Sedatives/hypnotics adverse effects

Coadministration of ritonavir with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse reactions due to possible effects of ritonavir on the hepatic metabolism of certain drugs (see Contraindications). 

Zaleplon (Sonata) [C IV] [Sedotive/Hypnotic] Uses Insomnia Action A nonbenzodiazepine sedative/hypnotic, a pyrazolopyrimidine Dose 5-20 mg hs PRN -1- w/ renal/hepatic insuff, elderly Caution [C, /-] w/ mental/ psychological conditions Contra Component allergy Disp Caps SE HA, edema, amnesia, somnolence, photosens Interactions t CNS depression W/ CNS d es-sants, imipramine, thioridazine, EtOH X effects W/ carbamazepine, phenobarbital, phenytoin, rifampin EMS Concurrent EtOH can t adverse CNS effects OD May cause profound CNS depression symptomatic and supportive Zanamivir (Relenza) [Antiviral/Neuramidase Inhibitor] Uses Influenza A (including HlNl swine flu) B Action X Viral neuraminidase Dose Adults Feds > 7 y.2 inhal (10 mg) bid for 5 d initiate w/in 48 h of Sxs Caution [C, M] Contra Pulm Dz Disp Powder for inhal SE Bron-chospasm, HA, GI upset EMS Does not reduce risk of transmitting virus monitor for bronchospasm or other severe resp events OD May cause resp problems s5rmptomatic and supportive... 

All barbiturates (except phenobarbital) except when used to control seizures Are highly addictive and cause more adverse effects than most sedative or hypnotic drugs in elderly patients. High... 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Sedative antidepressants, such as amitriptyline, doxepin, or trazodone, in low doses, have hypnotic efficacy and may be less likely to evoke the adverse effects associated with higher doses. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Drug(s) Alcohol Classification/ Action Sedative-hypnotic Route/Method of Administration Oral, from various beverages [wine, beer, other alcoholic drinks] Effect Desired by User Euphoria relaxed inhibitions decreased anxiety sense of escape Principal Adverse Effects Physical dependence impaired motor skills chronic degenerative changes in the brain, liver, and other organs Additional Information See Chapter 6... 

Minor tranquilizers. Some of the most commonly reported adverse effects of the sedative- hypnotics, particularly when used long-term, include ... 

Both the neuroleptics and the sedative-hypnotics may cause severe, long-term adverse health effects, depending on the dosage and how long the drugs are in use. 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

Kava is most often used as a sedative-hypnotic to treat anxiety. The substance has been evaluated in Europe and in the USA for the treatment of anxiety in several placebo-controlled studies. Most of these trials have shown significant improvements in anxiety symptoms in patients with moderate to severe anxiety within 8 weeks after starting treatment. In one study, kava was compared with oxazepam, a benzodiazepine. Similar reductions in anxiolytic effects and fewer adverse effects were reported for the kava group. Kava appears to have a slow onset of action for the treatment of anxiety symptoms, most patients responding only after 4-8 weeks. Kava should not be used to treat acute symptoms of anxiety or panic attacks. 

The therapeutic profile and adverse effects of the non-benzodiazepine sedative-hypnotics... 

From the published clinical studies, it would appear that the partial agonists bretazenil and abercamil are less likely to cause physiological dependence, have lower reinforcing effects and a lower incidence of subjective effects associated with abuse liability than the conventional 1,4-benzodiazepine sedative-hypnotics. It is presently unclear whether the full agonists for the GABA-A receptor, zolpidem and zopiclone, offer a real advance in the treatment of insomnia although their adverse effect profiles and abuse liability may be lower than that of the conventional benzodiazepines. 

A number of sedative-hypnotics used in the past few decades have fallen into disfavor or have been withdrawn from the legitimate market because of their adverse effects and their potential for abuse. The following are a few of these. 

Antihistaminics are popular as nonprescription (over-the-counter) sleep remedies (e.g., diphenhydramine, doxylamine, p. 118), in which case their sedative side effect is used as the principal effect. The hypnotic effect is weak adverse effects (e.g., atropine-like) and corresponding contraindications need to be taken into account. 

Trimipramine is a sedating tricyclic antidepressant that has been used as a hypnotic (1) it shares this activity with other drugs of its class, notably amitriptyline, dosulepin, doxepin, and trazodone, and with the tetracyclics mianserin and mirtazapine. Trimipramine may be preferred for this purpose, since it has less effect on sleep architecture, including REM sleep (2), and has only a modest propensity to produce rebound insomnia in a subset of patients (3). Sedative antidepressants may be particularly appropriate for individuals at risk of benzodiazepine abuse and patients with chronic pain (4). The usual pattern of tricyclic adverse effects, especially antimuscarinic and hypotensive effects and weight gain, can be expected. Some authors, enthusiastic about GABA enhancers, contend that antidepressants are not useful hypnotic alternatives (5). 

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