Bumetanide, sold under the brand name Bumex among others, is a medication used to treat swelling and

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. This includes swelling as a result of

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, liver failure, or kidney problems. It may work for swelling when other medications have not. For high blood pressure it is not a preferred treatment. It is taken by mouth, or by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

. Effects generally begin within an hour and lasts for about six hours. Common side effects include dizziness, low blood pressure, low blood potassium, muscle cramps, and kidney problems. Other serious side effects may include

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

and

low blood platelets Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care units, intensive care patients and is seen in a fifth of ...

. Blood tests are recommended regularly for those on treatment. Safety during

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 ...

and

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 ...

is unclear. Bumetanide is a

loop diuretic Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or c ...

and works by decreasing the reabsorption of sodium by the kidneys. Bumetanide was patented in 1968 and came into medical use in 1972. It is on the World Health Organization's List of Essential Medicines. 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 2020, it was the 270th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Uses

Medical uses

It is used to treat swelling and

. This includes swelling as a result of

, liver failure, or kidney problems. For high blood pressure it is not a preferred treatment. It is taken by mouth, or by

Other uses

It 2008, ESPN reported that four

NFL The National Football League (NFL) is a professional American football league that consists of 32 teams, divided equally between the American Football Conference (AFC) and the National Football Conference (NFC). The NFL is one of the major ...

players were being suspended under the steroid policy as a result of taking bumetanide. It is sometimes used for weight loss because, as a diuretic, it removes water, but it also masks other drugs, including steroids, by diluting the contents of the user's urine, yielding a lower concentration of filtered substances, which makes them less likely to be detected. Bumetanide was an undisclosed active ingredient in the

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

supplement StarCaps, which was removed from the market after its presence was discovered by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

Side effects

Common side effects include dizziness, low blood pressure, low blood potassium, muscle cramps, and kidney problems. Other serious side effects may include

and

. A large observational study concluded that people with a sulfonamide antibiotic allergy may be allergic to sulfonamide non-antibiotics, such as bumetanide, but this is likely due to certain people being at an increased risk in general to developing allergic reactions rather than cross-reactivity between sulfonamide-containing drugs. In smaller studies, the lack of cross-reactivity between sulfonamide antibiotics and sulfonamide non-antibiotics has been demonstrated. Blood tests are recommended regularly for those on treatment. Safety during

and

is unclear.

Mechanism of action

Bumetanide is a loop diuretic and works by decreasing the reabsorption of sodium by the kidneys. The main difference between bumetanide and furosemide is in their bioavailability and potency. About 60% of furosemide is absorbed in the intestine, and there are substantial inter- and intraindividual differences in bioavailability (range 10-90%). About 80% of bumetanide is absorbed, and its absorption does not change when it is taken with food. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect. Bumetanide is 40 times more potent than furosemide for people with normal

renal function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...

Synthesis

Bumetanide is synthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorination by

chlorosulfonic acid Chlorosulfuric acid (IUPAC name: sulfurochloridic acid) is the inorganic compound with the formula HSO3Cl. It is also known as chlorosulfonic acid, being the sulfonic acid of chlorine. It is a distillable, colorless liquid which is hygroscopic and ...

, forming 4-chloro-3-chlorosulfonylbenzoic acid, which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic acid. Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic acid, which when reacted with sodium phenolate is transformed into 5-amino-sulfonyl-3-nitro-5-phenoxybenzoic acid. Reduction of the nitro group in this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl-5-phenoxybenzoic acid. Finally, reacting this with butyl alcohol in the presence of sulfuric acid, followed by treatment with sodium hydroxide to hydrolyze the butyl ester, gives the desired bumetanide. : Bumetanide_synthesis

Research

In the brain, bumetanide blocks the

NKCC1 The Na-K-Cl cotransporter (NKCC) is a protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two differ ...

cation-chloride co-transporter, and thus decreases internal chloride concentration in

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

. In turn, this concentration change makes the action of GABA more hyperpolarizing, which may be useful for treatment of

neonatal An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s, which quite often are not responsive to traditional GABA-targeted treatment, such as

barbiturates Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as ...

. Bumetanide is therefore under evaluation as a prospective antiepileptic drug. The drug has also been studied as a treatment for

autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

References

External links

* {{Portal bar , Medicine Wikipedia medicine articles ready to translate Loop diuretics Benzoic acids Diphenyl ethers Carbonic anhydrase inhibitors NMDA receptor antagonists World Anti-Doping Agency prohibited substances Anilines