Effect of intravenous administration of cimetidine on renal excretion of calcium, phosphates, magnesium and adenosine cyclic monophosphate

An effect of cimetidine on parathyroid glands functioning in healthy subjects was evaluated. Serum calcium, phosphate, and magnesium concentrations together with renal excretion++ of these ions in healthy subjects as well as cAMP excretion++ in selected individuals were determined before and following intravenous administration of cimetidine (Altratmet Lek Ljublijana) in total dose of 500 mg (50 mg injected rapidly as a bolus following with 450 mg in an intravenous infusion during 60 minutes). No significant changes in serum calcium, phosphates, and magnesium concentrations were noted. Renal clearance of calcium and magnesium remained unchanged whereas renal phosphate excretion++ increased from 10.69 +/- 4.9 mL/min to 15.1 +/- 5.41 mL/min (p less than 0.02). Excretion++ of 3.5 cAMP increased from 2.65 +/- 2.19 nM/min to 5.16 +/- 2.0 nM/min (p less than 05). The obtained results do not exclude stimulating effect of intravenous cimetidine on parathyroid glands. Cimetidine given intravenously in the bleeding gastric or duodenal ulcers in the course of the primary hyperparathyroidism+ may decrease serum phosphate levels due to increased exretion of this ion with the urine.     

The pharmacokinetics of H2 receptor blocking agents in compensated liver cirrhosis

The bioavailability of oral and intravenous cimetidine and ranitidine was studied in patients with compensated liver cirrhosis. Single doses of 200 and 400 mg cimetidine were used for both administration routes, while ranitidine was administered in doses of 150 mg orally or 50 mg i.v. Plasma concentrations and urinary recovery were determined by the HPLC method. The pharmacokinetics of both of these drugs in the cirrhotic patients did not differ from those found in normal subjects. The two doses of cimetidine given i.v. gave rise to the same plasma concentrations, while after oral administration, 400 mg produced higher plasma concentrations than 200 mg. As to the pharmacokinetic parameters, neither cimetidine nor ranitidine administered i.v. offered any further advantages compared to the oral route. The urinary recovery of both cimetidine and ranitidine was higher after intravenous than after oral administration. It is concluded therefore that the pharmacokinetics of cimetidine and ranitidine is not altered in compensated liver cirrhosis.     

The effect of cimetidine on PBL from healthy donors and melanoma patients: Augmentation of T cell responses to TCGF mitogens and alloantigens and of TCGF production

Summary The effect of cimetidine, an H-2 receptor antagonist, on activation of PBL from both normal individuals and melanoma patients was studied. It has been shown that cimetidine enhanced, though moderately, the production of TCGF from normal PBL after PHA-P stimulation. In addition, cimetidine significantly augmented TCGF-induced proliferation of normal PBL, as well as proliferation induced by allogeneic cells (MLC) by PPD, Con A, and PHA. In PBL samples where coincubation with cimetidine had limited or no effect, preincubation of PBL with cimetidine prior to the addition of IL-2 and other T cell activators showed a significant enhancement effect. This effect mediated by cimetidine was further demonstrated on PBL from melanoma patients whose T cell responses were initially low. The possibilities are discussed that: (a) cimetidine treatment inactivates suppressor cell activity, thus enhancing T cell mediated responses; or (b) cimetidine may act directly at effector cell level.TCGF = T cell growth factor = Interleukin-2 or IL-2     

Cimetidine and ranitidine: comparison of effects on hepatic drug metabolism.

Paired studies of hepatic microsomal function were conducted in eight subjects during treatment with two histamine H2 antagonists, cimetidine and ranitidine. Cimetidine but not ranitidine inhibited the metabolism of antipyrine (phenazone) and demethylation of aminopyrine (aminophenazone) as measured by breath 14CO2 production after intravenous injection of 14C-aminopyrine. These results suggest that the metabolic inhibitory actions on the liver may be separated from H2 antagonist effects, and that ranitidine has an advantage over cimetidine by not inhibiting microsomal drug oxidative function.     

Cimetidine effects on prolactin release and production.

The effect of cimetidine 1600 mg. daily for three months on prolactin and related hormones is reported. Basal prolactin levels rose slightly but not significantly. There was no change in basal thyroid and sex hormone levels nor in the prolactin, gonadotrophin or thyrotrophin responses to releasing hormone stimulation. Since intravenous cimetidine induces a transient hyperprolactinemia it appears that cimetidine may facilitate release of prolactin but has no effect on its synthesis.     

Mapping of phase response properties of monopolar ECG voltages

In the present investigation an attempt has been made to study the phase response properties of monopolar chest lead ECG voltages. Using a generator model of the heart an equivalent circuit of ECG network has been developed. The equivalent impedance between WCT and probe electrode has been determined by reduction techniques. From this equivalent impedance the phasor characteristics of monopolar ECG voltages have been analysed for change in probe electrode locations. The source of the generated voltage, i.e., the heart, will develop a different voltage for its different condition. There will also be a change in impedances. Thus for the normal subject the distribution of the phasor of the ECG voltages will be different from that of the abnormal one. A software tool has been developed to evaluate the relative phase response of ECG voltages. The data acquisition of monopolar ECG records of chest leads V1 to V6 from chart recorder has been done with the help of AutoCAD application package. The harmonic constituents of ECG voltages have been evaluated at each harmonic plane and the phase characteristics have been studied in polar coordinate for normal subjects as well as for a typical case. An interesting result has been observed in typical cases which are indicated in the paper.     

Prophylactic effect of cimetidine in duodenal ulcer disease.

Fifty-seven symptom-free patients with duodenal ulcer entered a double-blind trial to assess the prophylactic effect of cimetidine. Patients were randomly allocated to receive cimetidine 400 mg twice daily (29 patients) or placebo (28 patients). The trial was designed to imitate daily clinical practice, so duodenal ulcer disease was diagnosed by means of x-ray examination. Three patients from each group withdrew from the trial. All remaining patients continued to receive treatment for 12 months or until symptoms recurred. Three out of 26 patients suffered relapses during cimetidine treatment, compared with 20 out of 25 receiving placebo. No side effects were attributable to cimetidine. Long-term cimetidine treatment had no curative effect as relapses occurred soon after treatment was stopped. The estimated chance (cumulative remission rate +/- 2 SE) of remaining symptom-free 13 weeks after one year''s cimetidine treatment had been completed was 47 +/- 21%. Maintenance treatment with cimetidine is a suitable alternative to elective in surgery in patients with duodenal ulcer subjects frequent relapses. Further study is needed to establish the optimal duration and safety of prolonged cimetidine treatment.     

Is cimetidine being prescribed indiscriminately? An analytic survey of patients who present with symptoms of peptic ulcer disease.

An analytic survey was done to determine the influence of previously documented peptic ulcer disease (PUD) on the frequency of prescribing cimetidine to patients who present at a family medicine centre with symptoms of PUD. It was found that of 293 patients who presented with such symptoms over 1 year cimetidine was prescribed to 57 (19%). From the 236 patients who did not receive cimetidine 57 patients were selected at random for comparison. Information on these two groups of patients was obtained by chart review. The patients who received cimetidine were found to be significantly more likely (p less than 0.001) to have previously documented PUD than those who did not receive cimetidine. In patients in whom subsequent confirmation of PUD was not obtained, either because the results of investigations were negative or because the investigations were not ordered, cimetidine was prescribed to 63% of those who had previously documented PUD, compared with only 6% of those who did not. Of the patients who were investigated 73% of those with previously documented PUD had positive results, compared with 8% of those without previously documented PUD. The positive results were obtained by endoscopic examination in 88% of the patients with previously documented PUD, whereas upper gastrointestinal tract roentgenography was the definitive test in 73% of the patients without previously documented PUD. These findings suggest that previously documented PUD influences both the frequency of prescribing cimetidine and the investigations that are carried out.     

Cimetidine inhibits the pentagastrin-induced release of calcitonin in normocalcaemic man

Pentagastrin stimulates the release of calcitonin from normal C-cells in the human thyroid. In the present investigation the effect of cimetidine on the liberation of calcitonin in response to intraarterial pentagastrin (0.6 μg · kg^?1) was studied in 14 normocalcaemic patients undergoing surgery for thyroid adenomas. Cimetidine was administered as a bolus injection of 200 mg followed by an intravenous infusion of 1.5 mg · kg^?1 · h^?1. In seven patients not given cimetidine, mean calcitonin concentration in the thyroid vein rose from 419 ± 58 to 2787 ± 645 pM in response to pentagastrin. In seven patients given cimetidine, mean calcitonin concentration only increased from 107 ± 33 to 166 ± 51 pM after pentagastrin. The difference between the two groups was statistically significant both during basal conditions (P < 0.001) and in response to pentagastrin (P < 0.01). The results suggest that pentagastrin affects normal C-cells via release of histamine and that cimetidine markedly interferes with this mechanism.     

Comparison of the results of the treatment with pirenzepine combined with cimetidine and sucralfate of stomach ulcer resistant to cimetidine

Increased inhibition of gastric acid release through simultaneous blockade of H2-receptors and muscarine-receptors or administration of gastroprotective agent is theoretically justified in patients with peptic ulcer unresponsive to cimetidine. The study involved 70 patients with peptic ulcer previously treated with cimetidine in daily dose 1000 mg for 6 weeks without an effect. Patients were divided into two groups: group 1 treated with cimetidine plus pirenzepine, and group 2 given sucralfate in daily dose 4.0 g. Pirenzepine to patients of group 1 was given in a single dose of 50 mg before bedtime. Both groups were comparable in age, sex, disease onset, smoking, gastric acid secretion, and ulcer size. Healing was evaluated with endoscopic technique following 2 and weeks of therapy. Ulceration healed up within 2 weeks in 40% of patients treated with cimetidine combined with pirenzepine and in 31.4% patients treated with sucralfate. After 4 weeks, healing of ulceration was 71.4% and 68.6%, respectively. Large ulcers (over 1 cm in diameter) and previous partial gastrectomy did not affect healing rate. The obtained results suggest that administered therapies enable recovery in over 2/3 of patients with peptic ulcer unresponsive to a 6-week therapy with cimetidine alone.     

急性心肌梗死静脉溶栓治疗和心电监护的体会

目的探讨静脉溶栓治疗和心电监护对急性心肌梗死（AMI）的疗效。方法全部病例均符合WHO规定的AMI诊断标准,治疗均给予尿激酶（UK）100U～150万U,加生理盐水100ml,静脉点滴,30min滴完。同时给予心电监护,以期能及时发现患者存在的各种心律失常。结果本组72例中,均无牙齿出血、消化道出血及出血性脑卒中等并发症的发生,1例出现静脉穿刺部位皮肤瘀斑;所有患者均好转出院。结论静脉溶栓治疗和心电监护对急性心肌梗死（AMI）的疗效可靠,值得在基层医院使用。     

Evaluation of captopril levels in chronic congestive heart failure, stages NYHA III and IV]

Thirty eight patients, aged between 25 and 81 years (mean age 56.9 years) with diagnosed chronic congestive heart failure of NYHA III and IV stages have been examined. The following phases of therapy have been distinguished depending on the used drugs: phase 0--digoxin in a daily dose of 0.25 mg and furosemide in a daily dose of 40-150 mg (mean value 72.4 mg) for 14 days; phase A1A2--nifedipine has been added in a daily dose of 40-80 mg (mean value 64.0 mg), lasting also for 14 days; phase B1B2--captopril (Lopirin--Squibb) has been added to the previous drugs in a daily dose of 25-150 mg (mean value 67.4 mg) in three divided portions for 28 days; phase C1C2--captopril has been withdrawn and drugs as in phase A1A2 have been administered for 14 days. Routine laboratory tests, ECG, a 24-hour ECG-records with Holter's technique, exercise ECG, chest X-ray, and 2D and M echocardiography were performed prior to and after 7 days as well as after each phase of the studies. A significant improvement in the left ventricle functioning assessed with Cubet's echo 2D has been observed in phase B1B2 in comparison with phase A1A2. These parameters have been the following: EF 42.61% vs 31.52%; CO 3.2 vs 2.9 L/min; SV 57.15 vs 44.24 mL (p < .001). Moreover, a decrease in heart volume (X-ray) from 1,145.25 mL to 1,088.25 mL, an increase in exercise tolerance (exercise ECG) in 52.6% of the patients, decrease in Lown's class in 11 out of 24 patients have been noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial Infarction Detection and Localization Using Optimal Features Based Lead Specific Approach

ObjectivesObjective of this paper is to present a reliable and accurate technique for Myocardial Infarction (MI) detection and localization.Material and methodsStationary wavelet transform has been used to decompose the ECG signal. Energy, entropy and slope based features were extracted at specific wavelet bands from selected lead of ECG. k-Nearest Neighbors (kNN) with Mahalanobis distance function has been used for classification. Sensitivity (Se), specificity (Sp), positive predictivity (+P), accuracy (Acc), and area under the receiver operating characteristics curve (AUC) analyzed over 200 subjects (52 health control, 148 with MI) from Physikalisch-Technische Bundesanstalt (PTB) database has been used for performance analysis. To handle the imbalanced data adaptive synthetic (ADASYN) sampling approach has been adopted.ResultsFor detection of MI, the proposed technique has shown an AUC = 0.99, Se = 98.62%, Sp = 99.40%, PPR = 99.41% and Acc = 99.00% using 12 top ranked features, extracted from multiple leads of ECG and AUC = 0.99, Se = 98.34%, Sp = 99.77%, PPR = 99.77% and Acc = 99.05% using 12 features extracted from a single ECG lead (i.e. lead V5). For localization of MI, the proposed technique has an AUC = 0.99, Se = 98.78%, Sp = 99.86%, PPR = 98.80%, and Acc = 99.76% using 5 top ranked features from multiple leads of ECG and AUC = 0.98, Se = 96.47%, Sp = 99.60%, PPR = 96.49% and Acc = 99.28% using 8 features extracted from a single ECG lead (i.e. lead V3).ConclusionThus for MI detection and localization, the proposed technique is independent of time-domain ECG fiducial markers and can work using specific leads of ECG.     

Evidence for induction of hepatic microsomal cytochrome P-450 by cimetidine: binding and kinetic studies

The interaction of cimetidine with liver microsomes has been examined by spectral and equilibrium partition studies. First, difference spectroscopy has been used to evaluate the proportion of cytochrome P-450 in rat liver microsomes that exhibits an affinity for cimetidine in the pharmacologically relevant, low micromolar range of drug concentration. The value of 0.45 so obtained has confirmed that a substantial proportion of rat liver cytochrome P-450 has a high binding affinity for this drug. Second, a study of the binding of cimetidine to human liver microsomes by difference spectroscopy and partition equilibrium has detected a similar interaction, thus providing direct support for the postulate that the clinically observed impairment of oxidative drug metabolism may be due in part to inhibition of cytochrome P-450 monooxygenase by cimetidine. Hepatic microsomes from cimetidine-pretreated rats have been shown to exhibit elevated cytochrome P-450 specific content but a decreased proportion of sites with high affinity for the drug; this finding has been shown not to be the consequence of cimetidine-mediated, time-dependent, irreversible monooxygenase inhibition. Although cimetidine pretreatment caused enhanced specific activity of 7-ethoxyresorufin O-dealkylation, the specific activities for O-dealkylation of 7-ethoxycoumarin and 4-nitroanisole were decreased, as were those for the N-dealkylation of morphine, ethylmorphine, aminopyrine, and dimethylnitrosamine. Since cimetidine pretreatment was shown to cause no change in the Michaelis constants for oxidation of morphine or 7-ethoxyresorufin, it is argued that these results provide strong presumptive evidence for changes in the relative abundance of isoenzymes catalyzing these various oxidations. Thus, a dual role of cimetidine, acting both as inhibitor and inducer of the cytochrome P-450 system, is proposed to account for the impaired oxidative metabolism of some drugs that occurs during coadministration with this H2-receptor antagonist.     

Cimetidine and gastric cancer: preliminary report from post-marketing surveillance study.

Widespread publicity has been given to te possibility that cimetidine treatment might cause gastric cancer. Preliminary data are given from a post-marketing surveillance study in four centres. A total of 9940 patients taking the drug entered study and 9504 were observed for at least a year. Seventy-four cases of gastric cancer were identified in those taking cimetidine, but 23 of these were diagnosed before the use of the drug and 29 others with advanced malignancy had received cimetidine within the previous six months only. Ten of the remaining 22 had gastric cancer diagnosed within a year of starting treatment, and 12 after more than a year; only four of the total group had histologically "early" cancer. The occurrence of gastric cancer a long time after starting cimetidine treatment cannot be explained in every case, but it is noteworthy that in control group (which is not directly comparable) gastric cancer was observed in eight patients. The hypothesis that cimetidine treatment predisposes to gastric cancer cannot be excluded by our findings: in our view, however, they do not support such an association.     

Comparative evaluation of the effects of intravenous administration of cimetidine and ranitidine on several cardiovascular parameters

We have compared the effects of intravenous administration of cimetidine and ranetidine on some cardiovascular parameters. Five healthy volunteers received both cimetidine (3, 5 mg/Kg) and ranetidine (1, 5 mg/Kg). Heart rate, blood pressure and PEP/LVET were recorded at baseline and 5, 10, 30, 45 minutes after administration of both drugs. Intravenous administration of cimetidine and ranetidine did not induce any significant alterations in cardiovascular variables.     

Combined treatment of advanced malignant melanoma with coumarin and cimetidine

Summary Immunostimulant therapy with coumarin and cimetidine was evaluated in 17 patients with advanced malignant melanoma. Induction therapy with coumarin 100 mg daily was given for 8 weeks, whereupon cimetidine 1000 mg daily was added. No patients had been previously treated with cytotoxic drugs, and all patients had a good performance status. In 16 patients progressive disease was observed, and only 1 patient experienced no change in condition, lasting 30 weeks. We conclude that treatment with this schedule of coumarin and cimetidine is without effect in advanced malignant melanoma.     

Postmarketing surveillance of the safety of cimetidine: mortality during second,third, and fourth years of follow up.

A previous report analysed the pattern of mortality during the first year of follow up among 9928 patients taking cimetidine who were recruited to a postmarketing drug surveillance study in Glasgow, Nottingham, Oxford, and Portsmouth. A further analysis has now been conducted extending the period of follow up to four years. The 12 month report noted that cimetidine was being given, knowingly or unknowingly, in the late stages of many diseases and also to counter the adverse gastric effects of other drugs used in the treatment of serious disorders. This finding was underlined by a steady fall in the excess death rate among cimetidine users with increasing length of follow up, such that by the fourth year the pattern of observed deaths was not much different from that expected on the basis of national rates. Some excess of observed over expected deaths from gastric cancer, lung cancer, and urinary disorders was still apparent after four years of follow up, but there was no evidence that cimetidine was responsible. Indeed, no fatal disorder emerged as being associated with cimetidine during the follow up period. Deaths from the complications of disease related to gastric acid occurred in only 38 of the 9928 subjects over the four years. These findings provide further evidence of the safety of cimetidine.     

A symmetry approach to electrocardiogram analysis

A qualitative characteristics of a symmetry of correlations in ECG parameters has been studied in experiments on rats with the adaptation syndrome and hypertonic patients (I-II stages). A geometrical model of cardiac cycle shaped as a rectangular triangle with temporal and amplitude ECG parameters as catheti. A total correlation between the ECG parameters is given: QT--QRS/QT--PQ.RR--PQ/RR--QRS = R--P/R--T = 1,309. In healthy individuals, the deviation from the ideal proportion constitutes less than 5%, and in patients with cardiovascular diseases, the deviations are substantial.