Side effects, sedative

Generally, patients with a history of seizures, convulsive disorders, or psychiatric disturbances, and also elderly patients with cerebrovascular disease, should be regarded as patients at risk of developing the more serious side effects (SED-9, 206). 

Chloramphenicol may cause retinal bleeding (as a symptom of aplastic anaemia), alterations in the perception of colours, and optic neuritis. The latter type of side effect has been observed especially in children with cystic fibrosis receiving chloramphenicol in relatively high doses for fairly long periods (38 ). Deficiency of B vitamins is believed to be the cause of the optic neuritis, and perhaps also of the polyneuritis, peripheral neuritis, and paraesthesiae of the legs sometimes seen after prolonged courses of treatment with chloramphenicol and thiam-phenicoL Administration of extra vitamins may protect patients from this type of reversible side effect (SED VIII, p. 610 38 ). 

Some new cases of bone marrow depression, a well-known side effect (SED VIII), have been reported (9, 10 ). In 3 cases of acute agranulocytosis (2 secondary to methi-mazole and 1 secondary to propylthiouracil)... 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

In 2000, Simig et al. began to conduct structure activity relationships on 25 by employing the Pictet-Gams reaction. Compound 25 had been identified as an anxiolytic agent that does not show sedative side-effects. ... 

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet "antihistamines." This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

GABAergic transmission, tiagabine has sedative side effects. 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

There is no shortage of AEDs (Fig. 16.7) but it is not appropriate to consider them in detail in this text other than to see how their mechanisms of action comply with and illustrate those proposed above (Fig. 16.6) for the control of epileptic seizures (see Meldrum 1996 Upton 1994). The decision on which drug to use depends not only on their proven efficacy in a particular type of epilepsy (some drugs are inactive in certain forms) but also what side-effects they have—many are sedative — how they interact with other drugs and how often they need to be taken. Compliance is a problem over a long period if dosing is required more than once a day. It is probably acceptable in reality, if not scientifically, to divide the drugs into old-established AEDs and new AEDs. Only the latter have been developed chemically to modify the known synaptic function of the amino acids. 

As sedation is one of the major side effects associated with antihistamines, the test compounds were also evaluated for their sedative potentials. This was determined by measuring the reduction in locomotor activity using an ac-tophotometer [6,7]. The test compounds and the reference standards (chlorpheniramine maleate and cetirizine) were administrated orally at a dose of 5 mg/kg in 1% CMC. 

Whether due to their antihistaminic activity or their sedative side effects, pruritus caused by contact dermatitis can be relieved with the use of sedating oral antihistamines such as... 

Sodium oxybate (yhydroxybutyrate a potent sedative-hypnotic) improves excessive daytime sleepiness and decreases episodes of sleep paralysis, cataplexy, and hypnagogic hallucinations. It is taken at bedtime and repeated 2.5 to 4 hours later. Side effects include nausea, somnolence, confusion, dizziness, and incontinence. 

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