Sedative agents

Sales for hypnotic—sedative agents ia the United States for 1993 were estimated to be 139,000,000. Anticonvulsant sales for 1993 were estimated at 525,000,000. U.S. sales of antianxiety agents including both the BZs and buspirone-hke agents for 1993 were estimated at 1,046,000,000. 

It is possible to form 2-imino-4-imidazolines, such as 59, in situ from creatinine. Treatment of this heterocycle 3-chlorophenylisocyanate leads to a sedative agent,... 

Trepipam (69) is a sedative agent apparendy acting via dopaminergic mechanisms. It can be synthesized by attack on the less hindered terminus of styrene oxide (66) by 4,5-dimethoxyphe-nethylamine (65) to give 67. Cyclodehydration catalyzed by strong acid then leads to 68 and N-... 

The CSHT is, therefore, a form of decrement time when the specified percentage is 50%. When using propofol infusions, the decrement time is commonly quoted as the time taken to reach a plasma level of 1.2 pg.ml-1, as this is the level at which wake up is thought likely to occur in the absence of any other sedative agents. 

The pharmacological activity of a series of 3,5,6-trialkyluracils was studied, considering them as analogues ofbarbitone, and it was found that they did possess sedative action. The 3,5-dibutyl-6-methyl derivative (XLVlll) was reported to be a comparatively potent sedative agent [372]. Partition coefficient and metabolic studies would be of interest in comparing such compounds with the barbiturates. 

Mephobarbital is used as a sedative agent for relieving anxiety and tension as well as for major and minor epileptic attacks. Synonyms for this drug are barbefenal, enfenemal, and methylphenobarbital. 

Glutethimide is a hypnotic and sedative agent intended to treat insomnia. The hypnotic effect is roughly analogous to that of pentobarbital. It is given to patients who cannot... 

Chlorprothixene has an antipsychotic and sedative action. It has expressed antiemetic activity. It is used in various psychoses, schizophrenia, reactive and neurotic depression with prevalent anxious symptomatology, and in conditions of excitement associated with fear and stress. It may be used in small doses as a sedative agent in neurosis. Synonyms of chlorprothixene are clothixene and tarasan. 

Alkaloids such as boldine, codeine, narceine and morphine are active factors in their receptors. Boldine has morphine-like properties and is active on opioid receptors. It may be used to treat stomach disorders and as metabolic stimulant. As it is similar to morphine, boldine can also be considered in the possible development of treatments for narcotic dependence. Codeine also binds to opiate receptors, and specifically functions to reduce bronchial secretions. Codeine can also be used as a cough suppressant when acting on the centre of the medulla oblongata and as a sedative agent. 

The withdrawal syndrome from ethanol includes anxiety, insomnia, possibly convulsions and visual hallucinations (delirium tremens - the Dts). It is treated or better still prevented by a calm environment, adequate (but not excessive) hydration, and careful monitoring, with the added use of anticon-vulsive/sedative agents, mainly benzodiazepines to prevent or treat convulsions. The preventive effects of benzodiazepines on withdrawal morbidity has been clearly demonstrated. There do not seem to be major differences between benzodiazepines, such as chlordiazepoxide or diazepam or others. Because of the abuse potential in these highly susceptible patients, these should be rapidly weaned, and proper prevention of relapse instituted. Other drugs such as meprobamate and clomethiazole (Hemineurin) are commonly used in some countries. The effectiveness... 

C. Thalidomide caused a high incidence of pho-comelia, particularly in Europe, where it was approved as a sedative agent. There is no definitive evidence associating teratogenic activity with the other compounds. 

Conscious sedation implies that patients have a depressed level of consciousness but nevertheless have intact protective reflexes, the ability to maintain their airway, and the ability to respond appropriately to requests and physical stimulation (Kennedy and Luh-mann, 1999). Sedative agents familiar to psychiatrists that are used in this manner for procedures include chloral hydrate, given orally or rectally in a dose of 25 to 100 mg/kg midazolam, given intramuscularly or intravenously in a dose of 0.05 to 0.15 mg/kg, rectally in a dose of 0.3 to 0.5 mg/kg, or orally in a dose of 0.2 to 0.75 mg/kg and midazolam, which is felt to be preferable to diazepam for this purpose (Kennedy and Luhmann, 1999). Midazolam is also available in a nasal spray (Ljungman et ah, 2000). 

Dopamine, the free catechol corresponding to (1-1), plays an important role as a neurotransmitter, particularly in the CNS. The synthesis of a dopamine-related sedative agent starts with the condensation of homoveratramine (1-1) with styrene oxide (1-2) to afford the carbinol (1-3). Treatment of that product with a strong acid leads to an attack on the electron-rich aromatic ring by the resulting carbocation there is thus obtained the benzazocine (1-4). The secondary amine is then methylated by reaction with formaldehyde and formic acid to yield trepipam (1-5) [1]. 

Depressive disorders can lead to death in other ways (Table 6-9). For example, depressed individuals are more prone to accidents that result from their impaired concentration and attention. They also often attempt to self-medicate, particularly with alcohol or other sedative agents, which may lead to death as a result of organ toxicity, as well as accidents. Psychotic depressive patients may act irrationally, putting themselves at greater physical risk. Although rare today, patients have died of severe malnutrition secondary to catatonic symptoms that precluded the ability to care for their basic needs. Depression can also contribute to a higher morbidity and mortality rate in patients with co-morbid medical disorders. For example, a large database indicates that depression may predispose to the development of ischemic heart disease and increase the risk of cardiac-related death ( 51). 

Hypothermia is common during anesthesia, and adversely affects outcome. It primarily results from internal redistribution of body heat from the core to the periphery. Premedication with sedative agents can affect perioperative heat loss by altering core-to-peripheral heat distribution. This has been analysed in a prospective randomized study in 45 patients undergoing arthroscopic knee ligament reconstruction surgery (47). Heavy premedication caused initial hypothermia. Moderate premedication reduced perioperative heat loss. No premedication was associated with significantly lower intraoperative core temperatures than in sedated patients. 

Phenothiazines are antiemetic, antianxiety and sedative agents and they may change the affective response to pain (particularly methotrimeprazine). 

Pharmacodynamic interactions. Many TCAs cause sedation and therefore co-prescription with other sedative agents such as opioid analgesics, antihistamines, anxiolytics, hypnotics and alcohol may lead to excessive drowsiness and daytime somnolence. The majority of TCAs can have undesirable cardiovascular effects, in particular prolongation of the QT interval. A similar risk of QT prolongation arises with many other cardiovascular drugs including amiodarone, disopyramide, procainamide, propa-... 

Stoltzfus DP. Advantages and disadvantages of combining sedative agents. Crit Care Clin 1995 11(4) 903-12. 

Isoflurane is a potent inhalation anesthetic. An isomer of enflurane, it has many of the same adverse effects. It is hardly metabolized (about 0.2%), which has encouraged its prolonged use as a sedative agent or bronchodilator in patients with acute severe asthma. However, it may not be as inert in all patients. 

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