Cimetidine classification

GERD INFO: Part 1( ( I cannot change the title, so I added it here)
Hello!
​
What I'm about to write is based on my medical knowledge (on the verge of finishing med school) and my experience with GERD.
What GERD basically means is that the Lower Esophageal Sphincter (LES) does not do its job. That is: it may not close tightly enough or it may just relax inappropriately or for too long. Reflux is normal as long as it is not too long, that is the lower esophagus is not exposed to acid for more than 4% of the day. (figures vary here, I've also read articles where it says 5 or 6%). Anyway, it sort of seems that the lower esophagus is somehow prepared for the fact that the LES isn't the best and strongest design of the human body.
CAUSES for GERD:

• Let's start with anatomical causes. Normally, you'd want to have a portion of the esophagus in the abdomen, it being a positive pressure zone. The positive pressure from the abdomen is exerted on the walls of the abdominal esophagus (also containing the LES) and helps it stay shut. Another important element is the angle of His that functions as a valve.https://en.wikipedia.org/wiki/Angle_of_His

If there's a portion of the esophagus that is supposed to be in the abdomen slides up into the thorax, like in a sliding hiatal hernia (because the esophageal hiatus is wide= the whole in the diaphragm through which the esophagus goes from the thorax into the abdomen), the angle of His is disrupted and, furthermore, a portion of the esophagus is in the thorax. Now, the thoracic cavity is a negative pressure zone because of the lungs that sit laterally and because of the breathing. Conclusion: a sliding hiatal hernia can cause GERD. Causes for sliding hiatal hernia: eating a lot of food at once and consuming carbonated beverages afterwars, playing instruments that require blowing air (trumpet) and lifting heavy things involving the abdominal muscles.

• Other causes of GERD include: whenever the pressure in the abdomen is high. For example pregnant women can experience reflux. Also, people that are overweight and obese, especially if fat is distributed around the abdomen.
• Eating fatty and acid foods: fatty foods and other foods (you can look them up on the internet) may also lead to reflux because they lead to lowered LES tone. (that is, it doesn't hold closed so strongly)
• Lying down right after eating and with a full stomach. That's because the gastric contents exert a high pressure on the esophagus and it tends to open. It also opens when burping to let the air go out and if you lie down and you burp, some gastric contents may also escape, right up into your mouth and you may feel it. Also, digestion involves contractions of the stomach: it sort of squeezes itself from the gastric fundus* (the uppermost portion) to the piloric opening so that food that is digested and is starting to be liquid gets into the duodenum. Naturally, this also leads to an increase in pressure.

*By the way, the gastric fundus contracts during digestion. This is the basis of the Nissen fundoplication or wrapping of the gastric fundus around the esophagus. With the fundus contracting, it squeezes the esophagus and does not allow food to go back up.

• Functional reasons. These ones are harder to diagnose and they simply mean that something is not functioning as is should. These are diagnosed by rulling out other causes.

Anyway, GERD means chronic exposure of the esophageal mucosa to the gastric acidic contents. Everybody can have a reflux episode once in while, but more than 2 reflux episodes per week over the course of more weeks could be GERD.
The reflux itself can be

• acid from the stomach- bad because while the stomach is built to resist its acid, the esophagus is not. Imagine having acid on your skin and having it stay there. It would hurt, wouldn't it? Now add pepsin, an enzyme that digests proteins at an acidic pH. You have the perfect ingredients to get an esophagitis, which is inflammation of the esophageal mucosa. The inflammation appears because there has been damage and the body tries to fix it up. It's like your skin being exposed to something erosive and getting damaged. With ongoing exposure, the esophagitis gets worse and it can even lead to bleeding.
• acid from the stomach + bile from the duodenum( reflux from the duodenum to the stomach and to the esophagus)- worst and harder to treat. The bile salts work like detergents and have an even more harmful effect on the esophagus and they even hurt the gastric mucosa. What works here well, supposedly, is sucralphate. But more about the treatment later.

Esophagitis itself can have more causes, but here I'm going to talk about GERD esophagitis. Normally, the lower esophageal walls have some form of protection againts the physiologic/ normal reflux as long as the mucosa is in tip-top condition and normal. It secretes mucus and bicarbonate ions that neutralize the normal reflux. When the LES becomes incompetent, the defense mechanisms are overwhelmed and soon the mucosa starts to feel the erosive action of the acid and the digestive action of pepsin. The patient is alerted by the burning feeling in the epigastric region= pyrosis (right about where the sternum ends). Now, medical books state that the pain has a rather poor correlation to the esophagitis severity, that is the pain may be high and the esophagitis not that severe and vice-versa. Some people may have pathological acid exposure and no pain. They may have extra-digestive symptoms, that is the larynx being affected by reflux damaging it- hoarse voice in the morning, for example.https://en.wikipedia.org/wiki/Laryngopharyngeal_reflux
Esophagitis, depending on severity, is grade with the Los Angeles classification.https://www.endoscopy-campus.com/en/klassifikationen/los-angeles-klassifikation-zur-einteilung-des-schweregrads-der-refluxoesophagitis/
As a patient, you don't want esophagitis, your goal is to keep the esophagus in a normal condition. That's because, apart from the symptoms, chronic esophagitis/ inflammation may lead to dysplasia of the esophagus. That is, under constant inflammation, the esophageal cells somehow react and adapt themselves and they change their structure. To be more precise, instead of them becoming a stratified squamos epithelium, they become a stomach-like epithelium (gastric metaplasia) or an intestinal-like epithelium (intestinal metaplasia). This condition is called Barrett's Esophagus and while you might think that this is ok, because now that part of the esophagus is resistant to acid, it is not good. Those cells are not supposed to become metaplasic, they are supposed to be squamos cells. And the fact that they are forced to become something else makes it very likely that they won't listen to the rules of the body and how they should behave, thus making them rebel against the body= cancer. Now, you won't get Barret's esophagus the moment you have acid exposure, it takes years of untreated GERD to get to it, but that doesn't mean you should not treat it. On the contrary, you have to do everything that's in your power to keep the disease under control and live a normal life.
DIAGNOSIS: Normally, to diagnose GERD, one should provide proof of the higher than normal acid exposure of the esophageal mucosa, which is done with a 24-hour pH test.details pubmed article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236049/
However, this gives us no clue on the state of the esophageal mucosa, which is why an endoscopy is usually performed, even though it does not give direct information on GERD. You can see the result of the reflux, the damage it has done, not the process of reflux whereas with the pH test you can determine how much the esophagus has a pH of under 4. But the upper endoscopy is far more valuable since you can also take a biopsy if you're suspicious of the lesions, thus giving you the most accurate picture of it.
Another way would be manometry, but this is rarely done, maybe before Nissen surgery. It gives information on the function of the LES and the rest of the esophageal muscles.
TREATMENT: ideally, treatment would incluse fixing the broken LES or the LES function, but since that can only be done surgically, it is an option left for cases that don't respond to medical therapy, high hiatal hernias, etc and it is only performed after a manometry and a pH test.
Thus, with drugs, we treat the effect and not the cause. With drugs we make the stomach secrete less acid, we neutralize the acid whenever it bothers us.
I would like to stress out the difference here.

• Anti-acids are drugs that neutralize the acids by way of a chemical reaction. They usually have a higher, alkaline pH. Water dilutes the acid, it can't really be called an anti-acid drug, yet it too offers short-term relief. Anti-acid drugs include: magnesium hydroxide salts (side effect of diarrhea), calcium salts (side effect: constipation) and a combination between magnesium and calcium. And there's sucralphate. https://en.wikipedia.org/wiki/Antacid https://en.wikipedia.org/wiki/Sucralfate

Anti-secretory drugs inhibit the acid secretion of the stomach. While both antacids and anti-secretory drugs result in less acid in the stomach, the antacids do that only temporarily, because the stomach will keep on producing acid, that's its job, that's how its programmed to work and for good reason. The acid has an important role in digestion, in sterilization of food. Yet, when talking about esophagitis and GERD, we want to heal esophagitis and prevent further episodes, which is why we need to tell the stomach to take a break. This is where these drugs come into play, they stop the acid secretion of the stomach.

1. H2 blockers: cimetidine (the first that appeared, has nasty anti-androgenic side effects=> not EDIT widely used anymore), ranitidine, roxatidine. Acid secretion is stimulated by histamine acting on the H2 receptor on the parietal cells. H2 blockers compete with the binding of histamine over there, so instead of histamine binding, the drug binds, however the drug does not have any effect over there whatsoever. Imagine the H2 receptor as the gas pedal of the parietal cell, when histamine binds to it, it kicks the parietal cell into drive and tells it to pump acid. But when the H2 blocker drug binds over there, it does not push the gas pedal and the parietal cells stay put. These drugs block the acid secretion for about 12 hours or so, which is why they're taken 2 times a day for continuous acid secretion inhibition. They are moderately efficient in healing of the esopaghitis, healing which takes quite some weeks. For them to have good absorbtion rates, they should not be taken with antacids at the same time, they need an acidic pH for them to be absorbed.
2. PPI- proton pump inhibitors. These block the proton pump, the tool which the parietal cells use to secrete acid. If there's no tool, they don't work. These are by far the most efficient drugs that block acid and they have the highest healing rate. They need to be taken a minimum of 4 weeks , up to 8 weeks. They work best when taken 30 minutes before eating because it takes 30 minutes for them to get absorbed and they work best when the gastric secretion is up and running (and the parietal cells use their tools and then the PPI can perfectly block it). So, 30 minutes before eating. After blocking of the proton pump, the parietal cells need to build up new tools= secrete new proton pumps, which takes time, which is why this drug blocks the acid for far longer than H2 blockers. In my experience, if one takes 40 mg esomeprazole and, after 3 days, almost all the acid secretion is blocked (98%) . Then, when interrupting the drug, it also requires about 3 days for the acid secretion to return to normal. NOTE: the stomach was built to secrete acid and it senses that, because of the PPI treatment, the pH inside is NOT acidic anymore = it's too high. This makes the gastrin levels go high in the blood in an attempt to force the stomach to spew as much acid as it can, but it won't really be able to do that, because the PPI has blocked the proton pump= the tool. Yet, when you stop taking PPI abruptly, the tool becomes free and can now be used. You would expect gastrin, the boss in charge of the acid secretion, to calm down, but since it got annoyed with the prolonged acid inhibition, its levels will fall down rather slowly<=> it will stimulate the acid secretion more than it should, especially on day 3 after giving up the drug. This is called acid rebound, which is why PPI need to be stopped gradually. What might work for you is: let's say you take 40mg of PPI per day and today is the last day of the treatment. You can skip a dose tomorrow, take it the day after tomorrow and keep taking it that way for several days, then take one pill every 3 days and then stop it. Or you could lower the dose in half, but DO NOT CUT THE PILL IN HALF because it has a protective coating and cutting it destroys it, thus rendering the drug useless.

Well, this post turned out to be quite longer than I expected it would and I still have much more to write. I want to share my knowledge with you because it might help you and/ or make your life better. Also, many doctors, even gastroenterologists, don't really know the intricate details of GERD if they don't have it. As they say, a patient knows his disease best.
So, I will continue in part 2 with the details on how to manage GERD in the long run. I can't really say for sure when I'll have time to write it, but I'll do my best for it to be soon.
Also, Ask Me Anything that you do not understand. If you ask me about your specific instance of disease , there's a possibility that I might not answer your question without consulting you, which I cannot do on reddit. Sorry. I don't want to make more harm than good.
Primum non nocere.
https://en.wikipedia.org/wiki/Primum_non_nocere
EDIT: Thank you for my first gold, kind stranger!

Synonyms: Evy, Exiba, Lemix, Mimetix, Talentum, Vivimex, Zeimer, Abixa, Akatinol memantina, Akatinol Memantine, Akatinol, Albix, Alois, Alpex Valcox, Alzant, Apo-Memantine, Axura, Carrier, Cloridrato de Memantina, CO Memantine, Cogito, Conexine, Cordure, Demantin, Demax, Dementa, Ebixa, Eutebrol, Fentina, Ilumin, Korint, Limember, Lindex, Lucidex, Manotin, Melanda, Melarth, Memantine Canon, Memantin Pliva, Memantine Teva, Memanxa, Memax, Memikare, Memorix, Memox, Merital, Mimetix, Modualz, Namenda, Namenda XR, Neuro-K, Neuroplus, PMS-Memantine, Pronervon, ratio-Memantine, Witgen, Zarlyn.
Active substance: Memantine.
Memantine reduces the actions of chemicals in the brain that may contribute to the symptoms of Alzheimer's disease.
Memantine is used to treat moderate to severe dementia of the Alzheimer's type.
ATC - Memantine N06DX01
Pharmacological group - Other means of neurotropic.
Nosological classification (ICD–10)
F00 Dementia in Alzheimer’s disease (G30 +);
F01 Vascular dementia;
F03 Dementia , unspecified;
F04 Organic amnesic syndrome, not induced by alcohol and other psychoactive substances;
G20 Parkinson’s Disease;
G21 Secondary parkinsonism;
G22 Parkinsonism in diseases classified elsewhere;
G35 Multiple Sclerosis;
G45.9 Transient cerebral ischemic attack , unspecified;
G95.9 Disease of spinal cord , unspecified;
I69 Effects of cerebrovascular diseases;
R25.2 cramps and spasms;
R41.3.0 * Reduced memory;
R53 Malaise and fatigue;
S06 intracranial injury.
Memantine Composition, structure and packing
Tablets, film-coated white, oblong, biconvex, scored on both sides.
Memantine Pharmacological action
Drug improving cerebral metabolism, used to treat dementia. Memantine is a noncompetitive NMDA-receptor antagonist, has a modulatory effect on the glutamatergic system. Regulates ion transport, blocks calcium channels normalizes membrane potential, improves the transmission of nerve impulses. The drug improves cognitive processes, increases daily activity.
Memantine Akatinol Pharmacokinetics
Absorption and distribution
After oral administration of memantine rapidly and completely absorbed from the gastrointestinal tract. C max is achieved within 2–6 hours
With normal renal function, accumulation of memantine were observed.
Breeding
Dualfaze excretion. T 1/2 is an average of the first phase of 4–9 h, in the second phase - 40–65 hours excreted in the urine.
Memantine Dosage
The drug is taken orally with meals. Mode set individually. Recommend to begin treatment with the appointment of the minimum effective dose.
Adults with dementia syndrome prescribed drug for the 1st week of treatment at a dose of 5 mg/day for 2 weeks - at a dose of 10 mg/day during the third week - 15–20 mg/day . If necessary, may further increase the weekly dose of 10 mg to achieve a daily dose of 30 mg.
The optimal dose is reached gradually by increasing the dose every week.
Memantine Akatinol Overdose
Symptoms may increase the intensity of side effects.
Treatment: gastric lavage, activated charcoal, symptomatic therapy.
Memantine Akatinol Drug Interactions
With simultaneous use of Memantine Akatinol with L-dopa preparations, agonists of dopamine , anticholinergics action of the latter may be exacerbated.
With simultaneous use of Memantine Akatinol barbiturates, neuroleptics may decrease effect of the latter.
In a joint application Akatinol Memantine may change (increase or decrease) the effect of dantrolene or Batrafen, so doses should be selected individually.
Avoid co-administration with amantadine , ketamine and dextromethorphan.
In a joint application with the drug Memantine Akatinol may increase plasma concentrations of cimetidine, procainamide, quinidine, quinine and nicotine .
When combined with memantine may reduce plasma concentrations of hydrochlorothiazide.
Memantine at Pregnancy and lactation
Akatinol Memantine is contraindicated during pregnancy and lactation ( breastfeeding ).
Memantine Side effects
Determining the incidence of side reactions often (≥ 1/10), often (≥ 1/100, <1/10), rare (≥ 1/1000, ≤ 1/100), rare (≥ 1/10, 000, ≤ 1/1000), very rare (≤ 1/10 000), the frequency is not set (the currently available data on the incidence of adverse reactions are absent).
From the body as a whole - Often Headache; Rarely Fatiguability.
On the part of the psyche -Often Drowsiness; Rarely Confusion, hallucinations
From the nervous system -Often Dizziness; Rarely Gait disturbance; Very rare Convulsions.
Cardio-vascular system - Rarely Hypertension, venous thrombosis/thromboembolism. Rarely Heart failure.
From the digestive system - Often Constipation; Rarely Nausea, vomiting.
The respiratory system - Often Dyspnea; Infections -Rarely Fungal infections .
Memantine Indications
Alzheimer’s type dementia of all severities;
Vascular dementia of all severities;
Mixed dementia of all severities.
Memantine Contraindications
Pronounced renal dysfunction;
Pregnancy;
Lactation (breastfeeding);
Age 18 years (not enough data);
Hypersensitivity to the drug.
Be wary prescribers in thyrotoxicosis, epilepsy, convulsions (including history), myocardial infarction, congestive heart failure.
Memantine Cautions
Effects on ability to drive vehicles and management mechanisms
In patients with Alzheimer’s disease at the stage of moderate or severe dementia usually compromised ability to drive vehicles and management of complex mechanisms. Furthermore, memantine may cause a change in the rate of reaction, so patients receiving outpatient treatment, should use extreme caution when driving or operating machinery.
Memantine Reviews
Ivan 43 years, With Akatinol Memantine been working for five years. In general, the drug is very happy. Do not substitute for people with cognitive impairment whose brains starts causing trouble. Prescribe drugs to people with varying degrees of severity of dementia, frontal psyche negative manifestations, patients undergoing neuroinfections, patients with toxic encephalopathy and dismetabolic. And almost always the effect was positive. There was only one case when Akatinol Memantine gave the opposite effect (Talked to medical representative of the manufacturer in this regard. It's like going to Japan to conduct research for the study of this issue). In two patients, the effect was not observed even when the maximum dose. And in one patient clear mind comes in waves. All the rest have changed in unbelievable way. Some of them every year come to me for advice or just to say thank you. You can buy Akatinol.
"I had a very interesting case. Treated me lady 73h years. Cognitive average severity of the disorder. And the family is heavy, and it (but she does not understand). Native is not periodically learned, was written at the corners, did not live in our time. Grandma treat, recommendations on the house painted. After 2 months, the children came. they told me that their mother again is a social way of life. But the most "unpleasant" remembered that her sons for 30 thousand have "
Barbara, 28 years, Akatinol Memantine appointed my child to a children's neurologist. Propyl month. The doctor extended course for another three months. By now familiar flew to Moscow and I was asked to bring a large package Akatinol Memantine, the same Table 90. At the end of the course, I noticed that the child was more than call some syllables and words, and even began chants)). He became a child perseverance in the classroom with a speech therapist. Many drugs have a delayed effect that is manifested after a certain time after receiving treatment. Apparently, due to the fact that the course we have been long, the effect began to manifest itself in the application of this preparation.
http://drdoping.com/blog/akatinol-memantine-tablets-instructions-for-use-dosage-side-effects-reviews

Adamantane derivative, the chemical structure and pharmacological properties similar to amantadine. Is a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptors (black substance), thereby reducing the excessive stimulatory effect of cortical glutamate neurons in neostriatum developing on the background of inadequate allocation of dopamine. Reducing the flow of Ca2+ in neurons, reduces the possibility of their destruction. Possesses nootropic, cerebrovasculature, antihypoxic and psychoactive effect. A greater impact on stiffness (rigidity and bradykinesia). Improves weakened memory, concentration, reduces fatigue and symptoms of depression.
Indications:
Dementia moderate and severe degrees of severity in Alzheimer's disease.
Contraindications:
•hypersensitivity to any component of the drug
•severe liver failure
•pregnancy
•breastfeeding
•the age of 18 years (the efficacy and safety of the drug has not been studied).
Caution: epilepsy, renal failure, hyperthyroidism, spasms in anamnesis, arterial hypertension, myocardial infarction history, heart failure.
Application of pregnancy and breast-feeding:
Memantine has the ability to slow the development of the fetus. At the time of treatment with memantine breastfeeding should be interrupted.
Side effects:
From the nervous system: dizziness, headache, drowsiness, gait disorders, confusion, hallucinations, convulsions, psychosis, irritability.
Gastrointestinal: constipation vomiting, pancreatitis, nausea.
Infections and infestations: fungal infection.
From the CCC: increased blood pressure, venous thrombosis, thromboembolism.
From the body as a whole: weakness, fatigue, allergic reactions.
Drug interactions:
While the appointment may weaken the effect of barbiturates and neuroleptics.
The effect of baclofen and dantrolene can change under the influence of memantine, and therefore may require adjustment of their doses.
The effects of levodopa, dopamine receptor agonists and anticholinergics are aggravated by concomitant use of NMDA antagonists. Due to the fact that memantine and amantadine are the antagonists of NMDA receptors, should avoid simultaneous use in connection with risk of development of toxic effect. Are also potentially toxic combination of memantine with ketamine, dextromethorphan, and phenytoin.
For transport of amantadine, cimetidine, ranitidine, quinidine, quinine and nicotine in the body use the same renal cationic system, which may determine the interaction of these drugs with memantine, resulting in an increase in its concentration in blood plasma.
While the use of memantine may decrease the concentration of metoprolol in blood serum.
While the use of warfarin and other indirect anticoagulants requires careful monitoring of PV and INR.
Method of application and dose:
Inside, regardless of meals.
During the first week the daily dose is 5 mg (in the morning). In the second week the daily dose is 10 mg (5 mg 2 times a day). During the third week of a daily dose — 15 mg daily (10 mg morning and 5 mg in the evening). From the fourth week the daily dose is 20 mg per day. The maximum daily dose of 20 mg per day. Dose adjustment in elderly patients (older 65 years) not required.
When moderate renal insufficiency (Cl creatinine 50-80 ml/min) dose adjustment is not usually required when Cl creatinine 30-49 ml/min the daily dose initially 10mg, then after 7 days under the condition of good endurance dose can be increased up to 20 mg. In severe renal failure (Cl creatinine 5-29 ml/min) daily dose should not exceed 10 mg.
At easy and moderate hepatic insufficiency (class and on the classification of child-Pugh) dose adjustment is not required.
Overdose:
Symptoms: dizziness, tremor, agitation, drowsiness, dizziness, agitation, stupor, seizures, aggressiveness, hallucinations, unsteady gait, vomiting, diarrhea.
Treatment: gastric lavage, the appointment of activated carbon symptomatic therapy. There is no specific antidote.
Special instructions:
In alkaline urine requires more careful monitoring of such patients because of slowing of excretion of memantine.
It is known that Alzheimer's disease affects the ability to drive a car in addition, treatment with memantine can also change the speed of reaction that should be considered when driving and mechanisms.