Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 67-year-old patient took 5 mg of ergotamine daily for 18 months. His headaches and dysphoria were greatly improved by stopping this drug. Brain imaging by CT and magnetic resonance techniques showed numerous atrophic lesions that may represent infarcts due to occlusion of superficial cortical vessels.
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PMID:Bilateral focal cortical atrophy and chronic ergotamine abuse. 392 72

1. Twelve healthy subjects received 10 mg morphine HCl delivered transdermally from an occlusive reservoir applied to a small area of skin, painlessly de-epithelialised by vacuum suction. On a separate occasion, 10 mg morphine HCl was given as an i.v. infusion over 20 min. 2. Venous blood samples were collected serially for 72 h and assayed for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by h.p.l.c. Pupil size, salivation, and central nervous effects (nausea, fatigue, headache, feeling of heaviness and dysphoria/euphoria) were also measured. 3. After transdermal application morphine was absorbed by a first-order process to produce relatively constant plasma drug concentrations over 11 h. The absolute bioavailability of transdermal morphine was 75% (65-85%; 95% CI). The plasma concentrations of both M6G and M3G were lower after transdermal administration than after i.v. infusion, and a considerable delay (of up to 1 h) was observed before the metabolites were detectable. AUC ratios for M3G and M6G relative to morphine were similar after both modes of administration. 4. Non-analgesic effects were less pronounced at the lower plasma drug and metabolite concentrations observed after transdermal delivery than after the i.v. infusion of morphine. 5. Transdermal administration of morphine warrants investigation as an alternative route of morphine delivery.
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PMID:Transdermal administration of morphine to healthy subjects. 791 76

The levels of N-acetyl-beta-glucosaminidase (NAG) in urine from 35 patients with bipolar affective disorder were compared with scores for the 90 items (symptoms) of the Symptom Checklist (SCL-90). There were significant negative correlations between NAG levels and 23 of the SCL-90 variables (symptoms). These symptoms could be grouped into the following categories: anxiety, unusual or psychotic thinking, suicidal thinking, dysphoria, irritability, nausea, headaches, memory problems, and loss of interest. Serotonin abnormalities may play a role in the production of many of these symptoms. The hypothesis that NAG could be a marker for a serotonin activity is discussed.
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PMID:Association of levels of N-acetyl-beta-glucosaminidase with specific psychiatric symptoms in bipolar patients. 834 66

There may be a population of patients subject to frequent headache and in whom optimal analgesic effect is obtained only by frequent but controlled use of opiate drugs and in whom adverse drug effects are minimal. It is emphasized again that the reality is that there are currently a large amount of opioids being prescribed for headache patients because of patients' demands. One of the major considerations for physicians prescribing such treatment is familiarity with the legal guidelines. The federal law requires physicians to register if they are to maintain or detoxify with opioids addicts defined as "any individual who habitually uses any narcotic drug so as to endanger the public morals, health, safety, or welfare, or is so far addicted to the use of narcotic drugs as to have lost the power of self-control with reference to his addiction." A subsequent regulation, however, stated that the law was not intended to impose any limitation on prescription of narcotics for intractable pain. There are also many different state regulations covering, for example, limitations on amounts to be prescribed and reporting of patients who are habitual narcotic users. Obviously, headache patients who request liberal amounts of opioids must be screened. There has been considerable recent effort to provide guidelines regarding which patients with nonmalignant pain might be poor candidates for opioid treatment by reason of both probable treatment failure and risk of drug overuse. Many of these guidelines are not relevant to headache patients in whom pain is rarely continuous and rarely demands scheduled analgesia, as is often the case with pain of other types. There is general agreement that any previous history of any type of substance abuse is an important indicator of danger of recurrence of such behavior. Evaluation of psychological state and personality structure is of great importance. The more evidence of emotional disturbance, the greater the danger both of poor results and of drug abuse. In the chronic daily headache population, treatment failure has been found to correlate with abnormalities on the Minnesota Multiphasic Personality Inventory (MMPI). It is possible that formal psychological testing prior to the prescription of opioid drugs will prove of value in identifying those headache patients at greatest risk for drug abuse. The importance of making opioid treatment part of a multifaceted pain program has been emphasized. Portenoy emphasizes the need for (1) careful discussion with the patient (and often family) of the potential side effects of the drugs, and (2) scrupulous monitoring of adherence to the appropriate dosage and maintenance of prescription by a single physician. The more psychological disturbance evidenced by the patient, the more the risk with failure of drug treatment and of drug abuse. Finally, the analgesic needs of the patient with frequent migraine are different from those of the patient with tension-type headache. Migraine infrequently occurs more than two or three times a week for any period and usually responds to ergotamine, dihydroergotamine, sumatriptan, or a phenothiazine. Addition of codeine or oxycodone for the occasional intractable attack may be needed. When demands in a migraine patient for opioids in amounts greater than 10 to 15 tablets per month occur, there is obvious cause for concern. The opioid agonist-antagonist butorphanol, now available in nasal inhalation form, is alleged to have low abuse potential because it tends to produce dysphoria (an unpleasant emotional state) rather than the euphoria of other opioids. It is therefore unscheduled. The drug, however, does have abuse potential, and the limits needed to be placed on its use are still uncertain. Markley recently recommended a restriction to not more than two bottles (30 treatments) per month. The population with frequent tension-type headaches presents the major problem. Large numbers of these patients use drugs--often in combination
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PMID:Opioids in headache treatment. Is there a role? 905 6

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

We carried out a Hungarian multicentre study to assess the frequency of the occurrence of warning symptoms preceding epileptic seizure. The data of 562 patients with epilepsy out of a total of 1124 were analysed on the basis of questionnaires filled in under standard conditions. About 50% of the patients experienced warning symptoms before a smaller or greater part of their seizures. Their appearance was fairly consistent and became mainly manifested in the form of headache, epigastric sensation and dysphoria. In relation to epileptological basic data, it was found that warning symptoms appeared primarily in focal epilepsies and among them they mainly preceded generalized tonic clonic and complex partial seizures. Between the warning symptom and the onset of the seizure there was usually a longer interval during which (and generally also during the warning symptom) the patient remained able to act. About 20% of the patients enrolled in the study tried to inhibit the onset or mitigate the course of the seizure and about 10% judged their spontaneous activity carried out in that direction to be successful. The frequency of the occurrence of independent prognostic symptoms not followed by a seizure was relatively low, and among epileptics with warning symptoms the incidence of seizures occurring without a preceding event was not high either. Based on our experiences, we have drawn the conclusion that, in a significant part of epileptic patients, the warning symptoms render possible the supplementation of the therapy by the development of seizure-inhibiting or seizure-avoiding behaviour or activity.
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PMID:Hungarian multicentre epidemiologic study of the warning and initial symptoms (prodrome, aura) of epileptic seizures. 966 99

meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.
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PMID:Pharmacokinetic and pharmacodynamic profile of oral and intravenous meta-chlorophenylpiperazine in healthy volunteers. 969 Jun 94

Postpartum depression often occurs with symptoms of dysphoria, emotional instability, anxiety, insomnia, headache, loss of appetite reaching its peak 3-6 days after childbirth, with an incidence of 26-85% of women giving birth being affected. Postpartum contraception requires medical consultation during the puerperal period when the time of return of ovulation is also discussed. Oral contraceptives pose some risk of thromboembolism, especially in the first 10 days postpartum and also have an effect on lactation, but help faster return of menstruation and the diminution of menstrual flow. OCs should be prescribed 10-15 days postpartum. For women who nurse OCs containing progestational hormones could be prescribed which have a 99% effectiveness in the first year of use. Injectables also containing progestational hormones are commenced 7 days postpartum and are effective for 8-12 weeks. Implants are implanted 4 weeks postpartum and are effective for 5 years. The IUD could be inserted after the return of menstruation to avoid any risk of uterine perforation. Tubal ligation is usually performed 24-48 postpartum by periumbilical minilaparotomy. Natural methods are not recommended because of their low efficacy and difficulty of interpretation during this period, while barrier methods (both the male and female condom) using spermicides are more effective.
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PMID:[Postpartum contraception]. 1217 61

There have been a large number of studies conducted investigating the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with premenstrual dysphoric disorder (PMDD). The 12 randomised, controlled trials with continuous dose administration of SSRIs and the eight randomised, controlled trials with luteal phase dose administration (from ovulation to menses) are reviewed. All the treatment studies on fluoxetine, sertraline, paroxetine and citalopram have reported positive efficacy. Fluoxetine and sertraline have the largest literature, with a smaller number of studies endorsing paroxetine and citalopram. Mixed efficacy results have been reported with fluvoxamine. In general, adverse effects from the use of SSRIs in women with PMDD are the usual mild and transient adverse effects from SSRIs including anxiety, dizziness, insomnia, sedation, nausea and headache. Sexual dysfunction and weight gain can be problematic long-term adverse effects of SSRIs, but these effects have not been systematically evaluated with long-term SSRI use in women with PMDD. Serotonergic antidepressants have differential superiority over nonserotonergic antidepressants in the treatment of PMDD. Treatments that enhance serotonergic action improve premenstrual irritability and dysphoria with a rapid onset of action, suggesting a different mechanism of action than in the treatment of depression. It is possible that neurosteroids, such as progesterone metabolites, are involved in the rapid action of serotonergic antidepressants in PMDD. Future research needs to address less frequent dose administration regimens, such as 'symptom-onset' dose administration, and the recommended length of treatment.
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PMID:Selective serotonin reuptake inhibitors for premenstrual dysphoric disorder: the emerging gold standard? 1221 58

Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.
Headache 2003 Feb
PMID:Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. 1255 71


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