, neck pain, nocturnal leg cramps

Available in US: Yes

Tolperisone

Tolperisone is classified as an antispasmodic with the mechanism of action possessing lidocaine-like-activity by stabilizing nerve membranes of mono- and polysynaptic reflexes in the spinal cord by blocking in a dose-dependent manner.1 Tolperisone was shown to be more effective than placebo for patients with chronic low back pain and overall improvement with short term use over 21 days, but no reduction of muscle spasms or pain.1 Unlike other skeletal muscle relaxants, tolperisone has been shown to exhibit less somnolence or cognitive adverse effects when used with for up to 14 days.3 As a skeletal muscle relaxant with less CNS adverse effects than currently available in some analgesics, tolperisone may offer a more promising option for patients.

Brand names: Mydocalm

Formulation: oral

Potential targets: low back pain

Available in US: No, but the manufacturer is recruiting for Phase 3 STAR study under ClinicalTrials.gov #NCT04671082; utilized in Europe since the 1960s

Dantrolene sodium

Dantrolene is classified as an antispasmodic medication with the mechanism of action on the PNS by blocking the calcium channel of the sarcoplasmic reticulum to reduce the concentration of calcium and diminishing the potential for an actin-myosin interaction which could produce a muscle contraction.1,2 Dantrolene has shown some efficacy for use in spasticity in debilitating conditions that hinders functionality, but there is little evidence exhibiting effectiveness for musculoskeletal conditions.1 Despite dantrolene bypassing the CNS and avoiding the typical adverse effects, it is consequently associated with hepatotoxicity and muscular weakness.1

Dantrolene is still commercially available in oral and injectable formulations and FDA approved for the treatment of spasticity associated with upper motor neuron disorders such as cerebral palsy, multiple sclerosis, spinal cord injury, and stroke.

Brand names: Dantrium, Ryanodex

Formulations: Oral, injectable

Potential targets: Muscle relaxation after CNS injury

Available in US:  Yes

See also, a case report and review of dantrolene for muscle spasticity. 

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are used to inhibit the enzyme cyclooxygenase (COX) which is a bifunctional membrane-bound hemoproteinthat catalyzes the reduction of arachidonicacid to cyclic endoperoxide by bis-dioxygenation for the biosynthesisof prostaglandins, prostacyclin and thromboxanes.4

There are two principle isoforms of COX enzymes which are bifunctional enzymes consisting of both cyclooxygenase and peroxidase activity: COX-1 and COX-2. COX-1 is predominantly responsible for the production of prostaglandins necessary for maintaining normal endocrine and renal function, gastric mucosal lining, and hemostasis by mediating thromboxane A2 production to cause vasoconstriction and activate platelet aggregation. COX-2 is produced in response to inflammatory and mitogenic stimuli which is important in facilitating inflammation as well as the production of prostacyclin to promote vasodilation and inhibit platelet aggregation.5

Rofecoxib

Rofecoxib is a COX-2 selective NSAID consisting of a methylsulfone moiety and a lactone ring structure that makes it >800 times more selective for COX-2 than COX-1.6 In comparison to other NSAIDs, rofecoxib is about 6 to >20 times more selective for COX-2 than celecoxib, diclofenac, indomethacin, or meloxicam. As an NSAID with significant COX-2 specificity, rofecoxib has benefits of yielding effective analgesic and anti-inflammatory activity with reduced potential for GI-related adverse effects.6 Rofecoxib was originally FDA-approved for the management of acute pain in adults, primary dysmenorrhea, and osteoarthritis.4,6        

In a Cochrane review of 26 RCTs evaluating the efficacy and safety of rofecoxib use in osteoarthritis compared to placebo, celecoxib, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, acetaminophen, and diclofenac/misoprostol combination, evidence showed that rofecoxib was more effective than placebo, but displayed no difference in efficacy when compared to the other NSAIDs at equivalent doses. From a safety standpoint, rofecoxib resulted in fewer GI-related adverse effects compared to celecoxib, ibuprofen, and naproxen with only one trial comparing rofecoxib to celecoxib reporting on the overall rates of GI-related adverse events comparing high dose rofecoxib with low dose celecoxib.7

In a similar fashion, three trials examining cardiovascular safety of rofecoxib and celecoxib used non-comparable doses with the results of those studies suggesting that rofecoxib caused more patients to experience a significant increase in systolic blood pressure and peripheral edema. However, there was no difference between rofecoxib and celecoxib in studies conducted among the general populations.7

In another Cochrane review of two RCTs evaluating the efficacy and safety of rofecoxib use in rheumatoid arthritis, one trial compared to placebo which rofecoxib exhibited a greater degree of efficacy while having a similar a safety profile.The second trial, known as the VIOXX GI Outcomes Research (VIGOR) study,was primarily designed to assess the safety of rofecoxib compared to naproxen which showed similar efficacy and lower GI-related adverse effects and bleeding, but consequently revealed a greater incidental finding of non-fatal myocardial infarctionsin the rofecoxib population.8,9

Fortunately, the overall mortality rate and rate of death from cardiovascular causes were similar in the two study groups. In another significant study, the Adenomatous Polyp Prevention on VIOXX (APPROVe) trial compared rofecoxib to placebo to evaluate its effectiveness in preventing the recurrence of colon polyps, but was unfortunately terminated prematurely due to increased incidence of myocardial infarctions and ischemic cerebrovascular eventsinitially seen following 18 months of continuous treatment.9,10

Similar to other NSAIDs with nephrotoxic adverse effects, rofecoxib causes dose-independent reductions in glomerular filtration rate and acute renal failure as well as reversible interstitial nephritis.11 Rofecoxib was subsequently voluntarily withdrawn from the market in September 2004. However, other COX-2 selective NSAIDs such as celecoxib, diclofenac, etodolac, and meloxicam are still commercially available for clinical use.

Benoxaprofen

Benoxaprofen is a arylalkanoic and proprionic acid derivative NSAID initially FDA-approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike other NSAIDs, benoxaprofen is a weak COX inhibitor, but also has an additional mechanism of action by inhibiting 5-lipoxygenase and mononuclear leukocyte migration and their chemotactic response. Benoxaprofen had a long elimination half-life 28-35 hours which allowed for once daily dosing making it convenient for clinicians to prescribe and patients to be adherent to therapy.12,13

There was strong consideration that benoxaprofen had disease-modifying effects in rheumatoid arthritis.13 A clinical trial in 2,204 patients with either active rheumatoid arthritis or symptomatic osteoarthritis treated with benoxaprofen for an average period of 14 months was shown effective for continuous antirheumatic stabilization with a single daily dose.14

Compared to other NSAIDs in rheumatoid arthritis and osteoarthritis, benoxaprofen has been shown to be more effective than aspirin or ibuprofen and more effective than ibuprofen with comparable efficacy to aspirin respectively.14 When benoxaprofen was compared to other NSAIDs such as indomethacin, naproxen, and sulindac, there was no significant difference in efficacy with rheumatoid arthritis patients.12

From an adverse effect profile, benoxaprofen is somewhat unique as it is associated with low incidences of peripheral edema and peptic ulcers, but has a high frequency of phototoxicity and onycholysis.12,14 Photosensitivity typically appears within 48 hours of treatment initiation and resolves 48 hours following discontinuation. Unfortunately, benoxaprofen was voluntarily withdrawn from manufacturer due to cholestatic jaundice with nephrotoxicity and hepatotoxicity. However, benoxaprofen is not unique with respect to its dual activity as a weak inhibitor of COX and its inhibitory effects on mononuclear leukocytes as sulindac has comparable potency and is still commercially available for clinical use.12

Choline Magnesium Trisalicylate

Choline magnesium trisalicylate (CMT) is a non-acetylated salicylate arylpropionic acid and arylacetic acid derivative NSAID that structurally contains choline salicylate and magnesium salicylate with analgesic and anti-inflammatory properties similar to aspirin. CMT does not inhibit platelet aggregation induced by two physiological aggregating agents, collagen and arachidonic acid or spontaneous platelet aggregation.15 The acetyl moiety on aspirin’s hydroxyl group facilitates it to alter factors of platelet function by irreversible acetylation of COX and thus inhibits the conversion of arachidonic acid to thromboxane A2 resulting in suppressing platelet aggregation and prolonged bleeding time. Unlike aspirin, CMT lacks an acetyl moiety and has choline and magnesium substituents on the carboxyl groups of the three salicylate molecules in its structure and as a result there is no interference with platelet aggregation or effect on bleeding.16

CMT may be an alternative NSAID for patients prescribed lithium as non-acetylated salicylates may be preferred to minimize risk for potential drug interactions and inducing lithium toxicity.17 However, CMT should still be used with caution and or avoided in patients with renal dysfunction, and compelling cardiovascular comorbidities such as congestive heart failure and coronary artery disease while prescribed other anticoagulants such as P2Y12 antagonists, phosphodiesterase-3 enzyme inhibitors, vitamin k antagonists, and direct-acting oral anticoagulants.

The most common adverse effects with CMT are similar to traditional NSAIDs with tinnitus and gastrointestinal issues (ie, gastric upset, heartburn, epigastric pain, diarrhea). CMT is FDA-approved for use in the relief of mild to moderate pain, management of acute painful shoulder, management of pyrexia, relief of sighs/symptoms of osteoarthritis, rheumatoid arthritis, and other arthritis (long-term management and acute flares), and anti-inflammatory or analgesic management (in children) of juvenile idiopathic arthritis and other appropriate conditions.

Zomepirac

Zomepirac is a pyrrole acetic acid a NSAID structurally similar to tolmetin, but is more lipophilic and may potentially have central analgesic effects. Zomepirac is nearly equivalent in potency to indomethacin and tolmetin as a COX-1 inhibitor of prostaglandin synthesis and was 2 or 3 times less active than diclofenac, but more active than aspirin, ibuprofen, or naproxen.Zomepirac is typically dosed 100 mg every 4 to 6 hours as needed, but should not be dosed greater than 400mg/day for three months or longer or exceed 600mg/day as these doses have not been studied and are not recommended.18,19

In looking at the data, zomepirac has demonstrated efficacy in relieving moderate to severe acute postoperative orthopedic, gynecologic, abdominal, and thoracic as well as dental pain.18-20 Zomepirac displayed greater efficacy over some opioids and may have been considered a viable option as an opioid sparing analgesic. In singe-dose studies in patients with acute pain, zomepirac 100mg exhibited greater efficacy compared to codeine 60 mg as well as other single agent non-opioid analgesics and other analgesic combinations. In single-dose crossover studies comprised of patients with moderate to severe postoperative pain, oral zomepirac 100 or 200mg was compared to intramuscular morphine 16mg and provided comparable analgesic effects and suggesting a “ceiling effect” of analgesic activity while also indicating that oral zomepirac was about one-sixth as potent as intramuscular morphine, but with a slower onset and longer duration of action.19

Adverse effects of zomepirac are fairly similar to other commonly prescribed NSAIDs such as gastrointestinal-related, however zomepirac exhibited a higher incidence of urogenital symptoms (ie. dysuria, cystitis, urinary frequency, hematuria, pyuria, and urinary tract infections) compared to other common NSAIDs and should be monitored more closely if used longer than six months. Following a single 200-mg dose, zomepirac sodium was shown to prolong the template bleeding time and decrease platelet retention significantly. Unlike aspirin and similar to other NSAIDs, zomepirac platelet inhibition is reversible and returns to normal function after 24 to 48 hours following discontinuation of therapy.18,20 Unfortunately, zomepirac was voluntarily withdrawn in due to various case reports of anaphylactic reactions. However, other COX-1 selective NSAIDs such as indomethacin and tolmetin with similar potency are still commercially available for use clinically applicable.

Brand names: Zomax

Formulation: oral

Potential targets: moderate to severe acute postoperative orthopedic, gynecologic, abdominal, thoracic, and dental pain

Available in US: No

  Adjuvant Analgesics

Neuropathic pain can be one of the more challenging pain syndromes as intolerable symptoms may be intermittent, constant, aggravated, or spontaneous. Adjuvant analgesics consisting of antidepressants, anticonvulsants, as well as other medications with unique properties affecting the nerve cell membrane may be used to help minimize the frequency and intensity in alleviating neuropathic pain symptoms. Some adjuvant analgesics may benefit other medical conditions as well, such as comorbid mental health disorders, potentially minimizing the need for polypharmacy and pill burden.

Maprotiline

Maprotiline is a dibenzo-bicyclo-octadiene secondary amine tetracyclic antidepressant with a large lipophilic carbocyclic moiety and is distinguishable from tricyclic antidepressants by the presence of an ethylene bridge rendering its three-dimensional stereochemical configuration. Maprotiline exhibits similar activity as amitriptyline and imipramine, but has a more rapid onset of action and less anticholinergic adverse effects.21,22

Similar to imipramine, maprotiline exhibits strong norepinephrine reuptake inhibition activity across the nerve cell membrane as well as weak alpha-2 adrenergic blocking activity. Maprotiline undergoes first-pass hepatic metabolism primarily by N-demethylation, oxidative deamination, and aliphatic and aromatic hydroxylation to active formation of aromatic methoxy derivatives.21, 22 Maprotiline may initiated at 75 mg/day and can be titrated up to 225-300mg/day.22

In a double-blind cross over study with maprotiline 75mg/day compared to placebo in patients with chronic tension headache, treatment with maprotiline over a 6-week period was shown to be superior to placebo with mild side effects (drowsiness, dry mouth, increased appetite/weight gain).23 A study group consisting of patients with pain and depression were treated with maprotiline and gradually titrated to a target dose up to 300mg/day (150mg/day if 60 years or older) as tolerated resulted in 72% of patients responding with a greater than a 50% reduction in pain.24 In a randomized, double-blind, crossover trial, maprotiline was compared with amitriptyline in the treatment of postherpetic neuralgia displaying some pain relief, but was not as effective as amitriptyline unless treatment with amitriptyline had failed.25

Maprotiline has similar adverse effect profile as traditional tricyclic antidepressants given its anticholinergic activity with dizziness/faintness, blurry vision, dry mouth, constipation, orthostatic hypotension and tachycardia, but to a lesser degree as well as cutaneous rashes which are more common. Cardiovascular effects have been demonstrated with maprotiline as it can cause a decrease in standing systolic pressure, flattening of T-waves, an increase in heart rate and PR interval, prolongation of the pre-ejection period, as well as QT prolongation.22

Brand names: Ludiomil

Formulation: oral

Potential targets: depressionand anxiety

Available in US: Yes

More on the overlap between chronic pain conditions and psychiatric disorders.

  Antiarrhythmics

Mexiletine

Mexiletine is a class 1B antiarrythmic agent FDA-approved for the treatment of ventricular arrhythmias. Pharmacologically, mexiletine is a structural analogue of lidocaine and acts by blocking voltage-gated sodium channels decreasing the rate of depolarization of ventricular cardiac myocytes, but also has similar potency in local anesthetic properties.26,27

Mexiletine is a racemic mixture of R-(–)- and S-(+)-enantiomers that possess characteristic antiarrhythmic potency with the R-(–)-enantiomer exhibiting increased cardiac sodium channel binding and greater antiarrhythmic activity than the S-(+)-enantiomer, but neither of the isomers significantly changed the electrocardiographic intervals (PR, QRS, QTc) or refractory periods.26 Mexiletine has been used to treat various neuropathic pain syndromes including: alcoholic neuropathy, cancer and radiation-induced neuropathic pain, painful diabetic neuropathy, dysaesthetic pain associated with multiple sclerosis, HIV-induced neuropathy, myofascial pain, peripheral nerve disease, phantom limb pain, postherpetic neuralgia, spinal cord injury, thalamic (post-stroke) pain, and trigeminal neuralgia.28

Mexiletine has a narrow therapeutic range from 0.75 to 2 mg/L that correlates serum concentration level to both its antiarrhythmic efficacy as well as adverse effects.26 However, there are no serum mexiletine concentration levels that correlate with efficacy in relieving neuropathic pain syndromes that have been studied. Therapeutic doses of mexiletine have ranged from 300 to 675mg/day, but clinicians should be vigilant and avoid dosages that can result in serum concentrations exceeding >2 mg/L. Mexiletine is predominantly hepatically metabolized via CYP2D6 to p-Hydroxymexilitine so dosage adjustments are not necessary in patients with severe renal dysfunction or on hemodialysis.28 The consequences of genetic polymorphism to CYPD6 in patients receiving mexiletine for neuropathic pain remain unclear, but should be used with caution and monitored closely during initiation and dose titrations especially in the setting of potential clinically significant drug-drug interactions.26,28

Opioids may have a potential clinically significant drug interaction with mexiletine. Despite there being no studies designed to evaluate the effects of opioids on the pharmacokinetics of mexiletine, it has been reported that patients taking morphine have significantly lower mean concentrations of mexiletine 3 hours following the first dose. The mechanism caused by the lower mexiletine serum concentration is believed to be due to opioids inhibiting gastric emptying and in turn slowing the absorption of mexiletine.26 (More on opioids below.)

The most common adverse effects patients may experience with mexiletine are dizziness or lightheadedness, tremor, nervousness, ataxia, nausea, anorexia, and gastric irritation, but tolerability may be improved with food or reducing the dose.27 Mexiletineis still commercially available in oral formulations and FDA-approved for the management of ventricular arrhythmias, but may potentially be an alternative option as an adjunct analgesic for neuropathic pain who have failed response or cannot tolerate first line treatment options.

Brand names: Mexitil

Formulation: oral

Potential targets: neuropathic pain

Available in US: Yes

  Opioids

Opioids are not just purely mu-opioid agonists; some can be mixedmu opioid receptor agonist-antagonists, as well as agonists of the delta and or kappa opioid receptors with varying pharmacodynamic effects. Mixedmu opioid receptor agonist-antagonists are not used as often as full mu-opioid agonists due to their limited commercial availability, but as a result of their antagonist activity has less dependence and abuse potential.

Opioid analgesics may be considered as adjunctive therapy upon initiation and during optimization of non-opioid analgesics especially for severe pain, but dose and duration of therapy should be kept to a minimum where possible and consideration should be made to taper toward discontinuation as goals of therapy are met and as overall pain improves with optimization of non-opioid analgesics. If opioids are to be used, risk mitigation strategies such as obtaining an opioid treatment agreement or consent, review of prescription drug monitoring program reports, and conducting urine drug testing should be performed periodically as clinically indicated as recommended per established clinical practice guidelines as well as state regulations.

Butorphanol

Butorphanol is a synthetic phenanthrene kappa opioid receptor agonist, mixed mu opioid receptor agonist-antagonist, as well as apartial sigma receptor agonist which is responsible for psychotomimetic effects such as dysphoria, respiratory and vasomotor stimulation.29 potency of parental butorphanol ranges from 4 to 8 times more than morphine, 30 to 40 times more than meperidine, and 15 to 24 times more than pentazocine whereas oral is about 7 times more than codeine and 6 times more than pentazocine.29,30

Butorphanol’s antagonist activity is about 30 times more than pentazocine while only a fraction (1/40) of naloxone and given its high binding affinity to the mu opioid receptor, higher doses of naloxone may be necessary in order to reverse any adverse effects of butorphanol compared to pure opioid agonists such as morphine.29 The absorption of butorphanol is adequate via oral and parenteral routes, but undergoes extensive first-pass hepatic metabolism primarily by hydroxylation to the major metabolite hydroxybutorphanol and N-dealkykation to minor metabolite norbutorphanol which leaves oral bioavailability yielding about only 5 to 17%. With transnasal administration of butorphanol on the other hand, this route of administration bypasses the gastrointestinal tract, and improving bioavailability to about 48 to 70% similar to parenteral administration.30

Additionally, transnasal butorphanol absorbs rapidly while providing onset of analgesia within 15 minutes making it an ideal short-term treatment option for patients with moderate to severe acute postoperative, musculoskeletal and migraine headache pain. The bioavailability and pharmacokinetics of transnasal butorphanol may be influenced by age and sex as the median value for tmax was marginally higher in the elderly (older than 65 years) in elderly men (75%), but was significantly lower in elderly women (48%). However, the bioavailability in young men (68%) and young women (70%) the Cmax and AUC values were relatively similar.30

The most common adverse effects to be expected from butorphanol are sedation, drowsiness, dizziness, as well as nausea and/or vomiting. Unlike pure opioid agonists such as morphine which can cause respiratory depression in a dose proportional manner, butorphanol exhibits a ‘ceiling effect’ with respect to the degree of respiratory depression such as increasing doses beyond 2mg may not result in a corresponding increase in degree of respiratory depression, but the duration of respiratory depression increases with higher doses.29,30 Butorphanol has hemodynamic effects similar to pentazocine but to a lesser degree with cardiovascular effects consisting of: increased pulmonary artery and wedge pressure, increased left ventricular end diastolic pressure, increased systemic arterial pressure, increased pulmonary vascular resistance, as well as increases to cardiac index and cardiac work.29

Considering these cardiovascular effects, butorphanol should be used with caution or avoided where possible in patients with acute myocardial infarction, coronary insufficiency, or ventricular dysfunction. Butorphanol is FDA-approved for use in the relief of moderate to severe pain, as a supplement to balanced anesthesia, for the relief of postpartum pain, and as preoperative or preanesthetic medication with the ladder three indications utilizing injectable formulations only.29

Brand names: Stadol (International)

Formulation: nasal, injectable

Potential targets: moderate to severe pain, postpartum pain, perioperative

Available in US: Yes (generic); Stadol (US) was discontinued due to severe hypertension

Nalbuphine

Nalbuphine is a semi-synthetic phenanthrene kappa opioid receptor agonist and mixed mu opioid receptor agonist-antagonist structurally similar to oxymorphone and naloxone.29,31,32The potency of parental nalbuphine is equivalent to approximately 0.7 to 0.8 times that of morphine whereas oral is 3 times more than codeine.29,32

In comparison to pentazocine, nalbuphine is about 3 to 4 times more potent with a longer duration of action and 10 times more effective with its antagonist activity.29,31 Similar to butorphanol, nalbuphine exhibits sufficient absorption via oral and parenteral routes, but undergoes extensive first-pass hepatic metabolism with oral bioavailability yielding only about 20%.29

Much like any other opioid, the most common adverse effects exhibited with nalbuphine include sedation, drowsiness, dizziness, as well as nausea and/or vomiting.29 Comparable to butorphanol, nalbuphine also exhibits a “ceiling effect”, but to both the degree and duration of respiratory depression as escalating doses does not prolong the duration of respiratory depression beyond 3 hours regardless of dose and thus resulting in a plateau of the respiratory depression curve.29,31,32 In a study comparing nalbuphine and morphine in patients with acute myocardial infarction, nalbuphine did not cause any adverse clinical or hemodynamic effects despite decreasing heart rate and contractility, but maintained aortic pressure and hence sustaining the balance between myocardial oxygen supply and demand.29

Nalbuphine’s cardiovascular benefits with decreasing heart rate and contractility while maintaining aortic perfusion pressure may prevent further cardiac ischemia in patients with acute myocardial infarction. Nalbuphine is FDA-approved for use as an analgesic for moderate to severe pain, for preoperative analgesia, as a supplement to surgical anesthesia, and as obstetrical analgesia during labor.29

Brand names: Nubain

Formulation: injectable

Potential targets: moderate to severe pain, perioperative, labor

Available in US: Yes

Propoxyphene

Propoxyphene is a synthetic diphenyl heptane mu opioid receptor agonist, kappa opioid receptor agonist, and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagoniststructurally similar to methadone that has two centers of asymmetry and exists as four stereoisomers: alpha-dextrorotatory isomer, alpha-levorotatory isomer, dextropropoxyphene, and levopropoxyphene. Dextropropoxyphene exhibits analgesic activity and levopropoxyphene has antitussive activity while the other levorotatory isomers are relatively inactive, but overall none of the isomers can be converted into methadone.Propoxyphene is about 33.33% to 50% the potency of codeine which is deemed to be less efficacious than a 650 mg dose of aspirin.Propoxyphene has rapid absorption via oral route and undergoes extensive first-pass hepatic metabolism primarily by N-demethylation to norpropoxyphene and yielding bioavailability of about only 18-25% from a 65mg dose. Propoxyphene is both a CYP450 2D6 inhibitor and substrate and consequently may be subjected to genetic polymorphisms as well as potential drug interactions.33,34

In a review written by Miller and colleagues, among 243 articles referencing propoxyphene, only 20 double-blind or triple-blind clinical studies were identified creditable for review. Fifteen studies showed that codeine at lower or equal analgesic doses produced comparable or greater analgesic efficacy than propoxyphene, but within the same parameters no study demonstrated that codeine was inferior to propoxyphene. Seven studies showed that aspirin alone or aspirin in combination with phenacetin, and caffeine (at various doses) were comparable or had greater analgesic efficacy than propoxyphene.35

Not all of the comparison studies reviewed presented propoxyphene as inferior as two separate studies showed that propoxyphene hydrochloride 65 mg was superior to codeine 32.5 mg and aspirin 325 mg alone. When compared to placebo, nine studies showed propoxyphene to be superior while seven other studies it was not.35

Common adverse effects with propoxyphene are similar to other opioids which include: dizziness, lightheadedness, visual disturbances, somnolence, drowsiness, seizures, euphoria, nausea, vomiting, abdominal pain, constipation, urinary retention. The metabolite norpropoxyphene is primarily renally eliminated and if accumulated may result in potentially fatal CNS, cardiac, and respiratory adverse events such as cardiac arrest, pulmonary edema, seizures, and even mortality.34

Norpropoxyphene has more potent direct cardiac adverse effects which include: an increase in bradycardia, decreased contractility, decreased electrical conductivity, QTc interval prolongation, as well as local anesthetic properties similar to lidocaine or quinidine which may precipitate arrhythmias. Incidents of pulmonary edema and seizures were believed to be secondary to propoxyphene and its metabolite norpropoxyphene in both high-risk patients and at high doses. Prior to removal, propoxyphene was falling out of favor by clinicians and was perceived to have no therapeutic benefit in the management of acute and/or chronic pain while having greater mortality risk due to its cardiac and neurologic toxicity profile.34

In 2009, the FDA required the drug manufacturer to conduct a multiple-ascending dose (MAD) study which was a randomized, double-blind, placebo-controlled sequential multiple-ascending dose study of propoxyphene for 11 days evaluating 600 mg and 900 mg cohorts. The results of the MAD study were submitted to the FDA by the manufacturer showing significant QTc interval prolongations observed with propoxyphene 600 mg and 900 mg dose cohorts. In 2010, the FDA concluded that the safety risks of propoxyphene outweighed the benefits and recommended against its use due to significant abnormal heart rhythm and electrical activity changes with the prolonged PR interval, widened QRS complex and prolonged QT interval at therapeutically prescribed doses.36 

Propoxyphene was withdrawn by the manufacturer promptly afterward due to the FDA’s cardiotoxicity warning. Other short-acting immediate-release opioids such as codeine, hydrocodone, and oxycodone alone or in combination with acetaminophen are still currently available for use in acute severe breakthrough pain as clinically indicated.

Brand names: Darvocet-N (propoxyphene and acetaminophen)

Formulation: oral

Potential targets: breakthrough pain

Available in US: No, but similar products are still available

Levorphanol

Levorphanol has been referred to as the “forgotten opioid” that is phenanthrene mu, delta, and kappa opioid receptor agonist and non-competitive NMDA receptor antagonist structurally similar to morphine, but without an oxygen and a 6-hydroxyl group.37-39 Similar to morphine, levorphanol has anticholinergic effects and like methadone, levorphanol inhibits the uptake of serotonin and norepinephrine.38 However, unlike methadone, levorphanol has a shorter and more predictable half-life of about 11 to 16 hours with a longer duration of action, and no CYP450 or P-gp drug interactions or associated with any QTc prolongation risk.37

Levorphanol exhibits good absorption through the intramuscular, subcutaneous, and oral routes of administration and undergoes phase II metabolism via glucuronidation to levorphanol-3-glucuronide that is renally eliminated. In some special populations such the elderly, palliative care, and SCI patients, levorphanol may be a viable option and may require a lesser need for coadministration of adjuvant analgesics.37

Common adverse effects with levorphanol are similar to other opioids such as nausea, vomiting, sedation, dizziness, constipation, pruritis, urinary retention, but a unique adverse effect is a potential increase in bile duct pressure which should be avoided in bili­ary surgery patients.39 Levorphanol is FDA-approved for management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Brand names: Levo-Dromoran

Formulation: oral

Potential targets: severe pain

Available in US: Yes

  Clinical Takeaways

Pharmacologic options of the past for treating acute, chronic, and perioperative pain may still be of clinical use. While some analgesic medications, including adjuvants, have been voluntarily withdrawn from the market by the manufacturer, others are still available and simply remain forgotten or underutilized. Pain practitioners across specialties are encouraged to refamiliarize themselves with these drugs in case they may benefit a particular patient who is refractory to or contraindicated for more widely used products.

Not all pharmacologic treatment options, however, are viable for every case; as with any prescription, risks and benefits must be weighed. Having a fuller, even if older, arsenal of potential treatment modalities for pain management can only serve to benefit the clinician and the patient. All pharmacologic treatment options old and new should be reconsidered based within patient-specific clinical parameters and trialed as potential alternative analgesics where possible.

  Miguel Escanelle, MD, and Christopher P. Emerson, MD, MS, contributed to the research of this article.

This commentary is the sole opinion of the author and does not reflect the opinion of employers, employee affiliates, and/or pharmaceutical companies mentioned or specific drugs discussed.  It was not prepared as part of official government duties for Dr. Pham.  Dr. Pham dedicates this article mentor and friend Jeffrey Fudin, PharmD.

Last updated on: September 8, 2021

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Belladonna

also known as Atropa belladonna, Atropa acuminata, Baccifère, Belle-Dame, Belle-Galante, Bouton Noir, Cerise du Diable, Deadly Nightshade, Devil's Cherries, Devil's Herb, Divale, Dwale, Dwayberry, Grande Morelle, Guigne de la Côte, Herbe à la Mort, Herbe du Diable, Morelle Furieuse, Naughty Man's Cherries, Poison Black Cherries, Suchi, and other names.

Belladonna in Italian means “Beautiful Lady” and as you may have already guessed, this plant bears the name of the third Fate of the Greek mythology. Atropos was the Fate that was cutting the thread of life and therefore Belladonna was under her jurisdiction. There are two different stories where potentially the name Belladonna comes from.

The first story can be tracked in myths and legends that surround the plant. It was said that in the forests where the plant was grown, passengers could see a beautiful lady with long black shining hair and big dark eyes appear when the moon grew smaller and dark in its waning phase. Some stories say that the woman would seduce the male passengers only to be found dead next morning, others state that they would wake up constantly thinking about her until they became completely mad, and finally there are some stories where practicioners would pay tributes to the plant for the dark lady to appear and teach them the mysteries of magic. A closer look to these stories will help you understand that the plant is associated with death, hallucinations, beauty, seduction and magic. In addition, the Goddess that appears to be associated with the plant is Hecate and all the above characteristics give a good, however partial, description of her.

Belladonna is rightfully known as the plant used most throughout the history of stealth assassination.

Spies, as well as taste-testers hired by kings and the wealthy to sample food for poisons, learned that it’s possible to develop a tolerance to belladonna. By exposing himself to the toxins by taking small sips of a brew made from the plant over time, an assassin could demonstrate a drink was safe to consume, and his mark would swallow the poison willingly. Made from the plant’s berries, such a drink retains a sweet taste, and can pass as wine.

According to history, Scotland’s King Duncan I, in 1030, passed around bottles of the deadly drink to an army of Danes, which killed them all without his having to lift a sword.

Used on tips of arrows.  In Ancient Rome, it was said to have killed Emperor Augustus. 

Thought to be the poison that caused Juliet to appear dead in Shakespeare’s “Romeo and Juliet."

Witches were believed to use a mixture of belladonna, opium poppy and other plants, typically poisonous (such as monkshood and poison hemlock), in flying ointment, which they applied to help them fly to gatherings with other witches.

In the past it was also used to encourage astral projection and produce visions.

Used in funeral rituals to help the loved ones of the deceased to let go and move forward. Used to invoke Circe. Gather berries when they are ripe (around Samhain.) 

Belladonna is used in cursing and hexing a lot. Stuffing poppets with any parts of the plant, can really mess a persons day up. Some also use it in to tear apart relationships. As well as woman have been known to use it for seduction.

It is important to note that ingesting even small amounts of the leaves or berries can be deadly. Small children and infants are particularly at risk. Be sure to use caution when storing medicines that contain belladonna.

Belladonna contains two chemicals used for medicinal purposes.

The first chemical is scopolamine, which is used primarily for reducing body discharges. It is also helpful in reducing stomach acid, which can help with both nausea and acid reflux.

Scopolamine is also used for controlling the heart rate and relaxing muscles.

The second compound extracted from belladonna is atropine. Similar to scopolamine, atropine can be used to help reduce bodily discharge, but it is not as effective as scopolamine when used as a muscle relaxant and in heart rate control.

Also, atropine can be used to dilate the eyes. In some cases, atropine works as an antidote to insect poison and chemical warfare agents.

Once extracted, one or both chemicals are combined with other medications to help treat some diseases and conditions.

Some of the treatments target:

motion sickness

irritable bowel syndrome

stomach ulcers

excessive nighttime urination

diverticulitis

Parkinson's disease

pink eye

Like many well-known plants and extracts, belladonna is available in some over-the-counter alternative medications and supplements.

Unlike traditional medicines, the U.S. Food and Drug Administration (FDA) do not regulate supplements, which means they are often not tested for safety or the effectiveness of their claimed outcomes.

Companies that have made products containing belladonna state that it can improve various conditions.

These include:

the common cold

fever

whooping cough

hay fever

earache

asthma

motion sickness

flu

a cough and sore throat

joint and back pain

arthritis pain

spasms, or colic-like pain in the stomach or bile ducts

nerve problems

gout

inflammation

Parkinson's disease

hemorrhoids

Belladonna is an ingredient in creams, some liquids, ointments, and, in some cases, suppositories.

There is little research into belladonna's effectiveness at treating any of the above conditions. It is important to consider the potential side effects before taking belladonna as a supplement.

Belladonna is considered a toxic plant with historical uses as a poison. Despite being sold as an over-the-counter supplement, it is likely not safe to consume. It is also important to be aware that the FDA do not monitor the quality and purity of belladonna supplements.

There are some side effects to consider before using belladonna. These side effects include:

dry mouth

red, dry skin

inability to sweat

muscle spasms

blurred vision

enlarged pupils

hallucinations

inability to urinate

convulsions

seizures

coma

Women who are pregnant or breastfeeding may be at additional risk, as some of belladonna's side effects may appear in the unborn child, and it might dry up milk production.

In addition to the side effects, belladonna may make some conditions worse. These include disorders that some manufacturers claim belladonna helps.

Conditions that belladonna can make worse include:

acid reflux

Fever

rapid heartbeat

gastrointestinal (GI) tract infections

high blood pressure

constipation

urination problems

Belladonna has negative interactions with certain medications as well, such as those for allergies and depression. Side effects of the interaction include a rapid heartbeat and rashes

[Source|https://www.magicalrecipesonline.com/2013/01/belladonna-atropos-deadly-nightshade-the-charming-the-shady-the-deadly.html]

[Source|https://www.drugs.com/mtm/belladonna.html]

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