Phenformin Alcohol

Phenformin. Phenformin hydrochloride [834-28-6] (1-phenethylbiguanide, A/-(2-phenylethyl)imidodicarbonimidic diamide), is a white to off-white odorless crystalline power having a bitter taste. The melting point is 175—178°C. It is freely soluble in water and alcohol, and practically insoluble in chloroform, ether, and hexane. Its pH in solution is 6.0—7.0. 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

Adverse effect Lactic acidosis due to biguanides Dose-relation toxic effect Time-course time-independent Susceptibility factors genetic (slow phenformin metabolizers) age disease (impaired liver, kidney, or cardiac function, alcoholism)... 

In patients taking metformin, lactic acidosis is rare (3 per 100 000 patient-years) and is most often seen when contraindications to metformin (impaired kidney or liver function, alcoholism, circulatory problems, old age) are neglected or not detected (64). Although the relative risk of lactic acidosis with metformin is significantly lower than with phenformin or buformin (65), it has been repeatedly reported (SEDA-6, 371) (66), even in the absence of known contraindications (67). 

Biguanides, especially the older drug phenformin, have been associated with lactic acidosis. Thus metformin should be avoided in patients with conditions that increase the risk of lactic acidosis, including alcoholism. The answer is (D). 

The reasons for the raised blood lactate levels seen during the concurrent use of phenformin and alcohol are not clear, but one suggestion is that it may possibly be related to the competitive demands for isoenzymes by the reactions that convert alcohol to acetaldehyde, and lactate to pyruvate. A study in healthy subjects found that moderate alcohol consumption both improves insulin action, without affecting non-insulin mediated glucose uptake, and decreases lactate clearance. The increase in blood lactate with alcohol is therefore mainly due to inhibition of clearance. Alcohol did not appear to significantly affect beta-cell function. ... 

Metformin does not carry the same risk of lactic acidosis seen with phenformin and it is suggested in a paper prepared for and approved by The British Diabetic Association [now Diabetes UK] that one or two drinks a day are unlikely to be harmful in patients taking metformin. However, the drug should not be given to alcoholic patients because of the possibility of liver damage. 

Johnson HK, Waterhouse C. Relationship of alcohol and h3fperlactatemia in diabetic subjects treated with phenformin. Am J Med ( 96S) 45, 98-104. 

It is not clear if this opinion must also be extended to the other biguanides. Less cases of lactic acidosis are reported after buformin or metformin therapy. Czyzyk (81 ), in a study on increases in lactate levels induced by alcohol or fructose after pretreatment with biguanides, found a rise in lactate levels for all types of biguanides. Th re is no indication that buformin or metformin will prove more beneficial if they are compared with phenformin. 

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