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How are drugs absorbed & what could be reasons for why they aren't working for me?

pharmacology pharmacogenetic pharmacokinetics

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#1 farshad

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Posted 05 May 2019 - 02:32 PM


hello let me give you some of my background. I have suffered from social anxiety whole my life and it wasn't until I was around the age of 18 I started researching and looking into why and perhaps drugs that could help me. Anyway it took me a long time to figure things out because I started with zero experience and knowledge, on top of that im not the brightest guy im kinda slow but I have very good reasons for that which I won't get into. Anyway on my journey was I was experimenting with drugs and supplements I just bought whatever without even looking into the science and wasted a lot of money. it was not until I was around age of 19 that I looked into biology and stuff and, anyway to make a long story short I realize my anxiety is caused by excess CRHR1. To make the story even shorter I have found a drug or two that might help (valproic acid, lithium carbonate) in high dosages as they decrease this protein CRHR1 in the brain. but the thing is, when I take any drug or supplements they have zero effect on me, they just pass trough like I took nothing. For example rhodiola rosea used to have an stimulating effect on me, not anymore. Memantine effect was very strong and obvious but now nothing. Im not sure what the cause is but I can tell you, the CRHR1 excess has caused a tremendous stress and anxiety on my mind/body and my health has suffered very much, I have fatigue that you cannot imagine and I dont think many people would survive being in the same place i am. Anyhow(I love this word), what do you guys think could be the cause for this? it's not a tolerance thing because I dont abuse them and i have tried new drugs that i never taken before and yet no effect for example tianeptine should have an obvious effect im certain. My question is simple, given what I have told you so far, stress > health downgrade > fatigue > drugs not working, what could you make of this do any information so far, does it hold any merit? I just want drugs and supplements to work again so I can fix my social anxiety with the two latter drugs i've mentioned. No route of administration have an effect on me and I have tried many (topical,orally,sublingual,rectum,snorting). What I have not tried is injecting which is what I will do if nothing else works or if you guys have no advice for me. But first I wanna heal my body using Ubiquinol (Active COQ10) becuase im taking it orally and it has no effect so I will find a way to inject it directly into my bloodstream. I have ordered some probiotics and l-glutamine because they apparantly help with the GI tract were drugs are absorbed orally but then again wouldn't this be pointless because other ROA have not worked for me which bypass the gastrointestinal tract. https://www.ncbi.nlm...les/PMC3914806/ this study says probiotics when taken with a drug increased the drug by 43%. 

 

Other possibly causes:

 

-Inflammation

-Low mithochondria (your body needs energy to transport the drugs)

- free radicals (bad bacteria kills the drug before it can have an effect) OR the good bacteria are too busy fighting bad bacteria to use the drug

- Low pottasium or sodium? (energy for ATP)

 

here is a good video maybe give you guys some idea:

 

more info on my other threads:

https://www.reddit.c...on_with_severe/

https://www.reddit.c...ase_absorption/

https://www.reddit.c...lammatory_drug/


Edited by farshad, 05 May 2019 - 02:38 PM.


#2 farshad

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Posted 06 May 2019 - 01:24 AM

''Most of epithelial surfaces of human body such as the skin and the mucosa (sublingual) (and the nose snorting etc) , eyes  are colonized by a vast number of microorganisms, which are collectively known as microbiota or microbiome. ''  Use Probiotics To reduce the development of drug-resistant bacteria (bad bacteria/free radicals etc) and maintain the effectiveness of the drugs.

 

http://dmd.aspetjour...ontent/46/2/122

 

https://www.nature.c...working-1.22109

 

 

https://hummkombucha...d-bad-bacteria/ Stress etc >> bad bacteria takeover / free radicals etc >> health damage > cycle continutes as health detoriates (spelling?) >> bad bacteria everywhere in the body IE Skin, nose, eyes etc so no Route of administration when taking drugs work they just turn into toxins etc 

 


Edited by farshad, 06 May 2019 - 01:32 AM.


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#3 xEva

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Posted 06 May 2019 - 01:59 AM

farshad, I've seen your many posts and I feel for you. clearly, you have some unusual issues, which are hard to deal with. But. Why won't you see specialists? In your place, here is what I'd do:

 

1. do your genome (cheap 23andme) and pay a specialist to analyze your neurotransmitters, hormones, main metabolic enzymes.

 

2. consult endocrinologist and run tests

 

3. consult psychiatrist and run tests

 

Or, alternatively, you can enroll in a med school and specialize in psychiatry or endocrinology. Otherwise, on this forum and others, you are learning, without a doubt, but mostly it is grappling in the dark. You may stumble upon the solution by luck, but then again maybe not.

 

 

PS________

oops! you're in the US now -? You used to be in Europe! Oh well, never mind then, you probably don't have adequate or affordable med care, which means that indeed, you're on your on. Sorry about that.

 


Edited by xEva, 06 May 2019 - 02:11 AM.

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#4 farshad

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Posted 06 May 2019 - 02:09 AM

No offence but I don't need or want your sympathy or anyone elses, I know what im doing even tho it might not look like so. I try not to post as much because I don't wanna spam so it's surprising you say you've seen a lot of my posts.


Edited by farshad, 06 May 2019 - 02:27 AM.

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#5 farshad

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Posted 06 May 2019 - 05:04 PM

wow the only supplement that has had an profound effect is Probiotics, I can tell if I take it for a period of time I will get better. But I only took 50 billion (10x5billion capsules) which is low considering how many bacteria we have in our body, in the trillions. I ordered a different supplement which has 100 billion per capsule and I willl take 1 trillion. Probiotics are no joke they're the real thing!


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#6 farshad

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Posted 07 May 2019 - 02:05 AM



#7 farshad

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Posted 07 May 2019 - 11:20 PM

 

https://drugabuse.co.../liver-disease/

 

milk thistle has any1 tried it for liver function


Edited by farshad, 07 May 2019 - 11:25 PM.


#8 farshad

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Posted 08 May 2019 - 12:31 AM

https://www.livescie...body-nigms.html



#9 farshad

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Posted 08 May 2019 - 06:35 PM

maybe drugs metabolized by certain enzymes only like cyp3a4 can help me

https://upload.wikim...thway_WP229.png

https://www.reddit.c...tabolize_drugs/


Edited by farshad, 08 May 2019 - 07:18 PM.


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#10 farshad

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Posted 08 May 2019 - 08:13 PM

The body's immediate response is to release chemicals, called “stress hormones,” which are used by the body to make energy. ... The continuous increase in stresshormones can also result in suppression of the immune system's white blood cells, leading to an increased risk of infections.



#11 farshad

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Posted 12 May 2019 - 06:45 PM

https://www.msdmanua...ug-distribution



#12 farshad

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Posted 13 May 2019 - 09:42 PM

https://en.wikipedia...Allostatic_load

 

Allostatic load is "the wear and tear on the body" which accumulates as an individual is exposed to repeated or chronic stress. The term was coined by McEwen and Stellar in 1993. It represents the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrineresponse which results from repeated or prolonged chronic stress.

 

https://en.wikipedia...i/Myxedema_coma

 

https://en.wikipedia...i/Levothyroxine

https://en.wikipedia...riiodothyronine



#13 farshad

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Posted 15 May 2019 - 10:20 AM

BINGO!!! Is Coconut oil (the MCT content) the answer to my problem?

 

MCTs passively diffuse from the GI tract to the portal system (longer fatty acids are absorbed into the lymphatic system) without requirement for modification like long-chain fatty acids or very-long-chain fatty acids. In addition, MCTs do not require bile salts for digestion. Patients who have malnutritionmalabsorption or particular fatty-acid metabolism disorders are treated with MCTs because MCTs do not require energy for absorption, use, or storage.

 

https://en.wikipedia...in_triglyceride

 

https://en.wikipedia.../wiki/Dysbiosis

 

https://www.reddit.com/r/Microbiome/


Edited by farshad, 15 May 2019 - 10:50 AM.


#14 farshad

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Posted 16 May 2019 - 11:25 AM

https://www.nutrisha...id-supplements/

 

https://www.healthli...ds-101#section3

 

 

long chain fatty acids (OMEGA-3 etc) are shunted into and stored in adipose (fat) tissue. This is nature’s way of keeping energy stores in reserve without the fats needing to go through the liver process again.

short-chain-fatty-acids (butyrate) & medium-chain (MCT OIL comes from Coconut oil) skip this process because they bypass the lymph system, your body does not store these medium-chain fatty acids in adipose (fat) tissue to use later when energy is low.

 
This direct transport to your liver is how they are able to supply energy more rapidly (similar to carbohydrates).

Edited by farshad, 16 May 2019 - 11:38 AM.

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#15 farshad

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Posted 17 May 2019 - 11:47 AM

https://en.wikipedia.org/wiki/Ketosis


Edited by farshad, 17 May 2019 - 11:48 AM.


#16 farshad

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Posted 19 May 2019 - 03:12 PM

https://en.wikipedia...bioavailability


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#17 farshad

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Posted 20 May 2019 - 01:55 PM

https://selfhacked.c...le-supplements/

TUDCA, milk thistle (LIVER)

 

Carnitor - an L-carnitine supplement that has shown to improve the body's metabolism in individuals with low L-carnitine levels. It is only useful for Specific fatty-acid metabolism disease.

 

 


Edited by farshad, 20 May 2019 - 02:28 PM.

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#18 farshad

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Posted 21 May 2019 - 10:35 AM

PURE MCT SOFTGELS IS WAY BETTER THAN COCONUT OIL

 

KRILL OIL TOO IS GOOD


Edited by farshad, 21 May 2019 - 10:35 AM.

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#19 farshad

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Posted 22 May 2019 - 11:38 AM

https://en.wikipedia.../wiki/Digestion


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#20 farshad

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Posted 22 May 2019 - 05:44 PM

https://en.wikipedia.../Beta_oxidation

https://en.wikipedia...transport_chain

 

 

 

After an oral dose, memantine is well absorbed. Its peak drug concentrations are attained in about 3-7 hours. Memantine shows linear pharmacokinetics when given at normal therapeutic doses. This drug can be taken without regard to food, as there is no effect of food on memantine absorption 

hmm.. I think I will have to go on a high dose memantine cycle 40mg-70mg on empty stomach and then workout in the gym(running treadmill hours) and take Ubiquinol + MCT oil softgels + t3/t4 hormone + probiotics + progesterone oil + longvida curcumin + 5a-dhp + pqq/mitoq/NADH+ etc try each see how they affect me,  I know it will heal my body soon because memantine is the only drug that has worked and it has almost 100% protein binding/availbility and long half-life and I Know for FACT it works but only on empty stomach and high dosage. Does not work aswell as it should but it works pretty good. for 2 weeks should be enough. The good thing with memantine is its an NMDA antagonist so it decreases anxiety and in turn lets your body heal itself if it is suffering from stress-related health damage. Then try different drugs when I feel better see if they work.


Edited by farshad, 22 May 2019 - 05:54 PM.

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#21 farshad

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Posted 23 May 2019 - 09:36 PM

niacin methylation


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#22 farshad

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Posted 24 May 2019 - 09:17 AM

so 1. Memantine in high dosage seems to be the only thing that slighlty works, and when I take any drugs or supplements while on memantine they Also work but slightly too. So I have thinking of taking ubiquinol , NR+ and MCT oil while on memantine so that my body can create energy even if it is little it will have some effect and add up within days of being on memantine too. Perhaps t4/t3 hormone too and curcumin by longvida to decrease inflammation....I also have 5a-dhp which is a direct precursor to gaba so I will use that too.

Im sure this will work meanwhile im going to the gym. If not I have some milk thistle and TUDCA for liver protection because the liver has over 500 functions in the body which I will take when on memantine.


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#23 farshad

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Posted 27 May 2019 - 03:11 PM

Betaine hydrochloride (Betaine HCl) is made out of betaine (TMG) and hydrochloric acid. It is a supplement that increases stomach acid


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#24 joelcairo

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Posted 03 June 2019 - 08:59 PM

If probiotics work for you, maybe try prebiotics (soluble fiber). I have seen some recent publications suggesting this is the superior way to go for gut flora health and diversity. I'm sure this is also much cheaper, as probiotic supplements are incredibly expensive.

 

But if that fails, switch back to probiotics. It's more important to do what works than to do what experts are currently recommending.

 


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#25 farshad

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Posted 07 June 2019 - 04:50 AM

 

 

Ginkgo biloba extract increases the microcirculation significantly in the skin and liver of elderly patients. It could be used as an adjuvant treatment option for patients suffering from impaired microcirculation (monocentric CT

transport drugs too to organs?

 

 

NAC boosts glutathione, the highest amount of which is in the liver. This helps explain why NAC has such a strong effect on protecting the liver from inflammation, drug poisoning, and serious liver diseases.

If the liver is damaged, inflammation and oxidative stress always rise. NAC can protect the liver by reducing inflammation and increasing antioxidant reserves.

NAC reduced liver damage in 85% of all cases, according to a large review. It could protect the liver from factors such as excessive alcohol and environmental pollutants [6].

Interestingly, NAC injections helped increase liver function better than glutathione in one study of 75 patients with Hepatitis B

iver Damage

N-Acetyl Cysteine has been used as an antidote to acetaminophen poisoning for over 50 years.

Commonly-used painkillers (such as Tylenol) contain acetaminophen, which can damage the liver and even cause liver failure at high doses. Acetaminophen is the most common cause of serious, sudden, liver damage [89].

NAC can safely prevent serious liver damage from acetaminophen and increase survival, according to several studies of over 400 patients [810].

Sudden, life-threatening liver damage can also be caused by various drugs, toxins, or hepatitis.

NAC helped protect the liver in 80 such cases. Patients with liver damage from drugs experienced the best results [11].

NAC has been studied a lot in intensive care units, as a possible way to reduce organ damage before and after surgery [12].

Bottom line?

Although NAC can help repair serious liver damage, it can also offer less drastic benefits for detox or liver support. It increases glutathione in the liver and helps to prevent liver damage from toxins, drugs, and pollutants.

 

 


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#26 farshad

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Posted 10 June 2019 - 12:26 PM

ketone supplements


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#27 farshad

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Posted 11 June 2019 - 11:14 AM

 

Liver disease may have complex effects on drug clearance, biotransformation, and pharmacokinetics. Pathogenetic factors include alterations in intestinal absorption, plasma protein binding, hepatic extraction ratio, liver blood flow, portal-systemic shunting, biliary excretion, enterohepatic circulation, and renal clearance. Sometimes alterations increase levels of bioavailable drug, causing normal drug doses to have toxic effects. However, levels and effects for an individual drug are unpredictable and do not correlate well with the type of liver injury, its severity, or liver function test results. Thus, no general rules are available for modifying drug dosage in patients with liver disease.

Clinical effects can vary independent of drug bioavailability, especially in chronic liver disease; eg, cerebral sensitivity to opioids and sedatives is often enhanced in patients with chronic liver disease. Thus, seemingly small doses of these drugs given to cirrhotic patients may precipitate encephalopathy. The mechanism of this effect probably involves alterations in cerebral drug receptors.

Adverse drug reactions do not appear to be more likely in patients with advanced liver disease; however, such patients may tolerate any hepatic adverse effects of drugs less well.

 

Effects of Liver Disease on Drug Metabolism
 
 

 



#28 farshad

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Posted 14 June 2019 - 02:44 PM

last shot https://en.wikipedia...idant_compounds


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#29 farshad

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Posted 15 June 2019 - 06:37 PM

hmm..

 

 

2) Phosphatidylcholine Improves Liver Health

Very low levels of phosphatidylcholine can cause liver damage and even death in mice [8]. An animal study showed that phosphatidylcholine can promote liver regeneration [27].

Low levels of choline and phosphatidylcholine can cause non-alcoholic fatty liver disease (NAFLD) in humans [2829]. Non-alcoholic fatty liver disease, as the name implies, is a disease in which fat build up in the liver due to causes other than alcohol.

A study (DB-RCT) using a combination of milk thistle (silybin) and phosphatidylcholine treatment showed a significant improvement in liver enzymes, insulin resistance, and liver tissue in 179 patients with non-alcoholic fatty liver disease [30].

Choline supplementation increases the ratio of phosphatidylcholine/phosphatidylethanol (PE) in the liver. This may prevent the progression of non-alcoholic fatty liver disease and increase the chance of survival after liver surgery [182731].

 


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#30 farshad

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Posted 17 June 2019 - 04:47 PM

Niacin


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