Spasms

  1. Antispasmodic
    • Pain associated with skeletal muscles (musculoskeletal pain)
    • Not recommended 1st line (American Pain Society- NSAIDs and/or APAP 1st line)
    • Used short term (2-3 weeks)
    • Choice of Agent: preference, cost, tolerability, ADRs
    • cyclobenzaprine (Flexeril)
    • carisoprodol (Soma)
    • chlorzoxazone (Lorzone, Parafon)
    • metaxalone (Skelaxin)
    • methocarbamol (Robaxin)
    • orphenadrine (Norflex)
  2. Antispastic
    • Conditions (spasms): Multiple Sclerosis, Cerebral Palsy, Post Stroke, Spinal Cord Injury
    • Treatment is multimodal
    • - Start the dose low and titrate up to an effective dose
    • - Treatment Refractory Spasms → Surgery
    • baclofen (Kemstro, Gablofen, Lioresal)
    • dantrolene (Ryanodex, Dantrium)
    • botulinum toxin type a (Botox)
  3. Antispamodic and Antispastic
    • diazepam (Valium)
    • tizanidine (Zanaflex)
  4. baclofen
    • Lioresal, Gablofen
    • Antispastic
    • Short ½ life
    • Who- MS, spinal cord injury
    • Dose- 5 mg TID, titrate every 3 days, max dose 80 mg/day
    • Monitor- ALT/AST (baseline and every 6 months)
    • ADR- CNS Depression (sedation, dizziness)
    • Abrupt discontinuation may cause seizures and hallucinations
  5. Baclofen Pump
    • Intrathecal baclofen
    • Antispastic
    • Indication- Oral baclofen failure
    • Dose: Screening- Adjust dose based on response
    • - Initial 50 mcg- Increase dose in 25 mcg increments Q24 H until 4-8 H positive clinical response is seen
    • - Ideal- Positive response to a single bolus dose of 100 mcg/2ml or less
    • Establish oral tolerability prior to pump placement and/or 50 mcg (given over 1 minute) intrathecal test dose (relief 4-8 H)
    • Maintenance Dose (max 100 mcg)
    • - <8 H test dose efficacy- Double the screening dose
    • - >8 H test dose efficacy- Dose is the same as test dose
  6. dantrolene
    • Dantrium
    • Antispastic
    • Not 1st line
    • Indication- Muscle Spasms, Malignant Hyperthermia, NMS (off label)
    • - Associated with muscle weakness
    • Dose: 25 mg QD x 7 D (titrate up)
    • - Then 25 mg TID x7 D, then 50 mg TID x7 D, Then 100 mg TID (max 100 mg QID)
    • - Discontinue medication if no benefit is seen within 45 days
    • BBW: Hepatotoxicity
    • - Monitor at baseline and Q3 months
    • Common ADRs: Flushing, D/N, Fatigue, Drowsiness, Malaise
  7. botulism Toxin A
    • Botox
    • Antispastic
    • Neck Spasms, overactive bladder, Dystonia (small muscle groups)
    • MOA- DEC muscles contractions (via ACh) and causes muscle relaxation
    • ADR: Injection site pain, headache, flu like symptoms
    • Dosing- not interchangeable among agents
    • - Dose is dependent on indication
    • - Cumulative dose should not exceed 360 units/3 months
  8. cyclobenzaprine
    • Flexeril
    • Antispasmodic
    • Dose- 5 mg TID or 10 mg TID
    • Anticholinergic properties (Structure similar to TCAs)
    • - Avoid in elderly
    • QT Prolongation (like Celexa, Geodon, Pimozide, TCA)
    • - Avoid in cardiac abnormalities
  9. carisoprodol
    • Soma
    • Antispasmodic
    • Schedule IV
    • - Metabolized to active additive metabolite: meprobamate
    • - Use is limited by abuse and physical dependence potential (Not 1st line)
    • Dose- 350 mg QID (might see TID)
    • Other ADR- Drowsiness and idiosyncratic reactions, allergy
    • - Idiosyncratic- Dizziness, weakness, fatigue- resolves on own
  10. Metaxalone
    • Skelaxin
    • Antispasmodic
    • Dose- 800 mg TID-QID
    • Benefit- Less sedation and abuse potential
    • Rare ADR- Leukopenia and Hemolytic Anemia
    • - DNU in pts with already this
  11. methocarbamol
    • Robaxin
    • Antispasmodic
    • Dose 1,500 mg QID x 2-3 days → 750 mg QID
    • - Also indicated for tetanus
    • Common ADRs: Dizziness, Headache, Lightheadedness, Somnolence (drowsiness)
    • Patient Counsel – Discoloration of urine (brown, red, orange)
  12. orphenadrine
    • Norflex
    • Antispasmodic
    • Dose- 100 mg BID
    • Anticholinergic properties (structure similar to diphenhydramine like Flexeril)
    • - Blurred vision, dry mouth, N/V, GI upset
    • - Avoid in elderly (sedation)
  13. diazepam
    • Valium
    • Antispasmodic/Antispastic
    • Dose- 2 to 10 mg TID to QID
    • Other benzodiazepines may be used
    • Last line- Abuse potential, drug-drug interactions, ADRs
  14. tizanidine
    • Zanaflex
    • Antispasmodic/Antispastic
    • Alpha 2 Adrenergic Agonist (Hypotension)
    • 4 mg (initial), increase 2-4 mg every 6-8 hours (Max 36 mg/day)
    • LFTs - Monitor baseline, 1, 3, and 6 months
    • ADR – Sedation, dry mouth, asthenia
  15. Cerebral Palsy
    • Botulinum Toxin Type A (Botox)
    • - Inhibits ACh preventing muscle contraction
    • - Injected locally to affected area (small muscle groups)
    • Baclofen (Lioresal)
    • - Intrathecal (Baclofen Pump) aids in relief of pain & spasms in patients not tolerant to oral baclofen
    • Diazepam (Valium)
    • Tizanidine (Zanaflex)
  16. Secondary Conditions of Cerebral Palsy
    • Malnourishment – Nasogastric tube feeding, gastrostomy
    • Fractures, Osteopenia, Osteoporosis
    • Mental Health conditions
    • Bladder Dysfunction
    • Bowel Dysfunction
    • - Laxative and enemas use followed by fiber and stool softeners
    • Sleep Disturbance – Particular in vision impairment
    • - Melatonin 3 mg at bedtime
    • Drooling
    • - Anticholinergic agents- Scopolamine (patch formulation), Glycopyrrolate
  17. Traumatic Brain Injury
    • Establish an airway- oxygenation and prevents aspiration
    • Maintain systolic blood pressure > 90 mmHg
    • - NS or LR for fluid resuscitation
    • - Vasopressors or Inotropic if hypotension persists
    • - Monitor for renal dysfunction, lactic acidosis, peripheral ischemia
    • - Vasopressor- NE, vasopressin; Inotropic- contractions
    • Evaluate blood glucose (mental status changes)
    • - Hypoglycemia- 50 mL IV of 50% Dextrose
    • Evaluate intracranial and extracranial injuries
    • - Maintain Intracranial pressure 7-15 mmHg (>20 High- bad, Tx)
    • - Maintain Cerebral Perfusion Pressure 50-70 mmHg (Low- bad, pressure pushing blood into brain)
  18. Intracranial Hypertension Tx
    • Analgesics, Sedatives, Paralytic agents
    • Morphine Sulfate (1st)
    • - Fentanyl and Sufentanil may cause mild increase in ICP (Alt)
    • Propofol (Diprivan) 5 mg/kg/hour infusion time < 48 hours
    • - Monitor: Triglycerides, Propofol infusion syndrome (infuse >48H)
    • - PIS: hyperkalemia, metabolic acidosis, rhabdomyolysis
    • - Other: Etomidate, Pentobarbital, short acting BZDs
    • Hypothermia- reduces oxygen consumption
    • Osmotic Agents- Mannitol 0.25-1 g/kg Q4 H
    • - Caution: renal dysfunction, CHF, Pulmonary edema (exacerbate)
    • - Alternative: Furosemide (monitor K+: hypokalemia)
    • Barbiturates (high doses)
    • - Not responding to other mechanisms of ICP lowering
    • - Pentobarbital 25 mg/kg (IV loading dose) 1-2 mg/kg/hr (maintenance) ICP controlled for 24-48 hours taper down over 24-72 hours
    • - DN D/C abruptly- rebound spikes in ICP
    • - Adverse effects: cardiovascular (Hypotension)
    •   * Decrease dose, administer fluids, or vasopressors when indicated
    • Not Recommended: hyperventilation & Corticosteroids
    • - Hyperventilation- vasoconstriction lowers ICP
    • - Steroids- GI bleed, glucose intolerance
  19. TBI Seizures
    • Terminate- Diazepam (5-40 mg) or Lorazepam (2-8 mg)
    • Prevent- Phenytoin 15-20 mg/kg (loading) 5 mg/kg/day (maintenance)
    • Risk factors- GCS score < 10, cortical contusion, depressed skull fracture, hematoma, penetrating head wound, seizure within 24 hours of injury
    • Not recommended after 7 days
  20. TBI Supportive Care
    • Fluid and electrolyte (Na, Mg, K, P) management
    • Nutrition
    • Hyperthermia
    • Infections (INC need/demand of body, mental status changes)
    • DVT prophylaxis
    • - Heparin 5,000 units SQ Daily
  21. TBI Neuropsychiatric Sx (Mood)
    • Depression- Most common (SSRIs)
    • - Avoid anticholinergics- worsens cognition- TCA)
    • - Other options: ECT, Stimulants (off label)
    • Mania- Less common than depression
    • - Treat with CBZ, VPA (anticonvulsants)- Lack of Supportive Literature
    • Anxiety- Antidepressants, Buspar, Naltrexone
    • - Avoid: BZDs (cognitive impairment), Antipsychotics (slows recovery)
    • Psychosis- Treatment is dependent on lesion location
    • - Left and Right Temporal Lobe: Anticonvulsants
    • - Frontal Lobe: Dopaminergic agents
    • - Stay away from Antipsychotics- make worse
    • Apathy- Stimulants, Amantadine (INC DA), Bromocriptine
    • Psychostimulants - Methylphenidate and Dextroamphetamine
    • Dopaminergic Agents- Amantadine, Bromocriptine, L-Dopa
    • Antidepressants- SSRIs
    • Anticonvulsants- Carbamazepine and Valproic Acid
    • Other- naltrexone, beta blockers, buspirone
    • - Naltrexone- OCD, cutters/self-injury (Sx of anxiety): INC DA
  22. Spinal Cord Injuries
    • Incomplete- paralysis w/some sensitivity/movement
    • Complete- paralysis
    • Paraplegia- 2 lower limbs
    • Tetraplegia- all 4 limbs
  23. SCI Tx
    • Immobilize the Patient
    • Next Step: ABCs of trauma
    • - Airway- Establish adequate airway
    • - Breathing- Adequate oxygenation and breathing
    • - Circulation- Neurogenic Shock is common in spinal cord injury (hypotension, slowed heart rate)
    •   * 1st Line Treatment – Fluid Resuscitation
    •   * 2nd Line Treatment – Vasopressors or Inotropic agents (NE, Phenylephrine, DA)
  24. Steroids for SCI
    • IV high dose Methylprednisolone (w/in 8 H- neuroprotective)
    • - Decreases inflammation
    • Risk of use may outweigh benefit
    • - Complications – Infections, GI Bleeding, Increase glucose
    • Dose- 30 mg/kg (bolus) then 5.4 mg/kg/hr for 23-47 hours
    • - Do not use in penetrating spinal cord injuries (infection)
    • - Us is not recommended past 24-48 H
  25. Multiple Sclerosis Risk Factors
    • Genetics- More common in white Scandinavian decent
    • Environment- cigarettes associated w/greater risk and severe progression
    • Geography- Incidence is greater the further away from the equator (north)
    • - US: Higher above 37th parallel
    • Rising incidence in females living in urban areas
    • Viral and Bacterial Infections- activate demyelination in genetically susceptible individuals
    • - Greatest association: Epstein-Barr virus
    • 5% familial recurrence rate- high risk w/IL-2a and IL-7a mutations
  26. MS Assessment of progression
    • Expanded Disability Status Scale (EDSS)
    • - Evaluates neurologic function (scale of 1-10) 1- no Sx, 10-death
    • MRI – detects new lesions and changes in current lesions
  27. MS Risk factors for Attacks
    • Infections
    • Heat
    • Childbirth (pregnancy- protective)
    • Sleep deprivation
    • Stress
    • Malnutrition
    • Anemia
    • Organ dysfunction
  28. MS Tx of Acute Attacks & Exacerbations
    • Functional disability or worsening symptoms over 2 wks
    • - Prior to treatment determine if attack is secondary to the disease (MS)
    • IV corticosteroids
    • - Methylprednisolone- Decreased edema associated with demyelination
    •   * May increase the time between attacks & shortens duration of attack
    •   * Recovery is more common when started w/in 2 wks of onset
    •   * Dose- 500 to 1,000 mg/day x 3-10 days (Sx Improvement in 3-5 D)
    •   * ADR- Short term- Sleep disturbance, metallic taste, GI upset (rare)
    •   * Chronic use- Increased glucose, insulin requirements may increase
    •   * Long term- Acne, fungal infections, mood changes, GI hemorrhage (rare)
    •   * Severe attacks- Plasma exchange or IVIG
    • - An equipotent dose of prednisolone or dexamethasone may be used
    • Adrenocorticotropic Hormone (ACTH) is FDA approved
  29. Disease Modify Tx
    • 1st line- Interferon products or glatiramer
    • - Benefits may not be seen until years 1-2 of use
    • 2nd line- Fingolimod, natalizumab, mitoxantrone
    • - Used if 1st line agents are not effective or intolerable
    • - BBWs
    • Other agents approved for relapsing MS- Teriflunomide and dimethyl fumarate
  30. Interferon b1b
    • Betaseron, Extavia
    • Indicated for relapsing of multiple sclerosis
    • - Therapeutic dose causes a reduction in relapse & disease burden
    • Efficacy is due to immune modulating properties
    • 48 H b/w doses
  31. Interferon b1a
    • Avonex, Rebif
    • Each formulation should be refrigerated. May be kept at room temperature for 30 days
    • Reduce relapse rates and slows the progression of the disease
    • - Confirmed via the EDSS – 1 point reduction (med is working)
  32. Interferon ADR
    • Common
    • - Injection site reaction
    •   * Rotate injection site (butt & thighs)
    •   * Administer at room temperature
    •   * Apply Lidocaine or ice before and after injection
    • - Flu like Sx
    •   * Give NSAID/APAP prior to and after injection
    •   * Dose at bedtime
    • -Redness, swelling, menstrual irregularities
    • Uncommon
    • - Depression: monitor and treat accordingly
    • - SOB, tachycardia, thyroid dysfunction
  33. Interferon Monitoring
    • Pregnancy category C
    • CBC (transient DEC)
    • Platelets
    • LFT (transient INC)
    • - Baseline, 1 month, Q3 months x1 year, Q6 months
  34. glatiramer acetate
    • Copaxone
    • Indicated for relapsing remitting multiple sclerosis
    • - Decreases inflammation, demyelination, and axon damage at the site of the MS lesion
    • - Decreases relapse rates by approximately 29%
    • Pregnancy category B
    • Refrigerate syringe, may leave at room temperature for 1 week
    • ADR- Pain, itching at injection site, Chest tightness & flushing (self-limited)
  35. natalizumab
    • Tysabri
    • Indicated for relapsing of multiple sclerosis
    • - Used in patients with a lack of response to other options
    • BBW- Progressive Multifocal Leukoencephalopathy
    • - Risk Factors- Long term use, JCV, prior immunosuppressive agent use
    •   * Patients must be enrolled in TOUCH program
    •   * Assess for John Cunningham Virus (JCV) at baseline & every 6 months
    • Pregnancy Category C
  36. fingolimod
    • Gilenya
    • Indicated for relapsing multiple sclerosis
    • ADR- 1st dose (monitor for bradycardia x 6 H & pulse/BP taken Q1H (after 6 H- D/C if still CV issues)
    • - AV block, infections, macular edema, bradyarrhythmia, elevated BP and LFTs, decreased FEV
    • Baseline CBC, LFTs, ophthalmologic exams, EKG (in at risk patients)
    • RARE- lymphoma
    • Pregnancy Category C
  37. mitoxantrone
    • Novantrone
    • Indicated for reduction of relapse in SPMS, PPMS, RRMS
    • Lifetime max dose 140 mg/m2 (Calculate BSA)
    • ADR- Nausea, alopecia, menstrual irregularities, UTI, URTI
    • Use is limited by risk of cardiotoxicity and leukemia
    • - Prior to each dose or if CHF signs occur monitor EKG and and left ventricular EF
    • Pregnancy Category D
  38. teriflunomide
    • Aubagio
    • Indicated for relapsing form of multiple sclerosis
    • Dispensed by specialty pharmacies
    • ADR- Elevated LFTs, alopecia, N/D, HA, influenza, paresthesias
    • BBW: Hepatotoxicity
    • - Monitor LFTs 6 months prior to use and 6 months after initiation (once monthly)
    • Pregnancy Category X (males- DNU, use backup contraception)
    • - Medication remains in serum for 2 years after discontinuation
    •   * Cholestyramine washout can be used to clear the drug
  39. dimethyl fumarate
    • Tecfidera
    • Indicated for relapsing form of multiple sclerosis
    • - Decreases relapsing rates by 50%
    • ADR- Lymphocytopenia, Elevated LFTs, Flushing, GI effects
    • Monitoring- CBC prior to therapy and annually after initiation
    • Pregnancy Category C
  40. MS Sx Management (Gait, Spasticity)
    • Baclofen 10 mg TID titrate up to 40-80 mg/day (anti-spastic)
    • - Diazepam 0.5 - 1 mg may be added
    • - Baclofen pump is available
    • Tizanidine (Zanaflex) 4mg HS range 2-36 mg/day
    • - May be used in combination with Baclofen
    • Alternative Options
    • - Clonazepam, Dantrolene Sodium
    • - Gabapentin, Pregabalin, Tiagabine
    • Other options
    • - Botox- limited to small muscle groups
  41. MS Sx Management (Bowel, Bladder)
    • Anticholinergic
    • - oxybutynin chloride (Ditropan 10–20 mg/day)
    • - tolterodine (Detrol 2–4 mg/day)
    • - propantheline bromide (Pro-Banthine 45–90 mg/day)
    • - hyoscyamine (Levsin 0.75–1.5 mg/day)
    • - dicyclomine hydrochloride (Bentyl 30–80 mg/day)
    • Antimuscarinic
    • - trospium chloride (Sanctura 40 mg/day)
    • - solifenacin succinate (Vesicare 5–10 mg/day)
    • - darifenacin hydrobromide (Enablex 7.5–15 mg/day)
    • - fesoterodine (Toviaz; 4–8 mg/day).
    • Alternative (Anti-diuretic hormone)
    • - desmopressin acetate (DDAVP 0.2–0.6 mg/day)
  42. MS Sx Management
    • Tremors- Propranolol, Primidone, Isoniazid.
    • Depression- Antidepressants
    • - Consider the adverse effects of the agent chosen
    • Fatigue- Stimulants , Amantadine, Modafinil
    • Sexual Dysfunction- PDE3 inhibitors
    • Cognitive Dysfunction
    • - Cholinesterase inhibitors
    • - Stimulants
    • Sensory Symptoms
    • - Gabapentin, pregabalin, and duloxetine
    • - Carbamazepine – Trigeminal Neuralgia
  43. tetrabenazine
    • Xenazine
    • Chorea associated w/HD
    • Dose- 12.5 mg AM x 1 week then, 12.5 mg BID (Max 100 mg/day, 25 mg/dose)
    • Doses over 50 mg CYP 2D6 genotyping is recommended
    • ADR- GI upset, insomnia, dizziness, fatigue, akathisia, and Parkinsonism
    • - May exacerbate depression, SI, and other psychiatric disorders
  44. HD Movement Disorders
    • DA agonists, glutamate antagonist, benzodiazepines
    • Antipsychotics are limited by their ability to cause movement disorders
    • Amantidine may exacerbate cognitive symptoms
  45. HD Psychiatric Disorders
    • Try non-pharm first
    • Antidepressants, antipsychotics, mood stabilizers
  46. Therapy
    • Patients benefit from each type of therapy
    • - Speech
    • - Occupational
    • - Psychotherapy
    • - Physical
  47. Amyotrophic lateral sclerosis (Lou Gehrig’s)
    • riluzole (Rilutek) 50 mg Q12 H
    • Inhibits glutamate
    • Increases life expectancy by 3 months
    • baclofen- muscle stiffness
    • Nutritional supplements- muscle decline and weight loss
Author
ebmalonzo
ID
319488
Card Set
Spasms
Description
IT 3 (MT 2): Spasms
Updated