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PubMed1976

The in vivo metabolism of progestins. I. The metabolic clearance rates of progesterone and medroxyprogesterone acetate in the dog.

[3H]Medroxyprogesterone acetate (MPA) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methyl-17alpha-hydroxy-pregn-1,4-diene-3,20 dione acetate. [14C]MPA was synthesized by acetylation of 6alpha-methyl-17alpha-hydroxy-pregn-4-ene-3,20-dione with [14C]acetic anhydride. These radioactive materials were used to determine the MPA metabolic clearance rates (MCRMPA)and volumes of distribution (VoMPA) in dogs by the single injection technique. The metabolism of progesterone was also studied in the same animals. The MCRMPA (696 +/- 51 l/day) was only one-half that of progesterone (1332 +/- 59). By contrast, the volumes of distribution for the two steroids were similar. The metabolic clearance rates and the volumes of distribution for MPA and progesterone did not change during treatment with amino-glutethimide, a drug which is known to alter steroid metabolism in man.

Aminoglutethimide↗

PubMed1984

Stimulation of progesterone synthesis in luteinized human granulosa cells by human chorionic gonadotropin and 8-bromo-adenosine 3',5'-monophosphate: the effect of low density lipoprotein.

Primary cultures of luteinized human granulosa cells reduced progestin secretion when taken from serum- and gonadotropin-containing medium into serum- and hormone-free medium. When added individually hCG, 8-bromo-cAMP and low density lipoprotein (LDL) stimulated progestin secretion by the cells after they spent 48 h in serum- and hormone-free medium. However, combinations of hCG or 8-bromo-cAMP and LDL were most effective in increasing steroidogenesis. The effects of hCG in enhancing steroidogenesis in the presence of LDL were first detectable after 3 h, but were most marked after 20 h of culture. hCG and 8-bromo-cAMP increased the conversion of [3H]cholesteryl linoleate, which had been incorporated into the core of LDL, into [3H]progesterone. hCG also stimulated cellular accumulation of LDL cholesterol, as assessed by incorporation of [1-14C]oleic acid into sterol esters or by measurement of total cellular cholesterol in the presence of amino-glutethimide to block steroidogenesis. In contrast to progesterone secretion, estradiol secretion was not affected by the addition of LDL in the absence or presence of 8-bromo-cAMP. We conclude that LDL cholesterol is required for maximal rates of progestin synthesis by human luteinized granulosa cells. When granulosa cells are stimulated by hCG, uptake of LDL cholesterol is promoted, and there is increased utilization of LDL cholesterol for steroid synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1978

Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect.

Since it had been demonstrated that L5418 has an anti-convulsant effect with no relation to its anti-inflammatory properties, comparative studies were carried out with the use of currently available anti-convulsant agents as controls. L-5418 inhibited tonic convulsions induced by maximal electroshock and strychinine in mice and prevented animals from the death sequence. L-5418 had an inhibitory effect on tonic convulsions induced by pentetrazol and N-sulfamoyl-hexahydroazepine (SaH 41-178), but not on clonic convulsions by those compounds at even a high dosage or on clonic convulsions induced by picrotoxin and bemegride. Trimethadione produced an inhibitory effect on both tonic and clonic convulsions. The hypnotic agents, phenobarbital and glutethimide inhibited both convulsions, but a higher dose was required in the case of clonic convulsions. Anti-convulsant agents are classified into three different groups according to their mode of action. L-5418 had the same mode of action as seen with diphenylhydantoin and carbamazepine. As L-5418 did not inhibit tremor induced by tremorine, an anti-Parkinson effect was ruled out. When L-5418 was administered alone, the animals did not lose the righting reflex nor show muscle relaxation observed in inclined screen and rotarod tests. Moreover, the compound had no influence on the aggressive behavior induced by electrical stimulation or olfactory bulb ablation. L-5418 possesses a selective anti-convulsant effect, yet has no sedative, tranquilizing or disturbing effects on movement such as equilibrium disturbance or muscle relaxation. L-5418 may prove useful for grand mal epilepsy as it is less toxic than diphenylhydantoin and carbamazepine.

Aggression↗

PubMed1985

Aminoglutethimide and metyrapone in the management of Cushing's syndrome.

Fifteen patients with endogenous Cushing's syndrome were treated with metyrapone and/or amino-glutethimide. The duration of the therapy varied from 19 up to 365 days. In patients with Cushing's disease, metyrapone (0.5-2.5 g/day) and aminoglutethimide (0.5-1.5 g/day) seemed equally effective in reducing the cortisol excretion (54 +/- 9 vs 40 +/- 7%). The majority of these patients also showed a clinical improvement. In 1 patient with adrenal adenoma, metyrapone induced a remission. In another patient with adrenocortical cancer, and in 2 with the ectopic ACTH syndrome, the cortisol excretion was significantly reduced by the combination of metyrapone and aminoglutethimide but no obvious clinical improvement was observed. Side effects i.e. rash and pruritus attributed to aminoglutethimide was seen in 3 patients which necessitated the omission of treatment in 2. On metyrapone a moderate hypertrichosis was observed in 1 patient. In conclusion both metyrapone and aminoglutethimide were useful as adjunctive therapy in Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1989

Testosterone concentrations in testicular interstitial fluid collected with a push-pull cannula or by drip-collection from adult rats given testosterone or aminoglutethimide.

This study was designed to investigate the differences in testosterone concentrations measured in testicular extracellular interstitial fluid obtained with a push-pull cannula or by post-mortem drip-collection. In the first experiment, testosterone-filled silicone elastomer capsules (2-16 cm lengths) or empty 2 cm capsules were implanted s.c. in adult male rats for 1 week. Animals were then anaesthetized and interstitial fluid was collected with a push-pull cannula for 1 h from one testis in each animal. Testicular and peripheral venous blood were then sampled and supernatant fluid was collected from the dispersed cells of the same testis. The contralateral testis in each animal was removed, and postmortem interstitial fluid obtained by drip-collection for 20 h at 4 degrees C. In animals given empty capsules, testosterone concentrations in drip-collected interstitial fluid were significantly (P less than 0.01) greater than testicular and peripheral venous blood levels, testicular fluid levels, and levels in interstitial fluid calculated from push-pull cannula samples. The concentrations of testosterone calculated in interstitial fluid collected with a push-pull cannula were never significantly greater than testicular venous blood levels. In animals with testosterone-filled capsules, testosterone concentrations measured in drip-collected interstitial fluid were similar to those calculated from push pull cannulae samples, and to testicular venous blood levels. In a second experiment, a group of adult male rats was pretreated with amino-glutethimide to block steroidogenesis. Two hours later, interstitial fluid was drip-collected from the testes of these animals and from a group of vehicle-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglutethimide↗

PubMed2000

Antiandrogen withdrawal syndrome associated with prostate cancer therapies: incidence and clinical significance.

The antiandrogen withdrawal syndrome is a well established phenomenon in prostate cancer. It is widely accepted that a subset of patients will benefit from the withdrawal of antiandrogen or steroidal hormone from hormonal therapy, exhibiting decreasing prostate-specific antigen (PSA) values and clinical improvement. The pathophysiology of antiandrogen withdrawal syndrome is not completely understood, although androgen receptor gene mutations seem to be the likely explanation. Currently, it is not possible to identify the subset of patients whose tumours will respond to antiandrogen or steroid withdrawal. Tumours that will respond may be classified as androgen-independent and hormone-sensitive tumours as opposed to androgen-independent and hormone-insensitive tumours that do not respond. Patients who respond to antiandrogen withdrawal experience approximately 6 months with improved quality of life; however, it is unknown if this translates into prolonged survival. At the very least, antiandrogen withdrawal offers a therapeutic modality that is not associated with adverse effects and improves quality of life even if only for a very limited time. Recent reports suggest that adding a secondary hormonal therapy such as amino- glutethimide, ketoconazole or steroidal hormones may enhance the response rate and prolong response time to the antiandrogen withdrawal syndrome. However, unless there is proof that this secondary hormonal manipulation prolongs survival, maintenance of quality of life is mandatory because of the possible adverse effects from these potent drugs. The fact that about 30% of patients will respond to antiandrogen or steroid withdrawal in hormone refractory prostate cancer must be taken into account in clinical trials of new cytotoxic agents which have been and will be conducted. Cessation of flutamide for at least 4 weeks and, in the case of bicalutamide, even 8 weeks, is mandatory before antiandrogen withdrawal syndrome can be excluded as the cause of decreasing PSA values. The antiandrogen withdrawal syndrome offers another piece of the puzzle of prostatic carcinoma, but at the same time it demonstrates how different advanced prostate cancer cells may react to therapeutic strategies and, therefore, hormone refractory prostate cancer remains a difficult challenge which must be solved in the future.

Androgen Antagonists↗

PubMed1976

Drug interactions and clinical pharmacokinetics.

Some drugs influence the gastro-intestinal absorption, distribution , metabolism or renal excretion of other drugs, i.e., processes involved in pharmacokinetic interactions. The clinical consequences of pharmacokinetic drug-drug interactions will be either an increase or a decrease in known therapeutic or toxic effects of the interacting drug. In order to evaluate the importance of drug interaction affecting gastro-intestinal absorption, it is necessary to distinguish between interactions which alter the rate of absorption of another drug and those which alter the amount of drug absorbed. Many drugs displace other drugs from their protein binding sites in vitro. This may cause an increase in the pharmacological effect of the displaced drug. However, much discrepancy exists between in vitro findings. In some cases, the enhanced effect only seems to be a temporary phenomenon. The degree of protein binding and the size of apparent volume of distribution (Vd) must also be taken into consideration. Perhaps the importance of interaction involving protein binding has been overemphasized. Barbiturates, glutethimide, rifampicin and phenytoin increase the rate of drug metabolism in man. The most important interactions reported are between oral anti-coagulants and barbiturates. After withdrawal of these hepatic microsomal enzyme inducing drugs, it takes 2 to 3 weeks before the rate of drug metabolism reaches the pretreatment level. In this period, risk of haemorrhage exists. Induction seems to be dose-dependent, but not all persons are inducible. Many drugs compete for the drug metabolising enzyme system in the liver and consequently some drugs inhibit the biotransformation of other drugs. The time course of these interactions depends on the pharmacokinetic properties of the drug involved, and these interactions also seem to be dose-dependent. The most important of such interactions, clinically involved the oral sulphonylurea hypoglycaemic drugs and the antiepilepic drug phenytoin. Drugs are eliminated by urinary excretion through three mechanisms: glomerular filtration, tubular reabsorption, and active tubular secretion. The most important interactions seem to be those involving competition for tubular secretion.

Acid-Base Equilibrium↗

PubMedDate not supplied

Pharmacokinetics of drug overdose.

Pharmacokinetics of drugs taken in overdose may differ from those observed following therapeutic doses. Differences are due both to dose-dependent changes and to effects of drugs or pathophysiological consequences of the overdose on kinetics. Dose-dependent changes in rate and extent of absorption, bioavailability (saturation of first-pass metabolism), distribution (saturation of protein binding sites) and metabolism are discussed. Gastrointestinal motility is affected both by specific drug actions, such as delayed gastric emptying by anticholinergic drugs, and by general nervous system depression caused by many drugs. Drug-induced circulatory insufficiency may retard tissue distribution and reduce clearance. Disturbances in blood and urine pH may alter distribution and clearance of weak acids and bases. Drug-induced renal or hepatic failure can significantly decrease clearance. Hypothermia is a common complication of drug overdose and might retard distribution and also reduce clearance. The data concerning pharmacokinetics during overdose are usually incomplete and difficult to interpret. Doses and times of ingestion are uncertain, duration of blood and urine sampling is often inadequate to distinguish absorption from distribution and elimination phases, active metabolites are not measured, protein binding is not determined and clinical features of patients not adequately described. We have, however, reviewed available data for salicylate, paracetamol (acetaminophen), barbiturates, ethchlorvynol, glutethimide, chloral hydrate, tricyclic antidepressants, lithium, phenytoin, ethanol, theophylline, digoxin, amphetamine and phencyclidine.

Acetaminophen↗

PubMed1989

Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics.

With the ever-increasing population of cigarette smokers, the potential for cigarette smoke to affect drug therapy both pharmacokinetically and pharmacodynamically is significant. The overriding pharmacokinetic effect is increased drug metabolism through the induction of liver enzymes. The constituents of tobacco smoke, primarily nicotine, have their own pharmacological effects which may potentiate or antagonise the desired pharmacological effect of a particular drug, thereby affecting its efficacy. Furthermore, end-organ responsiveness may also be altered by tobacco. These latter 2 aspects constitute altered clinical pharmacodynamics. Approximately 30 drugs have been evaluated in terms of cigarette smoking. Induction of liver enzymes has been shown to increase the metabolism of imipramine, meprobamate, oestrogens, pentazocine, phenylbutazone, theophylline and warfarin. Nicotine has been shown to inhibit diuresis, alter ulcer healing, impair subcutaneous absorption, affect protein binding and stimulate catecholamine release; these effects have been evaluated in terms of therapy with frusemide (furosemide), histamine H2-antagonists, insulin, lignocaine (lidocaine) and beta-blockers, respectively. The interactions have not been correlated with clinical significance in all cases. Diminished end-organ responsiveness may account for reduced drowsiness in smokers receiving chlorpromazine and benzodiazepines, compared with non-smokers. Smoking has been associated with diminished pain tolerance, requiring increased dosages of morphine, pethidine (meperidine) and propoxyphene. Enzyme-inducers such as carbamazepine, phenytoin and phenobarbitone appear to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already maximally stimulated. Codeine, corticosteroids and nortriptyline do not appear to be affected by cigarette smoke. The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy. The effect of smoking on paracetamol (acetaminophen) has been variable, depending on the extent of smoking, and does not appear to be of clinical significance.

Animals↗

PubMed1994

Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations.

The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Anxiety Agents↗

PubMed1975

Sleep and hypnotic drugs.

In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past.

Adult↗

PubMed1985

Action of drugs and chemical agents on rat liver regeneration.

Chemical agents and drugs of widely differing pharmacological activity have been administered to partially hepatectomized male rats and the extent of liver regeneration ascertained over a period of 10 days. Of the large number investigated, the following fed ad lib in diets supplemented in a basal ration at the weight percentages indicated, proved to be hepatotrophic: anticonvulsants - mephenytoin (0.15), methsuximide (0.15), phensuximide (0.15) and primidone (0.10); benzodiazepines - clobazam (0.10), flurazepam hydrochloride (0.12), halazepam (0.070), oxazepam (0.030) and temazepam (0.10); anti-inflammatory agents - benoxaprofen (0.040), ibuprofen (0.10 and 0.20), naproxen (0.040) and sulindac (0.075); sedatives and hypnotics - ethinamate (0.75), glutethimide (0.075), methaqualone (0.030 and 0.10) and methprylon (0.30) and the analgesic and antipyretic, aminopyrine (0.15); antifungal - griseofulvin (0.50); anti-androgen - cyproterone acetate (0.020 and 0.050); uricosuric - sulfinpyrazone (0.050 and 0.20); skeletal muscle relaxant - chlorzoxazone (0.20); hydrocholeretic - florantyrone (0.30); anti-hypertensive - prazosin hydrochloride (0.010) and the thyroid inhibitor, methimazole (0.025). The feeding of several of the stimulants at the given levels to intact males elicited wet and dry liver enlargement. Most of the current test agents as screened in operated rats, had little effect on the regeneration and in fact, tended to depress the process when higher levels were fed or injected.

Animals↗

PubMed1975

Comparison of radioimmunoassay with thin-layer chromatographic and gas-liquid chromatographic methods of barbiturate detection in human urine.

A radioimmunoassay (I) for barbiturates was compared with thin-layer chromatographic (II) and gas-liquid chromatographic (III) methods for barbiturate detection in human urine. Timed urine samples were obtained from volunteers who had ingested 100 mg of a barbiturate. I detected barbiturate in all urines tested up to 76 h after the dose, and III in all up to 52 h and in 90% up to 76 h. II detected barbiturates in 90% of all urine samples for only 30 h, after which is reliability declined. Glutethimide interfered with radioimmunoassay of barbiturate, producing false positives. I is sensitive, reliable, and fast, and lends itself to screening large numbers of urine samples for barbiturates. For routine urine surveillance, however, we found I to be less useful than II, which is still the method of choice. I has, however, proved to be an excellent method for confirming results of II.

Adult↗

PubMed1997

[A systematic screening and identification method for 29 central nervous system drugs in body fluid by high performance capillary electrophoresis].

A systematic screening method has been developed for the detection of 29 central nervous system (CNS) drugs in human plasma, urine and gastric juice by high performance capillary electrophoresis (HPCE). The first step is sample preparation. The patient's or normal human plasma (0.5 ml) spiked with CNS drugs was extracted with 2 x 4 ml dichloromethane, while 2 ml of patient's or spiked urine was extracted with 2 x 6 ml chloroform. The combined extract from plasma or urine was evaporated to dryness in a rotation evaporator at 35 degrees C. The residue was dissolved in 100 microliters methanol and subsequently 400 microliters of redistilled water was added. The patient gastric juice (3 ml) was centrifuged at 2,000 r.min-1 for 5 min. The supernatant was filtered through 0.45 micron microporous membrane for injection onto capillary columns. The second step was to perform CZE separation in acidic buffer composed of 30 mmol.L-1(NH4)3PO4(pH 2.50) and 10% acetonitrile (condition A). Most of the benzodiazepines (diazepam, nitrazepam, chlordiazepoxide, flurazepam, extazolam, alprazolam) and methaqualone were baseline separated and detected at 5-13 min, while thiodiphenylamines showed group peaks at 3-5 min and barbiturates migrate with electroosmotic fluid (EOF) together. The third step is to separate the drugs in basic buffer constituted of 70 mmol.L-1 Na2HPO4(pH 8.60) and 30% acetonitrile (condition B). The thiodiphenylamines and some other basic drugs could be well separated, which include thihexyphenidyl, imipramine, amitriptyline, diphenhydramine, chlorpromazine, doxepin, chlorprothixene, promethazine and flurazepam, while the rest of the CNS drugs did not interfere with the separation. The last step was to separate the drugs by micellar electrokinetic chromatography (MEKC) in such a buffer as 70 mmol.L-1 SDS plus 15 mmol.L-1 Na2HPO4 (pH 7.55) and 5% methanol (condition C). Barbiturates (barbital, phenobarbital, methylphenobarbital, amobarbital, thiopental, pentobarbital, secobarbital) and some hydrophobic drugs (glutethimide, alprazolam, clonazepam, carbamazepine, trifluoperazine, oxazepam) could be well separated. These drugs might be identified by both the relative migration time (rtm = tdrug/tEOF) and the ratios of peak heights (rh) monitored at different wavelength, since the ratios are characteristic of the spectrum of a drug. This method has been used in several real clinical samples of intoxication. For example, perphenazine and doxepin were detected in the gastric juice and phenobarbital in blood and gastric juice of an intoxicated patient.

Central Nervous System Agents↗

PubMed1975

Simple, highly selective screening method for barbiturates in urine.

I present a new, simple colorimetric method for detecting and estimating barbiturates in urine. After the barbiturates are extracted with ether, an aliquot of the washed ether phase is added to the color reagent (a bivalent mercury/dithizone chelate in chloroform). On addition of diluted pyridine and shaking, a pinkish-violet color appears if a barbiturate is present. The overall sensitivity of the above method was evaluated by probit analysis in the case of sodium phenobarbital. The concentration of sodium phenobarbital in urine detectable at least 99% of the time was 6.72 mg/liter, with 95% confidence limits of 5.37 to 10.36 mg/liter. Sodium phenobarbital, 10 mg/liter, can be detected in the presence of phenytoin (50 mg/liter), glutethimide (100 mg/liter), or bemegride (100 mg/liter). The whole procedure requires less than 10 min. An excretion study illustrates application of the procedure.

Amobarbital↗

PubMed2002

[Acute toxicological cases during a ten-year period in our clinic].

INTRODUCTION: There's a fact, that Hungary has held the first places in suicidal statstics. METHODS: The authors studied toxicological cases between 1989 and 1998 at the 1st Department of Medicine of the Medical and Health Science Centre, at the University of Debrecen, paying special attention to suicidal poisoning cases. RESULTS: 2% of the patient turnover accounted for acute poisoning cases, the number of which increased during the 10 years in question. 70% of the cases were of suicidal intentions, 20% were unintentional, these poisonings were not committed on purpose, while the proportion of iatrogenic intoxication cases was 10%. Amongst the failed suicide cases there was a higher proportion of women, whereas a higher percentage of men accounted for "successful" suicide cases. When examining auto-intoxication cases it turned out that the medicine most frequently used was meprobamate, besides benzodiazepines. Mortality rate was highest in the glutethimide intoxication cases. Most poisonings with suicidal intentions took place in the 2nd quarter of the year. Most completed suicides were committed on Wednesdays and Thursdays. 81% of the iatrogenic intoxication cases happened to be with digitalis and coumarin overdose. Nearly 50% of the cases turned out to be combined intoxications. 40% of the men took alcoholic drinks during the auto-intoxications. In the case of 135 patients extracorporeal detoxification therapy was applied, which consisted mostly of hemoperfusion. Three quarters of the patients needed psychiatric care and every fourth patient was admitted to the Department of Psychiatry. 6.9% of the poisonings were fatal. CONCLUSIONS: The growing number of toxicological cases--amongst these suicidal poisonings--compels us to pay more attention to the setting up of interdisciplinary based prevention as well as running effective toxicological centres. All physicians have a responsibility to recommend psychiatric care for people suffering from mental problems or depression and for the unsuccessful or potential suicide seeking help for the first time. Family doctors in primary medical care and who meet patients first have an important role in this job.

Adolescent↗

PubMed1976

Localization of radiolabeled enzyme inhibitors in the adrenal gland.

Tissue distribution studies were performed in rats and dogs at five time intervals between 10 min and 24 hr after the intravenous injection of one of the following radiolabeled adrenocortical enzyme inhibitors: 3H-amino-glutethimide, 125I-3-iodoaminoglutethimide, 3H-SKF-12185, 125I-3-SKF-12185, 3H-metyrapone. 3H-metyrapol. 3H-amphenone B, and 3H-SU-10603. In rats, 3H-SKF-12185 showed the highest uptake in the whole adrenal (3.5% kg dose/gm at 1 hr). In dogs, 3H-metyrapol showed the highest uptake in the adrenal cortex (9% kg dose/gm at 1 hr), and the peak cortex-to-liver concentration ratio was 57 at 2 hr. These peaks uptakes were comparable to those obtained with the conventional iodocholesterols, but they were reached much earlier, with elimination of most of the adrenal radioactivity by 24 hr. These properties would permit the use of 123I as the label and a higher tracer dose, resulting in a higher photon flux. Thus, the radiolabeled enzyme inhibitors show promise as adrenal-scanning agents, with a markedly shortened scanning procedure, a lower absorbed radiation dose, and better resolution.

Adrenal Gland Diseases↗

PubMed1992

The treatment of sleep disorders.

Narcolepsy is clinically associated with cataplexy, sleep paralysis and hypnagogic hallucinations. It is treated by reassurance (that there is no physical disease) and by stimulants such as ephedrine and amphetamine on an intermittent basis. The special tricyclic antidepressant clomipramine is also used, and mono-amine oxidase inhibitors (MAOIs) are useful in theory. Obstructive sleep apnoea is an important and often unrecognised cause of daytime somnolence. It is treated by weight reduction (pickwickian syndrome), hormones, or recently, with continuous positive pressure apparatus. Night terrors (pavor nocturnus) and sleepwalking typically occur during deep sleep (stage 3 and 4 throughout the episode) in children. In a night terror the child sits up with a scream, with eyes open, but inaccessible. He eventually falls asleep calmly. Sleepwalking, too, shows the features of inaccessibility and subsequent amnesia for the episode. Both conditions are normally treated with reassurance (to the parents) but may occasionally warrant benzodiazepines. Enuresis usually occurs in non-rapid eye movement (NREM) sleep, especially stages 3 and 4. The reason for the efficacy of tricyclic antidepressants is not precisely known. Delirium tremens (DT) is treated as a rebound excess of REM sleep, with benzodiazepines and other drugs. It is the withdrawal syndrome (with or without major seizures) to the barbiturate-alcohol group of drugs, which includes alcohol, chloral, paraldehyde, glutethimide, methylprylone, ethchlorvynol, meprobamate and meprobamate-diphenhydramine. Insomnia may be treated by the above drugs, by analgesics, antidepressants, major tranquillisers (neuroleptics) and miscellaneous other compounds. For the majority of patients, however, the most suitable group seems to be the benzodiazepines. The benzodiazepines are much safer than their predecessors, in both acute and chronic usage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗