Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 32-year-old man sustained a severe head injury in a road traffic accident. On admission, he was in deep coma (6 on the Glasgow coma scale). The aortic knuckle was difficult to identify on a plain chest film. Twenty hours after admission, the aortic knuckle had completely disappeared and the mediastinal shadow had become enlarged. The diagnosis of a ruptured aortic isthmus was confirmed by angiography. Surgical repair of this lesion may be carried out either with simple aortic cross-clamping, or by using cardiopulmonary bypass (CPB). Either technique may worsen other injuries, especially head injury, by initiating severe arterial hypertension or coagulation disturbances. In this patient, the technique chosen was aortic cross-clamping with permanent monitoring of the intracranial and cerebral perfusion pressures. Anaesthesia was obtained with 5 mg.kg-1 of thiopentone, 30 mg.kg-1 x h-1 of sodium gamma hydroxybutyrate and 8 micrograms.kg-1 x h-1 of fentanyl. Surgery lasted for 90 min, with 33 min of aortic clamping. The increase in arterial blood pressure was controlled with 0.25 mg.kg-1 x h-1 of thiopentone and nicardipine which was stopped 8 min before unclamping. The postoperative course was uneventful. Sedation was stopped after 8 days, and the patient regained consciousness two days later. These remained a paraplegia with no sensory deficit, which had totally receded 15 months later. Carrying out this emergency surgery without CPB means that the intracranial pressure must imperatively be monitored during surgery. Any intracranial hypertension should delay the surgery.
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PMID:[Traumatic rupture of the aortic isthmus in a patient with severe head injury]. 833 63

Traditional centrally acting antihypertensives have been associated with a high incidence of adverse effects and are no longer recommended as first-line therapy. The newer imidazoline receptor agonists must overcome this reputation if they are to gain recognition as potential first-line agents for hypertension. Methyldopa, a centrally acting alpha(2)-agonist, is characterized by a number of serious adverse reactions that limit its use. Although unpredictable idiosyncratic or hypersensitivity reactions are uncommon, these include hepatitis, myocarditis, and hemolytic anaemia. Less serious problems such as abnormal liver function tests, positive Coombs test, drug-induced fever, and pancreatitis also occur. Central side effects include drowsiness, fatigue, lethargy, sedation, depression, psychotic reactions, nasal stuffiness, impotence, and exacerbation of Parkinsonism. In hypertensive men, methyldopa is less well tolerated than either captopril or propranolol, and up to 20% of patients discontinue therapy because of adverse effects. Clonidine acts primarily as an alpha(2)-agonist but also acts as an agonist at imidazoline receptors in the rostroventrolateral medulla. It is equipotent to most other antihypertensives but is considerably less well-tolerated in comparative trials. The principal adverse effects of clonidine are drowsiness, sedation, lethargy and dry mouth. Reserpine acts primarily by depleting central catecholamine neurotransmitter stores. It was very extensively used in early hypertension trials, but its central side effects of sedation, nasal stuffiness, and severe depression are now considered so undesirable that the drug is seldom prescribed. The imidazoline (I1) agonists moxonidine and rilmenidine act selectively and have very little central alpha(2)-agonist activity. In comparative studies against placebo and other reference antihypertensives, the only adverse effect consistently associated with these drugs was dry mouth (approximate placebo-corrected incidence 10%). Sedation was not pronounced. Withdrawal syndromes are complex pathophysiologic processes and occur with a variety of antihypertensive drugs. Cessation of therapy with clonidine and, to a lesser extent, methyldopa may result in a severe withdrawal syndrome characterized by restlessness, sweating, anxiety, tremor, palpitations, and headache. There may be a rapid rise in blood pressure, often with a true "rebound" to higher than pretreatment levels. Plasma and urinary catecholamine levels are increased, and fatalities have been reported. It is important to stress that such a syndrome has not been recorded, in animal or human studies, with either moxonidine or rilmenidine.
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PMID:Aspects of tolerability of centrally acting antihypertensive drugs. 887 99

Rilmenidine is an imidazoline derivative that appears to lower blood pressure (BP) by an interaction with imidazoline (I1) receptors in the brainstem (and kidneys). Rilmenidine is as effective in monotherapy as all other first-line classes of drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists. It is well tolerated and can be taken in combination for greater efficacy. Sedation and dry mouth are not prominent side effects and withdrawal hypertension is not seen when treatment is stopped abruptly. Recently, in addition to a reduction in BP, this agent has been shown to improve glucose tolerance, lipid risk factors, and insulin sensitivity. These changes would be consistent with a reduction in long-term cardiovascular risk, as would recently described actions on the heart (reducing left ventricular hypertrophy) and the kidney (reducing microalbuminuria). Although no data are yet available from prospective long-term outcome studies, rilmenidine could represent an important new development in antihypertensive therapy and the prevention of cardiovascular disease.
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PMID:Update on rilmenidine: clinical benefits. 1172 91

The relative efficacies and cardiorespiratory effects of three injectable anesthetic combinations containing medetomidine were evaluated in ring-tailed lemurs (Lemur catta). In addition, the direct effects of medetomidine on heart rate and blood pressure were evaluated in lemurs anesthetized with isoflurane. For injectable anesthesia, captive adult ring-tailed lemurs were anesthetized with medetomidine and ketamine (0.04-0.06 mg/kg, i.m. and 3 mg/kg, i.m., respectively), medetomidine, butorphanol, and ketamine (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 3 mg/kg, i.m., respectively), or medetomidine, butorphanol, and midazolam (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 0.3 mg/kg, i.m., respectively). For inhalation anesthesia, lemurs were mask-induced and maintained with isoflurane for 30 min before receiving medetomidine (0.04 mg/kg, i.m.). Sedation produced by medetomidine-ketamine was unpredictable and of short duration. Both medetomidine-butorphanol-ketamine (MBK) and medetomidine-butorphanol-midazolam (MBMz) provided adequate anesthesia for routine physical exams; however, the effects of MBMz lasted longer than those of MBK. Heart rates and respiratory rates were within clinically normal ranges for all groups, and lemurs remained normotensive throughout the study. Common side effects such as hypertension and bradycardia associated with the use of alpha2-adrenergic receptor agonist combinations in other species were not observed. Likewise, medetomidine administration had no effect on HR in lemurs receiving isoflurane. Lemurs in all groups were well ventilated and remained well oxygenated throughout the procedures, though arterial partial pressure of O2 was lowest in the MBMz group. All three injectable medetomidine combinations were effective in ring-tailed lemurs but only MBK and MBMz provided adequate depth and duration of anesthesia for use as sole regimes. For many clinical procedures in lemurs, MBMz offers advantages over MBK because of its longer duration of action and its rapid and more complete reversibility with specific antagonists.
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PMID:Comparison of the efficacy and cardiorespiratory effects of medetomidine-based anesthetic protocols in ring-tailed lemurs (Lemur catta). 1288 34

Sedation and analgesia can be routinely prescribed in head injury patients. The goals of such sedation are three: brain protection, prevention and treatment of intracranial hypertension and therapeutic facilitation. In such situation, the use of sedative and analgesic therapy should respect the rate of cerebral blood flow/cerebral oxygen consumption coupling while preserving cerebral perfusion pressure and decreasing the intracranial pressure. This treatment should have an analgesic and myorelaxing action with short and predictable time of action. The ideal sedation agent with all these properties does not exist. Only the combination of several different pharmacological classes of compounds may reach this goal. Benzodiazepines are the most frequently used agents. In most of the cases they are associated with analgesic agents such as opioid or ketamine. Opioids may be the basic analgesic agents because they do not produce brain haemodynamic modifications if arterial pressure is maintained. Among them, sufentanil, thanks to its pharmacokinetics properties, remains the most prescribed opioid. However, in the future, remifentanil that presents a fast elimination may be more frequently used for neurological follow up of patients. Ketamine whose use is subject of debate, has the main advantage of maintaining haemodynamic status. Ketamine has no side effects on brain haemodynamic when used with propofol or midazolam. Taking into account their deleting effect on haemodynamic status and immune system, barbituric are no longer used as long term sedative agents. However, their use is still recommended in the cases of refractory intracranial hypertension. Propofol remains the ideal sedative agent because of its short duration action but its use is limited by its cost. Its use may be recommended for short time sedations with or without an opioid drug. The curare use should be restrain to refractory intracranial hypertension to usual treatments and happening during stimulation.
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PMID:[The agents used for sedation in neurointensive care unit]. 1515 48

Captive rhinoceros species are most frequently sedated and/or anaesthetised with the potent opioid, etorphine hydrochloride in combination with an alpha-2 adrenoreceptor agonist or the butyrophenone, azaperone. Carfentanil citrate based combinations have also been used to a lesser extent. In recent years butorphanol tartrate based combinations have been used with good success to induce neuroleptanalgesia. Sedation and anaesthesia are complicated by the large size of all rhinoceros species and their sensitivity to potent opioids. Potential complications include respiratory depression, hypoxaemia, hypertension, pulmonary shunting and ventilation/perfusion mismatch. The pharmacology of the principal drugs used for sedating/anaesthetising rhinoceros is reviewed. Techniques for sedating/anaesthetising the various species and potential complications associated with chemical restraint are discussed.
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PMID:A review of drugs and techniques used for sedation and anaesthesia in captive rhinoceros species. 1547 25

The properties of dexmedetomidine (DEX) that result in titratable sedation and sympathetic modulation suggest that it would be suitable for use during carotid endarterectomy (CEA) performed under regional anesthesia. We performed a randomized, double-blind study in 56 patients having CEA under regional anesthesia and compared hemodynamic control using DEX versus a conventional sedation technique using midazolam and fentanyl standard (STD). Sedation was titrated to a Ramsay Sedation Score of 2-4 in both groups. The primary outcome was the number of pharmacological interventions required to treat deviations of arterial blood pressure and heart rate outside of predetermined limits. We also compared recovery hemodynamic profiles, patient satisfaction, and adverse cardiac and neurological events. There was no difference in the overall rate of hemodynamic interventions (DEX 80% versus STD 79%; P = 1.0). However, the nature of interventions differed in that patients in the DEX group were less likely to require treatment for hypertension and/or tachycardia (DEX 40% versus STD 72%; P = 0.03). The number of interventions per patient for hypertension and/or tachycardia was also lesser in the DEX group (P = 0.02). There were no significant differences in the numbers of patients needing intraoperative treatment for hypotension or bradycardia or in the need for intraarterial shunting. In the postanesthesia care unit, more patients in the DEX group required hemodynamic drug interventions (DEX 11, 44%, versus STD 4, 14%; P = 0.03). These were primarily for hypotension (DEX 7, 28% versus STD 3, 11%; P = 0.16). The number of patients requiring no additional pain relief in the postanesthesia care unit was significantly larger for patients in the DEX group (DEX 18, 72% versus STD 11, 38%; P = 0.027). DEX provides an acceptable alternative, without superiority to standard techniques for sedation during awake CEA.
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PMID:A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. 1649 13

Clonidine is a preferential alpha-2 agonist drug that has been used for over 35 years to treat hypertension. Recently, it has also been used as a preoperative medication and as a sedative/anxiolytic drug. This randomized, double-blind, placebo-controlled crossover clinical trial characterized the effects of oral clonidine pretreatment on intravenous catheter placement in 13 patients. Parameters measured included the bispectral index (BIS), Observer's Assessment of Alertness/Sedation Scale (OAA/S), frontal temporal electromyogram (EMG), 30-Second Blink Count (Blink), Digit Symbol Substitution Test (DSST), State Anxiety Inventory (SAI), fingertip versus forearm skin temperatures, and multiple questionnaires. Oral clonidine significantly decreased SAI scores, OAA/S, EMG, and Blink, but did not cause statistically significant BIS or DSST reductions. Subjects preferred oral clonidine pretreatment prior to venipuncture compared to placebo. Questionnaires also indicated that clonidine provided minimal sedation, considerable anxiolysis, and some analgesia. Fingertip versus forearm skin temperature differentials were decreased. Reduced fingertip versus forearm temperature differentials suggest increased peripheral cutaneous blood flow prior to venous cannulation. Oral clonidine pretreatment not only helped control patient anxiety and pain but also provided cardiovascular stability.
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PMID:Oral clonidine pretreatment prior to venous cannulation. 1686 91

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.
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PMID:Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. 1761 33

Sedation-analgesia occupies an essential place in the specific therapeutic arsenal of the brain-injured patients. The maintenance of the perfusion of the brain, its relaxation and its protection are the fundamental objectives whose finality is to avoid the extension of the lesions and to preserve the neuronal capital. Sedation is instituted when patients are severely agitated or present a deterioration of their state of consciousness (GCS< or =8). Under cover of mechanical ventilation, sedation is the first line treatment of intracranial hypertension, a common pathway of various acute brain diseases of traumatic, vascular or other origin. The use of the combination of hypnotic and opioids is the rule. The combined action of these two classes reinforces and improves their sedative effects. Midazolam is the 2 benzodiazepine of reference. Propofol is more and more frequently added to the combination of hypnotic and opioids. The "propofol infusion syndrome" is a severe limitation to its long term administration in particular among patients presenting a severe septic or inflammatory state. Propofol will be imperatively stopped in the event of metabolic acidosis, rhabdomyolysis, acute renal insufficiency, hyperkaliemia or increase in the blood triglyceride levels. The use of thiopental is restricted to the most severe cases. Its use as a monotherapy at high doses is abandoned to the profit of a co-administration with midazolam or even with the combination of midazolam and propofol. Thiopental overdose is very frequent in the event of associated hypothermia. Etomidate does not have its place apart from induction in fast sequence. The neuro-protective effects of ketamine require to be demonstrated in man before being recommended routinely. Withdrawal of sedation can be responsible for a state of agitation which can be controlled by neuroleptics.
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PMID:[Sedation and analgesia for the brain-injured patient]. 1861 62


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