Biguanide
Encyclopedia
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s used for diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
or prediabetes
Prediabetes
Prediabetes is the state in which some but not all of the diagnostic criteria for diabetes are met. It is often described as the “gray area” between normal blood sugar and diabetic levels. While in this range, patients are at risk for not only developing type 2 diabetes, but also for cardiovascular...
treatment. They are also used as antimalarial drug
Antimalarial drug
Antimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
s.
The disinfectant polyaminopropyl biguanide (PAPB) features biguanide functional groups.
Examples
Examples of biguanides:- MetforminMetforminMetformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
- widely used in treatment of diabetes mellitus type 2Diabetes mellitus type 2Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and... - PhenforminPhenforminPhenformin is an anti-diabetic drug from the biguanide class. It was marketed as DBI by Ciba-Geigy but was withdrawn from most markets in the late 1970s due to a high risk of lactic acidosis, which was fatal in 50% of cases....
- withdrawn from the market in most countries due to toxic effects - BuforminBuforminBuformin is an oral anti-diabetic drug of the biguanide class, chemically related to metformin and phenformin. Buformin was marketed by German pharmaceutical company Grünenthal as Silubin.-Chemistry and Animal Toxicology:...
- withdrawn from the market due to toxic effects - ProguanilProguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
- an antimalarial drugAntimalarial drugAntimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
.
History
Galega officinalisGalega officinalis
Galega officinalis, commonly known as goat's rue, French lilac, Italian fitch or professor-weed, is an herbaceous plant in the Faboideae subfamily. It is native to the Middle East, but it has been naturalised in Europe, western Asia, and western Pakistan...
(French lilac) was used for diabetes treatment in traditional medicine for centuries. In the 1920s, guanidine
Guanidine
Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...
compounds were discovered in Galega extracts. Animal studies showed that these compounds lowered blood glucose levels. Some less toxic derivatives, synthalin
Synthalin
Synthalin was an oral anti-diabetic drug. Discovered in 1926 it was marketed in Europe by Schering AG of Berlin as a synthetic drug with insulin-like properties that could be taken orally...
A and synthalin B, were used for diabetes treatment, but after the discovery of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
they were forgotten for the next several decades. Biguanides were reintroduced into Type 2 diabetes treatment in the late 1950s. Initially phenformin
Phenformin
Phenformin is an anti-diabetic drug from the biguanide class. It was marketed as DBI by Ciba-Geigy but was withdrawn from most markets in the late 1970s due to a high risk of lactic acidosis, which was fatal in 50% of cases....
was widely used, but its potential for sometimes fatal lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
resulted in its withdrawal from pharmacotherapy in most pharmacopeias (in the U.S. in 1977). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.
Pharmacotherapy
Biguanides do not affect the output of insulin, unlike other hypoglycemic agents such as sulfonylureaSulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
s and meglitinide
Meglitinide
Meglitinides, aka "Glinides", are a class of drugs used treat diabetes type 2.They bind to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells in a similar manner to sulfonylureas but at a separate binding site. This inhibits a tonic, hyperpolarizing outflux of potassium,...
s. Therefore, not only are they effective in Type 2 diabetics but they can also be effective in Type 1 patients in concert with insulin therapy.
Mechanism of action
The mechanism of actionMechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
of biguanides is not fully understood. However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
in the liver, and, as a result, reduce the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma.
Side effects and toxicity
The most common side effect is diarrheaDiarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
, therefore metformin is contraindicated in renal insufficiency. Renal functions should be assessed before starting metformin. Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it. However, when metformin is combined with other drugs (combination therapy), hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
and other side effects are possible.