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Overdoses of Muscle Relaxants <\/p>\n
(From Maryland Poison Center)<\/p>\n
<\/p>\n
Cyclobenzaprine (Flexeril<\/p>\n
\u00ae) <\/b> <\/p>\n
Cyclobenzaprine is a tricyclic amine, which is structurally similar to the tricyclic antidepressants (TCAs).<\/p>\n
In fact, cyclobenzaprine exposure can result in a false positive urine toxicology screen for TCAs. Its<\/p>\n
skeletal muscle relaxant effect is thought to be mediated through inhibition of brain stem somatic<\/p>\n
neuron activity. The typical adult dose is 10 mg three times daily. Clinical effects seen in overdose are<\/p>\n
related to cyclobenzaprine\u0092s anticholinergic (specifically, antimuscarinic), antihistaminic, and sedative<\/p>\n
properties. Despite the similarities to TCAs, one 5-year review of 402 cyclobenzaprine exposures<\/p>\n
found the major toxicity to be anticholinergic effects with less neurologic and cardiovascular effects.<\/p>\n
Patients may present with CNS depression or agitation, delirium, and hallucinations. Tachycardia may<\/p>\n
be noted in addition to hypertension, hyperthermia, flushed skin, dry mucous membranes, dilated<\/p>\n
pupils, urinary retention, and decreased bowel sounds.<\/p>\n
<\/p>\n
Baclofen (Lioresal<\/p>\n
\u00ae) <\/b> <\/p>\n
Baclofen is a structural analogue of gamma-aminobutyric acid (GABA). It binds to presynaptic GABA<\/p>\n
B <\/p>\n
receptors in the brain and spinal cord and decreases neurotransmitter (e.g., catecholamines,<\/p>\n
glutamate, substance P) release from excitatory pathways. Baclofen also binds to postsynaptic GABA<\/p>\n
B <\/p>\n
receptors and similarly results in inhibition. These actions block the excitatory effects of the sensory<\/p>\n
input from limb muscles. Baclofen is used orally and intrathecally to control muscle spasticity, restless<\/p>\n
leg syndrome, hiccups, and pain. The normal oral adult dose is 40 to 80 mg\/day. Intrathecal doses of<\/p>\n
300 to 800 mcg\/day are used for spasticity of spinal cord origin, and can be administered continuously<\/p>\n
by a pump. Because approximately 85% of an oral dose is excreted unchanged in the urine, dose<\/p>\n
adjustments must be made in patients with renal dysfunction. Common clinical effects seen after an<\/p>\n
acute baclofen overdose include lethargy and confusion. In severe oral or intrathecal overdose, coma,<\/p>\n
seizures, respiratory depression, bradycardia, hypotension, and rarely conduction disturbances and<\/p>\n
dysrhythmias may develop.<\/p>\n
Abrupt discontinuation of intrathecal baclofen can result in withdrawal symptoms such as hyperthermia,<\/p>\n
tachycardia, altered mental status (i.e., hallucinations, delirium), and muscle rigidity. In rare cases<\/p>\n
symptoms may progress to rhabdomyolysis, multiple organ-system failure, and death. Withdrawal can<\/p>\n
be prevented by reintroducing the patient to baclofen.<\/p>\n
Baclofen is abused, mainly by adolescents. Hypothermia, bradycardia, mild hypertension, seizures,<\/p>\n
and respiratory and CNS depression have been described following recreational use.<\/p>\n
<\/p>\n
Methocarbamol (Robaxin<\/p>\n
\u00ae) <\/b> <\/p>\n
Methocarbamol is similar to carisoprodol and meprobamate. It is hepatically metabolized. It is believed<\/p>\n
that methocarbamol acts at the interneurons of the spinal cord where it blocks multisynaptic<\/p>\n
reflexes. The usual adult dose is 6 to 8 g\/day in divided doses. The onset of effects is about 30<\/p>\n
minutes and can last up to 24 hours. Although overdose data are limited, CNS depression is the most<\/p>\n
likely manifestation. Drowsiness and dizziness are common at therapeutic doses.<\/p>\n
<\/p>\n
Tizanidine (Zanaflex<\/p>\n
\u00ae) <\/b> <\/p>\n
Tizanidine is an imidazole derivative similar to clonidine, which acts through central alpha-2 receptor<\/p>\n
agonism. The usual adult dose is 4 to 8 mg three times daily. At therapeutic doses, tizanidine has<\/p>\n
minimal antihypertensive effects compared to clonidine and is much less potent. It undergoes extensive<\/p>\n
first-pass metabolism, which contributes to its 40% bioavailability. Following overdoses, patients<\/p>\n
Overdoses of Muscle Relaxants<\/p>\n
may present with hypotension and bradycardia, along with coma and respiratory depression. Miosis,<\/p>\n
agitation, and hyposalivation are also possible.<\/p>\n
Orphenadrine (Norflex\u0099)<\/p>\n
Orphenadrine is an analogue of diphenhydramine (Benadryl\u00ae). Its pharmacologic action is similar to<\/p>\n
cyclobenzaprine (i.e. inhibition of brain stem somatic neuron activity). The normal adult dose is 100<\/p>\n
mg twice daily. Oral bioavailability is nearly 100%; however, absorption may be delayed due to the<\/p>\n
drug\u0092s anticholinergic effects on gastric motility. Peak plasma levels usually occur within 2 to 4 hours<\/p>\n
after ingestion. Orphenadrine produces marked anticholinergic effects in overdose including mydriasis,<\/p>\n
tachycardia, agitation, CNS depression, hallucinations, hyperthermia, dry mouth, decreased<\/p>\n
gastrointestinal motility, urinary retention, and dry, flushed skin. Cardiac dysrhythmias have also<\/p>\n
been reported with orphenadrine overdoses and may be due to its sodium channel blocking effects,<\/p>\n
similar to the class 1A antiarrhythmics.<\/p>\n
<\/p>\n
Metaxalone (Skelaxin<\/p>\n
\u00ae) <\/b> <\/p>\n
Metaxalone most likely exerts its muscle relaxant effects through CNS depression, rather than directly<\/p>\n
affecting skeletal muscles. The typical adult dose is 800 mg three to four times daily. Onset of<\/p>\n
effects is usually within 1 hour with a duration of 4 to 6 hours. Little information is available regarding<\/p>\n
poisonings with metaxalone. Sedation and CNS depression are the primary expected effects.<\/p>\n
<\/p>\n
Chlorzoxazone (Parafon Forte<\/p>\n
\u00ae DSC) <\/b> <\/p>\n
Chlorzoxazone inhibits reflex pathways in the spinal cord that produce and maintain muscle tone.<\/p>\n
The usual adult dose is 250 to 750 mg three or four times daily. Chlorzoxazone is 100% bioavailable<\/p>\n
orally with an onset of action within one hour. It is metabolized by cytochrome P450 2E1. Overdose<\/p>\n
data are limited, but CNS and respiratory depression requiring intubation have been reported.<\/p>\n
Management Options<\/p>\n
The treatment of all muscle relaxant poisonings should begin with administration of activated charcoal<\/p>\n
to limit absorption if the patient\u0092s mental status can tolerate it and the ingestion is recent. Intubation<\/p>\n
and mechanical ventilation secondary to respiratory depression may be required with some<\/p>\n
agents. Patients with persistent neurologic symptoms need to be admitted to the hospital. Muscle<\/p>\n
relaxant-induced seizures or anticholinergic agitation and delirium usually respond to benzodiazepines<\/p>\n
and barbiturates. EKG monitoring is recommended for orphenadrine. If the QRS interval is<\/p>\n
prolonged beyond 100 msec, sodium bicarbonate should be administered. IV fluids should be used<\/p>\n
for hypotension, and for refractory hypotension, vasopressors such as dopamine and\/or<\/p>\n
norepineprhine can be added. Symptomatic bradycardia can be reversed with atropine. Naloxone<\/p>\n
has been used with relative success to reverse the neurologic effects of clonidine, thus it may be of<\/p>\n
use in tizanidine overdoses. Hemodialysis can be considered in cases of life-threatening overdoses<\/p>\n
of baclofen, but its use is rarely reported.<\/p>\n
In conclusion\u0085<\/p>\n
Skeletal muscle relaxant overdoses are commonly encountered, with carisoprodol and<\/p>\n
cyclobenzaprine being the most frequently reported. All overdoses to muscle relaxants will present<\/p>\n
with some degree of CNS impairment, but there are some notable differences. Cyclobenzaprine and<\/p>\n
orphenadrine can produce profound anticholinergic effects, while tizanidine can cause hypotension<\/p>\n
and bradycardia and baclofen can cause seizures.<\/p>\n
References for this article are available on request.<\/p>\n
(From Maryland Poison Center)<\/p>\n
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