Diphenoxylate/atropine, also known as co-phenotrope, is a combination of the medications diphenoxylate and

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

, used to treat

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 ...

. It should not be used in those in whom ''Clostridioides difficile'' infection is a concern. It is taken by mouth. Onset is typically within an hour. Side effects may include abdominal pain, angioedema,

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

heart problems Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...

, feeling tired, dry mouth, and trouble seeing. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

is safe and use when

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

may result in side effects in the baby. It works by decreasing contractions of the bowel. The combination was approved for medical use in the United States in 1960. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2019, it was the 339th most commonly prescribed medication in the United States, with more than 900thousand prescriptions. It is sold under the brand name Lomotil among others. The medication is in Schedule V in the United States.

Contraindications

Absolute contraindications are: * Patients under 6 years of age *

Allergy 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 ...

to diphenoxylate or atropine * Diarrhea associated with

pseudomembranous enterocolitis ''Clostridioides difficile'' infection (CDI or C-diff), also known as ''Clostridium difficile'' infection, is a symptomatic infection due to the spore-forming bacterium ''Clostridioides difficile''. Symptoms include watery diarrhea, fever, na ...

, diarrhea caused by

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

treatment, or diarrhea caused by

enterotoxin An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat labi ...

-producing

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

, such as Clostridium difficile * Obstructive

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

Side effects

The drug combination is generally safe in short-term use and with recommended dosage. In doses used for the treatment of diarrhea, whether acute or chronic, diphenoxylate has not produced addiction. It may cause several

side-effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

, such as dry mouth,

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 ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

and

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure. ...

. Since it may also cause drowsiness or

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

, it should not be used by motorists, operators of hazardous machinery, etc. It is not recommended for children under two years of age.

Interactions

Interactions with other drugs: *

Antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s (e.g. Elavil, Prozac) * Monoamine oxidase inhibitors (e.g. Nardil, Parnate) *

Opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

analgesics *

Sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

s (e.g. Ambien, Sonata)

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 ...

that is caused by some

s such as

cefaclor Cefaclor, sold under the trade name Ceclor among others, is a second-generation cephalosporin antibiotic used to treat certain bacterial infections such as pneumonia and infections of the ear, lung, skin, throat, and urinary tract. It is also avail ...

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...

can worsen.

Toxicity

It may cause serious health problems when

overdosed A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

Sign A sign is an object, quality, event, or entity whose presence or occurrence indicates the probable presence or occurrence of something else. A natural sign bears a causal relation to its object—for instance, thunder is a sign of storm, or me ...

s and

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s of adverse effects may include any or several of the following:

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...

(slow or stopped breathing), dilated eye pupils, nystagmus (rapid side-to-side

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

movements), erythema ( flushed skin), gastrointestinal

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

paralytic ileus Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction. The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

(rapid pulse), drowsiness and hallucinations. Symptoms of

toxicity 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 ...

may take up to 12 hours to appear. Treatment of overdose must be initiated immediately after

diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...

and may include the following: ingestion of

activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an interv ...

, laxative and a counteracting medication (narcotic

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

Mechanism of action

Diphenoxylate is anti-diarrheal and atropine is anticholinergic. A subtherapeutic amount of

sulfate is present to discourage deliberate overdosage. Atropine has no anti-diarrheal properties, but will cause

when overused. The medication diphenoxylate works by slowing down the movement of the

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

s. In some cases it has been shown to ease symptoms of opiate withdrawal.

History

Diphenoxylate was developed in 1954 as part of

US Navy The United States Navy (USN) is the maritime service branch of the United States Armed Forces and one of the eight uniformed services of the United States. It is the largest and most powerful navy in the world, with the estimated tonnage of ...

and

CIA The Central Intelligence Agency (CIA ), known informally as the Agency and historically as the Company, is a civilian intelligence agency, foreign intelligence service of the federal government of the United States, officially tasked with gat ...

-funded research on nonaddictive substitutes for

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

Society and culture

Names

The UK

British Approved Name A British Approved Name (BAN) is the official, non-proprietary, or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). The BAN is also the official name used in some countries around the world, because ...

(BAN) generic name for diphenoxylate and atropine is co-phenotrope. As of 2018, the combination drug is marketed in the US and some other countries under the following brands: Atridol, Atrolate, Atrotil, Co-Phenotrope, Dhamotil, Dimotil, Intard, Logen, Lomanate, Lomotil, Lonox, and Reasec.

Legal status

In the United States, it is classified as a Schedule V controlled substance by federal law, and is available only for a medical purpose.DEA, Title 21, Section 829
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References

External links

* {{DEFAULTSORT:Atropine Diphenoxylate Antidiarrhoeals Combination drugs Wikipedia medicine articles ready to translate