digoxin and Alcoholism

This review addresses possible involvement of endogenous digitalis-like sodium pump ligands (SPL) in the mood control and ethanol addiction. Endogenous SPL include cardenolide and bufadienolide classes. Multiple SPL and multiple isoforms of the Na/K-ATPase, one of the key membrane enzymes, comprise a complex regulatory system. In the nervous system, pattern of expression of Na/K-ATPase is based on multiple alpha/beta isoform combinations. Clinical studies demonstrate changes in the activity of Na/K-ATPase in patients with bipolar and unipolar mood disorders. The effects of ethanol on the Na/K-ATPase are concentration-dependent and are associated with both inhibition and activation of enzyme activity. Reinforcing effect of ethanol as well as its voluntary consumption may be affected by digitalis glycosides and endogenous SPL.

Topics: Affect; Alcoholism; Animals; Cardenolides; Digoxin; Enzyme Inhibitors; Humans; Ligands; Saponins; Sodium-Potassium-Exchanging ATPase

The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N-glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites, as well as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. The same biochemical patterns were obtained in those with right hemispheric chemical dominance. Alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration occur in right hemispheric, chemically dominant individuals.

Topics: Adult; Alcoholism; Analysis of Variance; Cholesterol; Digoxin; Disease Susceptibility; Dolichols; Dominance, Cerebral; Enzyme Inhibitors; Erythrocytes; Female; Glycoconjugates; Glycosaminoglycans; Hepatolenticular Degeneration; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Liver Cirrhosis, Alcoholic; Male; Membrane Proteins; Neurotransmitter Agents; Polyisoprenyl Phosphates; Sodium-Potassium-Exchanging ATPase; Tryptophan; Tyrosine; Ubiquinone

Cardiac glycosides affect several pathways central for tumor formation. We sought to evaluate the association between digoxin use and colorectal cancer (CRC) risk.. We conducted a nested case-control study using The Health Improvement Network (THIN), a medical record database representative of the broader UK population. Study cases were defined as those with a diagnostic code for CRC. Each case was matched to up to four eligible controls on age, sex, practice site, and duration of follow-up before index date using incidence density sampling. Exposure of interest was digoxin therapy before index date. The odds ratios (ORs) and 95% confidence intervals (CIs) for CRC associated with digoxin use were estimated using conditional logistic regression analysis, adjusted for BMI, alcoholism, smoking history, diabetes mellitus, heart disease, chronic NSAIDs use and previous screening colonoscopies.. The case-control analysis included 20 990 CRC patients and 82 054 controls whose mean follow-up time before index date was 6.5 years (SD 4.0). The adjusted OR for CRC among current digoxin users was increased compared with non-users with an adjusted ORs of 1.41 (95%CI 1.25-1.59, p < 0.0001), 1.45 (95%CI 1.22-1.72, p < 0.0001) and 1.41 (95%CI 1.00-1.99, p = 0.049) for first prescriptions 1-5 years, 5-10 years and more than 10 years before index date respectively. Similar results were observed when cumulative duration and number of digoxin prescriptions were analyzed. The risk was not elevated for past digoxin users.. Current digoxin use is associated with increased CRC risk.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alcoholism; Anti-Inflammatory Agents, Non-Steroidal; Body Mass Index; Case-Control Studies; Colorectal Neoplasms; Comorbidity; Digoxin; Female; Humans; Incidence; Male; Middle Aged; Risk Factors; Sex Factors; Smoking

The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N -glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway was also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. The same patterns were obtained in individuals with right hemispheric chemical dominance. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. Alcoholic cirrhosis, addiction, and acquired hepato -cerebral degeneration occur in right hemispheric chemically dominant individuals. Ninety percent of the patients with alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration were right-handed and left hemispheric dominant by the dichotic listening test. However, their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.

Topics: Adult; Alcoholism; Analysis of Variance; Digoxin; Dominance, Cerebral; Hepatolenticular Degeneration; Humans; Hypothalamus; Liver Cirrhosis, Alcoholic; Middle Aged; Telencephalon

An ethylic hypertensive patient with a BMI of 51.4 developed persistent atrial fibrillation with high ventricular rates. External electrical cardioversion was attempted, but failed in spite of high energy shocks (350 joules). Sinus rhythm was restored by internal cardioversion (12 joules). The value and indications of the techniques are briefly discussed.

Topics: Alcoholism; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Body Mass Index; Chronic Disease; Combined Modality Therapy; Digoxin; Electric Countershock; Humans; Hypertension; Male; Middle Aged; Obesity, Morbid; Patient Selection

We surveyed Accident and Emergency (A&E) consultants in England by questionnaire, on their management of patients presenting with AF. Completed questionnaires were received from 124 (45%). Most (42%) would use digoxin as first-line treatment for rate control of AF; 28% would not treat AF acutely but would refer the patient to the medical team; 59% would cardiovert a patient with AF in A&E, if there was evidence of cardiovascular compromise. Some 51% would not routinely initiate any anticoagulation therapy. Faced with a patient in fast AF who was haemodynamically unstable, 67% would immediately opt for electrical cardioversion, 13% would refer the patient directly to the medics and 15% would initially treat with intravenous digoxin. Given a patient in fast AF and cardiac failure, 55% would treat with digoxin. Asked about AF related to Wolff-Parkinson-White syndrome, 37% would initially give adenosine, 23% would opt for immediate DC cardioversion and 25% would refer directly to the medics; however, a minority would still give a rate-limiting calcium antagonist or digoxin. The majority (79%) would not treat AF in a known alcoholic with acute intoxication who was haemodynamically stable. Consultants were more likely to initiate treatment if the patient had signs of shock or heart failure. Where there were underlying medical problems they were more likely to refer the patient directly to the medical team. There was a general reluctance to initiate anticoagulation, and some difference in opinion over how long AF should have persisted for anticoagulation to be necessary in the context of electrical cardioversion. Given the current evolution of A&E as an acute speciality, A&E clinicians should at least initiate management of patients with AF and be prepared to care for them for some time in A&E.

Topics: Alcoholism; Anticoagulants; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Electric Countershock; Emergency Service, Hospital; England; Health Care Surveys; Heart Failure; Humans; Practice Patterns, Physicians'; Referral and Consultation; Surveys and Questionnaires; Thyroid Diseases; Wolff-Parkinson-White Syndrome

Topics: Alcoholism; Animals; Cardenolides; Digoxin; Enzyme Inhibitors; Ethanol; Male; Rats; Rats, Wistar; Saponins; Sodium-Potassium-Exchanging ATPase; Substance-Related Disorders

The overall prognosis for patients with congestive heart failure is poor. Defining specific populations that might demonstrate improved survival has been difficult. We therefore examined our patient database for patients with congestive heart failure who demonstrated sustained improvement in left ventricular function and associated resolution of signs and symptoms of congestive heart failure.. We identified 11 patients with severe congestive heart failure (average ejection fraction 21.9 +/- 4.23% (+/- SD) who developed spontaneous, marked improvement over a period of follow-up lasting 4.25 +/- 1.49 years. All 11 patients were initially symptomatic with exertional dyspnea and fatigue for a minimum duration of 3 months. They form a subset of a larger group of 97 patients with chronic congestive heart failure that we have followed with sequential ejection fraction measurements. All 11 patients were treated with digitalis diuretics, and either converting-enzyme inhibitors or a combination of isosorbide dinitrate and hydralazine. Ten of the 11 patients had a history consistent with chronic alcoholism, and each reportedly abstained from alcohol during follow-up.. During the follow-up period, the average ejection fraction improved in 11 patients from 21.9 +/- 4.23% to 56.64 +/- 10.22%. Late follow-up indicates an average ejection fraction of 52.6 +/- 8.55% for the group. Congestive heart failure resolved in each case.. We conclude that selected patients with severe congestive heart failure can markedly improve their left ventricular function in association with complete resolution of heart failure. This appears to be particularly evident in those patients with chronic alcoholism who subsequently abstain.

Topics: Aged; Alcoholism; Captopril; Digoxin; Diuretics; Enalapril; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Remission Induction; Stroke Volume

We used hemofiltration to treat a patient with digoxin overdose complicated by refractory hyperkalemia, congestive heart failure, chronic renal failure, and complete atrioventricular heart block. Hemofiltration was associated with a progressive fall in plasma digoxin level and potassium level. This was accompanied by resolution of the heart failure and complete heart block. Hemofiltration appears to provide a therapeutic alternative in digoxin overdose.

Topics: Alcoholism; Blood; Combined Modality Therapy; Digoxin; Heart Failure; Humans; Male; Middle Aged; Time Factors; Ultrafiltration

Topics: Alcoholism; Brain Neoplasms; Digoxin; Evaluation Studies as Topic; False Negative Reactions; False Positive Reactions; Humans; Hypertension, Renal; Iodine Radioisotopes; Lung Diseases; Mammography; Mass Screening; Models, Theoretical; Pelvimetry; Prognosis; Radionuclide Imaging

Topics: Aged; Alcoholism; Allopurinol; Arrhythmias, Cardiac; Chloral Hydrate; Colchicine; Digoxin; Drug Synergism; Gastrointestinal Hemorrhage; Gout; Hospitals, Teaching; Humans; Liver Diseases; Male; Middle Aged; Nitroglycerin; Patient Care Team; Pharmacists; Pharmacy Service, Hospital; Quinidine; Warfarin; Washington