Gastric Acid Drugs

Gastric Acid Drugs

Gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) medications include proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (PPIs) and H₂ receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists (also known as H₂ blockers). The drugs work through different mechanisms to suppress acid secretion Secretion Coagulation Studies by parietal cells Parietal cells Rounded or pyramidal cells of the gastric glands. They secrete hydrochloric acid and produce gastric intrinsic factor, a glycoprotein that binds vitamin B12. Stomach: Anatomy in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy. The most common indications include peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease, GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD), and dyspepsia Dyspepsia Impaired digestion, especially after eating. Lactose Intolerance. Adverse effects of PPIs include malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, acute interstitial nephritis Acute interstitial nephritis Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of kidney tubules and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see glomerulonephritis. Infiltration of the inflammatory cells into the interstitial compartment results in edema, increased spaces between the tubules, and tubular renal dysfunction. Acute Kidney Injury, and an increased risk of Clostridioides difficile infection. Adverse effects of H₂ blockers include CNS effects, bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias/ hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia, and galactorrhea Galactorrhea Excessive or inappropriate lactation in females or males, and not necessarily related to pregnancy. Galactorrhea can occur either unilaterally or bilaterally, and be profuse or sparse. Its most common cause is hyperprolactinemia. Hyperprolactinemia. Both classes are associated with drug interactions related to the cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury system.

Last updated: Oct 10, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

PPIs

H₂ Receptor Antagonists

References

Overview

Physiology of acid secretion Secretion Coagulation Studies

Parietal cells Parietal cells Rounded or pyramidal cells of the gastric glands. They secrete hydrochloric acid and produce gastric intrinsic factor, a glycoprotein that binds vitamin B12. Stomach: Anatomy are located in the body of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and secrete hydrochloric acid Hydrochloric acid A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. Caustic Ingestion (Cleaning Products) ( HCl HCL Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia) into the lumen.

Water and CO₂ are combined to produce hydrogen (H⁺) ions and HCO₃ ions by the action of the carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors enzyme.
H⁺ is transported to the lumen of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy via the H⁺/K⁺ ATPase pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols.
HCO₃ is exchanged for chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes (Cl⁻) ion.
H⁺ and Cl⁻ combine to form the final product Product A molecule created by the enzymatic reaction. Basics of Enzymes: HCl HCL Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia

Ion transport in parietal cells:
Carbonic acid disassociates into a hydrogen (H⁺) ion and bicarbonate (HCO₃^–). The H⁺ is exchanged for potassium (K⁺) in the apical membrane by the H⁺/K⁺ ATPase. Bicarbonate is exchanged for chloride (Cl^–) in the basolateral membrane, which then moves into the lumen. The Na⁺/K⁺ ATPase pump in the basolateral membrane creates the cell’s electrochemical gradient.
Image by Lecturio.

Receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and regulation

Acid production is stimulated by:

Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS → muscarinic receptors Muscarinic Receptors Asthma Drugs
Histamine release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology by enterochromaffin-like (ECL) cells → H₂ receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
Gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology by gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions cells → cholecystokinin-2/cholecystokinin-B receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

Drug classes

Common medication classes used to control gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) secretion Secretion Coagulation Studies include:

Proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (PPIs)
H₂ receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists

PPIs

Definition

Proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors are a group of drugs irreversibly inhibiting the H+/K+ ATPase pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols in gastric parietal cells Parietal cells Rounded or pyramidal cells of the gastric glands. They secrete hydrochloric acid and produce gastric intrinsic factor, a glycoprotein that binds vitamin B12. Stomach: Anatomy.

Chemistry

Composed of 2 moieties:
- Benzimidazole
- Pyridine
Weak bases Weak bases Acid-Base Balance
Includes:
- Omeprazole
- Lansoprazole
- Pantoprazole
- Rabeprazole

Proton pump inhibitors structure — The basic chemical structure for proton pump inhibitors (PPIs):
Notice the benzimidazole structure on the left and the pyridine ring on the right.
Image: “Common structure of proton pump inhibitors” by Anypodetos. License: Public Domain

Formula of benzimidazole — The basic chemical structure for proton pump inhibitors (PPIs):
Notice the benzimidazole structure on the left and the pyridine ring on the right.
Image: “Common structure of proton pump inhibitors” by Anypodetos. License: Public Domain

Mechanism of action

Administered as a prodrug Prodrug Nitroimidazoles → concentrated in secretory canaliculi of the parietal cell Parietal cell Rounded or pyramidal cells of the gastric glands. They secrete hydrochloric acid and produce gastric intrinsic factor, a glycoprotein that binds vitamin B12. Gastroesophageal Reflux Disease (GERD)
Converted to an active form (a sulfonamide Sulfonamide The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim cation) → covalently binds to the H⁺/K⁺ ATPase pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols
Causes irreversible inhibition → prevents movement of H⁺ into the gastric lumen → ↓ acid secretion Secretion Coagulation Studies
Inhibits both basal acid output and meal-stimulated output

Acid secretion — Mechanism of action of proton pump inhibitors (PPIs):
The drugs accumulate in the gland lumen, convert to the active form, and covalently bond to the H⁺/K⁺ ATPase, which results in irreversible pump inactivation and reduced acid secretion.
Image by Lecturio.

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:

The most common route of administration is oral, but the medications can also be given intravenously.
Inactive prodrugs
Acid labile Acid labile Vibrio → formulated as acid-resistant, enteric-coated tablets or capsules
Pass through the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy → absorbed in the alkaline intestinal lumen
Bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics is ↓ by the presence of food and should be administered 30–60 minutes prior to food intake.

Distribution:

Lipophilic
Readily cross into acidified areas (e.g., the lumen of the parietal cell gland)
The serum half-life is short (called “hit-and-run” drugs because the duration of action is prolonged by approximately 24 hours).
3–4 days for maximum effect

Metabolism:

Rapid, hepatic 1st-pass metabolism
Cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
- CYP2C19
- CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)
Dose reduction is required in severe liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease.

Excretion:

Renal (primary)
Feces

Indications

Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease ( PUD PUD Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease)
Stress ulcer prophylaxis Prophylaxis Cephalosporins
Gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD))
Gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
Zollinger-Ellison syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis
Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection: component of triple and quadruple therapy
NSAID-induced ulcers

Adverse effects

General:
- Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
- Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
- Abdominal pain Abdominal Pain Acute Abdomen
Nutritional side effects on prolonged therapy:
- Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion of vitamin B₁₂
- ↓ Calcium absorption Calcium absorption Digestion and Absorption → ↑ risk of fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures in elderly
- Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements deficiency
- Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes
↑ Risk of infection:
- Clostridioides difficile
- Bacterial gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis
- Community-acquired and nosocomial pneumonia Nosocomial pneumonia Pneumonia in Children
Gastrointestinal:
- Microscopic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis
- Hypergastrinemia Hypergastrinemia Pancreatic Neuroendocrine Tumors (PanNETs)
- Atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis
- Colonization Colonization Bacteriology of the intestine by multidrug resistant Multidrug resistant Resistant to at least 1 agent in > 3 antibiotic categories Pseudomonas organisms
Other:
- Acute interstitial nephritis Acute interstitial nephritis Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of kidney tubules and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see glomerulonephritis. Infiltration of the inflammatory cells into the interstitial compartment results in edema, increased spaces between the tubules, and tubular renal dysfunction. Acute Kidney Injury
- Drug-induced lupus Drug-Induced Lupus Systemic Lupus Erythematosus

Drug interactions

Interactions due to CYP450 enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
- ↓ Activity:
  - Clopidogrel Clopidogrel A ticlopidine analog and platelet purinergic p2y receptor antagonist that inhibits adenosine diphosphate-mediated platelet aggregation. It is used to prevent thromboembolism in patients with arterial occlusive diseases; myocardial infarction; stroke; or atrial fibrillation. Antiplatelet Drugs requires CYP219 for action → concurrent use of PPI can ↓ anticoagulant and antiplatelet action
  - Theophylline Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3. Asthma Drugs
  - HIV HIV Anti-HIV Drugs protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs
- PPIs inhibit the metabolism of:
  - Warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants
  - Diazepam Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. Benzodiazepines
  - Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
↓ Gastric acidity can alter the absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of medications:
- Ketoconazole Ketoconazole Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. Azoles
- Amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants (e.g., dextroamphetamine Dextroamphetamine The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monoamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. Stimulants)