Review of Cimetidine Drug Interactions

1983 ◽  
Vol 17 (2) ◽  
pp. 110-120 ◽  
Author(s):  
Eugene M. Sorkin ◽  
Diane L. Darvey
Keyword(s):  
Blood Flow ◽  
Drug Interactions ◽  
Hepatic Blood Flow ◽  
Hepatic Clearance ◽  
Hepatic Metabolism ◽  
Rapid Onset ◽  
Related Drug ◽  
Cytochrome P 450 ◽  
Acid Labile ◽  
Hepatic Cytochrome

The literature on cimetidine drug interactions has been thoroughly reviewed. Several different mechanisms have been proposed for cimetidine-related drug interactions. These mechanisms include: (1) impaired hepatic drug metabolism due to inhibition of hepatic microsomal enzymes, (2) reduced hepatic blood flow, resulting in decreased clearance of drugs that are highly extracted by the liver, (3) increased potential for myelosuppression when administered concurrently with other drugs capable of causing myelosuppression, and (4) altered bioavailability of acid-labile drugs. Cimetidine binds reversibly to the hepatic cytochrome P-450 and P-448 systems, resulting in decreased metabolism of drugs that undergo Phase I reactions (e.g., dealkylation and hydroxylation). In contrast, glucuronidation pathways are unaffected. The rapid onset and reversal of cimetidine's inhibition of hepatic metabolism indicates an effect on hepatic enzyme systems. Cimetidine also has been reported to decrease hepatic blood flow. Drugs that are highly extracted by the liver, such as propranolol, lidocaine, and morphine, may be postulated to have a decreased hepatic clearance. Cimetidine, through its effect on gastric pH, may increase the absorption of acid-labile drugs or may decrease the absorption of drugs. There have been reports of increased potential for myelosuppression when cimetidine is administered concurrently with drugs capable of causing bone marrow suppression. An understanding of the mechanisms involved in cimetidine drug interactions allows the clinician to prevent and predict these interactions.

Nicardipine increases hepatic blood flow and the hepatic clearance of ICG in patients with cirrhosis

1990 ◽  
Vol 11 ◽  
pp. S24
Author(s):  
JC García-Paqán ◽  
F Feu ◽  
L Ruiz del Arbol ◽  
I Cirera ◽  
P Pizcueta ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Hepatic Clearance

Nicardipine increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis

1994 ◽  
Vol 20 (6) ◽  
pp. 792-796 ◽  
Author(s):  
Juan Carlos García-Pagán ◽  
Fausto Feu ◽  
Angelo Luca ◽  
Mercedes Fernández ◽  
Pilar Pizcueta ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Hepatic Blood Flow ◽  
Hepatic Clearance

Regulation of Gluconeogenesis and Ketogenesis during Rest and Exercise in Diabetic Subjects and Normal Men

1977 ◽  
Vol 53 (5) ◽  
pp. 411-418 ◽  
Author(s):  
L. Sestoft ◽  
J. Trap-Jensen ◽  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Ketone Bodies ◽  
Venous Blood ◽  
Hepatic Metabolism ◽  
Hepatic Uptake ◽  
Diabetic Group ◽  
Hepatic Venous Blood ◽  
Juvenile Diabetic ◽  
Normal Men

1. The splanchnic—hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast. 2. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic—hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood. 3. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load. 4. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood. 5. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow.

Vaccine-Drug Interactions

1984 ◽  
Vol 18 (9) ◽  
pp. 697-700 ◽  
Keyword(s):  
Adverse Reaction ◽  
Drug Interactions ◽  
Adverse Reactions ◽  
Underlying Mechanism ◽  
Interferon Inducer ◽  
Warfarin Sodium ◽  
Phenytoin Sodium ◽  
Patients At Risk ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Interaction between a vaccine and a drug has been reported only with influenza vaccine and four drugs (aminopyrine, phenytoin sodium, theophylline, and warfarin sodium), and with BCG vaccine and theophylline. Some of these interactions still are unconfirmed. The underlying mechanism of the interaction is thought to be due to the vaccine (as an interferon-inducer) inactivating the hepatic cytochrome P-450 system; this results in depressed drug metabolism and reduced clearance. Because this is a nonspecific mechanism it could occur with other vaccines and it is possible that other vaccine-drug interactions are unrecognized. The clinical significance of vaccine-drug interactions is not fully determined; available evidence suggests that adverse reactions to warfarin or theophylline are rare after influenza vaccination and their possibility should not deter physicians from vaccinating those elderly patients at risk from influenza. Physicians should, however, monitor the response of these patients to medication in the immediate period following vaccination in case an adverse reaction occurs.

EFFECT OF CORTISOL ON UTILIZATION AND HEPATIC RELEASE OF GLUCOSE IN THE MARSUPIAL BRUSH-TAILED OPOSSUM, TRICHOSURUS VULPECULA

1976 ◽  
Vol 68 (2) ◽  
pp. 257-264 ◽  
Author(s):  
I. R. McDONALD ◽  
KHIN AYE THAN
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Glucose Concentration ◽  
Specific Activity ◽  
Blood Glucose Concentration ◽  
Hepatic Glucose Production ◽  
Hepatic Clearance ◽  
Glucose Production ◽  
Term Effect ◽  
Metabolic Clearance

SUMMARY Brush-tailed opossums were prepared surgically with indwelling hepatic and jugular venous catheters for blood sampling without disturbance in the conscious state. Hepatic extraction of [125I]Rose Bengal was 21 ± 3 (s.d.)% and hepatic clearance, used as a measure of hepatic blood flow, was 42·5 ± 7 ml/kg/min. Hepatic release of new glucose, calculated from the thoracic vena caval-hepatic venous difference in glucose specific activity at equilibrium during i.v. infusion of [14C]glucose and hepatic blood flow, was 3·5 ± 0·8 mg/ kg/min. This was not changed by i.v. infusion of 10% ethanolic saline or cortisol in ethanolic saline, at 1 mg/kg/h for 90 min, although the cortisol infusion caused the peripheral blood glucose concentration to rise from 56·5 ± 7·3 to 83·2 ± 10·3 mg/100 ml. The rate of metabolic clearance of glucose fell from 6·1 ± 1·1 to 4·2 ± 0·9 ml/kg/min during i.v. cortisol infusion. Daily i.m. injection of 1 mg cortisol acetate/kg for 5 days caused an increase in hepatic new glucose release to 8·0 ± 1·6 mg/kg/min. The findings support the proposition that, in this marsupial, the short-term effect of cortisol on plasma glucose concentration is due to inhibition of peripheral glucose utilization, whereas the long-term effect is due to increased hepatic glucose production.

Hepatic clearance of indocyanine green in man under thermal and exercise stresses

1965 ◽  
Vol 20 (3) ◽  
pp. 384-394 ◽  
Author(s):  
Loring B. Rowell ◽  
John R. Blackmon ◽  
Richard H. Martin ◽  
John A. Mazzarella ◽  
Robert A. Bruce
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Indocyanine Green ◽  
Blood Lactate ◽  
Hepatic Blood Flow ◽  
Rectal Temperature ◽  
Hepatic Clearance ◽  
Work Capacity ◽  
Heart Rates ◽  
Icg Clearance

At 78 and 110 F hepatic clearance of indocyanine green (ICG), O2 intake, heart rate, blood lactate, and rectal temperature were measure on nine men unacclimatized to heat during treadmill exercise, requiring 45–95% of maximal O2 intake (max Vo2). Percentage of resting ICG clearance was inversely proportional to percentage of maximal O2 intake at 78 F (ggr = -0.78) and 110 F (ggr = -0.81). Clearance of ICG was 20% less at 110 F than at 78 F at all metabolic rates above 26% of maximal Vo2. Measurements of hepatic blood flow in three men at 110 F validate these estimates of percentage decrements in hepatic blood flow. Submaximal and maximal Vo2 and maximal heart rates were unaltered by heat, but maximal heart rates were reached during submaximal work at 110 F. Decreased work capacity at 110 F was unrelated to rectal temperature or blood lactate; the latter was unaffected by temperature. The liver and the kidneys may divert to the skin sufficient blood to obviate the need for additional increments in cardiac output during work at high temperature. Maximal decrements in hepatic blood flow at lower work intensities may contribute to diminished work capacity at 110 F. hepatic blood flow during exercise; lactic acid and heat stress; rectal temperature; heart rate and temperature; maximal o2 intake, influence of temperature; temperature redistribution of blood flow; work capacity, effect of heat Submitted on October 30, 1964

The effect of SKF-525A and of altered hepatic blood flow on lidocaine clearance in the cat

1977 ◽  
Vol 55 (1) ◽  
pp. 7-12 ◽  
Author(s):  
W. Wayne Lautt ◽  
F. Steve Skelton
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Intravenous Infusion ◽  
Intramuscular Injection ◽  
Hepatic Clearance ◽  
Hepatic Uptake ◽  
Extraction Ratio ◽  
Hepatic Extraction ◽  
Vascular Conductance ◽  
Altered Blood

Hepatic blood flow and hepatic uptake of lidocaine were determined in cats during constant intravenous infusion of lidocaine. Lidocaine clearance is directly linked to hepatic blood flow with reductions in flow being reflected in equal reductions in hepatic clearance. Altered blood flow did not result in altered rates of lidocaine extraction. Lidocaine extraction ratio was 28%.Hepatic blood flow and lidocaine metabolism were measured before and 60 min after an intramuscular injection of SKF-525A (50 mg/kg). SKF-525A produced a reduction in hepatic clearance of lidocaine to 60% of control values, entirely as a result of a reduction in hepatic extraction ratios. Hepatic blood flow and vascular conductance were not affected by SKF-525A.

Measurement of hepatic blood flow in the unanesthetized dog by a modified bromsulphalein method

1960 ◽  
Vol 15 (3) ◽  
pp. 473-478 ◽  
Author(s):  
William C. Shoemaker
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Hepatic Metabolism ◽  
Flow Measurements ◽  
Catheter Technique ◽  
Direct Measurements ◽  
Analytical Accuracy ◽  
Blood Flow Measurements ◽  
Experimental Preparation

Possible errors of the bromsulphalein method for estimation of hepatic blood flow are enumerated and an analytic method which takes into account the amount of hemolysis present in the samples is described. Improved analytical accuracy allows flow measurements to be carried out at lower bromsulphalein levels, which theoretically allow less extrahepatic bromsulphalein loss and provide larger gradients relative to the circulating level. A preparation for the study of hepatic blood flow and regional hepatic metabolism in the chronic unanesthetized dog is described. Modifications of the bromsulphalein method are proposed for use in this experimental preparation; these modifications include an attempt to obviate the problems of the retrograde hepatic vein catheter technique and a direct measurement of the portal-hepatic venous bromsulphalein concentration gradient. Comparison of hepatic blood flow measurements by the modified bromsulphalein method with direct measurements of flow in the in situ perfused liver have shown comparable results. Submitted on September 18, 1959

Hepatic Blood Flow in Patients with Tumors of the Liver

1963 ◽  
Vol 44 (6) ◽  
pp. 733-739 ◽  
Author(s):  
Kathleen M. Wartnaby ◽  
I.A.D. Bouchier ◽  
C.E. Pope ◽  
Sheila Sherlock
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Tumors Of The Liver
Sign in / Sign up

Export Citation Format

Share Document