What Is Cimetidine?

This product has a significant effect on inhibiting gastric acid secretion. It can significantly inhibit basic and nocturnal gastric acid secretion. It can also inhibit gastric acid secretion caused by histamine, subpeptide gastrin, insulin and food, and reduce its acidity. Corrosive gastritis caused by chemical stimulation has a preventive and protective effect, and it also has obvious curative effects against acute gastric ulcer and upper gastrointestinal bleeding.

This product has a significant effect on inhibiting gastric acid secretion. It can significantly inhibit basic and nocturnal gastric acid secretion. It can also inhibit gastric acid secretion caused by histamine, subpeptide gastrin, insulin and food, and reduce its acidity. Corrosive gastritis caused by chemical stimulation has a preventive and protective effect, and it also has obvious curative effects against acute gastric ulcer and upper gastrointestinal bleeding.
Chinese name
Cimetidine
Foreign name
cimetidine
CAS NO
51481-61-9
Chinese alias
Cimetidine; cimetidine
English alias
Cimetidine
Molecular formula
C10H16N6S
Molecular weight
252.34
EINECS
257-232-2

Cimetidine compound profile

Cimetidine This information

Chinese name
Chinese alias: Cimetimidin; Cimetimidin; Taiweimei; N'-methyl-N "-[2 [[(5-methyl-1H-imidazol-4-yl) methyl] thio] Ethyl] -N-cyanofluorene; cimetidine
English name: Cimetidine (base or and unspecifieds salts)
English alias: 2-cyano-1-methyl-3- (2-(((5-methylimidazol-4-yl) methyl) thio) ethyl) guanidine; Cimetidine A; Tagamet / C10H16N6S / 252.34 / 51481-61-9
CAS number: 51481-61-9
Molecular formula: C 10 H 16 N 6 S
Molecular weight: 252.33900
Exact mass: 252.11600
PSA: 114.19000
LogP: 1.37918

Cimetidine physical and chemical properties

Appearance and properties: The white crystal has a light sulfur odor, which is almost odorless and bitter. Soluble in methanol, soluble in ethanol, slightly soluble in isopropanol, slightly soluble in water, and soluble in dilute hydrochloric acid.
Density: 1.27 g / cm 3
Melting point: 139-144 ° C
Boiling point: 488ºC at 760 mmHg
Flash point: 248.9ºC
Water solubility: 0.5 g / 100 mL at 20 ºC
Storage conditions: 2-8ºC

Cimetidine Safety Information

Symbol: GHS08
Signal Word: Danger
Hazard statement: H360
Cautionary statement: P201; P308 + P313
Customs code: 2933990090
WGK Germany: 3
Danger category code: R60
Safety instructions: S53-S26-S36 / 37 / 39-S45
RTECS number: MF0035500
Dangerous goods mark: T [1]

Cimetidine safety term

S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
After accidental contact with eyes, rinse immediately with plenty of water and seek medical advice.
S36 / 37 / 39Wear suitable protective clothing, gloves and eye / face protection.
Wear appropriate protective clothing, gloves and goggles or masks.
S45In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
In case of accident or if you feel unwell, seek medical advice immediately (show the label if possible).
S53Avoid exposure-obtain special instructions before use.
Avoid contact. Obtain special instructions before use.
Risk term R60May impair fertility.
May impair fertility.

Cimetidine production method

Intermediate (I) and 2-aminoethanethiol hydrochloride are reacted in the presence of hydrogen bromide, and then neutralized with potassium carbonate to obtain compound (II). Then react with the corresponding thiourea to obtain cimetidine 2.4-hydroxymethyl-5-methyl-1H-imidazole hydrochloride and 2-aminoethanethiol hydrochloride, react in the presence of hydrogen bromide, After neutralizing with potassium carbonate, the obtained compound was reacted with the corresponding thiourea to obtain cimetidine [1] .

Cimetidine determination method

Method name: Cimetidine API-Determination of Cimetidine-Non-aqueous titration
Application range: This method uses the titration method to determine the content of cimetidine in cimetidine.
This method is applicable to cimetidine drug substance.
Principle of the method: Add glacial acetic acid for the test product, and after dissolving, add the crystal violet indicator solution, titrate the solution with perchloric acid until the solution is blue, and correct the result of the titration with a blank test. Cimetidine content.
Reagent:
Glacial acetic acid
2. Perchloric acid titrant (0.1mol / L)
3. Crystal violet indicator liquid
4. Reference potassium hydrogen phthalate
equipment:
Sample preparation: 1. Perchloric acid titration solution (0.1mol / L)
Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL of acetic anhydride per 1g of water), add 8.5mL of perchloric acid (70 ~ 72%), shake well, let cool, add an appropriate amount of anhydrous glacial acetic acid 1000mL, shake well and leave for 24 hours. If the test sample is easily acetylated, the water content of the solution must be determined by the moisture measurement method, and then the water content of the solution is adjusted to 0.01% ~ 0.2% with water and acetic anhydride.
Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and slowly titrate with this solution to Blue, and the titration results are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.
Crystal violet indicator liquid
Take 0.5 g of crystal violet and add 100 mL of glacial acetic acid to dissolve.
Operation steps: Precisely weigh about 0.2g of the test sample, add 20mL of glacial acetic acid, dissolve, add 1 drop of crystal violet indicator solution, and titrate with perchloric acid titrant (0.1mol / L) until the solution appears blue, and The results of the titration were corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 25.23mg of C 10 H 16 N 6 S.
Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards [2] .

Cimetidine Pharmacopoeia Description

Cimetidine source (name), content (potency)

This product is 1-methyl-2-cyano-3- [2-[[(5-methylimidazol-4-yl) methyl] thio] ethyl] guanidine. Calculated on dry basis, containing C 10 H 16 N 6 S shall not be less than 99.0%.

Cimetidine traits

This product is white or off-white crystalline powder; almost odorless and bitter.
This product is soluble in methanol, soluble in ethanol, slightly soluble in isopropanol, slightly soluble in water; soluble in dilute hydrochloric acid.
Absorption coefficient
Take this product, weigh it accurately, add hydrochloric acid solution (0.9 1000) to dissolve and quantitatively dilute it to make a solution containing about 8 g per 1 ml, according to UV-Vis spectrophotometry (Appendix IVA of the second edition of the Pharmacopoeia, 2010 edition), at 218nm The absorbance was measured at a wavelength of 5%, and the absorption coefficient () was 751 to 797.

Cimetidine identification

(1) Take about 50mg of this product, add 10ml of water, dissolve at a slight temperature, add 1 drop of ammonia test solution and 2 drops of copper sulfate test solution to form a blue-gray precipitate; add an excess of ammonia test solution, and the precipitate will dissolve.
(2) Take about 50mg of this product, it will burn, and the gas produced can make the lead acetate test paper appear black.
(3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (atlas of Atlas 142).

Cimetidine check

Clarity and color of acid solutions
Take 3.0g of this product, add 12ml of 1mol / L hydrochloric acid solution to dissolve, dilute to 20ml with water, shake well, the solution should be clear and colorless; if it is turbid, it should be turbidity standard solution No. 1 (Appendix B of Part Two of the Pharmacopoeia, 2010 Edition) For comparison, it must not be thicker; if it is colored, it must not be deeper than the yellow colorimetric standard colorimetric liquid No. 3 (Appendix A of the 2010 Pharmacopoeia Part II Method A). (For injection)
chloride
Take 1.0g of this product and check it according to law (Appendix A of Part Two of the 2010 Pharmacopoeia). It must not be more concentrated (0.008%) than the control solution made of 8ml of standard sodium chloride solution.
relative substance
Take this product, add the mobile phase to dissolve and dilute it to make a solution containing 0.4mg per 1ml as the test solution; take an appropriate amount and dilute with mobile phase to make a control solution containing 2g and 0.2g per 1ml ( 1) and (2). It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition). Octadecylsilane-bonded silica gel was used as the filler; methanol-water (240: 760) (containing 0.3 ml of phosphoric acid and 0.94 g of sodium hexanesulfonate per 1000 ml) was used as the mobile phase; the detection wavelength was 220 nm. Take about 40mg of this product, put it in a 100ml measuring bottle, add 10ml of 1mol / L hydrochloric acid solution, heat in a water bath for 2 minutes, let it cool, add 10ml of 1mol / L sodium hydroxide solution to neutralize, dilute to the mark with mobile phase, shake well (Provisional new), take 20l into the liquid chromatograph, record the chromatogram. The relative retention time of the amide analog to cimetidine is about 2.0, and the resolution from the chromatographic peak of cimetidine should be greater than 8.0. Take 20l of the control solution (2) and inject it into the liquid chromatograph. The peak signal-to-noise ratio of the cimetidine chromatographic peak is not less than 10; precisely measure 20l each of the test solution and the control solution (1) and inject them into the liquid chromatograph. Record the chromatogram to 3.5 times the peak retention time of the main component. If impurity peaks appear in the chromatogram of the test solution, the area of a single impurity peak must not be greater than 0.4 times (0.2%) the area of the main peak of the control solution (1); the sum of the area of each impurity peak must not be greater than 2 of the area of the main peak of the control solution (1). Times (1.0%). Any peak in the test solution that is less than 0.5 times the main peak area of the control solution (2) can be ignored.
Loss on drying
Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (Appendix L of Pharmacopoeia Part II of 2010 Edition).
Residue on ignition
Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.
Heavy metal
Take the residue left under the burning residue and inspect it according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the second method). The heavy metal must not exceed 10 parts per million.

Determination of Cimetidine

Take about 0.2g of this product and accurately weigh it. After adding 60ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution. Titrate with perchloric acid titration solution (0.1mol / L) until the solution is blue. The results were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 25.23mg of C 10 H 16 N 6 S.

Cimetidine Categories

H2 receptor blockers.

Cimetidine storage

Keep sealed.

Cimetidine

(1) Cimetidine tablets (2) Cimetidine capsules (3) Cimetidine sodium chloride injection

Cimetidine

The 2010 Edition of the Pharmacopoeia of the People's Republic of China [3]

Cimetidine drug description

Cimetidine classification

Digestive System Drugs> Acid and Gastric Mucosal Protection

Cimetidine traits

White or off-white crystalline powder; almost odorless and bitter. Soluble in methanol, soluble in ethanol, slightly soluble in isopropanol, slightly soluble in water, and soluble in dilute hydrochloric acid.

Cimetidine dosage form

1. Tablets: 200mg, 400mg, 800mg each;
2. Capsule: 200mg;
3. Injection: 200mg (2ml).

Cimetidine pharmacological effects

Animal pharmacology and toxicology: In vitro studies have shown that this product is a specific and competitive H2-receptor antagonist, which has no significant interaction with catecholamine -receptor, histamine H1-receptor or muscarinic receptor effect. According to the administered dose, and more precisely the blood concentration achieved, the efficacy of this product for humans and experimental animals is very similar. In all animal studies, blood concentrations of about 2 mol / L can inhibit the maximum gastric acid secretion by 50%. For rats, dogs, and mice, the half lethal dose for oral administration is about 2 to 3 g / kg, and the half lethal dose for intravenous administration is 100 to 150 mg / kg. For chronic toxicity experiments on dogs, 504 mg / After kg, some animals showed signs of liver and kidney damage. For rats and dogs, this product shows an antiandrogenic effect. After a dose of 150-950 mg / kg was administered to rats for 12 months, the prostate of male rats in each dose group shrank, and the testes and seminal vesicle glands shrank in the high-dose group. A dose of 41 to 504 mg / kg of the drug administered to a dog for 12 months resulted in weight loss of the prostate. Studies have found that this product has no significant effect on fertility. A 24-month toxicology study was performed on rats at dose levels of 150, 378, and 950 mg / kg / day (approximately 4 to 24 times the human recommended dose). Compared with the control group, the benign Leddy of the drug treatment group Leydig cell tumors have a higher incidence and are statistically significant. Tumors occurred in both the control and treatment groups, and the differences became apparent only in aged rats. For intravenous administration studies in dogs, tachycardia and hypotension were observed at a dose level of 25 mg / kg. Tachycardia occurred when the oral dose was 336 mg / kg. Propranolol can prevent or reverse the increase in heart rate. For humans, rats and dogs, the pharmacokinetics of this product and its absorption, metabolism and excretion are basically similar. Human pharmacology: Effect on basal (non-irritating) gastric acid secretion: a double-blind, placebo-controlled study of patients with duodenal ulcer, a single dose of cimetidine can significantly reduce basal gastric acid in the white sky belly and at night Secretion, and dose. The degree of inhibition is related to the achieved blood level. When the blood level exceeds 0.5 mg / L, the degree of inhibition can usually reach more than 80%. The duration of this level is also different at different doses. A single administration of a 200 mg dose disappears after 4 to 5 hours. At a 300 mg dose, the effect disappears after 7 to 8 hours. However, the 400 mg dose remains after 8 hours. effect. The effect of cimetidine is not only due to a significant reduction in gastric acid concentration, but also a reduction in gastric secretion. When the effective blood concentration is reached, the pH value of gastric acid usually reaches above 5.0, which indicates that pepsin will be inactivated during most of the treatment process. Effect on stimulating gastric acid secretion.We know that cimetidine is a kind of gastric acid secretion caused by histamine, pentagastrin, insulin, food or caffeine stimulation in normal people and patients with duodenal ulcer. Powerful inhibitor. When the blood drug concentration is 0.5 mg / L, the gastric acid secretion is inhibited by at least 50% or more, and when the blood drug concentration exceeds 1.0 mg / L, the gastric acid inhibition is 80 to 90%. The choice of dosing time related to experimental meals affects the level of blood drug levels. Data show that dosing at meals can properly control gastric acid secretion. Studies show that daily doses of 800 mg and 1 g reduce gastric acidity by 70% and 72%, respectively, in 24 hours. In these studies, cimetidine has different effects on pepsin concentration, but results from a decrease in gastric fluid volume Causes total pepsin secretion to decrease. As mentioned above, when the pH exceeds 5, all secreted pepsin is inactive during this period. This product significantly inhibits the increase in the concentration of internal factors caused by histamine stimulation, but does not affect the basic level of internal factors. In studies examining serum gastrin, as expected, elevations caused by irritants (food, etc.) were observed. In these studies, when the pH of the stomach was controlled in both the placebo and cimetidine groups, there was no significant difference in gastrin levels between the two groups. However, if the gastric pH was not controlled, the gastrin level in the cimetidine group was higher. This appears to be a higher pH level in the stomach due to cimetidine. Cimetidine has no effect on gastric emptying rate and lower esophageal sphincter (LOS) pressure.

Cimetidine pharmacokinetics

About 60% to 70% of the blood is rapidly absorbed by the intestine after oral administration, and the peak time (tmax) of the blood concentration is 45 to 90 minutes. Oral bioavailability (F) is about 70%. Young people tend to absorb this product better than older people. Low plasma protein binding. Taking a 300mg average peak concentration (Cmax) of 1.44ug / ml can inhibit basal gastric acid secretion by 50% for 4 to 5 hours. This product is widely distributed in body tissues (except the brain), is metabolized in the liver, and is mainly excreted by the kidneys. After 24 hours, about 48% of the oral amount is excreted from the kidney in the original form; 10% can be excreted from the feces. This product can be removed by hemodialysis. When the renal function is normal, the half-life (t1 / 2) is 2 hours, the creatinine clearance is 20 ~ 50ml / min, the half-life (t1 / 2) is 2.9 hours, when <20ml / min is 3.7 hours, and when the renal function is inadequate, it is 5 hour. This product can be transported through the placenta and excreted from milk.
Intravenous infusion of 3H-labeled cimetidine produced a peak blood concentration of 2.0-4.3 mol / L (0.5-1.1 mg / L) at a dose of 75-117 mg. Cimetidine has a plasma half-life of 123 ± 12 minutes. Urinary radioactivity demonstrates rapid excretion of the drug through the kidney (60% in 2.5 hours); 70% is excreted in its original form, and 19% is excreted as sulfone. Cimetidine binds to human plasma proteins at approximately 22%.

Cimetidine indications

1. Treat active duodenal ulcer and prevent recurrence of duodenal ulcer.
2. Gastric ulcer.
3. Reflux esophagitis.
4. Gastrinoma (Zollinger-Ellison syndrome).
5. Prevention and treatment of stress and drug ulcers.
6. Peptic ulcers and bleeding.
7. It can be used for the treatment of immune dysfunction and adjuvant treatment of tumor caused by various reasons.
8. It has also been reported that cimetidine can also be used to treat shingles and other herpes infections including the genitals. It can also be used for female androgenic alopecia, acne, hirsutism in women, shingles, etc. [4] .

Cimetidine contraindications

1. Those who are allergic to cimetidine.
2. Because cimetidine can pass through the placental barrier and can enter milk, pregnant women and lactating women should not use it to avoid causing fetal and infant liver dysfunction.
3. Acute pancreatitis has been reported in animal experiments and clinical applications, so cimetidine should not be used in patients with acute pancreatitis [4] .

Cimetidine dosage

Production:
1. Treatment of duodenal ulcer or pathological hypersecretory state, 0.2 ~ 0.4g once, 4 times a day, after meals and before bedtime, or 0.8g once, once before bedtime;
2. To prevent recurrence of ulcers, 0.4g once, before bedtime;
3. The dosage of patients with renal insufficiency is reduced to 0.2g once, once every 12 hours;
4. Reduce the dosage of elderly patients.
5. Pediatrics: Take orally, once per 5 ~ 10mg / Kg of body weight, 2 ~ 4 times a day.
Injection:
1. Intravenous infusion: 0.2g of this product is diluted with 250% to 500ml of 5% glucose injection or 0.9% sodium chloride injection or glucose sodium chloride injection. The drip rate is 1 to 4mg / kg per hour. , 0.2 ~ 0.6g each time.
2. Intravenous injection: Dilute with 20ml of the above solution slowly intravenously (2 ~ 3 minutes), once every 6 hours, 0.2g each time.
3. Intramuscular injection: 0.2g once, once every 6 hours.

Cimetidine adverse reactions

Adverse reaction characteristics: The incidence of adverse reactions of this drug is 1% or higher, mainly due to its antiandrogenic activity and the role of the central nervous system, which inhibits
1. The more common ones are diarrhea, nausea, vomiting, bloating, constipation, bitter mouth, dry mouth, mild elevation of serum aminotransferase, etc., occasional severe hepatitis, liver necrosis, liver steatosis, etc. In patients with cirrhosis, hepatic encephalopathy may be induced. Sudden discontinuation of the drug may cause chronic peptic ulcer perforation, which is estimated to be caused by high acidity that rebounds after discontinuation. It has also been reported that cimetidine can cause acute pancreatitis.
2. Blood system: Cimetidine has a certain inhibitory effect on the bone marrow, neutropenia and whole blood cells may appear; thrombocytopenia and agranulocytosis have also been reported; auto-immune hemolysis is reported only in individual cases Anemia, aplastic anemia, and eosinophilia. The adverse reactions of cimetidine in the blood system are more common in patients with severe complications, or receiving anti-metabolic hydrocarbon-based drugs or other treatments that cause granulocytopenia.
3. Nervous / mental system: (1) Dizziness, headache, fatigue, drowsiness, etc. are more common; a few patients may have reversible confusion, disorientation, restlessness, dull feeling, ambiguity, local convulsions, or epilepsy Seizures, delirium, depression, hallucinations, extrapyramidal reactions, and motor polyneuropathy. After the symptoms of neurotoxicity, generally only need to reduce the dose of the drug to disappear, can also be treated with pseudocholine drug physostigmine. (2) In the treatment of gastrointestinal complications of alcoholism, tremor delirium may occur, which is similar to alcohol withdrawal syndrome, and attention should be paid to differentiation. (3) The neuropsychiatric adverse reactions of cimetidine mainly occur in critically ill patients, elderly patients, young children, people with liver and kidney dysfunction, people with a history of mental illness, people with brain diseases, and high-dose medications are also prone to occur. In addition, those with hypothyroidism may be more sensitive to the neurotoxic effects of cimetidine.
4. Endocrine / metabolic system: Cimetidine has a mild anti-androgenic effect, and may have abnormal lipid metabolism, hyperprolactinemia, decreased plasma testosterone levels and increased gonadotropin levels, male breast development and breasts. Soreness and female galactorrhea.
5. Cardiovascular system: bradycardia, facial flushing, etc. may occur. Intravenous injection occasionally saw a sudden drop in blood pressure, atrial premature beats, cardiac arrest and respiratory arrest.
6. Urinary / reproductive system: (1) Cimetidine can cause transient serum creatinine levels and decrease in creatinine clearance. The mechanism is that cimetidine and creatinine compete for renal tubular secretion. There have also been reports of acute renal impairment, and renal function can return to normal after withdrawal. (2) Interstitial nephritis: It can disappear after stopping the drug. (3) Sexual dysfunction: Large doses (above 1.6g per day) can cause impotence, decreased libido, decreased sperm count, etc., but it can return to normal after stopping the drug. (4) Cimetidine treatment in patients receiving renal allogeneic metastasis can lead to acute metastatic body necrosis.
7. Eye: Optic neuropathy may occur. It is speculated that cimetidine has zinc chelation, which causes insufficient zinc content in the body, thereby causing optic neuropathy. There have also been reports of ophthalmoplegia.
8. Skin: Cimetidine can inhibit sebum secretion, induce exfoliative dermatitis, dry skin, sebaceous dermatitis, hair loss, etc .; allergic reactions (such as rash, giant urticaria), history-about syndrome, and middle Dissolution of toxic epidermal necrosis.
9. Musculoskeletal: Muscle spasm or myalgia can occur after long-term use.
10. Carcinogenicity: A long-term toxicity study of cimetidine on rats found that the incidence of benign Leydig cell tumors was higher than that of the control group, but this adverse reaction was not seen clinically.
11. Others: (1) Cimetidine can reduce gastric acidity and cause the growth of gastric microorganisms. In the case of nausea, infection can occur, which should be paid attention to. (2) Rare fever, hyposmia, etc. [4] .
Prevention of adverse reactions
(1) For cancerous ulcers, a clear diagnosis should be made before use to avoid delay in treatment.
(2) Due to the decrease of renal function in elderly patients, the elimination and slowing of this product can lead to an increase in blood drug concentration, so it is more prone to toxic reactions and symptoms such as dizziness and delirium.
(3) Disturbance to laboratory diagnosis, false positives in gastric occult blood test within 15 minutes of oral administration; blood salicylic acid concentration, serum creatinine, prolactin, transaminase and other concentrations may all increase; parathyroid hormone concentration may decrease .
(4) To avoid renal toxicity, check renal function during medication.
(5) This product has a certain inhibitory effect on the bone marrow. During the medication, pay attention to check the blood picture.
(6) The neurotoxic symptoms of this product are very similar to those caused by central anticholinergic drugs. Treatment with a pseudocholine drug, physostigmine, can improve the symptoms. Therefore, the simultaneous use of this product and central anticholinergics should be avoided to prevent aggravating central nervous system toxic reactions.
(7) The following conditions should be used with caution: severe heart and respiratory diseases; patients with systemic lupus erythematosus (SLE); organic encephalopathy; liver and kidney function damage.

Cimetidine considerations

In order to monitor the occurrence of toxic reactions to the organs of the human body, the liver, kidney function and blood image should be checked regularly before and during the treatment, especially for patients with original liver and kidney disease.
There is a "rebound phenomenon" after abrupt discontinuation: Sudden discontinuation of medication may cause chronic peptic ulcer perforation, which is estimated to be caused by high acidity of rebound after discontinuation. Therefore, the medication (400 mg per night) needs to be continued for 3 months after completing the treatment.
The application of this product may interfere with the experimental results: false positives may occur in the occult blood test of gastric juice within 15 minutes after oral administration; blood salicylic acid concentration, serum creatinine, prolactin, aminotransferase and other concentrations may increase; Adrenal hormone concentrations may decrease.
Acute pancreatitis has been reported in animal experiments and clinical applications, so it should not be used in patients with acute pancreatitis.
After taking regular doses, those with severe liver dysfunction will have twice the cerebrospinal fluid concentration of normal people, so they are prone to poisoning. After neurotoxicity, it usually disappears by just reducing the dose appropriately. The neurotoxic symptoms of this product are very similar to those caused by central anticholinergics, and their symptoms can be improved by treatment with the pseudocholine drug lentiline. Therefore, the simultaneous use of this product and central anticholinergics should be avoided to prevent aggravating central nervous system toxic reactions.
The following cases should be used with caution: severe heart and respiratory diseases; chronic inflammation, such as systemic lupus erythematosus, cimetidine may increase bone marrow toxicity; organic encephalopathy; moderate or severe damage to renal function.
Medication for pregnant and lactating women
Because it can pass through the placental barrier and can enter milk, pregnant women and lactating women are prohibited to avoid causing liver dysfunction of the fetus and infant.
Medication for children
Young children are prone to CNS toxicity and should be used with caution.
Medication for elderly patients
The kidney is an important organ for metabolism of this product. The clearance rate of this product through the kidney decreases with age. Therefore, the dose should be reduced for elderly patients to prevent the occurrence of toxic insanity.

Cimetidine drug interactions

Due to its lipophilicity and ability to bind the cytochrome P450 enzyme system, it interacts with many drugs:
Tetracycline: This product interferes with the absorption of tetracycline tablets, but does not interfere with the absorption of tetracycline syrup.
Chloramphenicol: Combined use may induce iron deficiency anemia.
Lincomycin: Combined use increases lincomycin absorption and increases blood concentration by 19%.
Ciprofloxacin: Used in combination to accelerate the healing of ulcers.
Ketoconazole: interferes with the absorption of ketoconazole in the gastrointestinal tract.
Benzodiazepines: This product can interfere with detoxification of drugs in the liver, significantly reducing plasma clearance of drugs such as diazepam, nitrazepam, flunazepam, clozazol (limienine), and increased blood concentrations by 1.2 to 2 Times. Aggravated sedation and other central nervous system depression symptoms, and can develop respiratory depression and circulatory failure. But without liver
Chlorhexidine or hydroxylazepam is not affected.
Clomethiazole: It can reduce its clearance rate, prolong sedation and hypnosis time and enhance its effect. It may even cause respiratory depression. Not suitable for use.
Amitriptyline: can lead to increased blood levels of amitriptyline.
Amiodarone: can cause elevated serum concentrations of amiodarone.
Procainamide: Procaine amine half-life can be prolonged, renal clearance is reduced, and renal clearance of the active metabolite N-acetylprocaine is significantly reduced. It is particularly significant in the elderly and those with renal dysfunction.
Propranolol (propranolol): It can significantly reduce the clearance of propranolol and increase the blood concentration by 2-3 times.
Lidocaine: It can significantly increase the blood concentration and half-life of lidocaine, and significantly reduce the systemic clearance rate.
Tocamide: This product significantly reduces the peak concentration of tocamide and the recovery of the original drug in urine, but the half-life and renal clearance are unchanged.
Verapamil (Vapiridine): The interaction is not clear.
Nifedipine (Xintongding): can increase the maximum blood concentration of nifedipine by 30%.
Nisoldipine: The dose of Nisoldipine should be reduced when combined.
Diltiazem: It is recommended to reduce the dose of diltiazem by 30 to 50% when combined.
Clonidine, minoxidil, guanethidine: cimetidine antagonizes the antihypertensive effect of this class of drugs, and combined use can reduce or reduce the antihypertensive effect.
Captopril: Combination may cause mental symptoms.
Metoclopramide (metolin): When used in combination, it can reduce the residence time of cimetidine in the stomach and affect its absorption, reducing the bioavailability of cimetidine to 82% to 63% and reducing the efficacy.
Sodium glyceride and glutamine: combined use can enhance the efficacy and accelerate the healing of ulcers.
Aluminum hydroxide and magnesium hydroxide: antacids containing aluminum and magnesium reduce the absorption of cim and reduce bioavailability.
Sucralfate: Combined use can reduce the efficacy of sucralfate.
Warfarin: Combined use can increase the blood concentration of warfarin and prolong the prothrombin time by 20% to 200%. Thereby enhancing the anticoagulant effect. However, the side effects will increase and the symptoms such as soft tissue and urinary tract bleeding are prone to occur, which is generally not suitable for use. If it must be combined, the dose of warfarin should be reduced, and its various coagulation parameters should be closely monitored to prevent bleeding.
New anticoagulation: Combined to enhance anticoagulant effect.
Diphenhydramine, Promethazine: Used in combination with cimetidine, because the H1 and H2 receptors are blocked, the vasodilation effect after exercise is inhibited, which can aggravate the symptoms of angina pectoris and intermittent claudication.
Morphine: Cimetidine significantly reduces morphine clearance and increases plasma concentrations, which can cause potentially fatal adverse reactions, including respiratory arrest, epileptic seizures, confusion, and generalized convulsions. Complex ketones can combat this adverse reaction.
Aspirin: When used in combination, it will increase the solubility of the drug, reduce decomposition, increase absorption, blood concentration will increase significantly, and its effect will increase. It should be used in combination to monitor blood concentration and reduce dosage.
Digoxin: It can increase or decrease the serum digoxin concentration. It should be used with caution and the serum concentration should be monitored.
Atropine: Combined use has a synergistic effect on the inhibition of gastric acid secretion, but the two have similar neurotoxic effects, so it is generally inappropriate to use them together.
Caffeine: Reduces clearance. Causes a 70% increase in plasma caffeine concentration. This can increase excitement in patients with insomnia and anxiety.
Ferric ammonium citrate: Cimetidine reduces gastric acid secretion, reduces the absorption of iron, affects the efficacy, and should not be used in combination.
Steroids or Adenosine (Ara, -A): Cimetidine combined with steroids or Ara-A in the treatment of hepatitis B patients, found to have a certain value for serum hepatitis B e antigen positive negative conversion.
Chloroquine: Cimetidine inhibits the metabolism of chloroquine in the liver, thereby slowing excretion.
Phenytoin sodium: The general dose of cimetidine increases the average plasma concentration of phenytoin sodium in 13 patients with epilepsy by 13% to 33%. Those with plasma concentrations that have reached the upper limit of the therapeutic range should be used with caution.
Theophylline: Combined use reduces theophylline clearance. Metabolism is significantly obstructed, t1 / 2 is prolonged, and plasma concentrations are increased by 2 to 3 times, which is likely to cause toxic reactions such as palpitations, systemic spasms, and even death. The two drugs should not be used in combination, and the theophylline dose should be reduced if necessary.
When used in combination with fluorouracil, it may reduce the efficacy and increase its toxicity.

Cimetidine overdose

The clinical signs of overdose are: shortness of breath or dyspnea, tachycardia.
Treatment: First remove the drugs that have not been absorbed in the gastrointestinal tract, and give clinical monitoring and supportive therapy. Those with respiratory failure should immediately undergo artificial respiration. Those with tachycardia can be given adrenergic blocking drugs.

Cimetidine poisoning

Cimetidine (metimiguanide, Taiweimei) is an H2 receptor antagonist, which can significantly inhibit gastric acid secretion caused by food, histamine or pentagastrin, and reduce its acidity. It has preventive and protective effects on corrosive gastritis caused by chemical stimulation. It was quickly absorbed by the small intestine after oral administration of 300 mg, and reached the blood concentration in 30 minutes, and reached the peak concentration in 90 minutes. The plasma protein binding rate is about 70%, and the half-life is about 2 hours. Widely distributed in systemic tissues, 44% to 70% are excreted from the urine in the original form, and 80% of the oral volume can be excreted in 12 hours. The LD50 of mice was 2.6 g / kg orally, 0.4 g / kg by intraperitoneal injection, and 0.15 g / kg by intravenous injection. Oral LD50 was 5.0g / kg in rats. The usual oral dose is 200 400mg, 800 1600mg / d; the daily dose for injection should not exceed 2g. The poisoning mainly damages the nervous system, blood system, cardiovascular system, liver and kidney.
Clinical manifestation
1. There are many adverse reactions, such as diarrhea, bloating, bitter mouth, dry mouth, and a slight increase in serum aminotransferase.
2. One application of large doses or long-term large doses can cause poisoning. Manifested as:
(1) Nervous system symptoms: headache, dizziness, hallucinations, depression, mental disorders, drowsiness, etc.
(2) Blood system: Leukocyte and thrombocytopenia and hemolytic anemia, and occasionally secondary aplastic anemia. (3) Liver toxicity: Transaminase and serum bilirubin are elevated, and liver necrosis occurs in severe cases.
(4) Renal toxicity: proteinuria, urea nitrogen and creatinine increase, severe cases lead to renal failure. (5) Cardiovascular system: arrhythmia is seen, and intravenous injection occasionally causes cardiac arrest.
(6) Endocrine disorders: sexual dysfunction, male breast enlargement, soreness and galactorrhea, impotence and sperm reduction; female patients have menstrual disorders.
3. Allergic reactions such as joint pain, muscle pain, itching of the skin, rash, fever and laryngeal spasm, and even exfoliative dermatitis, or anaphylactic shock.
diagnosis
The main points of diagnosis of cimetidine poisoning are:
There is a history of cimetidine application and the above manifestations appear.
treatment
The main points of treatment for cimetidine poisoning are:
1.- General adverse reactions can disappear on their own.
2. Liver and kidney function damage should be actively taken to protect liver and kidney function.
3. For severe arrhythmia, anti-arrhythmic drugs can be applied according to the type of arrhythmia.
4. Symptoms of allergic reactions can be treated with antihistamines or glucocorticoids [5] .

Cimetidine expert review

Cimetidine not only has the function of restoring immune function, but also has antiviral effect. Used to treat shingles infections, such as cold sores, herpes keratitis, and genital herpes infections. It has anti-androgenic effect and can be used to treat acne and inhibit prostate hyperplasia. It is easy to be accepted by elderly patients, but it should be taken for a long time to avoid recurrence [4] .

Cimetidine clinical treatment

It has a significant effect on inhibiting gastric acid secretion, it can significantly inhibit basal and nocturnal gastric acid secretion, and it can also suppress gastric acid secretion caused by histamine, subpeptide gastrin, insulin and food stimulation, and reduce its acidity. The corrosive gastritis caused by it has a preventive and protective effect, and it also has obvious curative effects against acute gastric ulcer and upper gastrointestinal bleeding. It is used to treat duodenal ulcer, gastric ulcer, upper gastrointestinal bleeding, chronic colitis, shingles, and chronic urticaria. It plays a role in fighting viruses and boosting immunity.
Cimetidine (cimetidine) is a selective H2 receptor antagonist marketed in 1975 for the treatment of peptic ulcers. In recent years, the drug has been newly discovered for the treatment of non-ulcerative diseases.

Cimetidine in the treatment of chronic hepatitis B

Shi Shishan et al. Used cimetidine 0.4 g, 3 times a day, orally to treat 70 patients with chronic hepatitis B. After 3 months of continuous medication, they stopped for 3 weeks and continued to take the medication for 3 months. The total course of treatment was 6 months. The control group was treated with Ganyanling with the same course of treatment. Vitamins and symptomatic treatment were added to both groups, but no antiviral drugs were added. Results The transaminase reversion rate in the treatment group was 82.9%, the HBsAg negative conversion rate was 17.1%, and the HBeAg negative conversion rate was 60%, which were significantly better than the control group's 50%, 13.3%, and 30% (p <0.05). The mechanism may be that the lymphocyte K cell activity in patients with chronic hepatitis B is significantly reduced, resulting in incomplete clearance of HBV, while cimetidine may enhance lymphocyte K cell activity, break immune tolerance, and restore cell-mediated immune responses. In addition, Japanese scholar Tatsuo Masuda and others used cimetidine 0.8 g orally daily, and applied steroids and adenosine arabinoside to treat 15 patients with HBeAg-positive chronic hepatitis B. The negative conversion rate was 100% after 7-9 months. The control group taking steroids and adenosine arabinoside was only 33.3%.

Cimetidine for cancer

Yang Jian et al. Used Cimetidine 0.2-0.3 g orally, twice or once a day. Treatment observations show that the drug can inhibit gastric cancer, lung metastatic cancer and other advanced cancers, liver cancer, melanoma, blood cancer, and ovarian cancer. Growth, delay metastasis, and improve symptoms. This is because cimetidine can eliminate the immunosuppressive effect of histamine and also enhance the ability of antibody synthesis in cancer-bearing animals. Cimetidine has shown significant anti-cancer effects in both mice and humans.

Cimetidine prevents blood transfusion reactions

Liu Donghua et al. Used cimetidine to prevent 101 transfusion reactions, and compared it with 99 cases of phenagen. In the treatment group, 0.4 g of cimetidine was given intravenously before blood transfusion, and in the control group, 25 mg of finacin was given intramuscularly. Results One case occurred in the treatment group and eight cases in the control group. The mechanism is related to the inhibition of histamine release.

Cimetidine for arrhythmia

Recent studies have shown that cimetidine has a counteracting effect on arrhythmia. Jing Youling and other studies have shown that the anti-lipid peroxidation of cimetidine may be one of the anti-arrhythmic mechanisms. The heart is rich in H2 receptors, which is mainly mediated by H2 receptors during acute myocardial ischemia. Cimetidine can selectively block H2 receptors, reduce the generation of oxygen free radicals, and exert its antiarrhythmic effect. . Some people used cimetidine and intravenous drip in polarizing solution to treat 3 cases of intractable arrhythmia in the early stage of acute myocardial infarction. One case disappeared earlier than 10 hours after treatment, and two cases occurred earlier than 10 after treatment It disappeared after 20 hours.

Cimetidine for treatment of increased androgen

Cimetidine has a non-steroidal antiandrogen-like effect, is a competitive inhibitor of dihydrotestosterone (DHT), and can reduce the plasma concentration of DHT, so it can be used to treat androgen-diverse diseases. Some people use cimetidine 0.4 g once a day to treat benign prostatic hyperplasia, and to return to normal urination in a short time. Some people abroad use this product to treat 45 cases of acne with an effective rate of 95.5%; using this product to treat female hirsutism can also make hair growth slow down quickly.

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