is the paxil hiding in my fat pockets?

[Paxilalmostkilledme]

I was reading from this website, http://ssri-research.com/dangers_of_tapering

and it seems to imply that I might have more paxil in my system since I am overweight. It's been 14 months and I still have paxil weight, I am wondering if I still have paxil in my system....is Paxil fat-soluble? I always thought it had a short half-life, meaning it was out of my system quickly.

is Paxil still in my fat cells?

The article seems to suggest that a thinner person might have a better time in protracted withdrawal. I would love to see a study on that.

[Katesmom]

When I first came here, we talked about this A LOT. These days, no one is talking about it anymore.

We used to always say that it is stored in fat cells. I have found that when I lose weight, I get symptoms. So, anecdotally, I would say that it is true.

I'm sure some of our knowledgeable folks will chime in soon.

[Dawn B.]

I think anything TOXIC can hide in your body for a very long time.
No matter what the drug co. says.

[Johnnny off Paxil]

This is correct and has been my experience..... so what do you do.. I still intend to lose that "bag of potatoes" I gained while on Paxil..


Regards Johnny

[Paxilalmostkilledme]

You guys are ahead of the curve....I had a few good months (Jan, Feb) where I was tempted to claim victory, until this past week. Today I felt so angry and told 2 people off, ,one for cutting me off in a grocery line ( I screamed "You're really something lady". I must have sounded like George Costanza from Seinfeld....only more angry. A crazy person says does that.

it got me thinking when I got home - that I am not done yet. After reading the article, I took my shirt off in the bathroom and looked at my fat. alot of the paxil bloat is gone, but not all. Even worse than seeing myself in the mirror was the thought of Paxil still being in my body. Geez.

[pokie]

You just made me think....wow if I had a silhouette of my body and poured paxil sized sugar tablets into it since the very beginning how many tablets would be in that silhouette-at 5'3 approx. 105lbs. Actually its making me sick.

[pokie]

Today I felt so angry and told 2 people off, ,one for cutting me off in a grocery line ( I screamed "You're really something lady".

Damn I wish I was there to see that-Ihave been laughing my *** off.

[Paxilalmostkilledme]

Honestly, I think she was a little scared.

I then muttered, What happened to manners?

Kinda crazy, kinda funny.

[pokie]

Its funny you are making me think back to when I had a fight with a woman at the grocery store. She was alot bigger than me and it was really bad. We were so loud that her boyfriend whispered to me that she was nasty so could I please just ignore her. I think she probably was a boyfriend abuser too he was acting very scared & uptight.

I notice myself doing thing like this too- it seems it comes out of no where.

Yours sounds really funny..............again wish I was there.

[Paxilalmostkilledme]

Originally Posted by pokie

You just made me think....wow if I had a silhouette of my body and poured paxil sized sugar tablets into it since the very beginning how many tablets would be in that silhouette-at 5'3 approx. 105lbs. Actually its making me sick.

judging from my gut I must still have a few months of Paxil in there!

[pokie]

Think I will post this in a seperate thread -interested in the answer.

[EricPaul]

Originally Posted by Paxilalmostkilledme

I was reading from this website, http://ssri-research.com/dangers_of_tapering

and it seems to imply that I might have more paxil in my system since I am overweight. It's been 14 months and I still have paxil weight, I am wondering if I still have paxil in my system....is Paxil fat-soluble? I always thought it had a short half-life, meaning it was out of my system quickly.

is Paxil still in my fat cells?

The article seems to suggest that a thinner person might have a better time in protracted withdrawal. I would love to see a study on that.

The person who wrote the article is a orthomolecular person and they perhaps don't understand the reason for protracted withdrawal. You need to be careful about the source of info you consider because there are a lot of people out there who don't know what they are going on about.

The reason people have protracted withdrawal is not because there is drugs hiding in fat or bone, but because of the changes the drug has caused to the receptors of the brain. This topic is routinely brought up on the benzo boards too. People think, and the alternative med people promote this kind of untruth, that because they have protracted withdrawal, then there must still be drugs in their bodies. This is not true. Protracted withdrawal is not caused by drugs being stored in fat or bone.

Here is an explanation by Ashton. This applies to all drugs, not just benzos.

NO EVIDENCE THAT BENZODIAZEPINES ARE
"LOCKED UP" IN TISSUES FOR YEARS
Professor C Heather Ashton DM, FRCP
March 2001
The Ashton Manual · Professor Ashton's Main Page

Question: Is the Post-Withdrawal Syndrome caused by benzodiazepines being "locked up" in tissues for years or is it the result of brain damage occasioned by long-term benzodiazepine use?

Answer: Benzodiazepines are fat soluble and do enter fatty tissues including the brain. But these tissues are in equilibrium with the blood, so that if the concentration in the blood is lower than that in fat, some will come out of the fat and re-enter the blood where it is metabolised and excreted. This will again lower the blood concentration, so more will leach out of the fat, and so on. So the body is more or less cleared, even of long half-life benzodiazepines, within 30 days. There is no evidence that benzodiazepines are "locked up" in tissues for years. I have looked into this question with an expert pharmacologist, Dr Clare Stamford of University College in London. There is a reference to this in the Manual (Chapter III, pp 33/34 in the UK version).

Long-term effects of benzodiazepines that persist after withdrawal are largely due to changes they have caused in GABA/benzodiazepine receptors, and not due to bits of drug being retained in the body. Of course lots of other factors, like post-traumatic stress disorder in people who have had a traumatic withdrawal experience, may also be operative in different individuals.

When writing the Manual I did attempt to find out from many sources, including Roche, whether anyone had measured benzodiazepine concentrations in tissues after withdrawal, even in animals. The answer was no. There was one post mortem study in geriatrics which found a surprisingly high concentration of benzodiazepines in muscles. But these were bedridden old people and there was no record of the doses of benzodiazepines they were taking or not taking before they died. Dr Clare Stamford at the University College in London, who has done a lot of rat benzodiazepine work, said that it was most unlikely that benzodiazepines could be sequestered for long periods of time in tissues as these are in equilibrium with blood and continually washed out.

Benzodiazepines are not known to be chemically bound anywhere like some metals – so it comes down to receptor changes that are only slowly reversible. The complete alleviation of long term symptoms with the benzodiazepine antagonist flumazenil seems to point in this direction (also mentioned in Chap III of the Manual). You could still get windows if your receptors were unstable, switching from one state to another. A similar thing, involving other receptors, is thought to account for rapid swings between mania and depression in so-called bipolar patients. You could call receptor changes brain damage if you wanted to, but I think they are reversible or potentially reversible; probably with receptors in different areas reversing at different rates, and some more readily than others.

The question of permanent damage is discussed in "Protracted withdrawal from benzodiazepines: The post-withdrawal syndrome" Psychiatric Annals 25, 174-179. This article is available here. The article clearly states that the evidence about permanent (structural) brain damage due to benzodiazepines is equivocal and there is at present no definite proof of this although some evidence is suggestive. However, occasionally people do have "withdrawal" symptoms which appear to be permanent and may persist till death. This has been reported in the medical literature by others and also observed by myself.

CLARIFICATION ABOUT BRAIN DAMAGE
by Professor Heather Ashton
August 29, 2002

I agree that there is an abundance of people with very long-term problems and I have never denied that benzos can cause lasting, possibly permanent, neurological and other symptoms (see my articles on protracted withdrawal syndromes). What I have said is that there is no convincing evidence to date that they cause structural brain damage - e.g. death of neurons, brain atrophy etc. I think that long-lasting changes are probably functional, at the level of the GABA/BZ receptors which fail to revert to their pre-benzodiazepine state, often leaving the nervous system hyperexcitable (paraesthesiae, formication, muscle twitches, fasciculation, sensory hypersensitivity, tinnitus, jaw and dental pain, insomnia etc.) or generally unregulated/uncoordinated (cognitive) problems. Being functional changes, they are potentially capable of resolving which is why many people do notice gradual, if incomplete, improvement over the years.

Professor Lader himself carried out CAT scan studies on long-term benzodiazepine users and failed to find definite structural brain changes. As you know I tried several times unsuccessfully to obtain a grant for MRI studies in long-term benzo users who have withdrawn (combined with neurocognitive and EEG measurements), and to my knowledge no such study has ever been performed. Several correspondents have had MRI scans which have been reported as normal. On the other hand, I have of course seen many patients with long-lasting tinnitus, paraesthesiae, muscle spasms and joint pains etc. which are reported in my papers on protracted withdrawal. See especially the 1991 paper.

However, neither CAT scans nor MRI can reveal functional as opposed to structural changes. A search for structural changes would require very careful comparisons of brain volumes, hippocampal size, ventricular volume etc, in benzo users compared to age, sex and IQ matched controls; or else prospective longitudinal studies, again comprising benzo users with matched non-users over the long term. Cerebral blood flow measurements (fMRI) or PET (positron emission tomography) of GABA receptors might be more informative about functional changes, but have not been carried out.

http://www.benzo.org.uk/ashanswer.htm

More about protracted withdrawal. Ssri drugs affect serotonin so this article applies to ssri drugs as well. Same mechanism of why people have protracted withdrawal, but different drug and receptor, but the mess caused is the basically the same and will take time to recover from.

http://www.benzo.org.uk/pha-1.htm

[EricPaul]

Here is an interesting article. This could be the reason for protracted ssri withdrawal, changes to the receptors.

Jefferson Scientists Show Several Serotonin-Boosting Drugs Cause Changes in Some Brain Cells

Some cells shriveled, while others took on corkscrew shapes
Researchers from Jefferson Medical College in Philadelphia have found changes in brain cells in rats treated with large doses of several anti-depressant or anti-obesity drugs. In some cases, the cells shriveled or took on abnormal corkscrew shapes. While the clinical significance of the findings isn’t known, the scientists say, they may raise new concerns about the prolonged use of such commonly prescribed drugs as fluoxetine (Prozac) and sertraline (Zoloft). The work also highlights the need for similar studies on other classes of drugs that act on the central nervous system.

The scientists, led by Madhu Kalia, M.D., Ph.D., M.B.A., professor of biochemistry, molecular pharmacology, anesthesiology, and neurosurgery at Jefferson Medical College of Thomas Jefferson University in Philadelphia, compared the effects of giving high doses for four days of four drugs – Prozac, Zoloft, sibutramine (Meridia) and dexfenfluramine (Redux) – on rat brain cells. Each rat received only one drug.

In the study, after the toxic doses of drugs were halted, and the animals’ brains subsequently examined, the researchers saw marked changes in some nerve terminals, which actively release the brain chemical serotonin.

These drugs, collectively known as Selective Serotonin Reuptake Inhibitors (SSRIs), increase the level of serotonin, which is vital to brain cell communication. Low serotonin levels are linked to mood and eating disorders.

Dr. Kalia and her colleagues at Jefferson and at the Centers for Disease Control and Prevention and the National Institute of Occupational Safety and Health in Morgantown, WVa., report their results March 6 in the journal Brain Research.

The question remains, what do these findings mean. "We don’t know if results with four days of drug treatment are clinically significant," Dr. Kalia says. "We don’t know if the cells are dying. That’s the key question. We need to do more studies to prove cell death. These effects may be transient and reversible. Or they may be permanent."

Prozac and Zoloft are Food and Drug Administration-approved medications for the treatment of depression and other central nervous system disorders. Meridia is marketed for the treatment of obesity. The anti-obesity drug Redux was pulled from the market in 1997 after reports of heart valve damage.

Methylenedioxymethamphetamine (MDMA), known as the street drug Ecstasy, is an amphetamine-derivative that is known to be toxic to some brain cells. MDMA and another drug, 5,7-dihydroxytryptamine (5,7-DHT), were used as controls because both drugs push serotonin out of the brain cells. The brain cell changes with SSRIs were similar to those observed with MDMA.

Serotonin is ubiquitous in the central nervous system, making it a frequent target of potential drugs. Drugs such as Prozac and Zoloft raise serotonin levels for depression and panic attacks, for example. Another class of SSRIs – anti-anorectics – includes drugs such as Meridia and its predecessor, Redux. Such drugs block the circulating serotonin, a neurotransmitter. Once brain cells use serotonin, it’s recycled in the brain. SSRIs keep serotonin from being recirculated back to the brain for subsequent use, allowing the chemical to stay active in the brain.

More than a decade ago, rat studies showed that high doses of Redux could change the shape of some brain terminals, says Dr. Kalia. Some researchers attributed the effect to the fact that the drug was also a serotonin releaser. It pumps extra serotonin out of the brain cell, depleting the brain cell nerve terminal, rather than just blocking serotonin from entering back into the cell.

"It was a big mystery why these brain terminals looked like corkscrews with high doses," Dr. Kalia remembers. But, she says, few scientists examined all SSRIs. "We asked the question, ‘Would other SSRI’s cause the same effects in high doses’?"

Because patients are using some of these drugs for long periods – and scientists aren’t sure of what the long-term effects of many of these drugs might be – she and her co-workers plan to do long-term studies in animals. "We would lower the doses to about 10 to 30 times the therapeutic dose and give it to the rats for six months or a year, looking at them at selected periods of time to ask the questions, ‘Can we see these changes in serotonin cells over the long term, or does the brain adjust?’" she says.

The scientists would then examine the long-term effects of the drugs and examine the behavioral and neurological effects of these brain changes. "We need to find out if these changes are effecting behavioral changes in the rat and in patients.

"The problems with human studies is we can't do such experiments in controlled environment," she explains. One difficulty with using such drugs, she says, is that several of them are given to patients who already have psychological problems such as depression and mood swings. They may or may not develop neurological problems following drug treatment. Though that isn’t necessarily the case with patients taking anti-obesity drugs, she points out, in any case, "the possibility of overlooking any drug-induced neurological changes must be considered."

Published: 2-29-2000
http://www.antidepressantsfacts.com/...y-Hospital.htm

[Paxilalmostkilledme]

that is really interesting. Hopefully the changes that these drugs cause are truly temporary and I don't have brain damage.Do you think it is possible that Paxil 1)caused changes in the body that remain for a long time and 2) that Paxil remains in fat cells?

number 2 would explain why people have what is known as "The Paxil Bloat"

Did you read the link from Merck on Fat soluble drugs?
http://www.merck.com/mmhe/print/sec02/ch011/ch011d.html

[EricPaul]

Originally Posted by Paxilalmostkilledme

that is really interesting. Hopefully the changes that these drugs cause are truly temporary and I don't have brain damage.Do you think it is possible that Paxil 1)caused changes in the body that remain for a long time and 2) that Paxil remains in fat cells?

number 2 would explain why people have what is known as "The Paxil Bloat"

Did you read the link from Merck on Fat soluble drugs?
http://www.merck.com/mmhe/print/sec02/ch011/ch011d.html

Yes, I read it and understood it. Did you understand it? It does not say anywhere that fat soluble drugs are retained or locked up in any tissues to cause protracted withdrawal. It says the exact same thing that Ashton wrote in the excerpt below, that they are excreted and eliminated from the body within a short period of time.

Did you read the information about fat soluble drugs by Ashton? The fat soluble drugs that Merck refers to are out of the body and excreted based on their half lives. They do not stay in the fat tissues for prolonged periods of time. All drug are excreted and are not locked up in any tissues.

"
Answer: Benzodiazepines are fat soluble and do enter fatty tissues including the brain. But these tissues are in equilibrium with the blood, so that if the concentration in the blood is lower than that in fat, some will come out of the fat and re-enter the blood where it is metabolized and excreted. This will again lower the blood concentration, so more will leach out of the fat, and so on. So the body is more or less cleared, even of long half-life benzodiazepines, within 30 days"

Here is how all drugs are excreted. They do NOT stay in the fat tissues as some uneducated people seem to think.

Excretion

Drugs are eliminated from the body either unchanged as the parent drug or as metabolites (a changed form of the drug).

Organs that excrete drugs eliminate polar compounds (water soluble) more readily than components with high lipid (fat) solubility. The exception to this premise is the lungs.

Lipid soluble drugs are not readily eliminated until they are metabolized to more polar compounds.

Possible sources of excretion include:

Breath
Urine
Saliva
Perspiration
Feces
Milk
Bile
Hair
The kidney is the most important organ involved in the elimination of drugs and their metabolites.

Substances excreted in the feces usually involve orally ingested unabsorbed drugs or metabolites excreted in the bile that are not reabsorbed from the intestinal tract.

Excretion of drugs in milk is relevant because excreted drugs can produce drug toxicity in the nursing infant. Pulmonary excretion (through breathing) is important as it pertains to the elimination of anesthetic gases and vapors, as well as alcohol.

Excretion through the kidneys

The kidneys are a pair of bean-shaped organs, each a little smaller than the fist and weighing about 0.25 pounds. They lie on the back of the abdominal cavity at the level of the lower ribs. They act as a pressure filter. On its way through the kidneys the blood is filtered. The liquid or "primary urine" consists of a considerable amount of the blood's water, together with all substances dissolved in this water (including drugs). The kidneys reabsorb most of the water and some of the dissolved substances. Components that are fat-soluble tend to diffuse back into the bloodstream.

The kidneys perform two major functions:

They excrete most of the end-products of body metabolism (including drugs); They closely regulate the levels of most of the substances found in body fluids.
Substances that must be excreted include the end-products of body metabolism, as well as sodium, potassium, and chloride, which frequently accumulate in the body in excess quantities. The kidneys must also be capable of conserving water, sugar, and the necessary quantities of sodium, potassium and chloride.
Since drugs are small particles dissolved in the blood, they too are usually filtered into the kidneys and then reabsorbed back into the bloodstream.

Water is reabsorbed from the kidney into the bloodstream to a much greater extent than most drugs, so the drugs become more concentrated inside the kidney than they are in the blood.

In order for the kidney to eliminate drugs from the body, the drug must somehow be prevented from being reabsorbed from the urine into the bloodstream.

The drug must be chemically changed into a compound that is less fat-soluble and therefore less capable of being reabsorbed.

Conversion

This process of converting fat-soluble drugs into water soluble metabolites that can be excreted by the kidney is carried out in the liver.

Usually (but not always) the process of metabolism decreases the pharmacological activity of a drug. Even though a metabolite might remain in the body (awaiting excretion), it would usually be pharmacologically inactive or less active and would not produce the effects of the parent drug to the same extent.

Many drugs can increase the rate at which an enzyme system metabolizes a variety of drugs, thereby increasing the speed with which a drug is eliminated.

Certain drugs induce an increase in enzyme activity. This process can decrease the pharmacological response to certain agents metabolized in the liver. For example, phenobarbital stimulates the production of enzymes that normally metabolize the anti-coagulant warfarin. Thus phenobarbital decreases the effect of warfarin by increasing the metabolism of warfarin.

Some drugs can also stimulate their own metabolism. This is one mechanism to explain why increasing doses of a drug must be administered in order to produce the same effect that smaller doses produced earlier.

Regarding the placental barrier referred to earlier, the fetus may excrete drugs through the umbilical cord back into the bloodstream of the mother. The mother can then eliminate the drug through the liver and kidneys. After delivery, however, the newborn baby is no longer attached to the mother and must deal on its own with any drug in its blood. Unfortunately, the newborn baby has few drug metabolizing enzymes in the liver and the kidneys may not yet be fully functional. This means, that the infant has great difficulty metabolizing and excreting drugs.

Biliary and fecal excretion

Many metabolites of drugs created in the liver are excreted into the intestinal tract in the bile. Hence the intestine is not only a site of absorption but it is also a site of excretion.

The net excretion by this route may be greatly reduced by subsequent reabsorption into the bloodstream of fat-soluble compounds further along the intestines. In this case drugs will undergo the process of excretion all over again and the drug effect is prolonged. This excretion/reabsorption phenomenon is called enterohepatic cycling

Metabolites may be excreted in the feces. More commonly, they are reabsorbed into the blood and ultimately excreted in the urine.

Excretion by other routes

Minute amounts of drugs are excreted into sweat, saliva and tears.

Drugs excreted into the saliva enter the mouth, where they are usually swallowed. Their fate thereafter is the same as drugs taken orally. Some drug concentrations in the saliva parallel those found in the plasma.

Since breast milk is more acidic than blood plasma, basic compounds may become slightly concentrated in this location.

Although excretion into hair and skin occurs in small quantities, it does have forensic significance.

http://www.forcon.ca/learning/excretion.html

[EricPaul]

Here is another explanation of how drugs work. They ALL are eliminated from the body. They do not stay locked up in body fat and are metabolized and excreted . Protracted withdrawal from any drug, fat or water soluble, is not due to any drugs being retained in the body. It is due to the changes of the receptors that the drugs have caused.

How Do Drugs Work?

To understand how drugs work, one must understand the concept of drug kinetics. In short, drug kinetics refers to the actions taken by the human body to deal with a medicine. These actions involve the processes of drug absorption into the body, distribution of that drug to various tissues, metabolism (or breakdown), and excretion (or elimination). Of the above processes, absorption is the most significant.

Absorption

Absorption is the process by which a drug passes from its site of administration into the circulation (bloodstream). The blood receives a drug from the site of administration and carries it to all the organs, including those on which the drug acts. The speed, ease, and degree of absorption are related to the route of administration. There are several sites at which drugs are commonly administered. They are as follows:

Intravenous administration (IV) - IV refers to the injection of a drug directly into the blood, most commonly into a peripheral vein.
Intramuscular injection (IM) - In an intermuscular injection, the drug is injected into the muscle. This type of injection may have erratic absorption. If suspended in an oil base, an IM medicine usually has a slow and even absorption. (i.e. penicillin IM)

Subcutaneous injection (SQ, SC) - With a subcutaneous injection, the drug is injected just beneath the skin. A subcutaneous injection provides slower absorption than an IM. (i.e. insulin)

Rectal administration - In this type of administration, the drug passes through the rectal lining (mucosa) into the blood. Absorption is highly variable and may cause irritation of the rectal mucosa. This route is mainly used for antinausea and antiemetic (antivomiting) drugs.

Oral route - This is the most commonly used route of administration for drugs. It uses the oral lining (mucosa) and the gastrointestinal tract (GI).

The oral mucosa administration includes sublingual (under the tongue) and buccal (in the cheek) methods. These methods provide convenient routes when rapid onset of action is required (i.e. sublingual nitroglycerin) and are convenient ways to administer drugs that are unstable in the gastointestinal environment.

Absorption of drugs from the GI tract depends on the drug’s ability to pass across intestinal cell membranes, withstand the highly acidic environment of the stomach, and resist destruction in the liver (first-pass effect). In most cases drugs pass through cell membranes of intestines by simple diffusion, from an area of high concentration (inside the lumen of the intestines) to an area of lower concentration (bloodstream). Active transport across the GI mucosa, very much like a shuttle system, is another way some substances are absorbed (i.e. Vitamin B12). Other factors that may affect absorption of drugs include food and other medications that may inactivate the drug.

Distribution

After the drug is absorbed, it is then distributed to various organs of the body. Distribution is influenced by how well each organ is perfused (supplied by blood), organ size, binding of the drug to various components of blood and tissues, and permeability of tissue membranes. The more fat-soluble a drug is, the higher its ability to pass across the cell membrane is. The blood-brain-barrier restricts passage of drugs from the blood into the central nervous system and cerebrospinal fluid. Protein binding (attachment of the drug to blood proteins) is an important consideration influencing drug distribution. Many drugs are bound to blood proteins such as serum albumin (the main blood protein) and are not available as active drugs.

Metabolism

Metabolism occurs via two types of reactions: phase I and phase II. The goal of metabolism is to change the active part of medications (also referred to as the functional group), making them more water-soluble and more readily excreted by the kidney. (ie. the body is trying to get rid of the “foreign” drug) Changing the molecular structure of drugs increases their water solubility and decreases their fat solubility, which speeds up the excretion of the drug in the urine. Phase I reactions involve oxidation, hydrolysis, and reduction. Oxidation and reduction processes make a molecule’s charge more positive or negative than the original drug. Regardless of the positivity or negativity, a charged molecule is dissolvable in water. (blood serum is primarily water) These reactions take place primarily in the liver by enzymes known as the cytochrome p-450 enzyme system. Oxidative metabolism may result in formation of an active metabolite or inactive compound. Phase II reactions involve conjugation (which means adding another compound) to form glucuronides, acetates, or sulfates, by adding glucose, acetate, or sulfate molecules, respectively. These reactions generally inactivate the pharmacologic activity of the drug and may make it more prone to elimination by the kidney.

Excretion

Excretion occurs primarily through the urine. Fecal excretion is seen with drugs that are not absorbed from the intestines or have been secreted in the bile (which is discharged into the intestines). Drugs may also be excreted in the expired air through the lungs, in the perspiration, or in breast milk. There are three processes by which drugs are eliminated through the urine: by pressure filtration of the drug through the kidney component called the Glomerulus, through active tubular secretion (like the shuttle system), and by passive diffusion from areas of high drug concentration to areas of lower concentration.

The above paragraphs explain what the human body does to the drug (pharmacokinetics). What the drug does to the body is called pharmacodynamics; this term refers to the action of the drug at the tissue-,cellular-, and molecular level. Pharmacodynamic processes are specific to and different for each drug.

http://www.editorsweb.org/medications/drugs-work.htm

[EricPaul]

Originally Posted by Paxilalmostkilledme

that is really interesting. Hopefully the changes that these drugs cause are truly temporary and I don't have brain damage.Do you think it is possible that Paxil 1)caused changes in the body that remain for a long time and 2) that Paxil remains in fat cells?

number 2 would explain why people have what is known as "The Paxil Bloat"

Did you read the link from Merck on Fat soluble drugs?
http://www.merck.com/mmhe/print/sec02/ch011/ch011d.html

Paxil bloat is not due to drugs being stored in the abdominal fat.

Paxil bloat is due to the effects these drugs have on the gastrointestinal system and the adrenal system.

Have you heard of the "enteric nervous system" aka the brain in the gut?

Here is an interesting article. It will help you understand the effects of psych drugs on the gastrointestinal system. Most people who take these types of drugs have problems with their gastrointestinal system, because the gut has more neuro receptors than the brain does!

http://query.nytimes.com/gst/fullpag...52C0A960958260

Complex and Hidden Brain in Gut Makes Stomachaches and Butterflies

EVER wonder why people get "butterflies" in the stomach before going on stage? Or why an impending job interview can cause an attack of intestinal cramps? And why antidepressants targeted for the brain cause nausea or abdominal upset in millions of people who take such drugs?

The reason for these common experiences, scientists say, is that the body has two brains -- the familiar one encased in the skull and a lesser known but vitally important one found in the human gut. Like Siamese twins, the two brains are interconnected; when one gets upset, the other does, too.

The gut's brain, known as the enteric nervous system, is located in sheaths of tissue lining the esophagus, stomach, small intestine and colon. Considered a single entity, it is a network of neurons, neurotransmitters and proteins that zap messages between neurons, support cells like those found in the brain proper and a complex circuitry that enables it to act independently, learn, remember and, as the saying goes, produce gut feelings.

The brain in the gut plays a major role in human happiness and misery. But few people know it exists, said Dr. Michael Gershon, a professor of anatomy and cell biology at Columbia-Presbyterian Medical Center in New York. For years, people who had ulcers, problems swallowing or chronic abdominal pain were told that their problems were imaginary, emotional, simply all in their heads, Dr. Gershon said. They were shuttled to psychiatrists for treatment.

Doctors were right in ascribing these problems to the brain, Dr. Gershon said, but they blamed the wrong one. Many gastrointestinal disorders like colitis and irritable bowel syndrome originate from problems within the gut's brain, he said. And the current wisdom is that most ulcers are caused by a bacterium, not by hidden anger at one's mother.

Symptoms stemming from the two brains get confused, Dr. Gershon said. "Just as the brain can upset the gut, the gut can also upset the brain" he said. "If you were chained to the toilet with cramps, you'd be upset, too."

Details of how the enteric nervous system mirrors the central nervous system have been emerging in recent years, said Dr. Gershon, who is considered one of the founders of a new field of medicine called neurogastroenterology.

Nearly every substance that helps run and control the brain has turned up in the gut, Dr. Gershon said. Major neurotransmitters like serotonin, dopamine, glutamate, norepinephrine and nitric oxide are there. Two dozen small brain proteins, called neuropeptides, are in the gut, as are major cells of the immune system. Enkephalins, one class of the body's natural opiates, are in the gut. And in a finding that stumps researchers, the gut is a rich source of benzodiazepines -- the family of psychoactive chemicals that includes such ever popular drugs as Valium and Xanax.

In evolutionary terms, it makes sense that the body has two brains, said Dr. David Wingate, a professor of gastrointestinal science at the University of London and a consultant at Royal London Hospital. The first nervous systems were in tubular animals that stuck to rocks and waited for food to pass by, Dr. Wingate said. The limbic system is often referred to as the "reptile brain."

As life evolved, animals needed a more complex brain for finding food and sex and so developed a central nervous system. But the gut's nervous system was too important to put inside the newborn head with long connections going down to the body, Dr. Wingate said. Offspring need to eat and digest food at birth. Therefore, nature seems to have preserved the enteric nervous system as an independent circuit inside higher animals. It is only loosely connected to the central nervous system and can mostly function alone, without instructions from topside.

This is indeed the picture seen by developmental biologists. A clump of tissue called the neural crest forms early in embryogenesis, Dr. Gershon said. One section turns into the central nervous system. Another piece migrates to become the enteric nervous system. Only later are the two nervous systems connected via a cable called the vagus nerve.

Until relatively recently, people thought that the gut's muscles and sensory nerves were wired directly to the brain and that the brain controlled the gut through two pathways that increased or decreased rates of activity, Dr. Wingate said. The gut was simply a tube with simple reflexes. Trouble is, no one bothered to count the nerve fibers in the gut. When they did, he said, they were surprised to find that the gut contains 100 million neurons -- more than the spinal cord has. Yet the vagus nerve only sends a couple of thousand nerve fibers to the gut.

The brain sends signals to the gut by talking to a small number of "command neurons," which in turn send signals to gut interneurons that carry messages up and down the pike, Dr. Gershon said. Both command neurons and interneurons are spread throughout two layers of gut tissue called the myenteric plexus and the submuscosal plexus. ("Solar plexus" is actually a boxing term that refers simply to nerves in the abdomen.) Command neurons control the pattern of activity in the gut, Dr. Gershon said. The vagus nerve only alters the volume by changing its rates of firing.

The plexuses also contain glial cells that nourish neurons, mast cells involved in immune responses, and a "blood brain barrier" that keeps harmful substances away from important neurons, Dr. Gershon said. They have sensors for sugar, protein, acidity and other chemical factors that might monitor the progress of digestion, determining how the gut mixes and propels its contents. "It's not a simple pathway," he said. "It uses complex integrated circuits not unlike those found in the brain."

The gut's brain and the head's brain act the same way when they are deprived of input from the outside world, Dr. Wingate said. During sleep, the head's brain produces 90-minute cycles of slow wave sleep punctuated by periods of rapid eye movement sleep in which dreams occur. During the night, when it has no food, the gut's brain produces 90-minute cycles of slow wave muscle contractions punctuated by short bursts of rapid muscle movements, Dr. Wingate said.

The two brains may influence each other while in this state, Dr. Wingate said. Patients with bowel problems have been shown to have abnormal rem sleep. This finding is not inconsistent with the folk wisdom that indigestion can produce nightmare.

As light is shed on the circuitry between the two brains, researchers are beginning to understand why people act and feel the way they do. When the central brain encounters a frightening situation, it releases stress hormones that prepare the body to fight or flee, Dr. Gershon said. The stomach contains many sensory nerves that are stimulated by this chemical surge -- hence the "butterflies." On the battlefield, the higher brain tells the gut brain to shut down, Dr. Gershon said. "A frightened, running animal does not stop to defecate," he said.

Fear also causes the vagus nerve to "turn up the volume" on serotonin circuits in the gut, Dr. Gershon said. Thus overstimulated, the gut goes into higher gear and diarrhea results. Similarly, people sometimes "choke" with emotion. When nerves in the esophagus are highly stimulated, people have trouble swallowing.

Even the so-called "Maalox moment" of advertising fame can be explained by the two brains interacting, said Dr. Jackie D. Wood, chairman of the department of physiology at Ohio State University in Columbus. Stress signals from the head's brain can alter nerve function between the stomach and esophagus, resulting in heartburn.

In cases of extreme stress, Dr. Wood said, the higher brain seems to protect the gut by sending signals to immunological mast cells in the plexus. The mast cells secrete histamine, prostaglandin and other agents that help produce inflammation, he said. "This is protective. If an animal is in danger and subject to trauma, dirty stuff in the intestines is only a few cells away from the rest of the body. By inflaming the gut, the brain is priming the gut for surveillance. If the barrier breaks, the gut is ready to do repairs," Dr. Wood said. Unfortunately, the chemicals that get released also cause diarrhea and cramping.

Such cross talk also explains many drug interactions, Dr. Gershon said. "When you make a drug to have psychic effects on the brain, it's very likely to have an effect on the gut that you didn't think about," he said. Conversely, drugs developed for the brain could have uses in the gut.

For example, the gut is loaded with the neurotransmitter serotonin. When pressure receptors in the gut's lining are stimulated, serotonin is released and starts the reflexive motion of peristalsis, Dr. Gershon said.

Now a quarter of people taking Prozac or similar antidepressants have gastrointestinal problems like nausea, diarrhea and constipation, he said. These drugs act on serotonin, preventing its uptake by target cells so that it remains more abundant in the central nervous system.

In a study to be published soon, Dr. Gershon and his colleagues explain Prozac's side effects on the gut. They mounted a section of guinea pig colon on a stand and put a small pellet in the "mouth" end. The isolated colon whips the pellet down to the "anal" end of the column, just as it would inside an animal, Dr. Gershon said.

When the researchers put a small amount of Prozac into the colon, the pellet "went into high gear," Dr. Gerhson said. The drug doubled the speed at which the pellet passed through the colon, which would explain why some people get diarrhea. Prozac has been used in small doses to treat chronic constipation, he said.

But when researchers increased the amount of Prozac in the guinea pig colon, the pellet stopped moving. The colon froze up, Dr. Gershon said, which is why some people get constipated on the drug. And because Prozac stimulated sensory nerves, he said, it can also cause nausea.

Some antibiotics like erythromycin act on gut receptors to produce oscillations, Dr. Gershon said. People experience cramps and nausea. Drugs like morphine and heroin attach to the gut's opiate receptors, producing constipation. Indeed, both brains can be addicted to opiates.

Victims of Alzheimer's and Parkinson's diseases suffer from constipation. The nerves in their gut are as sick as the nerve cells in their brains.

Just as the central brain affects the gut, the gut's brain can talk back to the head, Dr. Gershon said. Most of the gut sensations that enter conscious awareness are negative things like pain and bloatedness, Dr. Wingate said. People do not expect to feel anything good from the gut but that does not mean such signals are absent, he said.

Hence, the intriguing question: why does the human gut produce benzodiazepine? The human brain contains receptors for benzodiazepine, a drug that relieves anxiety, suggesting that the body produces its own internal source of the drug, said Dr. Anthony Basile, a neurochemist in the Neuroscience Laboratory at the National Institutes of Health in Bethesda, Md. Several years ago, he said, an Italian scientist made a startling discovery. Patients with liver failure fall into a deep coma. The coma can be reversed, in minutes, by giving the patient a drug that blocks benzodiazepine.

When the liver fails, substances usually broken down by the liver get to the brain, Dr. Basile said. Some are bad, like ammonia and mercaptans, which are "smelly compounds that skunks spray on you," he said. But a series of compounds are also identical to benzodiazepine. "We don't know if they come from gut itself, from bacteria in the gut or from food," Dr. Basile said. But when the liver fails, the gut's benzodiazepine goes straight to the brain, knocking the patient unconscious.

The payoff for exploring gut and head brain interactions is enormous, Dr. Wood said. For example, many people are allergic to certain foods, like shellfish. This is because mast cells in the gut mysteriously become sensitized to antigens in the food. The next time the antigen shows up in the gut, Dr. Wood said, the mast cells call up a program, releasing chemical modulators that try to eliminate the threat. The allergic person gets diarrhea and cramps, he said.

Many autoimmune diseases like Krohn's disease and ulcerative colitis may involve the gut's brain, Dr. Wood said. The consequences can be horrible, as in Chagas disease, which is caused by a parasite found in South America. Those infected develop an autoimmune response to neurons in their gut, Dr. Wood said. Their immune systems slowly destroy their own gut neurons. When enough neurons die, the intestines literally explode.

A big question remains. Can the gut's brain learn? Does it "think" for itself? Dr. Gershon tells a story about an old Army sergeant, a male nurse in charge of a group of paraplegics. With their lower spinal cords destroyed, the patients would get impacted.

"The sergeant was anal compulsive," Dr. Gershon said. "At 10 A.M. everyday, the patients got enemas. Then the sergeant was rotated off the ward. His replacement decided to give enemas only after compactions occurred. But at 10 the next morning, everyone on the ward had a bowel movement at the same time, without enemas," Dr. Gershon said. Had the sergeant trained those colons?

The human gut has long been seen as a repository of good and bad feelings. Perhaps emotional states from the head's brain are mirrored in the gut's brain, where they are felt by those who pay attention to them.

[Paxilalmostkilledme]

I think the article from Merck more than lays out the possibility of Paxil remaining in fat cells. Have you ever been on Paxil?

[rangerNY]

Originally Posted by EricPaul

Here is an interesting article. It will help you understand the effects of psych drugs on the gastrointestinal system. Most people who take these types of drugs have problems with their gastrointestinal system, because the gut has more neuro receptors than the brain does!

http://query.nytimes.com/gst/fullpag...52C0A960958260

Great article! Its now 12 years old, so it will be interesting to see what additional information has come to light since then.

[Paxilalmostkilledme]

very interesting articles - especially on the gut. any idea on how long it takes for the gut brain to return to normal?

[EricPaul]

Originally Posted by Paxilalmostkilledme

I think the article from Merck more than lays out the possibility of Paxil remaining in fat cells. Have you ever been on Paxil?

What in the article by Merck leads you to believe that paxil remains in the fat cells and how long does it remain there? I can't find that connection in the article? Can you paste an excerpt from the article that leads to this belief? Perhaps I am missing something?

I had the abdominal bloat (very awful bloat and dysfunction of the gastrointestinal system for years while ingesting crap and for some time when free) and I have very serious protracted withdrawal from benzodiazepines (over 4 years drug free and still suffering terrible effects and NO, it is not drugs stored in my fat cells that is causing all of this awfulness, it is damaged receptors in my brain from ingesting a nasty poison).

[EricPaul]

Originally Posted by Paxilalmostkilledme

very interesting articles - especially on the gut. any idea on how long it takes for the gut brain to return to normal?

It took mine about a year once drug free. But, this can be a protracted problem for some people. As you well know, these drugs, psych drugs, effect everyone differently so there is no way of knowing who will have what effect and for how long. But, over drug free time, things do get better for all, perhaps not 100%, but better and better as drug free time goes by.

[Paxilalmostkilledme]

"Some drugs accumulate in certain tissues, which can also act as reservoirs of extra drug" It does also say that some drugs take days to be expelled, which may or may not be the case for Paxil. My point is that it is possible for Paxil to be stored in a fat cell.

The Bloat is a main issue for me, and while it certainly has lessened, it has not completely disappeared. After reading those articles, I agree that Paxil has certainly screwed up areas of my body - I just hope that eventually my body will heal itself - 14 months is a long time to wait, I still have problems with concentration and mood. .and occasionally I still think of all the time on Paxil that I lost and burst into tears, but hey, at least I have the ability to cry again.

[rangerNY]

Originally Posted by Paxilalmostkilledme

I think the article from Merck more than lays out the possibility of Paxil remaining in fat cells. Have you ever been on Paxil?

The article appears to suggest that some drugs take longer to be eliminated due to storage in fatty tissue, but the time frame is days, not months or years.

"Some drugs, such as those that accumulate in fatty tissues, leave the tissues so slowly that they circulate in the bloodstream for days after a person has stopped taking the drug."

It might be possible for any given drug to take months to completely leave fatty tissue. This article does not suggest this, and drawing that conclusion would be sketchy science at best.

[EricPaul]

Originally Posted by rangerNY

The article appears to suggest that some drugs take longer to be eliminated due to storage in fatty tissue, but the time frame is days, not months or years.

"Some drugs, such as those that accumulate in fatty tissues, leave the tissues so slowly that they circulate in the bloodstream for days after a person has stopped taking the drug."

It might be possible for any given drug to take months to completely leave fatty tissue. This article does not suggest this, and drawing that conclusion would be sketchy science at best.

Could not have said this better myself. Thanks, yes, the drugs are out of there in days, and as Ashton wrote, are completely eliminated within 30 days for long half life benzos (up to 200 hour half life for valium). So paxil should very be well out of the body within 30 days or so after completely being off it.