Muscle Relaxants, Substance Abuse and CNS Stimulants

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Muscle Relaxants, Substance Abuse and CNS
Stimulants

• By Linda Self

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Muscle Relaxants

• Used to decrease muscle spasms or the spasticity
  associated with certain neurologic and
  musculoskeletal disorders
• Muscle spasmsudden, involuntary muscle
  contraction. Occurs with musculoskeletal trauma.
  Spasms may be tonic (sustained) or clonic
  (alternating)
• Spasticityincreased muscle tone or contraction,
  stiff, awkward movements. Caused by nerve damage
  in spinal cord and brain

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Mechanisms of Action

• 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

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Indications
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Indications

• 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

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Skeletal Muscle Relaxants

• Used in patients with low back problems or be
  associated with sprains (ligaments), strains
  (muscle/tendon) , or other musculoskeletal
  injuries

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Contraindications

• 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

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General Considerations

• 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

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Age-Related Considerations

• Safety and effectiveness in children not
  established
• Caution in elderly because of anticholinergic
  effects and because of sedation

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Individual Drugs

• Lioresal (baclofen) used in MS and SCI. PO or
  intrathecal (spinal). Decrease dose in renal
  impairment. Taper over 1-2 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.

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Individual Drugs

• 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

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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

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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

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Interactions

• 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

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Substance Abuse Disorders

• 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)

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Dependence

• 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)

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Dependence cont.

• 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

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CNS Depressants--Alcohol

• 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
  tissuecirrhosis)

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Alcohol

• 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

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Alcohol

• Causes increased intestinal motility
• Can damage intestinal mucosa resulting in
  nutritional deficienciesthiamine, 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

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Alcohol and Drug Interactions

• 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.

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Alcohol

• With antihypertensives, causes vasodilation and
  hypotensive effects
• With oral antidiabetic drugs, potentiates
  hypoglycemia
• With oral anticoagulants, variable depending on
  duration of alcohol ingestion

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Alcohol

• 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

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Alcohol Dependence

• 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

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Treatment of Alcohol Dependence

• 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

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Alcohol

• 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.

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Alcohol

• 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.

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Alcohol

• Key to abstinence is desire to stop drinking
• Need support and psychiatric help
• Antidepressants appear to decrease alcohol intake
  as well

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Barbiturate and Benzodiazepine Dependence

• 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

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Barbiturates

• Barbiturates largely replaced by benzodiazepines
• Examples Luminal (phenobarbital), Pentothal
  (thiopental), Nembutal (pentobarbital), Seconal
  (secobarbital)

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Barbiturate Dependence

• 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

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Benzodiazepines

• 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

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Benzodiazepines

• 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

• Commonly abused
• Produce tolerance and high degrees of
  psychological and physical dependence
• Not an issue when needed for pain management in
  terminal illnesses

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Treatment of Opiate Dependence

• Overdose will require supportive care
• Giving narcotic antagonist can precipitate
  withdrawal s/s
• Can achieve therapeutic withdrawal by gradually
  tapering dose

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Treatment of Opiate Dependence

• 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)

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LAAM

• 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

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CNS Stimulants

• Not recommended in children under 6 years of age
• May affect growth
• Ritalin (methylphenidate) is most commonly used
  drug for children with ADHD

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Amphetamines

• 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

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Amphetamine Dependence

• Produce stimulation and euphoria
• Effects are dose related
• Small amounts cause mental alertness, wakefulness
  and increased energy
• Large amounts can cause psychoses
• Tolerance develops

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Methamphetamine

• Psychostimulant
• Increases levels of norepinephrine, serotonin and
  dopamine
• Extremely neurotoxiccan 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

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Xanthines

• 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

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Xanthines

• 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

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Cocaine

• 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

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Cocaine

• 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

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Treatment

• Treat with Haldol or other antipsychotics
• Treat cardiac dysrhythmias with antidysrhythmics
• Need detox and psychiatric counseling

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Nicotine

• 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

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Nicotine

• 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

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Nicotine

• 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

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Treatment of Nicotine Addiction

• Wellbutrin or Zyban (buproprion) OR
• 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

• Psychoactive similar to methamphetamine
• Stimulant and psychedelic, create energizing
  effect
• Causes distortion in perception of time
• Affects primarily serotonin
• Neurotoxic
• addictive

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MDMA

• Can affect with body temperature regulation
• Cognitive impairment
• Causes tachycardia, elevated BP, involuntary
  teeth clenching, chills or sweating

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Analeptics

• 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

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Toxicity of CNS stimulants

• 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

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Others

• Ketamine
• Rohypnol (flunitrazepam)
• GHB (gamma hydroxybutyric acid)
• Dextromethorphan
• THC
• Absinthe