-
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)
-
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)
-
Antispamodic and Antispastic
- diazepam (Valium)
- tizanidine (Zanaflex)
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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)
-
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)
-
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
-
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
-
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)
-
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
-
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)
-
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
-
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
-
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
-
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
-
Spinal Cord Injuries
- Incomplete- paralysis w/some sensitivity/movement
- Complete- paralysis
- Paraplegia- 2 lower limbs
- Tetraplegia- all 4 limbs
-
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)
-
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
-
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
-
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
-
MS Risk factors for Attacks
- Infections
- Heat
- Childbirth (pregnancy- protective)
- Sleep deprivation
- Stress
- Malnutrition
- Anemia
- Organ dysfunction
-
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
-
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
-
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
-
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)
-
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
-
Interferon Monitoring
- Pregnancy category C
- CBC (transient DEC)
- Platelets
- LFT (transient INC)
- - Baseline, 1 month, Q3 months x1 year, Q6 months
-
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)
-
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
-
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
-
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
-
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
-
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
-
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
-
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)
-
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
-
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
-
HD Movement Disorders
- DA agonists, glutamate antagonist, benzodiazepines
- Antipsychotics are limited by their ability to cause movement disorders
- Amantidine may exacerbate cognitive symptoms
-
HD Psychiatric Disorders
- Try non-pharm first
- Antidepressants, antipsychotics, mood stabilizers
-
Therapy
- Patients benefit from each type of therapy
- - Speech
- - Occupational
- - Psychotherapy
- - Physical
-
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
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