Sedation and Sleep

Certain forms of dyspnea yield only to opiates. Especially in this category is the dyspnea of acute left ventricular failure and pulmonary edema. Most authorities agree that morphine is contraindicated in patients with pulmonary edema caused by chemical respiratory irritants. If needed in such cases for severe pain, its use should be combined with oxygen inhalation and positive-pressure therapy. In bronchial asthma, morphine is usually contraindicated because there is danger of addiction, the drug tends to depress respiration and to constrict bronchioles, and patients with asthma may be allergic to the drug. Deaths have occurred from the use of morphine in asthma. 

There is no good evidence that the use of codeine or papaverine shortens the duration of the common cold. Opiates tend to dry the mucosal lining of the throat and nose, but other measures such as atropine can accomplish this end. If headache and pain require relief, nonnarcotic analgesics should first be employed. If the symptomatic improvement afforded by codeine encourages patients 

Morphine depresses respiration by decreasing the responsiveness of the respiratory center to C02 

---

Adenosine and inosine can be transported across cell membranes in either direction, facilitated by a membrane-associated nucleoside transport protein. Concentrative transporters have also been identified. Messenger RNA for a pyrimidine-selective Na+-nucleoside cotransporter (rCNTl) and a purine-selective Na+-nucleoside cotransporter (rCNT2) are found throughout the rat brain. Most degradation of adenosine is intracellular, as evidenced by the fact that inhibitors of adenosine transport, such as dipyridamole, increase interstitial levels of adenosine. Dipyridamole is used clinically to elevate adenosine in coronary arteries and produce coronary vasodilation. In high doses, dipyridamole can accentuate adenosine-receptor-mediated actions in the CNS, resulting in sedation and sleep, anticonvulsant effects, decreased locomotor activity and decreased neuronal activity. 

FIGURE 13-33. Acute withdrawal of benzodiazepines in a benzodiazepine-dependent individual. If benzodiazepines are suddenly stopped in a patient who is tolerant to them and dependent on them, benzodiazepine receptors will experience this as an acute deficiency at their binding sites. Thus, the presence of desensitized benzodiazepine receptors actually worsens the impact of benzodiazepine discontinuation. The brain, which is used to too much benzodiazepine at its receptors, is suddenly starved for benzodiazepine. Therefore, the brain experiences the reverse of benzodiazepine intoxication, namely, dysphoria and depression instead of euphoria anxiety and agitation instead of tranquility and lack of anxiety insomnia instead of sedation and sleep muscle tension instead of muscle relaxation and at worst, seizures instead of anticonvulsant effects. These actions continue either until benzodiazepine is replaced or until the receptors readapt to the sensitivity they had prior to excessive benzodiazepine use. Alternatively, one can reinstitute benzodiazepines but taper them slowly, so that the receptors have time to readapt during dosage reduction, and withdrawal symptoms are prevented. 

Sedative-hypnotics fall into two general categories benzodiazepines and nonbenzodiazepines (Table 6-1). At present, benzodiazepines are typically used to promote normal sedation and sleep, especially in relatively acute or short-term situations. These agents will be addressed first, followed by a description of the nonbenzodiazepine hypnotics. 

All the barbiturates possess the properties of CNS depressants. Thus, in moderate doses they produce a drunken euphoric state. Similar to alcohol, barbiturates may produce a loss of motor coordination, a staggering gait, and slurred speech. Loss of emotional control and behavioral disinhibition arc also characteristic cfTccts. Sedation and sleep are produced by increased doses, and higher doses produce surgical anesthesia. Physiological effects include respiratory depression, which is responsible for most of the overdose deaths associated with barbiturates. In addition some depression of heart rate, blood pressure, and gastrointestinal activity is noted at higher doses. 

The clinical effects of sedative-hypnotics include sedation and sleep. Sedative-hypnotic drugs depress the function of the CNS and in a dose-dependent fashion produce drowsiness (sedation). Several sedative-hypnotic drugs, especially the older ones, produce sedation, sleep, unconsciousness, surgical anesthesia, coma, and ultimately may cause fatal depression of respiration and cardiovascular regulation. 

Sedation and sleep promotion can be achieved with drugs that are not classed as sedatives or hypnotics, including antihistamines (e.g., hydroxyzine) and opioid analgesics. Tricyclic antidepressants (TCAs) have been used in anxiety characterized by panic and/or phobias, and more recently the selective serotonin reuptake inhibitors (SSRIs) have been used. Propranolol has efficacy in performance anxiety and social phobias. 

Sedation and sleep enhancement Butylidenephthalide (20), Butylphthalide (30), Ligustilide (47), Sedanenolide (56)... 

ETHANOL Experimentation with ethanol is almost universal, and a high proportion of users find the experience pleasant. More than 90% of American adults report experience with ethanol, and 70% report some level of current use. The lifetime prevalence of alcohol abuse and alcohol addiction (alcoholism) in the U.S. is 5-10% for men and 3-5% for women. Ethanol is classed as a depressant because it indeed produces sedation and sleep. However, the initial effects of alcohol, particularly at lower doses, often are perceived as stimulation owing to a suppression of inhibitory systems see Chapter 22). 

It was between the years 1815 and 1820 that the first active principles were isolated from plants. The French apothecary Jean Fran9ois Derosne (1780-1846) probably isolated the alkaloid later known as narcotine in 1803, and the German apothecary Friedrich Sertumer (1783-1841) further investigated opium and isolated a new compound, morphium (1805), later named morphine. After administration to dogs, solutions of the white powder induced sedation and sleep in the dogs. His work was completed and... 

---