Acinil - General Information
A histamine congener, it competitively inhibits histamine binding to histamine H2 receptors. Acinil has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrins output. It also blocks the activity of cytochrome P-450 which might explain proposals for use in neoadjuvant therapy.
Pharmacology of Acinil
Acinil is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Acinil inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Acinil include an increase in gastric bacterial flora such as nitrate-reducing organisms.
Acinil for patients
Rare instances of cardiac arrhythmias and hypotension have been reported following the rapid administration of Tagamet (cimetidine hydrochloride) Injection by intravenous bolus.
Symptomatic response to Tagamet therapy does not preclude the presence of a gastric malignancy. There have been rare reports of transient healing of gastric ulcers despite subsequently documented malignancy.
Reversible confusional states have been observed on occasion, predominantly, but not exclusively, in severely ill patients. Advancing age (50 or more years) and preexisting liver and/or renal disease appear to be contributing factors. In some patients these confusional states have been mild and have not required discontinuation of Tagamet therapy. In cases where discontinuation was judged necessary, the condition usually cleared within 3 to 4 days of drug withdrawal.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 24-month toxicity study conducted in rats, at dose levels of 150, 378 and 950 mg/kg/day (approximately 8 to 48 times the recommended human dose), there was a small increase in the incidence of benign Leydig cell tumors in each dose group; when the combined drug-treated groups and control groups were compared, this increase reached statistical significance. In a subsequent 24-month study, there were no differences between the rats receiving 150 mg/kg/day and the untreated controls. However, a statistically significant increase in benign Leydig cell tumor incidence was seen in the rats that received 378 and 950 mg/kg/day. These tumors were common in control groups as well as treated groups and the difference became apparent only in aged rats.
Tagamet (cimetidine) has demonstrated a weak antiandrogenic effect. In animal studies this was manifested as reduced prostate and seminal vesicle weights. However, there was no impairment of mating performance or fertility, nor any harm to the fetus in these animals at doses 8 to 48 times the full therapeutic dose of Tagamet, as compared with controls. The cases of gynecomastia seen in patients treated for 1 month or longer may be related to this effect.
In human studies, Tagamet has been shown to have no effect on spermatogenesis, sperm count, motility, morphology or in vitro fertilizing capacity.
Teratogenic Effects. Pregnancy Category B : Reproduction studies have been performed in rats, rabbits and mice at doses up to 40 times the normal human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Tagamet. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cimetidine is secreted in human milk and, as a general rule, nursing should not be undertaken while a patient is on a drug.
Clinical experience in children is limited. Therefore, Tagamet therapy cannot be recommended for children under 16, unless, in the judgment of the physician, anticipated benefits outweigh the potential risks. In very limited experience, doses of 20 to 40 mg/kg per day have been used.
In immunocompromised patients, decreased gastric acidity, including that produced by acid-suppressing agents such as cimetidine, may increase the possibility of a hyperinfection of strongyloidiasis.
Tagamet, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.
Clinically significant effects have been reported with the warfarin anticoagulants; therefore, close monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when Tagamet is administered concomitantly. Interaction with phenytoin, lidocaine and theophylline has also been reported to produce adverse clinical effects.
However, a crossover study in healthy subjects receiving either Tagamet 300 mg q.i.d. or 800 mg h.s. concomitantly with a 300 mg b.i.d. dosage of theophylline (Theo-Dur, Key Pharmaceuticals, Inc.) demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg h.s. regimen, particularly in subjects aged 54 years and older. Data beyond 10 days are not available. (Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.)
Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping concomitantly administered Tagamet to maintain optimum therapeutic blood levels.
Alteration of pH may affect absorption of certain drugs (e.g., ketoconazole). If these products are needed, they should be given at least 2 hours before cimetidine administration.
Additional clinical experience may reveal other drugs affected by the concomitant administration of Tagamet.
Tagamet is contraindicated for patients known to have hypersensitivity to the product.
Additional information about Acinil
Acinil Indication: For the treatment and the management of acid-reflux disorders (GERD), peptic ulcer disease, heartburn, and acid indigestion.
Mechanism Of Action: Acinil binds to an H2-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.
Drug Interactions: Alfentanil Increases the effect of the narcotic
Alprazolam Increases the effect of the benzodiazepine
Aminophylline Increases the effect of theophylline
Amitriptyline Increases the effect of tricyclic agent
Amoxapine Increases the effect of tricyclic agent
Anisindione The ANTI-H2 increases the anticoagulant effect
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir This gastric pH modifier decreases the levels/effects of atazanavir
Carbamazepine Increases the effect of carbamazepine
Carmustine Increases myelosuppression caused by carmustine
Chlordiazepoxide Increases the effect of the benzodiazepine
Clomipramine Increases the effect of tricyclic agent
Clonazepam Increases the effect of the benzodiazepine
Clorazepate Increases the effect of the benzodiazepine
Clozapine Increases the effect of clozapine
Codeine Increases the effect of the narcotic
Desipramine Increases the effect of tricyclic agent
Diazepam Increases the effect of the benzodiazepine
Dicumarol The anti-H2 increases the anticoagulant effect
Dihydroquinidine barbiturate Increases the effect of quinidine
Dyphylline Increases the effect of theophylline
Dofetilide Increases effect/toxicity of dofetilide
Donepezil Possible antagonism of action
Doxepin Increases the effect of tricyclic agent
Dyphylline Increases the effect of theophylline
Enoxacin The agent decreases the absorption of enoxacin
Epirubicin Acinil can increase epirubicin levels
Estazolam Increases the effect of the benzodiazepine
Ethotoin Increases the effect of hydantoin
Fentanyl Increases the effect of the narcotic
Flecainide Increases serum levels of flecainide
Fluorouracil Increases the effect of and toxicity of fluorouacil
Flurazepam Increases the effect of the benzodiazepine
Fosphenytoin Increases the effect of hydantoin
Galantamine Possible antagonism of action
Halazepam Increases the effect of the benzodiazepine
Hydrocodone Increases the effect of the narcotic
Hydromorphone Increases the effect of the narcotic
Imipramine Increases the effect of tricyclic agent
Itraconazole The anti-H2 decreases the absorption of the imidazole
Levorphanol Increases the effect of the narcotic
Ketoconazole The anti-H2 decreases the absorption of the imidazole
Lidocaine Increases the effect and toxicity of lidocaine
Meperidine Increases the effect of the narcotic
Mephenytoin Increases the effect of hydantoin
Metformin Increases the effect of metformin
Methadone Increases the effect of the narcotic
Metoprolol Increases the effect of the beta-blocker
Midazolam Increases the effect of the benzodiazepine
Moclobemide Increases the effect of moclobemide
Morphine Increases the effect of the narcotic
Nalbuphine Increases the effect of the narcotic
Acenocoumarol The anti-H2 increases the anticoagulant effect
Nimodipine Increases the effect of the calcium channel blocker
Nifedipine Increases the effect of the calcium channel blocker
Nitrendipine Increases the effect of the calcium channel blocker
Nortriptyline Increases the effect of tricyclic agent
Oxtriphylline Increases the effect of theophylline
Oxycodone Increases the effect of the narcotic
Oxymorphone Increases the effect of the narcotic
Pentazocine Increases the effect of the narcotic
Phenytoin Increases the effect of hydantoin
Posaconazole Significant decrease of posaconazole levels
Pramipexole Increases the effect and toxicity of pramipexole
Propoxyphene Increases the effect of the narcotic
Procainamide The histamine H2-receptor antagonist increases the effect of procainamide
Propranolol Increases the effect of the beta-blocker
Protriptyline Increases the effect of tricyclic agent
Quinidine Increases the effect of quinidine
Quinidine barbiturate Increases the effect of quinidine
Rivastigmine Possible antagonism of action
Sildenafil Increases the effect and toxicity of sildenafil
Sufentanil Increases the effect of the narcotic
Tacrine Increases the effect and toxicity of tacrine
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Increases the effect of theophylline
Timolol Increases the effect of the beta-blocker
Tolazoline Anticipated loss of efficacy of tolazoline
Triazolam Increases the effect of the benzodiazepine
Trimipramine Increases the effect of tricyclic agent
Warfarin The anti-H2 increases the anticoagulant effect
Zaleplon Increases the effect and toxicity of zaleplon
Heroin Acinil increases the effect of the narcotic
Ketazolam Acinil increases the effect of the benzodiazepine
Labetalol Acinil increases the effect of the beta-blocker
Prazepam Acinil increases the effect of the benzodiazepine
Quazepam Acinil increases the effect of the benzodiazepine
Food Interactions: Best effect when taken with food.
Limit caffeine intake.
Generic Name: Cimetidine
Synonyms: Cimetidine Hcl; Cimetidine A/AB; Carbamazapine
Drug Category: Analgesics; Anti-Ulcer Agents; Adjuvants; Histamine Antagonists
Drug Type: Small Molecule; Approved
Other Brand Names containing Cimetidine: Acibilin; Acinil; Cimal; Cimetag; Cimetum; Dyspamet; Edalene; Eureceptor; Gastromet; Peptol; Tagamet; Tagamet HB; Tagamet HB 200; Tametin; Tratul; Ulcedin; Ulcedine; Ulcerfen; Ulcimet; Ulcofalk; Ulcomedina; Ulcomet; Ulhys;
Absorption: Rapid 60-70%
Toxicity (Overdose): Symptoms of overdose include nausea, vomiting, diarrhea, increased saliva production, difficulty breathing, and a fast heartbeat.
Protein Binding: 15-20%
Half Life: 2 hours
Dosage Forms of Acinil: Liquid Oral
Chemical IUPAC Name: 3-cyano-2-methyl-1-[2-[(5-methyl-1H-imidazol-4-yl)methylsulfanyl]ethyl]guanidine
Chemical Formula: C10H16N6S
Cimetidine on Wikipedia: http://en.wikipedia.org/wiki/Cimetidine
Organisms Affected: Humans and other mammals