Anti Ulcerant, PPIs, Proton Pump Inhibitors; Types, Uses

Classification of Proton Pump Inhibitors

Mechanism of Action of Proton-pump inhibitors

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H⁺/K⁺ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H⁺ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of drugs that are significantly more effective than H₂ antagonists and reduce gastric acid secretion by up to 99%.

Decreasing the acid in the stomach can aid the healing of duodenal ulcers and reduce the pain? from indigestion and heartburn. However, stomach acids are needed to digest proteins, vitamin B₁₂, calcium, and other nutrients, and too little stomach acid causes the condition hypochlorhydria.

The PPIs are given in an inactive form, which is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) with acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.

Medical Uses of Proton-pump inhibitors

These drugs are used in the treatment of many conditions, such as:

• Dyspepsia
• Peptic ulcer disease including after endoscopic treatment for bleeding
• As part of Helicobacter pylori eradication therapy
• Gastroesophageal reflux disease (GERD or GORD) including symptomatic endoscopy?-negative reflux disease and associated laryngopharyngeal reflux causing laryngitis and chronic? cough
• Barrett’s esophagus
• Eosinophilic esophagitis
• Stress gastritis and ulcer? prevention in critical care
• Gastrinomas and other conditions that cause hypersecretion of acid including Zollinger–Ellison syndrome (often 2–3x the regular dose is required)

Specialty professional organizations recommend that people take the lowest effective PPI dose to achieve the desired therapeutic result when used to treat gastroesophageal reflux disease long-term. In the United States, the Food and Drug Administration has advised that no more than three 14-day treatment courses should be used in one year.

Despite their extensive use, the quality of the evidence supporting their use in some of these conditions is variable. The effectiveness of PPIs has not been demonstrated for every case. For example, although they reduce the incidence of esophageal adenocarcinoma in Barrett’s esophagus, they do not change the length affected

Contra-Indications of Proton-pump inhibitors

• Clostridium difficile infection?
• Inadequate Vitamin B12
• Low amount of magnesium in the blood
• Liver problems
• Interstitial Nephritis
• Subacute cutaneous lupus erythematosus
• Systemic? Lupus Erythematosus
• Osteoporosis
• Broken Bone
• Allergies to Proton Pump Inhibitors

Side Effects of Proton-pump inhibitors

The most common

• Nausea and vomiting
• Severe stomach ache
• Severe diarrhea
• Vaginal thrush
• Skin rash
• A headache
• chest pain
• constipation
• a cough
• diarrhea or loose stools
• difficulty with breathing
• dizziness
• heartburn
• muscle pain

More common

• Abdominal or stomach pain, discomfort, or pain? when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।" data-rx-term="tenderness" data-rx-definition="Tenderness means pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।">tenderness?
• chills or fever
• difficulty with moving
• a headache, severe and throbbing
• joint or back pain
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in the chest
• discomfort in arms, shoulders, neck or upper back
• excessive sweating
• feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
• sudden tingling or coldness in an arm or leg
• sudden slow or difficult speech
• sudden drowsiness or need to sleep
• fast breathing
• sharp pain when taking a deep breath
• fast or slow heartbeat
• coughing up blood
• rust colored urine
• decreased amount of urine

Rare

• Anxiety
• change in vision
• seizures
• abnormal or fast heart rate
• tremors
• weight loss
• chest pain or tightness
• confusion
• a cough
• Agitation
• arm, back, or jaw pain?
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• fainting
• hallucinations
• a headache
• irritability
• lightheadedness
• mood or mental changes
• muscle pain or cramps
• muscle spasm or jerking of all extremities

Drug Interactions of Proton-pump inhibitors

Anti ulcerant may interact with following drugs, supplements, & may change the efficacy of the drug

• amiodarone
• azole antifungal medications (e.g., fluconazole, ketoconazole)
• caffeine
• calcium channel blockers (e.g., diltiazem, nifedipine, verapamil)
• carbamazepine
• carvedilol
• certain benzodiazepines (alprazolam, chlordiazepoxide, clonazepam, diazepam,flurazepam, midazolam, and triazolam)
• clopidogrel
• clozapine
• dasatinib
• glyburide (and other “sulfonylurea” insulin? is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes? medications)
• lidocaine
• metformin
• metoprolol
• pentoxifylline
• phenytoin
• propranolol
• salmeterol
• SSRIs (e.g., citalopram, fluoxetine, sertraline)
• sucralfate
• theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
• tramadol
• tricyclic antidepressants(e.g., amitriptyline, clomipramine, desipramine, trimipramine)
• warfarin

References