Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acute open angle glaucoma of the right eye was diagnosed in an 8-year-old male Yorkshire terrier which was presented with anorexia, depression, and trembling. Abnormal findings of the right eye on admission included elevated intraocular pressure (IOP; 40 mmHg), the presence of fibrin and flare in the anterior chamber, and immature cataract. Morphological abnormalities of the iridocorneal angle were not detected, and an open angle was seen in the eye. Although an elevated IOP was observed at one year after admission, lowering IOP (< or = 24 mmHg) was maintained with medical therapy using dichlorphenamide (DCPA) and timolol maleate, DCPA alone, or no-treatment for 1973 days. This case suggests that lower IOP can be maintained with medical therapy alone for a long period in a patient with open angle glaucoma.
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PMID:Long-term management of a glaucomatous eye in a dog treated with medical therapy alone. 1178 11

Brimonidine is an ophthalmic solution of 0.2% brimonidine tartrate used to lower intraocular pressure in human glaucoma patients. A retrospective study was conducted of brimonidine ophthalmic solution ingestion in 52 dogs reported to the ASPCA Animal Poison Control Center between January 1998 and December 2000. Eighty percent of the dogs were < 1-y of age. Approximate ingested dosages ranged from 0.18-5.55 mg/kg. Incidence of clinical signs were bradycardia (67%), depression (46%), ataxia (27%), hypotension (25%), pallor (23%), weakness (17%), change in mucous membrane color (17%), hypothermia (13%), vomiting or retching (13%.). Shock, weak pulses, and poor capillary refill time were also reported. Treatment involved early decontamination, supportive care, andyohimbine and atipamezole as specific alpha-2 antagonists that could be helpful in reversing the effects of brimonidine. Due to the possibility of severe cardiovascular effects developing, the ingestion of brimonidine ophthalmic solution in dogs should be considered dangerous.
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PMID:Clinical effects of brimonidine ophthalmic drops ingestion in 52 dogs. 1182 75

The involvement of vasopressin (AVP) in several pathological states has been reported recently and the selective blockade of the different AVP receptors could offer new clinical perspectives. During the past few years, various selective, orally active AVP V1a (OPC-21268, SR49059 (Relcovaptan)), V2 (OPC-31260, OPC-41061 (Tolvaptan), VPA-985 (Lixivaptan), SR121463, VP-343, FR-161282) and mixed V1a/V2 (YM-087 (Conivaptan), JTV-605, CL-385004) receptor antagonists have been intensively studied in various animal models and have reached, Phase IIb clinical trials for some of them. For many years now, our laboratory has focused on the identification of nonpeptide vasopressin antagonists with suitable oral bioavailability. Using random screening on small molecule libraries, followed by rational SAR and modelization, we identified a chemical series of 1-phenylsulfonylindolines which first yielded SR49059, a V1a receptor antagonist prototype. This compound displayed high affinity for animal and human V1a receptors and antagonized various V1a AVP-induced effects in vitro and in vivo (intracellular [Ca2+] increase, platelet aggregation, vascular smooth muscle cell proliferation, hypertension and coronary vasospasm). We and others have used this compound to study the role of AVP in various animal models. Recent findings from clinical trials show a potential interest for SR49059 in the treatment of dysmenorrhea and in Raynaud's disease. Structural modifications and simplifications performed in the SR49059 chemical series yielded highly specific V2 receptor antagonists (N-arylsulfonyl-oxindoles), amongst them SR121463 which possesses powerful oral aquaretic properties in various animal species and in man. SR121463 is well-tolerated and dose-dependently increases urine output and decreases urine osmolality. It induces free water-excretion without affecting electrolyte balance in contrast to classical diuretics (e.g. furosemide and hydrochlorothiazide). Notably, in cirrhotic rats with ascites and impaired renal function, a 10-day oral treatment with SR121463 (0.5 mg/kg) totally corrected hyponatremia and restored normal urine excretion. This compound also displayed interesting new properties in a rabbit model of ocular hypertension, decreasing intraocular pressure after single or repeated instillation. Thus, V2 receptor blockade could be of interest in several water-retaining diseases such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), liver cirrhosis and congestive heart failure and deserves to be widely explored. Finally, further chemical developments in the oxindole family have led to the first specific and orally active V1b receptor antagonists (with SSR149415 as a representative), an awaited class of drugs with expected therapeutic interest mainly in ACTH-secreting tumors and various emotional diseases such as stress-related disorders, anxiety and depression. However, from the recently described tissue localization for this receptor, we could also speculate on other unexpected uses. In conclusion, the development of AVP receptor antagonists is a field of intensive pharmacological and clinical investigation. Selective and orally active compounds are now available to give new insight into the pathophysiological role of AVP and to provide promising drugs.
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PMID:Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. 1243 36

Medetomidine is a relatively new sedative analgesic drug that is approved for use in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for clinical use in veterinary medicine and stimulates receptors centrally to produce dose-dependent sedation and analgesia. Significant dose sparing properties occur when medetomidine is combined with other anesthetic agents correlating with the high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs with medetomidine sedation in dogs; however, respiratory depression becomes most significant when given in combination with other sedative or injectable agents. The typical negative cardiovascular effects produced with other alpha2-agonists (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/- hypotension) are also produced with medetomidine, warranting precautions when it is used and necessitating appropriate patient selection (young, middle-aged healthy animals). While hypotension may occur, sedative doses of medetomidine typically raise the blood pressure, due to the effect on peripheral alpha2-adrenoreceptors. Anticholinergic premedication has been recommended with alpha2-agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac output produced by these agents; however, current research does not demonstrate a clear improvement in cardiovascular function. Negatively, the anticholinergic induced increase in heart rate potentiates the alpha2-agonist mediated hypertension and may increase myocardial oxygen tension, demand, and workload. Overall, reversal with the specific antagonist atipamezole is recommended when significant cardiorespiratory complications occur. Other physiological effects of medetomidine sedation include; vomiting, increased urine volumes, changes to endocrine function and uterine activity, decreased intestinal motility, decreased intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis. Decreased doses of medetomidine, compared with the recommended label dose, should be considered in combination with other sedatives to enhance sedation and analgesia and lower the duration and potential severity of the negative cardiovascular side effects. The literature was searched in Pubmed, Medline, Agricola, CAB direct, and Biological Sciences.
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PMID:A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. 1466 51

In the past few years, there have been many changes in ophthalmic anaesthesia. Application of drugs in general anaesthesia with excellent controllability enhances patient safety and allows a more efficient OR-management. Regional anaesthesia is gaining widespread use for ophthalmic surgery, especially topical anaesthesia for cataract surgery. Patients for ophthalmic surgery concomitantly often display high age and a high level of co-morbidity and, therefore, belong to the anaesthesiological risk groups ASA III-IV. Life-threatening adverse events including cardiovascular depression are associated with general and regional anaesthesia. Intervention by anaesthesiologists is frequently required for treatment of hypertension or dysrhythmias, and sedation. Thus, monitored anaesthesia care ("standby") is justified. Drugs applied for regional and general anaesthesia may change intraocular pressure. There are a lot of publications about the impact of anaesthesia on intraocular pressure (IOD), however, few on the effects of anaesthesia on pulsatile ocular blood flow. it has to be kept in mind that the effects of anaesthesia on intra-ocular pressure and pulsatile ocular blood flow may diverge. To avoid an increase of the IOD, especially during anaesthesia induction, drugs, such as succinylcholin, rocuronium and opiates, in particular remifentanil, can be applied. In addition, the use of the laryngeal mask may be advantageous compared to general anaesthesia associated with laryngoscopic tracheal intubation. The management of patients treated with anticoagulants and antiplatelet agents, has to be taken on the balance of risks. There are risks not only in continuing therapy, but also in discontinuing it perioperatively. Postoperative nausea and vomiting (PONV) remains a distressing and common problem after strabismus repair in particular in children. The incidence of PONV depends on the type of ophthalmic surgery and drugs applied. To reduce PONV in ophthalmic surgery, application of long-lasting opiates should be avoided, and non-opiate analgesics and, depending on the kind of operation, antiemetic prophylactics are recommended.
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PMID:[What's new in ophthalmic anaesthesia?]. 1470 36

SSRIs are the most commonly prescribed antidepressant drugs, in part because of their favourable safety profile compared with older antidepressants. However, the widespread use of SSRIs leads to an increased occurrence of rare adverse effects. This review, based on data from published experimental research, clinical studies and case reports, describes the role of serotonin in the control of intraocular pressure (IOP) and the evidence for IOP modifications in patients receiving SSRIs. In a small percentage of patients with depression, the cause of SSRI withdrawal has been the occurrence of ill-defined visual disturbances. It can be speculated that in some of these patients, the iatrogenic ocular alterations could have been due to changes in IOP. There have also been a limited number of case reports of acute attacks of glaucoma occurring during treatment with SSRIs. Although causality is not exactly specified, the relationship between SSRIs and this ocular adverse event is strongly implied. Nevertheless, in a small clinical study assessing the effect of a single dose of fluoxetine on IOP, the drug was shown to increase this parameter, although the effect was asymptomatic. The clinical signs of unexpected adverse drug effects are often disregarded, with the exception of those characterised by serious symptoms (such as acute angle-closure glaucoma in the case of IOP modifications). Also, the distribution of iridocorneal angle configurations in the general population implies that an adverse effect on IOP will be pauci- or asymptomatic in most patients (intermittent, sub-acute or progressive angle-closure glaucoma). As a result, it is likely that the incidence of SSRI-related IOP modifications is underestimated. Until the involvement of SSRIs in IOP modifications is better understood, ophthalmological consultations should be considered before starting and during treatment with any SSRI in patients with glaucomatous risk factors, especially those who are elderly.
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PMID:SSRIs and intraocular pressure modifications: evidence, therapeutic implications and possible mechanisms. 1659 50

Evidence suggests that ocular pathology could reduce light-stimulated neuronal signaling to the suprachiasmatic nuclei. This study investigated associations of ambient illumination with moods, while considering the contribution of ophthalmic dysfunctions. Seventy Black (59%) and White (41%) Americans participated in the study. Their average age was 68.27+/-5.97 years; 73% were women. Baseline data included: physical health, mood, and sociodemographics. Ophthalmic factors including visual acuity, visual field defects, intraocular pressure, vertical and horizontal cup-to-disk ratios, and nerve-fiber-layer thickness were assessed at SUNY Downstate's eye clinic. The following week, participants wore the Actiwatch-L at home to monitor ambient illumination and sleep. Cosine analyses were performed on the logarithm of measured illumination, yielding the mesor and acrophase of daily illumination exposure. Sleep was estimated with an automatic scoring algorithm. Of the sample, 25% reported visual impairment and 85% reported good to excellent health; 27% were visually impaired according to American criteria. Partial correlation analyses showed an inverse correlation of daily illumination levels to depressed mood [r(p)=-0.33, P<0.05], when age, sex, ethnicity, income, BMI, diabetes, hypertension, respiratory disease, and habitual sleep duration were controlled. With further control for ophthalmic factors, the magnitude and significance of the correlation diminished [r(p)=-0.26, NS]. Individuals receiving daily illumination later in the day reported more depressed moods [r(p)=0.36, P<0.01]; of note, this correlation was not significant after control for the covariates [r(p)=0.18, NS]. Regression analysis indicated that the ophthalmic factors explained 13% of the variance in depression. Our results show that both the level and timing of ambient illumination are associated with mood. Furthermore, they suggest that visual impairment has a mediating effect on the associations of ambient illumination with depression, supporting the notion that ocular pathology lessens the efficacy of daily illumination in promoting positive moods.
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PMID:Associations of ambient illumination with mood: contribution of ophthalmic dysfunctions. 1576 87

Normal intraocular pressure (IOP) glaucoma is a clinical condition characterized by pathologic optic nerve excavation and visual field impairment, defined as optic neuropathy with certain features of a disease known as glaucoma. Glaucomatous optic nerve lesion is characterized by optic disk excavation or depression, however, this feature may greatly vary. The level of IOP is considered only one of the multiple risk factors involved in the disease development. In normal IOP glaucoma, papillary lesions and visual field impairments may differ from those occurring in primary open-angle glaucoma. In modern ophthalmology, the terminology has been modified, so the term low IOP glaucoma has been replaced by the term normal IOP glaucoma. It is now believed that various factors play a role in the development of glaucomatous optic neuropathy in normal IOP glaucoma and show variable interference depending on IOP level. Additional studies are needed to define these interactions and their impact on the mechanism of glaucomatous excavation. This will hopefully pave the way to new therapeutic approaches and help in clinical decisions concerning the prognosis and treatment of individual patients.
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PMID:[Clinical approach to normal intraocular pressure glaucoma]. 1590 86

Bremazocine is a kappa-opioid receptor agonist with potent analgesic and diuretic activities. As an analgesic it is three- to four-times more potent than morphine, as determined in both hot plate and tail flick tests. Bremazocine and other benzomorphan analogs were synthesized in an effort to produce opiates with greater kappa-opioid receptor selectivity and with minimal morphine-like side effects. Unlike morphine bremazocine is devoid of physical and psychological dependence liability in animal models and produces little or no respiratory depression. While bremazocine does not produce the characteristic euphoria associated with morphine and its abuse, it has been shown to induce dysphoria, a property that limits its clinical usefulness. Similarly to morphine, repeated administration of bremazocine leads to tolerance to its analgesic effect. It has been demonstrated that the marked diuretic effect of bremazocine is mediated primarily by the central nervous system. Because of its psychotomimetic side effects (disturbance in the perception of space and time, abnormal visual experience, disturbance in body image perception, de-personalization, de-realization and loss of self control) bremazocine has limited potential as a clinical analgesic. However, its possible utility for the therapy of alcohol and drug addiction warrants further consideration because of its ability to decrease ethanol and cocaine self-administration in non-human primates. In addition, the ability of bremazocine-like drugs to lower intraocular pressure and to minimize ischemic damage in animal models suggests their possible use in the therapy of glaucoma and cardiovascular disease.
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PMID:Bremazocine: a kappa-opioid agonist with potent analgesic and other pharmacologic properties. 1600 40

Brain neuronal dysfunction has been implicated in pathogenesis of migraine but direct evidence is lacking. Scintillating scotoma of migraine is generally believed to originate at the visual cortex. While cortical spreading depression is a relatively late physiological alteration in migraine, its protective role in neuronal ischaemia is increasingly being recognized. Atenolol, nadolol, or verapamil prevent migraine but do not readily cross the blood-brain barrier or critically influence any brain or peripheral neuronal function. Typical migraine headache, aura, or scintillating scotoma has not been reported following enucleation or evisceration of the eye. In humans, pain and temperature fibres from only the ophthalmic division of the trigeminal nerve reach the upper cervical spinal segments. Pain in migraine attacks including occipital and nuchal discomfort reflects selective involvement of the ophthalmic nerve. Photophobia is largely a retinal reflex involving the ophthalmic division of the trigeminal nerve. Key clinical features of the migrainous scintillating scotoma are consistent with retinal origin. Spreading depression in the retina is well-established. A subtle regional ocular sympathetic deficit prevails in migraine patients and possibly impairs regulation of intraocular choroidal blood volume and intraocular pressure. Several first-line migraine prophylactic agents lower the intraocular pressure. The neuro-ophthalmological basis for a monocular origin of migrainous scintillating scotomata due to mechanical deformation of the posterior segment of the corneo-scleral envelope consequent to choroidal venous congestion and rise in intraocular pressure is presented. Study of distribution and displaceability of the migrainous scintillating scotoma can settle its site of origin. Headache of migraine possibly arises from a similar mechanical deformation of the anterior eye segment followed by antidromic discharge in the trigeminovascular system. Lateralizing negative deficits such as homonymous hemianopia probably reflect vasospastic complications of migraine. A rational explanation for the most characteristic clinical features of migraine and a new template to elucidate the pharmacological basis of anti-migraine drugs is offered.
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PMID:Migrainous scintillating scotoma and headache is ocular in origin: A new hypothesis. 1635 54


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