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

Chronic daily headache (CDH) is a particularly difficult type of headache to manage, with an uncertain pathophysiology. Intravenous administration of lignocaine has been suggested as a possibly useful option in the control of this syndrome. We have surveyed prospectively patients with CDH (selected for this study as those with 6 or more months of continuous pain with at least weekly exacerbations that, taken in isolation, would fulfil International Headache Society diagnostic criteria for migraine without aura). Intravenous lignocaine (2 mg/min) by infusion over a 2-day period rendered 26% of patients pain free, with a further 42% having at least a 50% improvement in the pain. Continued benefit was associated with commencement of prophylaxis with a tricyclic antidepressant or monoamine oxidase inhibitor after completion of the lignocaine infusion. In an animal model of craniovascular nociception, using electrical stimulation of the superior sagittal sinus and recording of single unit activity and sensory evoked potentials in the spinal trigeminal nucleus in the upper cervical spinal cord of the anaesthetised cat, the effect of lignocaine was examined. Lignocaine reduced both the probability of cell firing and the size of the trigeminal evoked potential in the animals studied. The reduction was both substantial (more than 25% in each case) and dose-dependent. Taken together the data suggest that CDH is likely to be a disorder of central craniovascular nociceptive control and that lignocaine acts to interrupt a part of the pathway involved but is unlikely to act at the central generator of the disorder.
 ...
PMID:Lignocaine and headache: an electrophysiological study in the cat with supporting clinical observations in man. 793 41

Major depression is a common and disabling disorder with far-reaching social and economic implications. Nonetheless, major depression is treatable by one of the many currently available antidepressants with response rates of approximately 65-70%. Treatment of depression has improved in recent years because of the availability of effective and well-tolerated antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). The currently available antidepressants are generally equally effective and are distinguished primarily by side-effect profiles. The side effects of tricyclic antidepressants (TCAs) are attributed to their nonspecific interaction with cholinergic, histaminergic, serotonergic, and dopaminergic receptors in the central nervous system. The secondary amine TCAs, nortriptyline and desipramine, are preferred among the TCAs because of a more favorable side-effect profile. The TCAs are cardiotoxic, and overdoses are frequently fatal. Adverse effects, including potentially fatal drug and food interactions, limit the use of the monoamine oxidase inhibitors (MAOIs); however, these agents have a role in the treatment of depression with comorbid anxiety, refractory depression, atypical depression, and bulimia. The SSRIs possess a class side-effect profile of headache, nausea, and sexual dysfunction. Individual differences in side effects may distinguish fluoxetine (nervousness, restlessness), sertraline (diarrhea, loose stools), and paroxetine (dry mouth). The SSRIs all inhibit certain cytochrome P450 isoenzymes involved in the metabolism of drugs, such as the TCAs, and each SSRI has been reported to increase plasma concentrations of concomitantly administered TCAs. Bupropion therapy is associated with a risk of seizure development, which can be minimized by multiple daily doses. Trazodone is sedating and can rarely cause priapism. The related compound, nefazodone, does not cause sexual dysfunction or priapism, but is associated with sedation. Venlafaxine, a recently available antidepressant that appears to have efficacy in treatment-refractory depression, may cause nausea that requires gradual upward dosage titration. Higher doses of venlafaxine may also cause elevations in blood pressure, heart rate, and serum cholesterol. As more is learned about the pathophysiology of depression, even more specific and well-tolerated antidepressants will be developed.
 ...
PMID:Contemporary management of depression. 799 23

There is a considerable overlap in migraine and depression incidence, and both conditions may be associated with low levels of 5-hydroxytryptamine (5-HT). During a migraine attack there is evidence for low levels of platelet 5-HT and possibly also low Vmax for 5-HT uptake; both these findings are also associated with the depressed state. Both conditions can be treated by tricyclic and monoamine oxidase inhibiting antidepressants. However, there are also clear differences: migraine attacks are brief and self limiting. Part of the migraine cascade occurs outside the blood brain barrier, presumably involving blood vessels and, unlike depression, migraine attacks can be ameliorated by drugs which only act peripherally. In addition, migraine patients, especially males, often have permanently low levels of platelet monoamine oxidase activity, whereas patients with unipolar depression tend to have raised levels of this marker. This low enzyme activity may reflect part of the vulnerability to migraine, often associated in the prodromal phase with agitation or hyperactivity. Migraine may form part of a family of brief recurrent self-limiting disorders, which involve disturbances of both mood and monoamines; during the headache phase of the attack, the links with depression are most apparent.
 ...
PMID:Migraine and depression: biological aspects. 836 71

Irreversible, nonselective monoamine oxidase (MAO) inhibitors have been reported adversely to interact with indirectly acting sympathomimetic amines present in many cough and cold medicines. This study investigated the safety and tolerability of concomitant administration to 12 healthy subjects of both genders (aged 19-36 years) of ephedrine and moclobemide, a reversible MAO-A inhibitor. A 2-day, randomized, crossover administration of placebo or ephedrine (two doses of 50 mg with a 4-h interval) was followed by 9 days open-label dosing with moclobemide, 300 mg b.i.d.. On the last 2 days of moclobemide dosing, the randomized crossover treatment of ephedrine and placebo was repeated. No subject was withdrawn from the study for tolerability reasons. Moclobemide treatment, however, increased the incidence of adverse events elicited by ephedrine, particularly palpitations and headache. The pharmacodynamic interaction between the two drugs was quantified by calculation of the area under the effect-time course (AUE) for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR). The difference in AUE between monotreatment with ephedrine and placebo was statistically significant for all three vital signs. Moclobemide potentiated the effect of ephedrine by a median factor of 3.2 for SBP, 3.8 for DBP, and 0.6 for HR. Ephedrine had no significant influence on the plasma concentrations of moclobemide or its metabolites. In conclusion, the combined use of moclobemide and high doses of sympathomimetic drugs should be approached with caution.
 ...
PMID:Modification of the cardiovascular effects of ephedrine by the reversible monoamine oxidase A-inhibitor moclobemide. 896 Oct 85

The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include beta-blockers, tricyclic antidepressants, and divalproex, and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs, and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.
Cephalalgia 1997 Apr
PMID:Preventive treatment of migraine: an overview. 913 40

Tricyclic antidepressants have been used for a long time in migraine prophylaxis and in the treatment of chronic tension-type headache. Because of their relatively frequent and unpleasant side effects, however, their use cannot be recommended without reservation. The selective and reversible monoamine oxidase inhibitor type A (MAO-A inhibitor), moclobemide (Aurorix), is much better tolerated and safer to use. For this reason, we began to use this substance in the prophylactic treatment of migraine and chronic tension-type headache. The obviously good efficacy in many cases prompted us to conduct a retrospective analysis of 61 headache patients treated with moclobemide. The patients, classified according to the diagnostic criteria of the International Headache Society, were treated for about 8 months on average with moclobemide. While on this therapy, 35 of the 42 migraine patients and 16 of the 17 patients with tension-type headache experienced good or very good improvement in their symptoms. In the migraine patients, the average number of monthly headache days declined from 7.8 before treatment to 1.2 at the end of treatment. In tension-type headaches, the effect occurred at the earliest 3-6 weeks and in the case of migraines at the earliest 6-8 weeks after the start of treatment. The therapeutic result was independent of any concurrent depression. Nine patients ended their treatment prematurely, seven because of side effects and two because of compliance problems. Treatment compliance, essential for the success of any long term treatment of headache, is promoted by open and detailed explanation of the treatment concept, and by medical supervision with individual adjustment of treatment. The patient should be instructed regarding the time required until the onset of action, the intended length of treatment, treatment of further headache attacks, and an appropriate lifestyle. The highly promising results with moclobemide in the prophylactic treatment of migraines and chronic tension-type headaches should be verified in a controlled study.
 ...
PMID:[Preventive treatment of migraine and chronic tension headache with moclobemide]. 932 19

In an open trial ginkgo biloba, an extract derived from the leaf of the Chinese ginkgo tree and noted for its cerebral enhancing effects, was found to be 84% effective in treating antidepressant-induced sexual dysfunction predominately caused by selective serotonin reuptake inhibitors (SSRIs, N = 63). Women (n = 33) were more responsive to the sexually enhancing effects of ginkgo biloba than men (N = 30), with relative success rates of 91% versus 76%. Ginkgo biloba generally had a positive effect on all 4 phases of the sexual response cycle: desire, excitement (erection and lubrication), orgasm, and resolution (afterglow). This study originated from the observation that a geriatric patient on ginkgo biloba for memory enhancement noted improved erections. Patients exhibited sexual dysfunction secondary to a variety of antidepressant medications including selective serotonin reuptake inhibitor (SSRIs), serotonin and nonrepinephrine reuptake inhibitor (SNRIs) monoamine oxidase inhibitor (MAOIs), and tricyclics. Dosages of ginkgo biloba extract ranged from 60 mg qd to 120 mg bid (average = 209mg/d). The common side effects were gastrointestinal disturbances, headache, and general central nervous system activation. The article includes a discussion of presumed pharmacologic mechanisms, including effects on platelet activating factor, prostaglandins, peripheral vasodilatation, and central serotonin and norepinephrine receptor factor modulation.
 ...
PMID:Ginkgo biloba for antidepressant-induced sexual dysfunction. 1008 37

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.
 ...
PMID:Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. 967 55

With the use of the newer antidepressants beyond the traditional tricyclics and monoamine oxidase inhibitors, newer options in headache prophylaxis are provided as well as the potential for undesirable and even potentially life-threatening interactions between medications. In this article, four patient reports of a specific interaction--the serotonin syndrome--are presented. These events resulted from transitioning headache patients from an older antidepressant (phenelzine) to a newer antidepressant (venlafaxine).
 ...
PMID:Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports. 967 20

Tolcapone is a potent, reversible catechol-O-methyltransferase (COMT) inhibitor with both peripheral and central activity. It has been demonstrated to improve motor function and allow levodopa dose reductions in Parkinson's disease (PD) patients who are experiencing either a stable response or motor fluctuations while on levodopa/dopa decarboxylase inhibitor therapy. Because striatal dopamine is metabolized by COMT and monoamine oxidase (MAO), central COMT inhibition alone or in combination with MAO inhibition might provide symptomatic benefit for patients not receiving levodopa. We conducted a pilot study to evaluate the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in early untreated PD patients. Patients were randomized to receive 200 mg tolcapone three times a day or placebo for the 8 weeks of the study. Open-label oral selegiline (5 mg in the morning and midday) was administered to all patients during the second 4 weeks of the study. There was no difference between treatment groups according to the investigator's assessment of tolerability at week 4. Ninety-five percent of tolcapone-treated patients and 98% of placebo-treated patients experienced excellent or good tolerability during the first 4 weeks (95% confidence interval [CI]: -10.3, 5.7; p = 0.57). A decrease in tolerability occurred in the tolcapone group during the second 4 weeks of the study following the addition of selegiline. The most commonly reported side effects were diarrhea (31% tolcapone, 7% placebo), nausea (21% tolcapone, 2% placebo), urine discoloration (12% tolcapone, 0% placebo), dizziness (12% tolcapone, 5% placebo), headaches (12% tolcapone, 10% placebo), and abdominal pain (10% tolcapone, 5% placebo). We did not identify symptomatic benefit associated with tolcapone alone or in combination with oral selegiline in this group of otherwise untreated PD patients.
 ...
PMID:A pilot evaluation of the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in untreated Parkinson's disease patients. Tolcapone De Novo Study Group. 968 68


<< Previous 1 2 3 4 5 6 7 Next >>