Structural Biochemistry/Pepcid

Background Information
Pepcid is a drug with generic name Famotidine that is manufactured by Merck and Co. It is classified as a Histamine H2 Receptor Antagonist with chemical name 2-[4-[2-(amino-sulfamoylimino-methyl)ethylsulfanylmethyl]-1,3-thiazol-2-yl]guanidine. Famotidine is used to treat and prevent ulcers in the stomach and intestines. Famotidine is also used to treat conditions in which the stomach produces too much acid and conditions in which acid comes up into the esophagus and causes heartburn, such as gastroesophageal reflux disease (GERD). The drug is available in suspension, injection, and tablet form. 15% to 20% of PEPCID in plasma is protein bound. Administered PEPCID tablets and suspension are incompletely absorbed and its bioavailability is 40-45%. PEPCID is excreted by renal (65-70%) and metabolic (30-35%) routes with the only metabolite identified is the S-oxide. It has a half life of 2.5-3.5 hours. The drug works by inhibiting gastric secretion. This is done through competitive inhibition of histamine H2 receptors. These receptors located in the parietal cell are responsible for the secretion of HCl in the stomach. When mast cells are agitated, they release the H2 substrate which will then bind the receptor site and produce HCL. The drug competes with the H2 for the receptor site to prevent binding and thus the release of gastric acid. Some of the severe side effects associated with the drug are seizures, Arrhythmia, and diarrhea.



History
Yamanouchi Pharmaceutical Co. developed pepcid (famotidine). In the mid-80s, Merck & Co. licensed pepcid and is marketed by a joint venture between Merck and Johnson & Johnson. A 2-guanidinothiazole ring was used as a replacement for imidazole-ring. In the end, many studies showed that famotidine was thirty times more active than cimetidine.

In the year 1999, pepcid RPD orally-disintegrating tablets were released. They were known to not be swallowed. Then in the year 2001, generic preparation became available. For example, Fluxid (Schwarz) or Quamatel (Gedeon Richter Ltd).

In addition, there was also a product called Pepcide Complete in the United States. However, in the United Kingdom, this product is known as Pepcidtwo. Pepcide Complete was a kind of product that had a combination of famotidine with an antacid in a chewable tablet to ameliorate the relatively slow onset of effects.

However, Pepcid carries some consequences. For example, famotidine is poorly soluble in the low pH of the stomach and it suffers from poor bioavailability (50%). Famotidine used in combination with antacids promotes local delivery of these drugs to the receptor of the parietal cell wall. Hence, many researchers out there are finding ways to develop innovative formulations of tablets, such as gastroretentive drug delivery systems. This is because this type of drug is known to be in stomach for a longer period of time and thus improve the bioavailability of drugs.

Medical Use
In different countries in the world, certain preparations of famotidine are available over the counter (OTC). For instance, in the United States, preparations of 10 mg and 20 mg tablets, sometimes even in the combination with a more traditional antacid, are all available as an over the counter drug. However, if an individual is deciding to take a larger dose, it is important that they consult with their doctor to give them a prescription. In this case, a prescription will allow them to get a good amount of famotidine they need from the OTC.

Commonly seen, pepcid is given to patients who are going through a surgery process. They are typically given before the operations to prevent postoperative nausea and to decrease any risk of aspiration pneumonitis. In addition, pepcid is given to some patients who take NSAIDs. Taking pepcid will basically prevent them from peptic ulcers because this medication usually serves as an alternative to proton-pump inhibitors. An interesting fact is that pepcide is not only given to humans but they are also given to animals such as dogs. They are given to dogs with acid reflux.

Many people who take famotidine also use this medication with the combination of H1 antagonist to treat and prevent urticaria. Urticaria is caused by an acute allergic reaction. Famotidine has been found to reduce the debilitating effects of chronic heart failure by blocking histamine.

Overall, pepecid or famotidine can be used as a useful drug, especially when it is used in a proper manner.

Side Effects of Pepcid
-Gastrointestinal

Gastrointestinal side effects including diarrhea (1.7%) and constipation (1.2%) have been stated. Vomiting, nausea, abdominal distress, anorexia, and dry mouth have been reported infrequently. Hypergastrinemia of uncertain clinical significance has also been reported.

-Nervous system

Grand mal seizure; psychic disturbances, which were alterable in cases for which follow-up was found, including hallucinations, confusion, agitation, depression, anxiety, decreased libido; paresthesia; insomnia; somnolence. Convulsions, in patients with reduced renal function, have been reported very rarely.

-Hepatic

Hepatic side effects have included mild elevations of liver function tests. The clinical significance of these elevations is unknown. Jaundice and cholestatic jaundice have been reported infrequently. Cases of drug-induced hepatitis have also been reported.

-Cardiovascular

Cardiovascular side effects have included decreases in stroke volume and cardiac productivity and may be clinically significant in patients with previous cardiac dysfunction. A variety of arrhythmias, including bradycardia, tachycardia, AV conduction defects (including AV block), and palpitations have also been reported rarely. Prolonged QT interval has been reported very rarely in patients with impaired renal function whose dose/dosing interval of famotidine may not have been adjusted properly.

-Hypersensitivity

Hypersensitivity side effects have infrequently included anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival infection, toxic epidermal necrolysis (very rare), erythema multiforme, and Stevens-Johnson syndrome.

-Renal Renal side effects have contained rare cases of interstitial nephritis.

-Endocrine

Endocrine side effects have included anti-androgen effects of reversible hyperprolactinemia and gynecomastia.

-Dermatologic

Dermatologic side effects have infrequently included alopecia, acne, pruritus, dry skin, and flushing. At least one case of contact dermatitis in a worker handling pepcid has been reported.

-Hematologic

Hematologic side effects including neutropenia have been reported. Rarely, reversible thrombocytopenia, agranulocytosis, pancytopenia, and leukopenia have been reported.

-Respiratory

Respiratory side effects including bronchospasm and interstitial pneumonia have been reported infrequently.

-Musculoskeletal

Musculoskeletal side effects have uncommonly contained musculoskeletal pain including muscle cramps and arthralgia.

-Other

Other side effects including tinnitus, fever, asthenia, fatigue, and taste disorder have been reported occasionally. At least one case of hyperpyrexia in association with pepcid use has been reported.