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Case presentation: A 32-year-old professional bodybuilder presented with acute decompensated heart failure. He gave a history of anabolic androgenic steroids (AAS) use for >2 years and mephentermin...

Background The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. Methods RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. Results We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. Conclusion Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.

Calcium, a physiological ion, causes vasoconstriction and has a positive ionotropic action on heart. Its use to prevent post-spinal hypotension has been suggested but never formally evaluated for patients undergoing caesarean section. This study investigated the hemodynamic effects of calcium administration in parturients with the primary aim of comparing the incidence of post-spinal hypotension.Sixty healthy full-term pregnant patients scheduled for caesarean section were randomly allocated to two equal groups to receive either calcium gluconate or normal Saline bolus over 20min by syringe infusion pump under electrocardiography monitoring immediately after the patient was turned supine following spinal anaesthesia. Blood pressure and heart rate were recorded at baseline, and at regular intervals following spinal. Maternal calcium levels were estimated before and after infusion. Neonatal blood gas analysis and calcium level were analyzed. Total mephentermine requirement was recorded in both groups.The heart rate values remained comparable to baseline value in group calcium gluconate while in group normal Saline, it decreased significantly at 8,12 and 16min. Blood pressure decreased significantly as compared to the baseline value from 4min onwards in both the groups. However, it was comparable in the two groups at all time points(0.622). Nineteen patients(63.33%) required mephentermine infusion in group calcium gluconate as compared to 23 patients(76.6%) in group normal Saline for maintenance of systolic blood pressure.(p=0.791) Umbilical venous pH (p=0.038) and partial pressure of carbon dioxide(p=0.038) were significantly better in group calcium gluconate.Calcium used for prophylaxis of hypotension in healthy parturients undergoing caesarean section reduced the vasopressor requirements and total mephenteramine dose, but the difference did not attain statistical significance.

Mephentermine is a sympathomimetic amine, frequently used as a vasopressor. It is structurally comparable to amphetamines, and World Anti-Doping Agency has prohibited its use as a performance-enhancing drug. However, its illegal consumption by several sportspersons and those appearing for physical endurance tests is a growing concern for health-care professionals. We present a case of misuse of intravenous mephentermine by a young male who abruptly increased its amount a few days prior to the sports competition and developed acute psychosis. The case report highlights the need for strict regulations for procuring methamphetamine and effective treatment strategies for managing its misuse.

Mephentermine is a vasopressor drug closely related to amphetamine and methamphetamine. Cases of abuse and dependence to mephentermine have dotted medical literature for a long time. Till date, 11 cases of dependence to mephentermine have been published. In this report, a case of mephentermine dependence is being discussed. The patient was a young adult male who was dependent to mephentermine for nearly 3 years. He was an athlete and was introduced to mephentermine by his peer for enhancing performance. He did not develop any major physical or psychiatric issue due to the drug. He was managed on out patient basis. Though cases of mephentermine dependence are few and far in medical literature, reports from other sources indicate that the problem could be more common and could be on rise. High index of suspicion and holistic care is likely to help patients and treating clinicians.

Mephentermine and phentermine, substances prohibited in sports by the World Anti-Doping Agency, were found for the first time in urine specimens following the administration of a therapeutic medication, oxethazaine. In a recent sporting event, a urine specimen donor who tested positive for mephentermine and phentermine claimed consumption of Mucaine((R)) for treating stomach pain was the reason for testing positive. Five volunteers were administrated oxethazaine (a topical anesthetic found in the multi-ingredient medication Mucaine and its generic equivalent, Stoin, both of which are available in Taiwan), mephentermine, and phentermine. Excretion profiles of mephentermine and phentermine following the administration of these drugs were found to be similar. However, the mephentermine/phentermine ratios found in urine specimens collected at different time points following the administration of oxethazine and mephentermine were found to be characteristically different.

The urine specimens of numerous athletes were found to be positive for mephentermine both in-competition and out-of-competition in Taiwan. The donor of one specimen claimed she had only taken Mucaine® (contains oxethazaine) for relieving symptomatic peptic ulcer and gastritis. Oxethazaine is not included in the prohibited list of the World Anti-Doping Agency; however, its metabolized compounds, mephentermine and phentermine, are included in that list. This study applied LC–MS–MS to analyze the excretions of three volunteers who ingested oxethazaine and presented positive results for mephentermine and/or phentermine. Thus, oxethazaine is the source of mephentermine and phentermine. Moreover, the results showed that 48 brands of gastric medicines containing oxethazaine were legally imported or locally manufactured in Taiwan, information which could be useful for limiting the misuse of oxethazaine by athletes. The data suggested that the sports associations should warn athletes about the risks of taking oxethazaine.

Nonmedical use of prescription stimulants such as phentermine (PT) has been regulated by law enforcement authorities due to its euphorigenic and relaxing effects. Due to high potential for its abuse, reliable analytical methods were required to detect and identify PT and its metabolite in biological samples. Thus a dilute and shoot liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for simultaneous determination of PT, N-hydroxyphentermine (NHOPT) and mephentermine (MPT) in urine. A 5μL aliquot of diluted urine was injected into the LC-MS/MS system. Chromatographic separation was performed by reversed-phase C18 column with gradient elution for all analytes within 5min. Identification and quantification were based on multiple reaction monitoring (MRM) detection. Linear least-squares regression with a 1/x(2) weighting factor was used to generate a calibration curve and the assay was linear from 50 to 15000ng/mL (PT and MPT) and 5 to 750ng/mL (NHOPT). The intra- and inter-day precisions were within 8.9% while the intra- and inter-day accuracies ranged from -6.2% to 11.2%. The limits of quantification were 3.5ng/mL (PT), 1.5ng/mL (NHOPT) and 1.0ng/mL (MPT). Method validation requirements for selectivity, dilution integrity, matrix effect and stability were satisfied. The applicability of the developed method was examined by analyzing urine samples from drug abusers.

This study compared the effects of intravenous infusions of ephedrine and mephentermine for maintenance of maternal arterial pressure and neonatal outcome in pregnant women receiving subarachnoid block for lower segment Caesarean section. Sixty patients who developed hypotension following subarachnoid block for Caesarean section were randomly divided into two groups of 30 each to receive an intravenous infusion of ephedrine or mephentermine. Hypotension was defined as a decrease in systolic blood pressure of > or = 20% from the baseline value or an absolute value of

This study was designed to determine the minimum effective dose (ED50) of mephentermine for prevention of post-spinal hypotension in women undergoing elective caesarean section. Dixon's up-down method of sequential allocation was used to determine the patient's dose of vasopressor drug. In our previous study, mephentermine appeared to be much more potent than ephedrine, so the present study was conducted using a lower initial dose and smaller dose interval for this vasopressor. Following administration of spinal anaesthesia, a prophylactic infusion of mephentermine was started with 5 mg infused over a period of 30 minutes as the initial dose and a dose interval of 1 mg. The ED50 of mephentermine of 3.7 mg (95% confidence interval 2.4 to 5.7 mg) was much less than that of ephedrine, as calculated in our previous study using the same methodology. Using these values gives a potency ratio of ephedrine to mephentermine of 1:6.8 (95% confidence interval 6.0 to 7.5).

This study compared the effects of intravenous infusions of phenylephrine and mephentermine on the prevention of maternal hypotension and neonatal outcome in patients receiving spinal anaesthesia for caesarean section. Sixty ASA 1-2 patients with term, uncomplicated singleton pregnancy undergoing caesarean section under spinal anaesthesia were randomly divided into two groups of 30 each, to receive a prophylactic intravenous infusion of either phenylephrine or mephentermine. The incidence of hypotension was statistically similar in the two groups. However, in patients receiving phenylephrine, 7 (23%) developed bradycardia and 6 (20%), reactive hypertension. Neonatal outcome, in terms of Apgar scores and umbilical artery pH, was similar in both the groups. To conclude, phenylephrine and mephentermine infusions are equally effective in preventing post spinal hypotension in patients undergoing caesarean section and are associated with a similar neonatal outcome.

Hypotension is common following spinal anesthesia. Various vasopressors have been indicated to prevent it. The study compares three such agents namely phenylephrine, ephedrine and mephentermine.The study included 90 patients undergoing elective and emergency cesarean section who developed hypotension following subarachnoid blockade. Parturient were randomly divided into three groups each group had 30 patients. Group P received bolus of Phenylephrine 25 microgram, where as group E received Ephedrine 5mg and Group M received Mephentermine 6mg.It was found that rise of blood pressure was significantly higher in case of phenylephrine group in first six minutes, after the bolus, there was significant reduction in the heart rate in phenylephrine group, but there was tachycardia following administration of bolus ephedrine and mephenteramine. Neonatal APGAR score were similar in all three groups.All three drugs maintained hemodynamics within 20 percent of the baseline values on intravenous administration.

A GC method was developed for the identification and quantitation of eight sympathomimetic amines in urine, i.e., amphetamine, methamphetamine, mephentermine, ephedrine, pseudoephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, and methylenedioxyethylamphetamine. Methoxyphenamine was used as the internal standard (IS). The assay is rapid, sensitive, and simple to perform. It involves a liquid-liquid extraction procedure with simultaneous in-solution derivatization of the organic layer with pentafluorobenzoyl chloride (PFB-CI), followed by GC/MS analysis. These derivatives and the IS were extracted from 1 mL alkaline urine into hexane before derivatization with PFB-CI. The organic layer was then removed and evaporated to dryness before dissolution with hexane for GC/MS analysis. Calibration curves for each analyte showed linearity in the range of 25-5000 ng/mL (r2or = 0.997). Recoveries ranged from 88 to 99%, with the precision of recoveries typicallyor = 5%. The LOD values ranged from 7 to 28 ng/mL, and the LOQ values ranged from 23 to 94 ng/mL. At least four ions were available for each analyte for confirmation of identity by MS.

The dosages and potency of intravenous mephentermine for prevention of post-spinal hypotension are not available in English literature. This study was designed to determine the minimum effective dose (ED50) of mephentermine and to compare its potency with that of ephedrine for prevention of post-spinal hypotension in parturients undergoing caesarean section. Dixon's up-down method of sequential allocation was used for vasopressor doses. Following administration of spinal anaesthesia, patients received a prophylactic infusion with 50 mg infused over a period of 30 minutes as the initial dose and dose intervals of 5 mg, of either ephedrine or mephentermine. The ED50of ephedrine was 25.0 mg (95% CI 15.5 to 40.4 mg). For mephentermine, the up-down method was abandoned due to the success of the minimum dose possible but the ED50appeared to be less than 5 mg. In conclusion, the minimum effective dose of mephentermine is much less than that of ephedrine for prevention of post-spinal hypotension. Another trial with a lower starting dose and smaller dose interval of mephentermine is required to determine the potency ratio of mephentermine and ephedrine.

BackgroundIntrathecal ketamine produces a short period of analgesia with stable haemodynamics. Midazolam with bupivacaine prolongs the duration of analgesia when administered intrathecally but does not prevent hypotension. The objective of this study was to assess the effect of a combination of intrathecal bupivacaine, ketamine and midazolam on the duration of analgesia and haemodynamic parameters.MethodsA prospective, randomized, double-blind study was carried out in 60 ASA I and II patients undergoing lower limb surgery under spinal anaesthesia. Patients were divided into three groups of 20 each. Patients in all the three groups received 3 mL of hyperbaric bupivacaine (0.5%) intrathecally. In addition, patients in Groups II and III received intrathecal ketamine (0.1 mg kg−1) and the same dose of ketamine along with midazolam (0.02 mg kg−1), respectively. All patients were evaluated for block characteristics, duration of pain-free period, total rescue analgesic requirement in the 24-h postoperative period, total dose of mephenteramine to treat hypotension and any central or neurological complication.ResultsNo patients in Group II required mephenteramine while 40% of patients in Group I and 10% in Group III required mephenteramine to maintain blood pressure after spinal anaesthesia. The mean ± standard deviation duration of pain-free period was 331.5 ± 89.9, 369.7 ± 124.2 and 730.5 ± 81.5 min in Group I, II and III, respectively. The pain-free interval was significantly greater in Group III compared to Groups I and II (P < 0.001). No patient had any complications.ConclusionA low dose of midazolam and ketamine with bupivacaine intrathecally results in prolonged analgesia and less haemodynamic fluctuations. However, the safety of this combination needs to be proved before its use in clinical practice.

Dear Editor, Mephentermine is an amphetamine-derived phenethylamine which shares a strong chemical similarity with both methamphetamine and the resulting stimulant actions of the alpha and beta adrenoceptors. It has been proposed that phentermine, which is a main metabolite of mephentermine, acts by inhibiting

Background Substance abuse is a serious health concern. This report presents the case of a 22-year-old Brazilian man with a history of mephentermine use who fulfils all the criteria for chemical dependence listed by ICD-10. Mephentermine is a sympathomimetic agent derived from methamphetamine which, in Brazil, is restricted to veterinary use. Case description The subject used the substance at a high dose (120 mg) to improve his physical performance while working out at a gym. His symptoms included anorexia and insomnia. After days of intense activity, he felt fatigue and soreness. A physical examination revealed scars on both forearms from the injections and a psychological examination revealed moderate speech and motor agitation. Conclusions Cases such as this may be common among the general public. They should have some bearing upon medical practice and public health policies involving drugs.

A laboratory study interested in the analysis of human hair for drugs-of-abuse was conducted to determine if drugs could be detected and quantified from hair. Supercritical fluid extraction (SFE) techniques followed by GC-MS analysis were applied to extract amphetamines from hair. The group of amphetamines included methylenedioxyamphetamine (MDA), methylenedioxymetamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA) and internal standard mephentermine (MP). To validate information on amphetamine use in hair, powdered hair samples free from drugs were collected and soaked in a known amphetamine standard solution. Authentic fortified case hair samples taken from known drug users known to have consumed amphetamines were also analyzed for amphetamine. Results from this study show that amphetamine use can be detected in spiked and authentic fortified human hair using SFE techniques for qualitative and quantitative reproducible results.

Mephentermine misuse or dependence has been rarely reported in the literature. This is surprising as mephentermine bears a close structural similarity to methamphetamine. Here we report a case of mephentermine dependence with induced psychosis. A 23-year-old professional weightlifter used to administer mephentermine (60 mg) for improving performance in tournaments. The patient became dependent on mephentermine in 2009, and his consumption increased to 100-150 mg every 2-3 days since August 2012 until his presentation in clinic in mid-October 2012. He developed psychosis and had persecutory delusions. Remission of psychosis was seen with stopping use of mephentermine and use of antipsychotic medication.

An automated LPME device for a dynamic LPME method was manufactured and its extraction efficiency was tested using spiked urine samples. The developed home-made LPME device was a programmable automated syringe dispenser to overcome deteriorating precision and difficulties in manually manipulating the plunger repeatedly. To establish the optimum parameters for benzene ethylamines, the effects of sampling volume, solvent volume, pH, salt-effect, choice of solvents, plunger speed, and number of samplings were investigated. Good repeatabilities for the extraction of mephentermine, ephedrine, methoxyphenamine, selegiline, and bupropion were obtained and the RSD values were 2.4, 1.9, 1.3, 1.6 and 1.5% at a concentration of 3 microg mL(-1) in spiked urine samples, respectively. The limit of detection was below 0.05 microg mL(-1) for the investigated drugs. This developed device for LPME analysis gave good validation results and improved convenience.

The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.

Isolated uterine arteries from nonpregnant human uteri and pregnant sheep uteri responded in a similar manner to 7 vasopressor drugs. Epinephrine and norepinephrine were equal in vasoconstrictor activity and about 10 times more active than phenylephrine and metaraminol which were also equally active. Ephedrine, mephentermine, and dopamine produced contractions of uterine arteries but only at high concentrations. Neither halothane (0.45 to 0.50 per cent), nitrous oxide (70 per cent), nor lidocaine (3 μg per milliliter) altered contractions to epinephrine or norepinephrine.

THE clinical use of mephentermine¶ to elevate the arterial-blood pressure in man is presumably based upon the rationale that its pressor action is primarily due to an increase in myocardial contractility, with little effect upon the peripheral arteriolar resistance. This concept is mainly derived from animal studies.1 , 2 Recently, it was reported3 that this agent caused an increase in the height of the I-J wave as measured by the ballistocardiograph and an increase of the vascular resistance of the fingers as recorded by a segmental and digital plethysmograph. The inference was that mephentermine had both cardiac and peripheral action. There has . . .

The hemodynamic responses to mephentermine were studied in dogs anesthetized with pentobarbital and in those treated with gallamine. Observations were made in normotensive animals and in animals made hypotensive by intravenous hexamethonium. Mephentermine regularly caused an increase in cardiac output and arterial pressure regardless of the control state of the animal. Calculated peripheral resistance increased in 18 of the 22 experiments. In this study, mephentermine raised the level of arterial pressure by increasing both cardiac output and peripheral resistance.

Almost every drug used in the treatment of myocardial infarction accompanied by shock can have serious adverse effects. Inadequate myocardial contractility apparently is at least partly responsible for the hypotension. Accordingly, sympathomimetic amines having direct myocardial actions (norepinephrine, mephentermine, metaraminol) appear to be more suitable than amines having little or no myocardial effect (methoxamine, phenylephrine). However, therapy must be tailored to individual needs; the amines are not interchangeable.

In addition to the development of several new mechanical and electrical techniques, advances in the treatment of cardiac arrest in the last 2 decades include the better use of established drugs and the appearance of a few new pharmacologic agents as well. Drugs are used for various purposes in all stages of cardiac resuscitation: in the prevention of cardiac arrest, in the emergency restoration of circulation of oxygenated blood, in the restoration of intrinsic cardiac rhythm and in the prevention of recurrent attacks of arrest. Reflex vagal standstill is prevented by intravenous administration of atropine and careful ventilation. Depressed cardiac rhythmicity and conduction are treated with sympathomimetic amines that arouse, maintain and accelerate cardiac pacemakers. Epinephrine or isoproterenol is given intravenously, usually in diluted solution. The rapid onset and offset of action of the drugs given in this way permit moment to moment control and make for safety and efficacy in their use. Recurrent ventricular tachycardia or fibrillation and premonitory ectopic ventricular activity are treated with depressant drugs (lidocaine or procainamide) given intravenously in repeated doses, again for rapid, controlled and effective action.

The effects of 5 sympathomimetic amines on myocardial contractile force were determined with the Walton-Brodie strain-gage arch in 16 patients undergoing operations for congenital heart disease. Equal doses of norepinephrine and epinephrine produced almost identical increments in myocardial contractile force; equipressor doses of methoxamine resulted in little or no change in the force of contraction. Mephentermine and metaraminol produced increments in myocardial contractile force similar to those following norepinephrine administration but the duration of action was longer. The results of these studies indicate that there are no qualitative differences in the actions of these amines on cardiac contractile force of dog and man and provide a basis for the rational clinical use of these agents.

Vasopressor drugs have three principal effects: (1) available blood is shunted to maintain the circulation of vital regions such as the myocardium and brain; (2) cardiac arrhythmias may be aborted by the direct pressor effect on the myocardium; (3) myocardial blood flow is improved because of the increased coronary perfusion pressure and also a vasodilating action. Vasopressor drugs such as norepinephrine, metaraminol, methoxamine hydrochloride, hypertensin, mephentermine and phenylephrine hydrochloride may terminate cardiac arrhythmias when hypotension exists. If they do not terminate the arrhythmia, they support the coronary circulation until other slower-acting anti-arrhythmic agents take effect.

The antifibrillary actions of Ambonestyl, quinidine, and mephentermine were studied on spontaneous ventricular fibrillation and on surgically induced ventricular fibrillation in the hypothermic dog. In addition, combinations of these agents were studied on spontaneous ventricular fibrillation in hypothermia. Mephentermine in a dose of 3 mg./Kg. significantly reduced the frequency of spontaneous ventricular fibrillation, whereas Ambonestyl and quinidine were not effective. When combined with either Ambonestyl or quinidine, mephentermine exerted the same antifibrillary effect. Surgically induced ventricular fibrillation in hypothermia was significantly reduced by quinidine (12 mg./Kg.) but not by Ambonestyl or mephentermine. The results indicate that the two situations (spontaneous and surgically induced fibrillation in hypothermia) are not entirely similar, that prevention of one does not imply prevention of the other, and that the factors predisposing the heart to fibrillation are different in the two conditions.

Mephentermine increased maximum breathing capacity in emphysema patients due to partial relief of existing bronehospasm. Small variations occurred in tidal volume, arterial-blood saturation, O 2 uptake and CO 2 removal per liter ventilation, and in respiratory quotient. There was an increase in expiratory minute volume, alveolar ventilation, frequency of respiration, O 2 consumption, CO 2 elimination, and arterial-blood pH; a decrease occurred in physiological dead space, physiological dead space/tidal volume ratio, and CO 2 content and tension in arterial blood. These changes were marked in normal individuals and in mitral stenosis patients, in contrast to the minimal effects obtained in emphysema cases. Bronehodilatation in emphysema, reduction of the physiological dead space and physiological dead space/tidal volume ratio, and changes in both direction in arterial-blood saturation as well as circulatory effects suggest that mephentermine affects the ventilation-perfusion relationships throughout the lung. The disproportionate increase in expiratory minute volume and frequency of respiration, while arterial-blood findings showed a significant decrease in CO 2 tension and a significant increase in pH, suggests an important central effect. In normal and in mitral stenosis patients, mephentermine produced an increase in heart rate, a decrease in mean right-atrial pressure, and an increase in cardiac output as a result of myocardial stimulation. Changes in pulmonary-artery pressure were variable. Pulmonary arteriolar resistance decreased in all three normal controls and in the majority of mitral stenosis cases, while wedge pressure changed very slightly. These changes are interpreted as pulmonary vaso-dilatation. Systemic pressure increased, while total systemic resistance decreased or remained essentially unchanged. Arteriovenous O 2 difference decreased in most eases with increased cardiac output, and vice versa. Increased cardiac output, associated with unchanged or falling systemic resistances and decreased arteriovenous O 2 difference, suggests vasodilatation with, increased peripheral blood flow. The fact that systemic resistance increases slightly in some cases must mean that vasocon-striction with decreased peripheral blood flow occurred in other vascular areas as a probable compensatory reaction. These effects led to an increase in arteriovenous O 2 difference and a reduction in cardiac output.

1.1. Shock accompanying myocardial infarction is associated with a mortality of approximately 80 per cent. 2.2. Pressor amines were administered to eighteen patients in shock accompanying myocardial infarction. ∗ Mephentermine (Wyamine), in a preliminary study, was found to be a safe effective pressor substance with little direct effect upon myocardial irritability in the doses employed. Seventeen patients were treated with mephentermine (three also received ephedrine) and one received ephedrine alone. 3.3. A pressor response was produced in sixteen patients. Fourteen emerged from the shock state with marked clinical improvement for more than two days. However, seven succumbed to secondary complications two to twenty-six days later. Seven patients recovered sufficiently to be discharged from the hospital. 4.4. Pressor therapy did not produce congestive failure in patients not previously in failure, nor did it aggravate pre-existing failure. 5.5. The use of pressor amines in the treatment of shock accompanying myocardial infarction appears to rest upon a firm clinical basis.

The oxytocic effect of norepinephrine was established by previous investigations, and the present paper shows the effects of other vasopressor drugs (methoxamine, mephentermine, and Novadral) upon the dynamics of the human pregnant uterus. The study covered a total of 48 doses administered to 26 pregnant women near term with dead or anencephalic fetuses. The effect was investigated by means of continuous monitoring of the amniotic pressure. The stimulating effect was constant. The dangers of using vasopressor drugs in pregnancies near term are noted.

SUMMARY The circulatory effects of single intravenous injections of 0.75 mg/kg mephentermine were investigated in five healthy volunteer subjects. Ninety min after the first injection, atropine 1–2 mg was administered i.v. and the injection of mephentermine repeated. Cardiac output was measured beat-by-beat with an analogue computer-ballistocardio-graph system, validated by dye-dilution cardiac outputs. The first injection of mephentermine increased mean arterial pressure, systemic vascular resistance, and left ventricular minute work, with no change in the other variables. The injection of atropine produced a sudden marked increase in heart rate, cardiac output, arterial pressure, and left ventricular work, and a fall in stroke volume. The repeat injection of mephentermine caused considerably smaller changes in the circulation than either previous injection. Atropine thus unmasked the beta-adrenergic stimulating effects of mephentermine, as well as a surprisingly prolonged action of the agent. It is suggested that the combination of atropine plus mephentermine be investigated as an approach to improved pressor therapy. Mephentermine is relatively slow in onset, with prolonged peak effects. For a given increase in arterial pressure, it produces much less drastic changes in other cardiovascular variables than does methoxamine.

This case history was presented because of two separate etiological factors producing shock, namely, gram-negative ( Aerobacter aerogenes ) bacteremia and myocardial infarction. In this case, shock was preceded by convulsive seizure and coarse tremors of the right arm and leg, instead of the usual occurrence late in the course of events. This was interpreted as an early toxic manifestation of impending gram-negative bacteremia with shock. Of special interest is the marked leukemoid reaction (73,750 white blood cells per cubic millimeter), with metaraminol bitartrate suspect. Leukemoid reaction does not occur in gram-negative bacteremia, which is more likely to produce hemolytic reactions. Leukemoid reaction of this degree is not characteristic of myocardial infarction. Other causes of sepsis were ruled out. The hypotensive state was profound and prolonged for a total of 30 days and responded to conventional therapy. Adrenal insufficiency was suggested as a cause of prolonged hypotension but is not well documented by steroid levels reported or by the Thorn test.

Mephentermine in non-stimulating doses (1 mg/kg) produces an acute ergotropic response (AER) when given intravenously with reserpine (1 mg/kg). The EEG and behavioral arousal obtained in rabbits by this drug combination was attributed to the release of brain norepinephrine because the precursor of norepinephrine (DL-DOPA) restored the AER in previously reserpinized animals. Conversely, norepinephrine, dopamine and the precursor of serotonin (5-HTP) all failed to restore the AER in reserpinized animals. The effects of iproniazid pretreatment, alpha methyl meta tyrosine pretreatment, chlorpromazine, pentobarbital, scopolamine, desmethylimipramine and imipramine on the AER are described. The AER was also produced in dogs. Reserpine given in combination with phenylethylamines may be a useful method for revealing important indirect central actions of the latter. In this regard, reserpine affected the central actions of mephentermine and methamphetamine differently. When given together, reserpine clearly enabled non-stimulant doses of mephentermine to cause an excitation that was not mimicked by subthreshold doses of methamphetamine. Conversely, pretreatment of rabbits with reserpine clearly reduced or abolished the CNS stimulation caused by high doses of mephentermine; whereas, threshold doses of methamphetamine characteristically produced CNS stimulation. The results suggest that mephentermine, in contrast to methamphetamine, acts predominantly or completely through indirect mechanisms in causing CNS stimulation.

SELF-POISONING with combinations of drugs is becoming increasingly common and such cases present considerable therapeutic problems. The difficulty in measuring blood and urine levels of many new sedatives and tranquillizers has meant that no firm guide-lines for treatment have been laid down; in particular, little evidence exists as to the value of measures such as forced diuresis and haemodialysis in increasing the rate of removal of the drugs from the body. In addition, precise details of the multiple drugs ingested are seldom available, and treatment often resolves itself into the application of good respiratory care and the correction of shock. This latter problem is often difficult, and persistent hypotension commonly contributes to the patient's death. The present case is reported because of the success of the therapeutic methods used, and the initial failure of forced diuresis.

The authors present case reports of three patients with similar pathology in their social, vocational, and sexual adjustment who developed paranoid or paranoid hallucinatory syndromes in conjunction with the abuse of mephentermine from Wyamine inhalers. Their symptomatology appeared clinically identical to amphetamine psychosis or acute paranoid schizophrenia. The authors conclude that, if abused, the Wyamine inhaler is potentially dangerous and that its availability on the market constitutes a loophole in the current regulations governing stimulant drugs.

The arterial pressure fell abruptly in 23.38% of 124 psychic patients during the first days of treatment with neuroleptics. About two weeks later it gradually rose to its initial values. The patients who do not feel well with the low arterial pressure need peripheral stimulants such as Effortil, Mephentermin, etc. Other complications of the neuroleptic therapy are the rhythm and conduction cardiac disorders (19.96% of the patients over 60 years of age showed rhythm and conduction disorders--polytopic and multiple extrasystoles, ventricular paroxysmal tachycardia, atrioventricular block III degree). These patients need active surveillance and emergency treatment with antiarrhythmic drugs. The modern treatment of psychic diseases with larger doses of neuroleptics requires regular clinical and ECC control, especially in older patients.