Muscle Relaxants, Substance Abuse
and CNS Stimulants
By Linda Self
Muscle Relaxants
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Used to decrease muscle spasms or the spasticity
associated with certain neurologic and musculoskeletal
disorders
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Muscle spasm—sudden, involuntary muscle contraction.
Occurs with musculoskeletal trauma. Spasms may be
tonic (sustained) or clonic (alternating)
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Spasticity—increased muscle tone or contraction, stiff,
awkward movements. Caused by nerve damage in spinal
cord and brain
Mechanisms of Action
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Centrally active except Dantrium
Cause general depression of the CNS
May block nerve impulses that cause increased muscle
tone and contraction
Lioresal and Valium increase GABA (gamma-aminobutyric
acid)
Dantrolene acts directly on muscles inhibiting the release
of calcium in skeletal muscle cells
Indications
Indications
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As adjuncts to other treatment measures such as physical
therapy
Spastic disorders which cause severe pain or inability to
tolerate physical therapy, perform ADLs
Dantrium in malignant hyperthermia
Skeletal Muscle Relaxants
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Used in patients with low back problems or be associated
with sprains (ligaments), strains (muscle/tendon) , or
other musculoskeletal injuries
Contraindications
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Caution in patients with liver or renal compromise
Caution if must be alert
Flexeril may have anticholinergic activity; caution in BPH,
glaucoma and cardiac dysrhythmias
General Considerations
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No muscle relaxants are considered safe during
pregnancy and lactation
Lioresal (baclofen) approved for spasticity in patients
with multiple sclerosis
Flexeril (cyclobenzaprine) not recommended for more
than three weeks
Age-Related Considerations
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Safety and effectiveness in children not established
Caution in elderly because of anticholinergic effects and
because of sedation
Individual Drugs
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Lioresal (baclofen) used in MS and SCI. PO or intrathecal
(spinal). Decrease dose in renal impairment. Taper over 12 weeks
Soma (carisoprodol) indicated for acute, painful,
musculoskeletal disorders. Can cause physical
dependence. Withdrawal s/s if stopped suddenly. Half-life
is 8 hours.
Flexeril (cyclobenzaprine). Contraindicated in patients
with CV disorders, recent MI and hyperthyroidism.
Individual Drugs
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Dantrium (dantrolene)
Acts directly on skeletal muscle to inhibit muscle
contraction. Used to relieve spasticity in neurologic
disorders and in Tx of malignant hyperthermia.
Use 1-2 days before surgery in those w/documented MH
Oral preparation has slow onset of action, IV is rapid
Can cause fatal hepatitis if used on maintenance basis
Individual Drugs
Zanaflex (tizanidine)
 Alpha 2 adrenergic agonist, similar to clonidine
 Given orally
 Can cause drowsiness, dizziness, constipation, dry mouth
and hypotension
 Can cause psychoses and hallucinations
Individual Drugs
Robaxin (methocarbamol)
 May be indicated to be used in tetanus (IV)
 Contraindicated with renal impairment
 Causes urine to have a green, brown or black color
Skelaxin
 Painful, musculoskeletal disorders
 Contraindicated in anemias, renal or hepatic compromise
Interactions
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Caution with other CNS depressants
MAOIs may potentiate effects by inhibiting metabolism of
muscle relaxants
Caution with antihypertensives as may increase effects of
BP lowering
Substance Abuse Disorders
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Substance abuse is self-administration of a drug for
prolonged periods or in excessive amounts resulting in
physical and/or psychological dependence
Most drugs of abuse affect the CNS
Include: alcohol, CNS depressants (narcotic analgesics),
CNS stimulants (cocaine, ecstasy, methamphetamine,
nicotine) and others (marijuana)
Dependence
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Physical dependence whereby withdrawal symptoms will
occur upon abrupt discontinuation
Includes a “craving” for the drug
Often will have unsuccessful attempts to decrease its use
Continued use despite disruption in life (job loss,
impaired relationships)
Dependence cont.
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Involves all socioeconomic levels
School aged children to elderly
Drug effects depend on the substance, route of
administration, duration of use and phase of substance
abuse
Abusers are not reliable sources of information on their
abuse
Often will only present for medical care when situation
mandates, e.g. withdrawal s/s or serious illness
Used for mind-altering effects
CNS Depressants--Alcohol
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Considered to be most abused drug in the world
Induces drug metabolizing enzymes that accelerate
metabolism .
Damages liver, increases production of lactate, decreases
excretion of uric acid, increases production of lipids
Results in irreversible changes in liver (necrosis,
inflammation, fibrous scar tissue==cirrhosis)
Alcohol
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Effects on CNS by enhancing activity of GABA
(inhibitory) or inhibiting glutamate (excitatory)
Women have less enzyme activity than men so absorb
30% more alcohol than men given comparable amounts
based on weight and size
Women become intoxicated more quickly from smaller
amounts and develop cirrhosis earlier
Alcohol
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Causes increased intestinal motility
Can damage intestinal mucosa resulting in nutritional
deficiencies==thiamine, folic acid and Vitamin B12
Damages myocardial cells resulting in cardiomyopathy
Can affect bone marrow w/ resultant anemia
May impair growth and development of fetus (fetal
alcohol syndrome)
Osteoporosis 2ndary to hypocalcemia
myopathies
Alcohol and Drug Interactions
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CNS depressants such as sedative-hypnotics, narcotic
analgesics, antianxiety agents, general anesthetics
Potentiates CNS depression so can cause excessive
sedation, respiratory depression. Can be lethal.
Alcohol
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With antihypertensives, causes vasodilation and
hypotensive effects
With oral antidiabetic drugs, potentiates hypoglycemia
With oral anticoagulants, variable depending on duration
of alcohol ingestion
Alcohol
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With Antabuse (disulfiram), produces distress. Causes:
flushing, tachycardia, bronchospasm, sweating, nausea and
vomiting
Disulfiram-like reaction may also occur with: Flagyl
(metronidazole), Diabenese (chlorpropamide), Orinase
(tolbutamide), others
Alcohol Dependence
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Occurs to extent of psychological dependence, physical
dependence and cross tolerance w/other CNS
depressants
S/S of withdrawal include: agitation, tremors, sweating,
tachycardia, fever, nausea, delirium, and convulsions
Delirium Tremens
Intensity of withdrawal depends on duration and amount
of ingestion
Treatment of Alcohol Dependence
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Benzodiazepine antianxiety agents are drugs of choice for
withdrawal syndromes
Valium (diazepam) or Librium (chlordiazepoxide)
Ativan (lorazepam) or Serax (oxazepam) better in elderly
Antiseizure medications not usually needed post-detox
Alcohol
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Two drugs for maintenance of sobriety
Antabuse (disulfiram)—interferes with metabolism of
alcohol and allows accumulation of acetaldehyde. If
alcohol ingested, acetaldehyde will cause n/v, syncope,
hypotension, headache and confusion. Can affect cardiac
functioning and even convulsions.
Caution in OTC meds that contain etoh.
Alcohol
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Second drug used to maintain sobriety is ReVia
(naltrexone).
Opiate antagonist that reduces craving for alcohol.
Thought to be related to blockade of the endogenous
opioid system which then decreases alcohol craving and
consumption.
Adverse effects include: anxiety, dizziness, drowsiness,
headache, insomnia, and vomiting.
Alcohol
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Key to abstinence is desire to stop drinking
Need support and psychiatric help
Antidepressants appear to decrease alcohol intake as well
Barbiturate and Benzodiazepine
Dependence
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Resembles alcohol dependence in symptoms of
intoxication and withdrawal
Includes physical dependence, psychologic dependence,
tolerance, and cross tolerance
Convulsions are more likely to occur during first 48
hours of withdrawal
S/S of withdrawal are less severe with benzodiazepines
than with barbiturates
Barbiturates
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Barbiturates largely replaced by benzodiazepines
Examples: Luminal (phenobarbital), Pentothal (thiopental),
Nembutal (pentobarbital), Seconal (secobarbital)
Barbiturate Dependence
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No antidote for overdose. Treatment is symptomatic and
supportive.
Withdrawal can be life-threatening
May treat with gastric lavage if within 3 hours of ingestion
If comatose, mechanical ventilation necessary
Diuresis or hemodialysis clear the drug
Benzodiazepines
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May need to treat supportively as well
Romazicon (flumazenil) is antidote, competes with
benzodiazepine receptors
Treatment of withdrawal involves administering
benzodiazepines or phenobarbital in gradually tapering
doses
Benzodiazepines
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Librium,Valium,Versed, Ativan, Xanax, Klonopin, Tranxene,
ProSom, Serax, Restoril, Halcion
Atypical benzodiazepine receptor ligands:
Sonata (zalepon) and Ambien (zolpidem)
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Opiates
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Commonly abused
Produce tolerance and high degrees of psychological and
physical dependence
Not an issue when needed for pain management in
terminal illnesses
Treatment of Opiate Dependence
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Overdose will require supportive care
Giving narcotic antagonist can precipitate withdrawal s/s
Can achieve therapeutic withdrawal by gradually tapering
dose
Treatment of Opiate Dependence
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Methadone used in treatment
Blocks euphoria, acts longer and reduces preoccupation
with drug use
LAAM (Orlaam) is synthetic, Schedule II narcotic used for
treatment of opiate dependence. Can be given three
times weekly (If M-W-F, Friday dosing needs to be larger
to prevent withdrawal s/s over weekend)
LAAM
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Can overdose if patient takes this medication and other
opiates
Has prodysrhythmic effects so need baseline ECG.
Can use ReVia (naltrexone) but then have to give
alternative non-narcotic analgesic. If undergoing elective
surgery, must stop taking ReVia 72h before procedure
CNS Stimulants
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Not recommended in children under 6 years of age
May affect growth
Ritalin (methylphenidate) is most commonly used drug
for children with ADHD
Amphetamines
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Increase amounts of norepinephrine, dopamine and
serotonin
Are Schedule II drugs under Controlled Substances Act
High potential for addiction and abuse
Concerta, Focalin, Ritalin, Daytrana, Adderall, Metadate,
Vyvanse
Amphetamine Dependence
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Produce stimulation and euphoria
Effects are dose related
Small amounts cause mental alertness, wakefulness and
increased energy
Large amounts can cause psychoses
Tolerance develops
Methamphetamine
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Psychostimulant
Increases levels of norepinephrine, serotonin and
dopamine
Extremely neurotoxic—can result in a secondary
Parkinsonism. Causes dopaminergic degeneration.
“Meth mouth”
Patriot Act 2005 removed active ingredients, ephedrine or
pseudoephedrine, were removed from regular OTC
access
Xanthines
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Caffeine
Stimulates cerebral cortex thus increasing alertness and
decreasing fatigue
Cause myocardial stimulation, diuresis, and increased
sescretion of pepsin and HCL, cerebrovascular
constriction, bronchodilation
Can cause restlessness, nervousness, anxiety, agitation,
insomnia, cardiac dysrhythmias and gastritis
Xanthines
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Frequently ingested stimulant in form of coffee, tea, cola
drinks
Develop tolerance and habituation
Combined with other medications to enhance absorption
and work as an additive with ergots, oxycodone, OTC
pain and cold remedies
Cocaine
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Powerful CNS stimulant
Prevents reuptake of dopamine, norepinephrine and
serotonin and prolongs neurotransmitter effects
Inhalation
Produces euphoria, increased energy and alertness, sexual
arousal, tachycardia, increased blood pressure and
restlessness
Cocaine
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As drug wears off, patient will feel depressed, fatigued and
drowsy
Can cause cardiac dysrhythmias, MI, convulsions, stroke
and death
Not physically addictive but cause psychologic
dependence
“Crack” cocaine highly addictive after first dose
Treatment
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Treat with Haldol or other antipsychotics
Treat cardiac dysrhythmias with antidysrhythmics
Need detox and psychiatric counseling
Nicotine
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Promotes compulsive use, abuse and dependence
Inhaling smoke from cigarrette delivers 1 mg of nicotine
Readily absorbed through the lungs, skin, mucous
membranes
Metabolized by liver, excreted by kidneys
GI effects: n/v, increases muscle tone and motility,
aggravates GERD and PUD
Nicotine
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Toxic effects include hypertension, cardiac dysrhythmias,
convulsions, coma, respiratory arrest, paralysis of skeletal
muscle
With chronic use, implicated in vascular disease and
sudden cardiac death
Nicotine
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Dependence is characterized by compulsive use and
development of tolerance and physical dependence
Compulsion when nicotine levels become low
S/S of withdrawal include: anxiety, irritability, difficulty
concentrating, restlessness, headache, increased appetite,
weight gain, and sleep disturbances
Treatment of Nicotine Addiction
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Wellbutrin or Zyban (buproprion) OR
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Nicotine replacement in form of patches or gum; inhaler
and nasal spray by prescription
Intended for use no longer than 3-6 months
Contraindicated in CAD
May use buproprion and nicotine in concert
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MDMA
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Psychoactive similar to methamphetamine
Stimulant and psychedelic, create energizing effect
Causes distortion in perception of time
Affects primarily serotonin
Neurotoxic
addictive
MDMA
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Can affect with body temperature regulation
Cognitive impairment
Causes tachycardia, elevated BP, involuntary teeth
clenching, chills or sweating
Analeptics
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CNS stimulants
Provigil (modafinil) for narcolepsy
Mechanism of action unclear
Not recommended in patients with LVH or ischemic
changes on ECG
Adverse effects include: chest pain, dizziness, dyspnea,
dysrhythmias, headache, nausea, nervousness, palpitations
Toxicity of CNS stimulants
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s/s agitation, dysrhythmias, combativeness, confusion,
hyperactivity, insomnia, irritability, nervousness, panic
states, restlessness, tremors, seizures, coma, circulatory
collapse and death
Tx is supportive. Gastric lavage within 4h of ingestion.
Activated charcoal (1g/kg). IV Valium
Others
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Ketamine
Rohypnol (flunitrazepam)
GHB (gamma hydroxybutyric acid)
Dextromethorphan
THC
Absinthe