Metformin Alcohol

METFORMIN ALCOHOL Enhanced effect of metformin and t risk of lactic acidosis. May mask signs and symptoms of hypoglycaemia... 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

Biguanides such as metformin are thought to inhibit mitochondrial oxidation of lactic acid, thereby increasing the chance of lactic acidosis occurring. Fortunately, the incidence of lactic acidosis in clinical practice is rare. Patients at greatest risk for developing lactic acidosis include those with liver disease or heavy alcohol use, severe infection, heart failure, and shock. Thus, it is common practice to evaluate liver function prior to initiation of metformin. 

Drugs that may affect metformin include alcohol, cationic drugs, cimetidine, furosemide, iodinated contrast material, and nifedipine. 

Topiramate may affect alcohol, amitriptyline, CNS depressants, lithium, oral contraceptives, digoxin, estrogens, hydantoins, metformin, risperidone, and valproic acid. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

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. 

Metformin Obscure Reduced hepatic and renal gluconeogenesis Decreased endogenous glucose production Type 2 diabetes Oral maximal plasma concentration in 2-3 h Toxicity Gastrointestinal symptoms, lactic acidosis (rare) cannot use if impaired renal/hepatic function congestive heart failure (CHF), hypoxic/acidotic states, alcoholism... 

If hypoxic states occur, discontinue drug therapy Therapy should be suspended for surgical procedures Alcohol is known to potentiate the effect of metformin on lactate metabolism—patients should be warned about the dangers of excessive alcohol intake... 

Of 308 patients 73% had contraindications, risk factors, or intercurrent illnesses necessitating withdrawal of metformin (31) 19% had renal impairment, 25% heart failure, 6.5% respiratory insufficiency, and 1.3% hepatic impairment 51% had advanced coronary heart disease, 9.8% atrial fibrillation, 3.3% chronic alcohol abuse, 2% advanced peripheral arterial disease, and 0.7% were pregnant. 

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). 

The use of metformin in patients with non-alcoholic fatty liver disease has been reported in two trials (123,124). Patients had abnormal liver function tests, which improved during the studies. No-one withdrew because of worsening of liver function tests or lactic acidosis. 

A 48-year-old man successfully committed suicide with metformin and alcohol (133). The authors used a simplified, rapid, and sensitive HPLC assay, with no interference from other drugs or toxic substances,... 

Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomised controlled trial of metformin versus vitamin E or prescriptive diet in non-alcoholic fatty liver disease. Am J Gastroenterol 2005 100 1082-90. 

Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for nondiabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005 21 871-9. 

ALCOHOL METFORMIN Enhanced effect of metformin and t risk of lactic acidosis. May cause a clisulfirain-like interaction Alcohol is known to potentiate the effect of metformin on lactate metabolism. It inhibits glucose production and release from many sources including the liver The onset of lactic acidosis is often subtle with symptoms of malaise, myalgia, respiratory distress and t non-specific abdominal distress. There may be hypothermia and resistant bradyarrhythmias... 

Kidney failure requires special attention because of metformin accumulation. Severe lactacidotic coma despite normal renal function has been reported in a 35-year-old diabetic man taking metformin and alcohol (Ryder, 1984). While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 0.1 to 1.8 0.2 mM) (Pedersen et al., 1989). Arterial blood gas analysis in one case revealed a pH of 6.76 and a bicarbonate level of 1.6 mM before treatment of lactacidosis. After therapy, which included oxygen, volume expansion and haemodialysis, the patient completely recovered (Gan et al., 1992). 

In order to avoid lactacidosis, it is important to select patients correctly and to ensure that contraindications such as renal involvement, advanced age and chronic alcoholism are observed before treatment with metformin (Lebech and Olesen, 1990). The role of lactic acid in the triggering of panic attacks has been discussed (Gin et al., 1989b). 

This patient should be treated by dietary measures. Particular attention should be paid to his alcohol intake. Liver disease should be excluded as its presence would preclude the use of metformin which would be an appropriate drug to treat his diabetes, or the use of fibric acid derivatives to treat his hyperlipidaemia. 

A 54-year-old obese patient with type 2 diabetes and a history of alcoholism probably should not receive metformin because it can increase his risk of (A) A disulfiram-like reaction Excessive weight gain Hypoglycemia Lactic acidosis Serious hepatotoxicity... 

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). 

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. 

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