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PubMed2001

Caffeine as a lipolytic food component increases endurance performance in rats and athletes.

Caffeine is one of the famous ergogenic aids in the athletic field. Caffeine has been known to stimulate lipolysis that spares stored glycogen utilization during moderate intensity exercise. Therefore, we investigated the effects of caffeine ingestion on exercise performance in rats and athletes. Rats were administered the caffeine (6 mg/kg) 1 h prior to the exercise then were run on a treadmill at a speed of 20 m/min. They were decapitated at 0 min, 30 min, 60 min of exercise, and exhausted time point. Human subjects ingested the caffeine (5 mg/kg) 1 h prior to the exercise. They exercised on a cycle ergometer at 60% of their VO2max for 45 min, and then the exercise intensity was increased to 80% of their VO2max until exhaustion. Blood and breathing gas samples were collected and calculated every 10 min during exercise. Respiratory exchange ratio of the caffeine trial was significantly lower than that of the placebo trial in the athletes' study (p<0.05). Blood free fatty acid (FFA) levels in studies of both rats and athletes were increased by caffeine ingestion during exercise (p<0.05). Blood lactate levels were also increased during exercise in both rats and athletes (p<0.05). Increased FFA and glycerol concentrations reduced glycogen utilization during exercise compared with placebo group in rats. In addition, endurance time to exhaustion was significantly increased by the caffeine ingestion in both rats and athletes (p<0.05). These results suggest that the caffeine ingestion enhanced endurance performance resulting from spare stored glycogen with increasing lipolysis from adipose tissues and fat oxidation during exercise both in rats and in athletes.

Adipose Tissue↗
PubMed1999

Molecular effects of taxol and caffeine on pancreatic cancer cells.

Pancreatic cancer is the fifth leading cause of cancer related deaths in the United States. Despite many recent advances in the treatment modalities, the mortality rate still remains very high. Paclitaxel (Taxol) and Caffeine have been used for the treatment of this disease, however the molecular mechanisms of these agents are not fully understood, which may be partly responsible for the failure of these agents in the treatment of pancreatic cancer. Human pancreatic adenocarcinoma cell lines, HPAC and PANC-1 containing wild-type and mutant p53 respectively, were used to investigate the effects of Taxol and Caffeine on cell growth, and their effects on the modulation of cell cycle and apoptosis related genes. Protein extracts from these cells treated with 100 nM of Taxol or 4 mM of Caffeine were subjected to Western blot analysis for this study. Drug treated cells were also analyzed to calculate the number of cells undergoing apoptosis. Dose and time dependent growth inhibition was observed in both PANC-1 and HPAC cells when treated with either Taxol or Caffeine. Western blot analysis showed an up-regulation of p21WAF1 in both cell lines treated with either Taxol or Caffeine. Furthermore, down-regulation of cyclin B and cdk1 was observed in Taxol and Caffeine treated HPAC cells. However, the results were drastically different in PANC-1 cells where cyclin B was down regulated only by Caffeine treatment and the level of cdk1 protein was undetectable in this cell line. Moreover, up-regulation of p53 and down-regulation of Bcl-2 was observed only in HPAC cells treated with Taxol. Apoptotic cell death analysis showed increasing number of cells undergoing apoptosis between 24 and 48 h of Caffeine treatment, however only Taxol showed greater than 50% cells under-going apoptosis only in HPAC cells. The up-regulation of p21WAF1 and down-regulation of cyclin B and cdk1 suggest their possible roles in G2/M cell cycle arrest caused by both Taxol and Caffeine as reported earlier. From these results we conclude that the differential molecular changes observed in this study may determine the cellular effects of these agents on pancreatic adenocarcinoma cells and that the effects of chemotherapeutic agents may be determined by the endogenous status of p53 mutation and, in turn, may determine the therapeutic effects of these agents in the treatment of pancreatic cancer.

Adenocarcinoma↗
PubMed2000

Relationship between the severity of alcoholic liver cirrhosis and the metabolism of caffeine in 226 patients.

OBJECTIVES: To evaluate the polygenic regulated caffeine metabolism in a group of 226 patients with liver alcoholic cirrhosis classified according to the Child score. METHODS: Over a 14-year period an hepatic function test, using caffeine as probe drug, has been systematically associated to the usual clinical and biochemical investigations performed in patients with liver alcoholic cirrhosis. "Caffeine test" consisted in a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7 dimethylxanthine (17X), 1-3 dimethylxanthine (13X), 1-3 dimethylurate (13U), 3-7 dimethylxanthine (37X), 1-7 dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolites ratios: (AFMU+1U+1X)/17U for CYPIA2, 17U/17X for CYP2A6, AFMU/(AFMU+ 1U+1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, whatever the Child score, caffeine metabolism was reduced by half in patients with alcoholic cirrhosis. The main cause was the decreased CYP1A2 activity. On the other hand, XO and CYP2A6 activities were increased and NAT-2 activity remained unchanged in slow acetylators (SA) and decreased in rapid acetylators (RA) Child B and C. Bimodality of NAT-2 distribution was unclear, but a right assignment of RA and SA phenotype in cirrhotic patients, confirmed by comparison with genotype, was obtained, using the antimode value of NAT-2 distribution used in healthy subjects. At last, there was an interindividual variability in caffeine metabolism as great as in the usual laboratory parameters. CONCLUSION: Metabolism of caffeine is decreased in patients with alcoholic liver cirrhosis. This decrease paralleled the modifications of the usual laboratory tests and does not bring additional information on the severity of the disease. But the equilibrium between the various metabolic pathways of caffeine is impaired. Beyond the changes of a specific enzymatic activity, this must be taken into account particularly for drugs whose metabolism is of the polygenic regulation type.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Caffeine metabolism before and after liver transplantation.

AIM: To study drug metabolism in patients before and after liver transplantation using caffeine as a probe drug. Forty-five patients undergoing liver transplantation for various liver diseases and who had well documented dossiers were selected for the study. Before the liver transplantation and 1 month, 1 year, and 6 years after liver transplantation, they were given 200 mg of caffeine by the oral route in the morning after voiding their bladder. Twenty-four-hour urine samples were collected and caffeine and metabolites were determined by HPLC: 1-methylurate (1U), 1-methylxanthine (1X), 1.7-dimethylurate (17U), 1.7-dimethylxanthine (17X), 7-methylxanthine (7X), 3-methylxanthine (3X), 1.3-dimethylurate (13U), 3.7-dimethylxanthine (37X), 1.3-dimethylxanthine (13X), 1.3.7-trimethylxanthine = caffeine (137X). Indices of enzyme activities were calculated from the following urinary elimination ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, 1U/1X for xanthine oxidase (XO), AFMU/(AFMU+1U+1X) for N-acetyltransferase (NAT-2). RESULTS: Compared with results obtained in a group of 70 healthy subjects, caffeine metabolism before liver transplantation was deeply depressed with a decreased elimination rate in the case of all metabolites and a decreased CYP1A2 activity. Caffeine metabolism began to return to the control values one month after transplantation. One year and 6 years after liver transplantation, quantitatively, the metabolism of caffeine was stable and not different from control, but with qualitative modifications. CYP1A2 activity was decreased with reduced urinary elimination rates of 1X and 17X. XO and CYP2A6 activities and 1U and 17U urinary elimination rates were increased. Immunosuppressive treatment was possibly responsible for the metabolic pathway changes. Almost the same modifications were observed in 9 patients after bone marrow transplantation who had been treated with the same immunosuppressive drugs, cyclosporine and azathioprine. During severe rejection phases in 6 of the liver transplant patients, caffeine metabolism was progressively decreased when the usual liver function tests showed moderate but uniform changes. CONCLUSION: Despite an apparent normal drug-metabolic function, immunosuppressive treatment induces stable variations in drugmetabolic pathways after liver transplantation which can be detected from the changes in caffeine metabolism.

Adult↗
PubMed1998

Effects of caffeine on NMDA-evoked 45Ca2+ release in the rate dentate gyrus in vivo.

Caffeine in 10(-2) M concentration per se activates ryanodine receptors (RyR) in vitro, thereby increasing the intracellular concentration of Ca2+ ([Ca2+]i). In general opinion, caffeine applied in vivo in much lower doses does not affect [Ca2+]i in neurones. However, it was recently demonstrated that caffeine in low concentrations in vitro potentiates evoked Ca2+ release in neurones via RyR. Microdialysis of the rat dentate gyrus (DG), combined with measurement of 45Ca2+ efflux, has been used in our laboratory to study in vivo NMDA-evoked calcium induced calcium release (CICR) via RyR. The aim of the present microdialysis study was to investigate in vivo effects of caffeine, applied systemically in a pharmacologically-relevant dose, and locally in the dialysis medium in very high concentration, on the NMDA-evoked CICR in DG neurones. To ensure steady brain concentration of caffeine, its systemic (i.p.) administration in a dose of 40 mg/kg was followed by a continuous i.p. infusion of 80 micrograms/kg/min and application of 0.4 mM caffeine in the dialysis medium. The results demonstrated that in the rat DG, local administration of 50 mM caffeine significantly stimulates a spontaneous 45Ca2+ efflux and its release induced by 5 mM NMDA. However, systemic administration of caffeine had no effect on spontaneous and NMDA-induced 45Ca2+ release in the rat DG, which supports the view that caffeine, applied in vivo, even in high doses, does not influence CICR in brain neurones.

Animals↗
PubMed1989

The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease.

STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration.

Adult↗
PubMed1999

Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine.

Venlafaxine is a clinically effective antidepressant. Caffeine is a metabolic probe for the quantitative measurement of CYP1A2 activity in vivo. This open-label study evaluated the effect of steady-state venlafaxine on CYP1A2-dependent metabolism, as measured by the pharmacokinetic disposition of caffeine, and urinary caffeine metabolite ratios (CMRs). Sixteen healthy subjects received 200 mg of caffeine orally before (Day 1) and after (Day 8) venlafaxine was titrated to steady-state (37.5 mg every 12 hours on Days 2-4, then 75 mg every 12 hours on Days 5-8). Samples were collected before and for 24 hours after caffeine dosing for the determination of caffeine in plasma and 1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,7-dimethyluric acid (17U), 1-methylxanthine (1X) and 1-methyluric acid (1U), and 5-acetylamino-6-amino-3-methyluracil (AAMU) in urine. Blood samples were obtained before venlafaxine doses on Days 7 and 8 (morning dose only) for the determination of trough venlafaxine and O-desmethylvenlafaxine levels. Venlafaxine did not significantly alter the pharmacokinetics of caffeine and its metabolites. Plasma caffeine AUC was unchanged and remained within the bioequivalence criteria (90% confidence interval: 87.9%-102%) in the presence of venlafaxine. Urine metabolite data showed variable increases and decreases in the CMR [(AAMU + 1U + 1X)/17U] for individual subjects. However, the mean CMR was altered by < 10% in the presence of venlafaxine. This in vivo study demonstrated that venlafaxine did not alter the pharmacokinetic profile of caffeine and confirms in vitro data that venlafaxine does not inhibit CYP1A2 metabolism. Therefore, venlafaxine appears to have a relatively low potential for drug interactions based on CYP1A2 inhibition.

Adult↗
PubMed1999

Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors.

We investigated the role of caffeine-sensitive intracellular stores in regulating intracellular calcium ([Ca(2+)](i)) and glutamatergic synaptic transmission from rod photoreceptors. Caffeine transiently elevated and then markedly depressed [Ca(2+)](i) to below prestimulus levels in rod inner segments and synaptic terminals. Concomitant with the depression was a reduction of glutamate release and a hyperpolarization of horizontal cells, neurons postsynaptic to rods. Caffeine did not affect the rods' membrane potentials indicating that caffeine likely acted via some mechanism(s) other than a voltage-dependent deactivation of the calcium channels. Most of caffeine's depressive action on [Ca(2+)](i), on glutamate release, and on I(Ca) in rods can be attributed to calcium release from stores: (1) caffeine's actions on [Ca(2+)](i) and I(Ca) were reduced by intracellular BAPTA and barium substitution for calcium, (2) other nonxanthine store-releasing compounds, such as thymol and chlorocresol, also depressed [Ca(2+)](i), and (3) the magnitude of [Ca(2+)](i) depression depended on basal [Ca(2+)](i) before caffeine. We propose that caffeine-released calcium reduces I(Ca) in rods by an as yet unidentified intracellular signaling mechanism. To account for the depression of [Ca(2+)](i) below rest levels and the increased fall rate of [Ca(2+)](i) with higher basal calcium, we also propose that caffeine-evoked calcium release from stores activates a calcium transporter that, via sequestration into stores or extrusion, lowers [Ca(2+)](i) and suppresses glutamate release. The effects of store-released calcium reported here operate at physiological calcium concentrations, supporting a role in regulating synaptic signaling in vivo.

Ambystoma↗
PubMed1999

Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.

Caffeine exposure sensitizes tumor cells to ionizing radiation and other genotoxic agents. The radiosensitizing effects of caffeine are associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints. The similarity of these checkpoint defects to those seen in ataxia-telangiectasia (A-T) suggested that caffeine might inhibit one or more components in an A-T mutated (ATM)-dependent checkpoint pathway in DNA-damaged cells. We now show that caffeine inhibits the catalytic activity of both ATM and the related kinase, ATM and Rad3-related (ATR), at drug concentrations similar to those that induce radiosensitization. Moreover, like ATM-deficient cells, caffeine-treated A549 lung carcinoma cells irradiated in G2 fail to arrest progression into mitosis, and S-phase-irradiated cells exhibit radioresistant DNA synthesis. Similar concentrations of caffeine also inhibit gamma- and UV radiation-induced phosphorylation of p53 on Ser15, a modification that may be directly mediated by the ATM and ATR kinases. DNA-dependent protein kinase, another ATM-related protein involved in DNA damage repair, was resistant to the inhibitory effects of caffeine. Likewise, the catalytic activity of the G2 checkpoint kinase, hChk1, was only marginally suppressed by caffeine but was inhibited potently by the structurally distinct radiosensitizer, UCN-01. These data suggest that the radiosensitizing effects of caffeine are related to inhibition of the protein kinase activities of ATM and ATR and that both proteins are relevant targets for the development of novel anticancer agents.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2000

Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants.

BACKGROUND: The xanthines have been shown to be effective in the treatment of apnea of prematurity. Limited reports are available in the literature concerning the use of these agents with apnea related to respiratory syncytial virus (RSV) infections. METHODS: A retrospective review was done to identify infants who received caffeine therapy for RSV-associated apnea. The number of apneic episodes during the 2 hours before the use of caffeine and the number of apneic episodes after the administration of caffeine were compared using a Wilcoxon nonparametric test. RESULTS: The 7 infants ranged in age from 14 to 64 days and in weight from 2.8 to 4.4 kg. The number of apneic episodes per hour for the 2 to 3 hours before the administration of caffeine ranged from 7 to 12, and the number of episodes during the 3 hours after the administration of the first dose of caffeine ranged from 0 to 2. The apneic episodes after caffeine responded to external stimulation. Apnea recurred in 3 infants, 18 to 24 hours after the first dose of caffeine. These infants received a second dose of caffeine (5 mg/kg). CONCLUSIONS: Caffeine should be considered in the treatment of apnea related to RSV infections in neonates and infants.

Apnea↗
PubMed2000

Slow-release caffeine: a new response to the effects of a limited sleep deprivation.

STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine 300 and 600 mg are efficacious doses but the optimal dose (maximum effect without any side effects) for both men and women is after all 300 mg. Globally, there is no difference between placebo and caffeine during the recovery night period. CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance to maintain a good level of vigilance and performance during limited sleep deprivation.

Adolescent↗
PubMed2001

Effect of caffeine on the genotoxic effects of gamma radiation and 4-NQO in diploid yeast.

Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways.

4-Nitroquinoline-1-oxide↗
PubMed2001

Caffeine clearance in patients with chronic viral hepatitis: before and after interferon therapy.

The purpose of this study was to evaluate caffeine clearance, a quantitative measurement of metabolizing capacity of the liver, in chronic hepatitis B and C before and after interferon treatment. Biochemical test using AST and ALT, virological test, and caffeine clearance were measured in eighteen patients with chronic hepatitis B and five patients with chronic hepatitis C at pre and post treatment with interferon. Caffeine clearance was determined in each patient using two point analysis following a 3.5 mg/kg oral administration of caffeine solution. Blood samples were subsequently collected at 12 and 16 hours after caffeine administration and assayed for serum caffeine level by HPLC technique. Clearance was calculated using the equation of Cl = Kel x Vd. It was found that caffeine clearances determined before and after interferon treatment were not significantly different in both chronic hepatitis B and C inspite of biochemical and virological responses after therapy. Caffeine clearance change in two diffferent groups of chronic hepatitis B defined as biochemical response and nonresponse were compared. Although caffeine clearance change between responders and nonresponders to interferon treatment was not significantly different, it tended to increase in those patients who had biochemical response to interferon. It appeared that metabolic capacity of the liver does not change with interferon therapy inspite of biochemical and virological responses.

Administration, Oral↗
PubMedDate not supplied

Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes.

Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a considerable role. The aim of the present study was to investigate the influence of imipramine, amitriptyline and fluoxetine on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that imipramine exerted a most potent inhibitory effect on caffeine metabolism. Imipramine decreased the rate of 3-N-, 1-N- and 7-N-demethylations, and 8-hydroxylation of caffeine, the effect on 3-N-demethylation being most pronounced (Ki = 33 microM). Amitriptyline showed distinct inhibition of 3-N- and 1-N-demethylation of caffeine, though its effect was less potent than in the case of imipramine (Ki = 57 and 61 pM, respectively). The influence of amitriptyline on 8-hydroxylation and especially on 7-N-demethylation of caffeine was weaker (Ki = 108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a narrower spectrum of cytochrome P-450 inhibition by amitriptyline than by imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree--CYP3A. In contrast to the tested tricyclic antidepressants, fluoxetine did not exert any considerable effect on the 3-N- or 1-N-demethylation of caffeine (Ki = 152 and 196 microM, respectively), which indicates its low affinity for CYP1A2. However, fluoxetine displayed a clear inhibitory effect on caffeine 7-N-demethylation (Ki = 72 microM), the reaction which is catalyzed mainly by other than CYP1A2 isoenzymes. Fluoxetine diminished markedly the 8-hydroxylation of the marker drug; as reflected by Ki values, the potency of inhibition of rat CYP3A by fluoxetine was similar to that of imipramine (Ki = 40 and 45 microM, respectively). In summary, CYP1A2 was distinctly inhibited by imipramine and amitriptyline, CYP3A by imipramine and fluoxetine, while other CYP isoenzymes (CYP2B and/or 2E1) by imipramine and fluoxetine.

Amitriptyline↗
PubMed2002

Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging.

BACKGROUND: Caffeine binds to the A2 receptors and inhibits adenosine's action of vasodilation or dipyridamole-induced vasodilation. Patients scheduled for (201)Tl myocardial perfusion using pharmacologic stress with dipyridamole or adenosine are advised to abstain from caffeine for 24 h before the test. This article reports on the residual serum caffeine levels of 36 patients after 24-h caffeine abstention and the clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. METHODS AND RESULTS: Heart rate, diastolic blood pressure, and systolic blood pressure were recorded before and after dipyridamole infusion. Sixty-six percent of the patients had detectable plasma caffeine but all values were within the range of 0.1-0.8 mg/L. No statistically significant change in diastolic and systolic blood pressures after dipyridamole infusion has been observed. The mean heart rate was increased by 18% after dipyridamole infusion in patients with zero caffeine, and the heart rate increase was inversely correlated with the serum caffeine levels (r = -0.22) with 81% confidence. CONCLUSION: A serum caffeine level of 2 mg/L is predicted to be the lower limit for false-negative dipyridamole (201)Tl myocardial perfusion. The increase of heart rate after dipyridamole infusion could be the simple indicator for the serum caffeine level. Rescheduling of the patient study or further adenosine challenge is necessary only if the heart rate increase is <5% after dipyridamole or adenosine infusion.

Aged↗
PubMed2002

Caffeine clearance in patients with hepatocellular carcinoma after transcatheter oily chemoembolization treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common neoplasm worldwide, particularly in Asia, with a grave prognosis. Transcatheter Oily Chemoembolization (TOCE) is now universally accepted as the method of choice for the treatment of inoperable HCC. The purpose ofthis study was to evaluate caffeine clearance, a quantitative liver function assessment, in HCC patients before and after treatment with TOCE. METHOD: Both conventional liver function test (LFT) and caffeine clearance were evaluated in twelve patients. Each patient took a 3.5 mg/kg single oral dose of caffeine solution before TOCE, 1 day and 5 weeks after treatment. Blood samples were subsequently collected at 0.5, 1.5, 3, 5, 10 and 24 hours after each dose of caffeine administration and assayed for serum caffeine level by the HPLC technique. Clearance (Cl) was calculated using the equation of Cl = Kel x Vd (Kel = elimination rate constant, Vd = volume of distribution) and half-life was determined using pharmacokinetic analysis. RESULTS: The mean caffeine clearance 1 day after TOCE (0.51 +/- 0.096) and 5 weeks after TOCE treatment (0.43 +/- 0.07) was significantly reduced compared with the mean caffeine clearance before treatment (0.79 . 0.2 ml/min x kg) with the p = 0.06 and p = 0.03, respectively. No significant changes (p > 0.05) in most conventional LFT were observed 5 weeks after treatment. CONCLUSIONS: In the present study, the authors found that caffeine clearance was reduced after TOCE in patients with HCC inspite of no changes in conventional LFT. Thus, the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in HCC patients post TOCE treatment.

Adult↗
PubMed2003

The effect of caffeine on the cardiovascular responses to head-up tilt.

BACKGROUND: Both caffeine and orthostasis have known cardiovascular effects. The possible interaction between these factors remains unknown. This study aimed to determine the effect of caffeine consumption on cardiovascular responses to head-up tilt. METHODS: Sixteen subjects underwent three +75 degree head-up tilts: i) control, ii) acute, after a dose of 5 mg x kg(-1) body mass of caffeine or placebo, and iii) chronic, following 7 d of caffeine or placebo consumption at a daily dose of 5 mg x kg(-1) body mass. Heart rate (HR), systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were measured using a Portapres BP monitor. RESULTS: The overall pattern of heart rate (HR) response in both caffeine and placebo groups showed a significant increase in HR after tilting for each tilt. Acute caffeine consumption significantly decreased resting HR (p < 0.05). After chronic consumption, resting HR was no longer significantly different. In the control condition, the overall pattern of response to tilt for SBP, DBP, and MAP showed no significant differences in either group. An acute dose of caffeine caused a significant fall (p < 0.05) in all BP variables in response to tilt. This effect was also seen after chronic caffeine consumption in SBP and MAP, but not in DBP. CONCLUSIONS: The results of this study indicate that both acute and chronic consumption of caffeine can lead to impaired cardiovascular function after exposure to an orthostatic challenge. This impaired function, reflected in a decreased resting HR and an inability to maintain MAP, is potentially due to impaired baroreflex function.

Adult↗
PubMed1992

Wake up and smell the coffee. Caffeine, coffee, and the medical consequences.

Caffeine is a methylxanthine whose primary biologic effect is antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate, and many prescription and over-the-counter drugs makes it the most commonly consumed stimulant drug. Initially caffeine increases blood pressure, plasma catecholamine levels, plasma renin activity, serum free fatty acid levels, urine production, and gastric acid secretion. Its long-term effects have been more difficult to substantiate. Most of the caffeine consumed in the United States is in coffee, which contains many other chemicals that may have other biologic actions. The consumption of coffee is a self-reinforcing behavior, and caffeine dependence and addiction are common. Coffee and caffeine intake have been linked to many illnesses, but definitive correlations have been difficult to substantiate. Initial trials showing coffee's association with coronary disease and myocardial infarction have been difficult to reproduce and have many confounding variables. Recent studies showing a larger effect over long follow-up periods and with heavy coffee consumption have again brought the question of the role of coffee in disease states to the fore. Caffeine in average dosages does not seem to increase the risk of arrhythmia. At present there is no convincing evidence that caffeine or coffee consumption increases the risk for any solid tumor. The intake of coffee and caffeine has clearly been decreasing in this country over the past two decades, largely brought about by the increasing health consciousness of Americans. Although there have been many studies that hint that the fears of increased disease with coffee drinking may be warranted, many questions have yet to be answered about the health effects of coffee and caffeine use.

Arrhythmias, Cardiac↗