Pharmacology of Histamine-2 Receptor Antagonists

Histamine-2 receptor antagonists (H2 blockers) reduce stomach acid production. They block the action of histamine, which stimulates stomach acid production. H2 blockers cure various gastrointestinal disorders.

List of Histamine-2 Receptor Antagonists

Ranitidine
Famotidine
Cimetidine
Nizatidine

Mechanism of Action of Histamine-2 Receptor Antagonists

Histamine-2 receptor antagonists (H2 blockers) work by inhibiting histamine at stomach H2 receptors.

Stomach Acid Production

Parietal cells in the stomach produce hydrochloric acid. Histamine binding to parietal cell H2 receptors stimulates acid secretion. Enterochromaffin-like (ECL) stomach cells emit histamine.

H2 Receptors

H2 receptors are G-protein coupled receptors on parietal cells. Histamine binding to these receptors activates the proton pump H⁺/K⁺-ATPase. The active proton pump transports hydrogen ions (protons) from the parietal cell into the stomach, producing gastric acid.

Blockade of H2 Receptors

H2 blockers compete with histamine to bind and activate parietal cell H2 receptors. H2 blockers reduce stomach acid production by occupying these receptors.

Acid Suppression

H2 receptor blockers reduce histamine-induced stomach acid production. GERD, peptic ulcers, and hypersecretory disorders like Zollinger-Ellison syndrome benefit from this acid secretion reduction.

H2 blockers only inhibit histamine at H2 receptors, which regulate gastric acid output. They do not alter other acid-producing stimuli like acetylcholine or gastrin. H2 blockers also have anti-inflammatory actions.

Pharmacological Actions of H-2 Receptor Antagonists

Histamine-2 receptor antagonists, commonly known as H2 blockers, have several pharmacological actions that contribute to their therapeutic effects. Here are the main pharmacological actions of H2 receptor antagonists.

1. Inhibition of Gastric Acid Secretion

H2 blockers primarily act by competitively binding to H2 receptors on parietal cells in the stomach. This inhibits the binding of histamine to the receptors and subsequently blocks the signaling pathway that stimulates the secretion of gastric acid. By reducing the production of gastric acid, H2 blockers help to alleviate symptoms associated with excessive acid, such as heartburn, acid reflux, and stomach ulcers.

2. Reduction of Basal and Stimulated Acid Secretion

H2 blockers not only decrease the basal (resting) level of gastric acid secretion but also reduce the acid production stimulated by various factors such as food, histamine release, acetylcholine, and gastrin. This comprehensive acid-suppressing effect helps to maintain a lower level of gastric acidity and promotes the healing of acid-related disorders.

3. Prolongation of Gastric Acid-Suppressive Effects

H2 blockers can provide sustained suppression of gastric acid secretion due to their long duration of action. Although the exact duration varies among different H2 blockers, their effects generally last several hours after a single dose, providing relief from symptoms over an extended period.

4. Limited Impact on Pepsin Secretion

H2 blockers have minimal direct effects on pepsin, an enzyme responsible for the breakdown of proteins in the stomach. Unlike proton pump inhibitors (PPIs), which can profoundly reduce pepsin secretion, H2 blockers primarily target acid secretion without significantly affecting pepsin levels.

5. Preservation of Other Gastric Functions

Unlike PPIs, H2 blockers have a more selective action on acid secretion, allowing other important gastric functions to be preserved. These include the release of intrinsic factor, a protein required for vitamin B12 absorption, as well as the natural bactericidal activity of gastric acid that helps prevent bacterial overgrowth in the stomach.

H2 blockers decrease stomach acid output less effectively than PPIs. However, these drugs are used in treatment for mild to moderate acid-related disorders. H2 blockers or PPIs depend on the illness, severity, and patient.

Therapeutic Uses of H-2 Receptor Antagonists

1. Gastroesophageal Reflux Disease (GERD)

H2 blockers lower stomach acid and improve symptoms. They relieve heartburn, regurgitation, and other stomach acid reflux symptoms.

2. Peptic Ulcers

H2 blockers treat open sores in the stomach or upper small intestine. H2 blockers reduce acid production to cure and prevent ulcers.

3. Zollinger-Ellison Syndrome

H2 blockers treat this unusual pancreatic tumor-induced stomach acid overproduction. H2 blockers reduce acid production and symptoms.

4. Dyspepsia

H2 blockers can treat indigestion. Reducing stomach acid can decrease abdominal pain, bloating, and discomfort.

5. Prevention of Stress Ulcers

Critically sick patients at risk of stress ulcers owing to trauma, surgery, or severe disease may be given H2 blockers prophylactically. H2 blockers protect sensitive stomach linings by lowering acid production.

Adverse Effects of H-2 Receptor Antagonists

Headache
Gastrointestinal Disturbances: diarrhea, constipation, nausea, vomiting, or abdominal discomfort.
Dizziness or Fatigue
Muscle Pain or Joint Pain
Allergic Reactions: these drugs produce rare allergic reactions such as rash, itching, swelling (particularly of the face, tongue, or throat), severe dizziness, or difficulty breathing.
Central Nervous System Effects: confusion or hallucinations

Drug Interactions of H-2 Receptor Antagonists

1. Antacids

H2 blockers reduce the absorption of aluminium and magnesium hydroxides. H2 blockers and antacids should be taken two hours intervals to avoid this interaction.

2. ProtonPump Inhibitors (PPIs)

H2 blockers and PPIs boost acid suppression. Unless prescribed by a medical professional, this combination can increase the chance of side effects without adding any benefit.

3. Cytochrome P450 Enzyme Interactions

H2 blockers, especially cimetidine, can decrease liver enzymes that metabolise drugs. This may elevate drug blood levels and cause side effects. H2 blockers, especially cimetidine, may interact with warfarin, phenytoin, theophylline, diazepam, and some antiretrovirals. Combining these drugs may require close monitoring and dosage modifications.

4. Drugs that Require Gastric Acid for Absorption

Some drugs need stomach acid to be absorbed. H2 blockers reduce stomach acid, which may reduce medicine absorption. Ketoconazole, itraconazole, iron supplements, and atazanavir. Consult to a medical professional about dose and alternatives.

5. Other interactions

H2 blockers may interact with antibiotics like clarithromycin, beta-blockers, and benzodiazepines like diazepam. Consult health care provider about drugs to avoid interactions.

Precautions and Contraindications

H2 blockers are safe and well-tolerated. H2 blockers must be administered with certain precautions and contraindications.

1. Allergies

H2 blockers should not be given to people with allergies. Allergic reactions can cause face, lingual, or laryngeal edoema, respiratory discomfort, and moderate dermatological symptoms. Any signs of an allergic response require immediate medical intervention.

2. Renal or Hepatic Impairment

H2 blockers should be monitored or adjusted for renal or hepatic impairment. Lowering the dosage may avoid drug or metabolite buildup.

3. Pregnancy and Breastfeeding

H2 blockers are considered safe during pregnancy and breastfeeding. Before using these medications, consult a doctor to assess the risks and benefits in specific situation.

4. Drug Interactions

As mentioned above, H2 blockers and other drugs can interact. Prescription, over-the-counter, and herbal treatments should be discussed with a doctor. Healthcare professionals can evaluate drug interactions and suggest treatment changes.

5. Age Factors

H2 blockers can cause cognitive decline and vertigo in the elderly. These drugs may need dosage modifications for older persons, so use cautious.

6. Prolonged Use

H2 blockers are used for a limited time to relieve symptoms or aid gastrointestinal healing. Prolonged use, especially at larger doses, may increase the risk of certain side effects such vitamin B12 insufficiency or infection susceptibility. A doctor should supervise long-term use.

7. Concomitant Medical Conditions

Patients with rare hereditary illnesses like porphyria should use H2 blockers with caution. H2 blockers may aggravate porphyria symptoms. Before starting H2 blocker medication, stomach cancer and atrophic gastritis patients should be thoroughly assessed.

Formulation and Dosage of H-2 Receptor Antagonists

1. Formulations

H-2 receptor antagonists are available in different formulations, including:

Oral tablets: These are the most common form and are usually taken with water.

Oral liquids: Some H-2 blockers may be available in liquid form for individuals who have difficulty swallowing tablets.

Injectable solutions: In some cases, H-2 receptor antagonists may be administered intravenously in a healthcare setting.

2. Dosage

H-2 receptor antagonist dose depends on numerous factors. The medicine, illness, severity, and patient characteristics are all considerations.

Cimetidine

The usual adult oral dosage ranges from 200 mg to 800 mg, taken two to four times per day. It is not used therapeutically due to its anti-androgenic effect.

Ranitidine

Formulations: Ranitidine is available in various forms, including tablets, capsules, and oral syrups

Dosage: The recommended adult dosage for ranitidine in the treatment of GERD or peptic ulcers is usually 150 mg taken orally twice daily or 300 mg taken orally at bedtime.