Sodium stibogluconate, sold under the brand name Pentostam among others, is a medication used to treat leishmaniasis. This includes leishmaniasis of the cutaneous, visceral, and mucosal types. Some combination of

miltefosine Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as ''Naegleria fowleri'' and '' Balamuthia mandrillaris''. This includes the three forms of l ...

, paramycin and liposomal amphotericin B, however, may be recommended due to issues with resistance. It is given by injection. Side effects are common and include loss of appetite, nausea, muscle pains, headache, and feeling tired. Serious side effect may include an irregular heartbeat or

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

. Sodium stibogluconate is less safe than some other options during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

. It is not believed to result in any problems if used during

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 ...

. Sodium stibogluconate is in the

pentavalent antimonial Pentavalent antimonials (also abbreviated pentavalent Sb or SbV) are a group of compounds used for the treatment of leishmaniasis. They are also called pentavalent antimony compounds. Types The first pentavalent antimonial, urea stibamine, was s ...

s class of medication. Sodium stibogluconate has been studied as early as 1937 and has been in medical use since the 1940s. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. In the United States, it is available from the

Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

Side effects

Sodium stibogluconate is exceedingly toxic to

veins Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...

. One of the practical problems is that after a few doses it can become exceedingly difficult to find a vein in which to inject the drug. The insertion of a

peripherally inserted central catheter A peripherally inserted central catheter (PICC or PIC line), less commonly called a percutaneous indwelling central catheter, is a form of intravenous access that can be used for a prolonged period of time (e.g., for long chemotherapy regimens ...

(PICC) does not prevent the problem and can instead exacerbate it: the entire vein along the course of the PICC line can become inflamed and thrombose. Large doses of sodium stibogluconate are often administered as dilute solutions.

Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

is a common deleterious effect of the drug, and the serum

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

or lipase should be monitored twice weekly; there is no need to stop treatment if the amylase remains less than four times the upper limit of normal; if the amylase rises above the cut-off, then treatment should be interrupted until the amylase falls to less than twice the upper limit of normal, whereupon treatment can be resumed. Cardiac conduction disturbances are less common, but electrocardiograph (ECG) monitoring while the medicine is injected is advisable and changes quickly reverse after the drug is stopped or the infusion rate is decreased. The drug can be given intramuscularly but is exceedingly painful when given by this route. It can also be given intralesionally when treating

cutaneous leishmaniasis Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sand fly. There are about thirty species of '' Leish ...

(i.e., injected directly into the area of infected skin) and again, this is exceedingly painful and does not give results superior to intravenous administration. Sodium stibogluconate can also cause a reduced appetite, metallic taste in mouth,

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 nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

diarrhoea 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 ...

, headache, tiredness, joint pains, muscle aches, dizziness, and

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...

Dosing

Sodium stibogluconate is available in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...

as Pentostam, where it is manufactured by GlaxoSmithKline. It is available in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

on a named-patient basis from the

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(CDC). As dosage regimens for treating leishmaniasis have evolved, the daily dose of antimony and the duration of therapy have been progressively increased to combat unresponsiveness to therapy. In the 1980s, the use of 20 mg/kg/day (instead of 10 mg/kg/day) of antimony was recommended, but only to a maximum daily dose of 850 mg. Recent research has suggested on the basis of recent efficacy and toxicity data that this 850-mg restriction should be removed. The evidence to date, which is in their research, suggests that a regimen of 20 mg/kg/day of pentavalent antimony, without an upper limit on the daily dose, is more efficacious and is not substantially more toxic than regimens with lower daily doses. It is recommend treating all forms of leishmaniasis with a full 20 mg/kg/day of pentavalent antimony. Treatment of cutaneous leishmaniasis usually lasts for 20 days and visceral and mucosal leishmaniasis for 28 days. The dose of sodium stibogluconate is by slow intravenous infusion (at least five minutes with cardiac monitoring). The injection are stopped if there is

cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...

ing or central chest pain. The chemotherapeutic index was established by Leonard Goodwin during the Second World War when a treatment was urgently required for Allied troops during the

invasion of Sicily The Allied invasion of Sicily, also known as Operation Husky, was a major campaign of World War II in which the Allied forces invaded the island of Sicily in July 1943 and took it from the Axis powers ( Fascist Italy and Nazi Germany). It bega ...

. The duration of treatment is usually 10 to 21 days and depends on the species of '' Leishmania'' and the type of infection (

cutaneous Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different d ...

visceral In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a ...

Chemical structure

The chemical structure of sodium stibogluconate is somewhat ambiguous, and the structure shown above is idealized. Its solutions may contain multiple antimony compounds, although this heterogeneity may be unimportant. It has been speculated that the active species contains only a single antimony centre.

Pharmacokinetics

Pentavalent antimony does not appear to accumulate in the body and is excreted by the kidneys.

Mechanism of action

The mechanism of sodium stibogluconate is poorly understood, but is thought to stem from the inhibition of macromolecular synthesis via a reduction in available ATP and GTP, likely secondary to inhibition of the citric acid cycle and glycolysis. Bermann et al. studied the effects of stibogluconate on ''Leishmaniasis mexicana'' and demonstrated a 56-65% reduction in incorporation of a label into purine nucleoside triphosphates (ATP and GTP) as well as between a 34-60% increase of label incorporation into purine nucleoside mono and di phosphates (AMP, GMP, ADP, and GDP) following 4 hour exposure to stibogluconate.

References

British National Formulary
* The Merck Index, 12th Edition. 742 {{Portal bar, Medicine Antimony(V) compounds Antiprotozoal agents Orphan drugs World Health Organization essential medicines Wikipedia medicine articles ready to translate