XENOZ TABLETS

Indications

• Gastroesophageal reflux disease (GERD)
• Erosive esophagitis
• Peptic ulcers
• Helicobacter pylori eradication
• Zollinger-Ellison syndrome

Dosage

Adults: The usual oral dose

Mechanism of action

Esomeprazole exerts its stomach acid-suppressing effects by covalently binding to cysteine residues on the H+/K+-ATPase enzyme at the secretory surface of gastric parietal cells. This action inhibits both basal and stimulated gastric acid secretion irreversibly, requiring the synthesis of new enzyme to restore acid production. By blocking the final step of gastric acid production, esomeprazole reduces gastric acidity in a dose-dependent manner.

Pharmacodynamics

Esomeprazole is a substituted benzimidazole that inhibits gastric acid secretion without exhibiting anticholinergic or H2 receptor antagonistic properties. It is indicated for the treatment of GERD, healing of erosive esophagitis, and eradication of H. pylori to reduce duodenal ulcer recurrence. The suppression of gastric acid secretion is dose-related and effective against various stimuli that promote acid secretion.

Pharmacokinetics

Esomeprazole is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It undergoes extensive hepatic metabolism primarily by the cytochrome P450 system, especially CYP2C19, resulting in several metabolites. The elimination half-life is approximately 1-2 hours, though its antisecretory effects last longer. It is excreted predominantly in the urine. Dose adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to esomeprazole or any of its components
• Concomitant use with rilpivirine-containing products

Adverse effects

• Abdominal pain
• Constipation
• Diarrhea
• Dizziness
• Dry mouth
• Headache
• Insomnia
• Nausea
• Skin reactions
• Vomiting
• Bone fractures
• Confusion
• Depression
• Drowsiness
• Leucopenia
• Malaise
• Myalgia
• Paraesthesia
• Peripheral edema
• Thrombocytopenia
• Vertigo
• Vision disorders
• Agranulocytosis
• Alopecia
• Gynaecomastia
• Hallucination
• Hepatic disorders
• Hyperhidrosis
• Hyponatraemia
• Nephritis
• Tubulointerstitial nephritis
• Pancytopenia
• Photosensitivity reaction
• Severe cutaneous adverse reactions (SCARs)
• Stomatitis
• Taste altered
• Hypomagnesaemia

Interactions

• Esomeprazole may increase the exposure to cannabidiol
• Esomeprazole may increase the exposure to cilostazol

Precautions

• Increased risk of fractures, particularly in the elderly and when used at high doses for over a year
• Caution in patients at risk of osteoporosis; adequate intake of calcium and vitamin D is recommended
• May increase the risk of gastrointestinal infections, including Clostridioides difficile
• Symptoms of gastric cancer should be ruled out before treatment
• Use with caution in patients with hepatic impairment

Pregnancy

Use with caution. The manufacturer advises avoiding use unless necessary since the effects on the fetus are not fully known.

Breast-feeding

Manufacturer advises avoiding use as esomeprazole is present in breast milk and may cause diarrhea in nursing infants. However, amounts are probably too small to be harmful.

Storage

Store in a cool, dry place below 25°C. Keep out of

Indications

• Osteoarthritis

Mechanism of action

Naproxen works by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2, which play a crucial role in the synthesis of prostaglandins from arachidonic acid. COX-1 is constitutively active in many normal tissues, while COX-2 is inducible and primarily mediates pain, inflammation, and fever. By blocking these enzymes, naproxen decreases the production of prostaglandins, leading to reduced inflammation and pain relief. The anti-inflammatory effects are associated with COX-2 inhibition, whereas adverse events, such as gastrointestinal upset, are linked to COX-1 inhibition.

Pharmacodynamics

Naproxen demonstrates its pharmacological activity primarily through the inhibition of cyclooxygenase enzymes, which reduces prostaglandin levels in various tissues including synovial fluid and gastric mucosa. While effective as an analgesic, naproxen can negatively impact blood pressure regulation and is associated with an increased risk of upper gastrointestinal bleeding, especially in patients with additional risk factors such as concurrent use of corticosteroids or anticoagulants, and a history of ulcers. Therefore, careful consideration of the risk-benefit profile is essential when prescribing naproxen.

Pharmacokinetics

Naproxen is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 to 4 hours after oral administration. It has a half-life of about 12 to 17 hours, allowing for twice-daily dosing in many cases. The drug is extensively metabolized in the liver, primarily via hepatic cytochrome P450 enzymes, and its metabolites are excreted in the urine. Renal function can impact the clearance of naproxen, necessitating caution in patients with compromised renal health.

Contra-indications

• Hypersensitivity to naproxen or any of its components
• Severe renal impairment
• Active peptic ulcer disease
• History of gastrointestinal bleeding related to NSAID use
• Severe heart failure

Adverse effects

• Gastrointestinal upset
• Nausea
• Vomiting
• Dyspepsia
• Abdominal pain
• Headache
• Dizziness
• Rash
• Increased blood pressure
• Gastrointestinal bleeding
• Renal toxicity

Interactions

• Increased risk of gastrointestinal bleeding when used with anticoagulants or corticosteroids
• May increase blood pressure when used with antihypertensive agents
• May enhance effects of other NSAIDs
• Potential interactions with methotrexate and lithium

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor renal function in patients with renal impairment or dehydration
• Assess for gastrointestinal risk factors in patients before prescribing
• Caution in elderly patients due to increased risk of adverse effects

Pregnancy

Naproxen should be avoided during pregnancy, especially during the third trimester, due to potential risks to the fetus.

Breast-feeding

Naproxen is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Extended-release tablets
• Oral suspension
• Suppositories

Mechanism of action

Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect that persists longer than 24 hours. Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Pharmacodynamics

Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and <i>H. pylori</i> eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H⁺/K⁺ ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_. PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.

Mechanism of action

As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme. Naproxen has pharmacologic actions similar to those of other prototypical nonsteroidal anti-inflammatory agents (NSAIAs). The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis. Naproxen inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2) (also referred to as prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2), respectively), have been identified that catalyze the formation of prostaglandins in the arachidonic acid pathway. Naproxen, like other prototypical NSAIAs, inhibits both COX-1 and COX-2. Although the exact mechanisms have not been clearly established, NSAIAs appear to exert anti-inflammatory, analgesic, and antipyretic activity principally through inhibition of the COX-2 isoenzyme; COX-1 inhibition presumably is responsible for the drugs' unwanted effects on GI mucosa and platelet aggregation. The anti-inflammatory, analgesic, and antipyretic effects of naproxen and other nonsteroidal anti-inflammatory agents (NSAIAs), including selective inhibitors of COX-2 (e.g., celecoxib, rofecoxib), appear to result from inhibition of prostaglandin synthesis. While the precise mechanism of the anti-inflammatory and analgesic effects of NSAIAs continues to be investigated, these effects appear to be mediated principally through inhibition of the COX-2 isoenzyme at sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Naproxen stabilizes lysosomal membranes and inhibits the response of neutrophils to chemotactic stimuli. The drug does not possess glucocorticoid or adrenocorticoid-stimulating properties. Naproxen lowers body temperature in patients with fever. Although the mechanism of the antipyretic effect of nonsteroidal anti-inflammatory agents is not known, it has been suggested that suppression of prostaglandin synthesis in the CNS (probably in the hypothalamus) may be involved. Naproxen-induced inhibition of prostaglandin synthesis may result in decreased frequency and intensity of uterine contractility. Prostaglandins E2 and F2alpha increase the amplitude and frequency of uterine contractions in pregnant women; current evidence suggests that primary dysmenorrhea is also mediated by these prostaglandins. Whether the increased production of prostaglandins associated with primary dysmenorrhea is mediated by COX-1 or COX-2 remains to be determined. Blood concentrations of a metabolite of prostaglandin F2alpha have been found to decrease in women with dysmenorrhea who were receiving naproxen. Therapy with naproxen has been effective in relieving menstrual pain and has reduced blood loss in women with menorrhagia, probably by inhibiting the formation of these prostaglandins. Administration of naproxen during late pregnancy may prolong gestation by inhibiting uterine contractions.

Pharmacodynamics

Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use. Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers.