H
2 antagonists, sometimes referred to as H2RAs and also called H
2 blockers, are a class of
medications
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
that block the action of
histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
at the
histamine H2 receptors of the
parietal cell
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the ...
s in the
stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
. This decreases the production of
stomach acid
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...
. H
2 antagonists can be used in the treatment of
dyspepsia
Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...
,
peptic ulcer
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...
s and
gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
. They have been surpassed by
proton pump inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
They are the most potent inhibitors ...
s (PPIs); the PPI
omeprazole
Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upper g ...
was found to be more effective at both healing and alleviating symptoms of ulcers and
reflux oesophagitis
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
than the H
2 blockers
ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
and
cimetidine
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 rec ...
.
H
2 antagonists are a type of
antihistamine
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
, although in common use the term "antihistamine" is often reserved for
H1 antagonists, which relieve
allergic reactions
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
. Like the H
1 antagonists, some H
2 antagonists function as
inverse agonist
In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.
A neutral antagonist has no activity in the absence of an agonist or inverse agon ...
s rather than
receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...
s, due to the
constitutive activity
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recepto ...
of these receptors.
The prototypical H
2 antagonist, called
cimetidine
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 rec ...
, was developed by
Sir James Black
Sir James Whyte Black (14 June 1924 – 22 March 2010) was a Scottish physician and pharmacologist. Together with Gertrude B. Elion and George H. Hitchings, he shared the Nobel Prize for Medicine in 1988 for pioneering strategies for rational ...
at Smith, Kline & French – now
GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
– in the mid-to-late 1960s. It was first marketed in 1976 and sold under the trade name
Tagamet
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 re ...
, which became the first
blockbuster drug
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
. The use of
quantitative structure-activity relationship
Quantitative may refer to:
* Quantitative research, scientific investigation of quantitative properties
* Quantitative analysis (disambiguation)
* Quantitative verse, a metrical system in poetry
* Statistics, also known as quantitative analysis ...
s (QSAR) led to the development of other agents – starting with
ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
, first sold as
Zantac, which has fewer adverse effects and
drug interaction
Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...
s and is more potent.
H
2 blockers, which all end in "-tidine", are not the same as H
1 receptor antagonists, which relieve allergy symptoms.
Class members
*
cimetidine
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 rec ...
*
ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
(withdrawn in USA, suspended in EU and Australia for carcinogen contamination in manufacturing process)
*
famotidine
Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Elli ...
*
nizatidine
Nizatidine is a histamine H2 receptor antagonist that inhibits stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.
It was patented in 1980 and approved for medical use i ...
*
roxatidine
Roxatidine acetate is a specific and competitive histamine H2 receptor antagonist drug that is used to treat gastric ulcers, Zollinger–Ellison syndrome, erosive esophagitis, gastro-oesophageal reflux disease, and gastritis
Gastritis is infl ...
*
lafutidine
Lafutidine (INN) is a second generation histamine H2 receptor antagonist having multimodal mechanism of action and used to treat gastrointestinal disorders. It is marketed in South Korea, Japan and India.
Medical use
Lafutidine is used to trea ...
*
lavoltidine
Lavoltidine ( INN, USAN, BAN; previously known as loxtidine, code name AH-23,844) is a highly potent and selective H2 receptor antagonist which was under development by Glaxo Wellcome (now GlaxoSmithKline) as a treatment for gastroesophageal r ...
(discontinued as carcinogen)
*
niperotidine
Niperotidine is a histamine antagonist selective for the H2 subtype. It was studied as a treatment for excessive gastric acidity, but withdrawn after human trials showed liver damage
Liver disease, or hepatic disease, is any of many diseases ...
(withdrawn as causing liver damage)
History and development
Cimetidine was the prototypical histamine H
2-receptor antagonist from which later drugs were developed. Cimetidine was the culmination of a project at Smith, Kline & French (SK&F; now GlaxoSmithKline) by
James W. Black
Sir James Whyte Black (14 June 1924 – 22 March 2010) was a Scottish physician and pharmacologist. Together with Gertrude B. Elion and George H. Hitchings, he shared the Nobel Prize for Medicine in 1988 for pioneering strategies for rational d ...
,
C. Robin Ganellin
Charon Robin Ganellin FRS (25 January 1934 – ) is a British medicinal chemist, and Emeritus Smith Kline and French Professor of Medicinal Chemistry, at University College London.
He has contributed much to the field of drug discovery and dev ...
, and others to develop a
histamine receptor
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.
There are four known histamine receptors:
* H1 receptor
* H2 receptor
* H3 receptor
* H4 receptor
Comparison
There ...
antagonist that would suppress stomach acid secretion.
In 1964, it was known that histamine stimulated the secretion of stomach acid, and also that
traditional antihistamines had no effect on acid production. From these facts the SK&F scientists postulated the existence of two different types of histamine receptors. They designated the one acted upon by the traditional antihistamines as H
1, and the one acted upon by histamine to stimulate the secretion of stomach acid as H
2.
The SK&F team used a classical design process starting from the structure of histamine. Hundreds of modified compounds were synthesised in an effort to develop a model of the then-unknown H
2 receptor. The first breakthrough was ''N
α''-guanylhistamine, a partial H
2-receptor antagonist. From this lead, the receptor model was further refined, which eventually led to the development of
burimamide, a specific
competitive antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of r ...
at the H
2 receptor. Burimamide is 100 times more potent than ''N
α''-guanylhistamine, proving its efficacy on the H
2 receptor.
The potency of burimamide was still too low for oral administration. And efforts on further improvement of the structure, based on the structure modification in the stomach due to the
acid dissociation constant
In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction
:HA ...
of the compound, led to the development of
metiamide. Metiamide was an effective agent; however, it was associated with unacceptable
nephrotoxicity Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxin ...
and
agranulocytosis
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...
. It was proposed that the toxicity arose from the
thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the ''thio-'' prefix); however, the properties of urea ...
group, and similar
guanidine
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...
analogues were investigated until the discovery of cimetidine, which would become the first clinically successful H
2 antagonist.
Ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
(common brand name Zantac) was developed by Glaxo (also now
GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
), in an effort to match the success of Smith, Kline & French with cimetidine. Ranitidine was also the result of a rational drug design process utilising the by-then-fairly-refined model of the histamine H
2 receptor and
quantitative structure-activity relationships (QSAR). Glaxo refined the model further by replacing the
imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
-ring of cimetidine with a
furan
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.
Furan is a colorless, flammable, highly ...
-ring with a
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
-containing substituent, and in doing so developed ranitidine, which was found to have a much better tolerability profile (i.e. fewer
adverse drug reaction
An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...
s), longer-lasting action, and ten times the activity of cimetidine.
Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. The H
2-receptor antagonists have since largely been superseded by the even more effective proton pump inhibitors (PPIs), with
omeprazole
Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upper g ...
becoming the biggest-selling drug for many years.
Pharmacology
The H
2 antagonists are competitive antagonists of histamine at the parietal cell's
H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: Histamine released by
enterochromaffin-like cells
Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell found in the gastric glands of the gastric mucosa beneath the epithelium, in particular in the vicinity of parietal cells, that aid in the production of gastric acid via th ...
(ECL) in the stomach is blocked from binding on parietal cell H
2 receptors, which stimulate acid secretion; therefore, other substances that promote acid secretion (such as
gastrin
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
Gastrin ...
and
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
) have a reduced effect on parietal cells when the H
2 receptors are blocked.
Clinical use
H
2-antagonists are used by clinicians in the treatment of acid-related
gastrointestinal condition
Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver ...
s, including:
[Rossi S (Ed.) (2005). '']Australian Medicines Handbook
Australian Medicines Handbook (AMH) is a peer-reviewed medicines prescribing guide for Australian health professionals. The handbook is available in paper and digital formats and is supplemented by the ''AMH Aged Care Companion'' and the ''AMH C ...
'' 2005. Adelaide: Australian Medicines Handbook. .
*
Peptic ulcer
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...
disease (PUD)
*
Gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
(GERD/GORD)
*
Dyspepsia
Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...
* Prevention of
stress ulcer
A stress ulcer is a single or multiple mucosal defect usually caused by physiological (not psychological) stress which can become complicated by upper gastrointestinal bleeding. This ulcers can be caused by shock, sepsis, trauma or other conditions ...
(a specific indication of ranitidine)
* Prevention of
aspiration pneumonitis during surgery. Oral H
2-antagonists reduce gastric acidity and volume and have shown to reduce the frequency of aspiration pneumonitis; however, this aspiration benefit has not been shown with IV H
2-antagonists.
People who suffer from infrequent heartburn may take either
antacids
An antacid is a substance which neutralizes stomach acidity and is used to relieve heartburn, indigestion or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhea. Marketed antacids contain salts of alu ...
or H
2-receptor antagonists for treatment. The H
2-antagonists offer several advantages over antacids, including longer duration of action (6–10 hours vs 1–2 hours for antacids), greater efficacy, and ability to be used prophylactically before meals to reduce the chance of heartburn occurring. Proton pump inhibitors, however, are the preferred treatment for erosive
esophagitis
Esophagitis, also spelled oesophagitis, is a disease characterized by inflammation of the esophagus. The esophagus is a tube composed of a mucosal lining, and longitudinal and circular smooth muscle fibers. It connects the pharynx to the stomach; s ...
since they have been shown to promote healing better than H
2-antagonists.
Adverse effects
H
2 antagonists are, in general, well tolerated, except for cimetidine, wherein all of the following adverse drug reactions (ADRs) are ''common''. Infrequent ADRs include
hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
. Rare ADRs include:
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, tiredness, dizziness, confusion,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, constipation, and rash.
In addition,
gynecomastia
Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
occurred in 0.1% to 0.5% of men treated for non-hypersecretory conditions with cimetidine for 1 month or longer and in about 2% of men treated for pathologic hypersecretory conditions; in even fewer men, cimetidine may also cause loss of libido, and
impotence
Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
, all of which are reversible upon discontinuation.
A 31-study review found that overall risk of pneumonia is about 1 in 4 higher among H
2 antagonist users.
According to a 2022 umbrella review of meta-analyses, the use of H2 receptor antagonist is associated with pneumonia, peritonitis, necrotizing enterocolitis, ''Clostridium difficile'' infection, liver cancer, gastric cancer, and hip fracture diseases.
Drug interactions
With regard to
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
, cimetidine in particular interferes with some of the body's mechanisms of
drug metabolism
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...
and elimination through the liver
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
(CYP) pathway. To be specific, cimetidine is an inhibitor of the P450 enzymes
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
,
CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...
,
CYP2C19
Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some pr ...
,
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
,
CYP2E1
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, includ ...
,
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
. By reducing the metabolism of drugs through these enzymes, cimetidine may increase their
serum concentration
In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', ''number concentration'', an ...
s to
toxic
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
levels. Many drugs are affected, including
warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
,
theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
,
phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
,
lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
,
quinidine
Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...
,
propranolol
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...
,
labetalol
Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...
,
metoprolol
Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...
,
methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
,
tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
, some
benzodiazepines
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...
, dihydropyridine
calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s,
sulfonylureas,
metronidazole
Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ef ...
,
and some recreational drugs such as
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
and
methylenedioxymethamphetamine
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
(MDMA).
The more recently developed H
2-receptor antagonists are less likely to alter CYP metabolism. Ranitidine is not as potent a CYP inhibitor as cimetidine, although it still shares several of the latter's interactions (such as with warfarin, theophylline, phenytoin, metoprolol, and midazolam).
Famotidine
Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Elli ...
has negligible effect on the CYP system, and appears to have no significant interactions.
[
]
References
{{Histaminergics