Drugs depressing skeletal muscle relaxants

Before the introduction of neuromuscular blocking drugs, profound skeletal muscle relaxation for intracavitary operations could be achieved only by producing levels of volatile (inhaled) anesthesia deep enough to produce profound depressant effects on the cardiovascular and respiratory systems. The adjunctive use of neuromuscular blocking drugs makes it possible to achieve adequate muscle relaxation for all types of surgical procedures without the cardiorespiratory depressant effects produced by deep anesthesia. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

Geriatric Considerations - Summary Carisoprodol is a skeletal muscle relaxant that at higher doses can cause CNS depression. It appears to have more use with acute muscle discomfort as compared to chronic use. Carisoprodol s metabolite is meprobamate and therefore may have abuse potential and cause sedation in older adults. The risks of fhis drug outweigh benefits in treating older adults. 

Geriatric Considerations-Summary Metaxalone is a skeletal muscle relaxant with a primary effect of general CNS depression. Older adults taking this drug are at risk of somnolence and injuries from falls. 

There is a very great demand for drugs for the relief of anxiety. This was formerly met by the use of alcohol, bromides or barbiturates, which carried the risk of abuse or dangerous toxicity. The first of the modern minor tranquilizers, introduced from 1946 onwards, were drugs described as skeletal muscle relaxants. These were mainly derivatives of polyhydric alcohols, but heterocyclic examples included metaxolone (161), which is related to the aryl ethers of glycerol, chlorzoxazone (162) and chlormezanone (163). Dantrolene sodium (164) is a muscle relaxant and CNS depressant. 

Chlorzoxazone (Paraflex, Parafon Forte DSC, Others) [Skeletal Muscle Relaxant/ANS Drug] Uses Adjunct to rest physical therapy to relieve discomfort associated w/ acute, painful musculoskeletal conditions Action Centrally acting skeletal muscle relaxant Dose Adults. 250-500 mg PO tid-qid Peds. 20 mg/kg/d in 3-4 + doses Caution [C, ] Avoid EtOH CNS depressants Contra Severe liver Dz Disp Tabs SE Drowsiness, tach, dizziness, hepatotox, angioedema Interactions T Effects W/ antihistamines, CNS depressants, MAOIs, TCAs, opiates, EtOH, watercress EMS Use of CNS depressants and concurrent EtOH use can T sedation urine may turn reddish purple or orange OD May cause N/V/D, dizziness, HA, X deep tendon reflexes, hypotension and resp depression symptomatic and supportive, activated charcoal may be effective... 

The question arises whether anxiolytic activity must always be accompanied by concomitant skeletal muscle relaxant and anticonvulsant activity as well as strong sedation. Can an anxioselective drug exist that will not interact significantly and additively with CNS depressant compounds, particularly alcohol More significantly, both from a medical and sociologic viewpoint, will it be possible to treat anxiety and stress without the added complication of potent sedative effects, dependency, and abuse ... 

II. Drugs utilized. Contrary to the popular belief that specific date rape drugs are involved In these crimes, a variety of drugs with amnestic or CNS depressant effects can be used to facilitate assault, including benzodiazepines, other sedative-hypnotic drugs, skeletal muscle relaxants, anticholinergics, hallucinogens, and of course, ethanol (Table 1-45). 

The concurrent use of small or moderate amounts of alcohol and therapeutic doses of drugs that are CNS depressants can increase drowsiness and reduce alertness. These drugs include antidepressants, antiemetics, antiepileptics, antihistamines, antipsychotics, anxiolytics, barbiturates, hypnotics, opioid analgesics, skeletal muscle relaxants, and others. This increases the risk of accident when driving or handling other potentially dangerous machinery, and may make the performance of everyday tasks more difficult and hazardous. 

Although it has been clinically available for a number of years, the United States Food and Drug Administration in early 1968 allowed labeling changes for diazepam (XXIV) to allow for new indications of use for the relief of muscle spasm and adjunctive use in convulsive disorders . It was reported that in cats the brain stem reticular system is the major locus of central nervous system depressant action of this centrally acting skeletal muscle relaxant. 

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

On the other hand, these compounds have a general depressant effect on the CNS that is, they cause a global decrease in CNS excitability that results in generalized sedation. It therefore seems possible that some of their muscle relaxant effects are caused by their sedative powers rather than a selective effect on specific neuronal reflex pathways.11,92 This observation is not to say that they are ineffective, because clinical research has shown that these drugs can be superior to a placebo in producing subjective muscle relaxation.8 20 80 97 However, the specific ability of these drugs to relax skeletal muscle remains doubtful, and it is generally believed that their muscle relaxant properties are secondary to a nonspecific CNS sedation. 

Nicotine is classified as a stimulant drug, but people who use it often report decreased arousal. That is, the perception is that nicotine has a calming effect, and nicotine users find this effeet reinforcing (Todd, 2004). The reasons for this perception of lowered arousal are complex. One factor may be nicotine s acute effect of relaxing the skeletal muscles (see Table 7.5 also see Jones, 1987b). Another pharmacological reason is nicotine s biphasic action at higher doses its effects are more depressant. 

Diazepam, in particular, has a very pronounced depressant activity on skeletal muscle. While all drugs of this class have some activity in this regard, due to the stabilization of excitable tissue in skeletal muscle, certain older drugs of the class (e.g., diazepam) may have a direct muscle relaxant effect. 

Musck Halothane causes some relaxation of skeletal muscle via its central depressant effects and potentiates the actions of nondepolarizing muscle relaxants (curariform drugs see Chapter 9), increasing both their duration of action and the magnitude of their effect. Halothane and the other halogenated inhalational anesthetics can trigger malignant hyperthermia this syndrome frequently is fatal and is treated by immediate discontinuation of the anesthetic and administration of dantrolene. 

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