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• You must administer surgical prophylaxis at the time of the first incision or as close as possible.  Redose if surgery is longer than four hours.  No need for post-op, except in cardiac procedures.
• Usually use cefazolin 2 g (3 g for patients above 120 kg), ceftriaxone, cefotetan, cefoxitin 2 g, clindamycin 900 mg, vancomycin 15 mg/kg
• Cefazolin 2g is preferred in most cases, one dose unless surgery > 4 hours or cardiac procedures
  • Prophylaxis by surgical procedure
    • GI: Cefazolin 2g
    • Billary: Cefazolin, cefoxitin, cefotetan or ceftriaxone 2g, or amp/sulbactam 3g
    • Appendectomy: cefoxitin or cefotetan 2g or cefazolin + metronidazole (anaerobic coverage)
    • Colorectal: cefazolin or ceftriaxone 2g + metronidazole with or without neomycin and erythromycin
    • Gynocological: cefazolin, cefoxitin or cefotetan 2g
    • Cardiac: cefazolin or cefuroxime 2g
    • Orthopedic – cefazolin 2g
    • Urologic: None

*See the seizure medication table  for quick reference.
*Seizure Emergencies

Epilepsy Treatment Options:

Know doses for narrow therapeutic index drugs like phenytoin, but mostly need to know what kind of seizure and major side effects that would cause you to choose a different therapy. Also know REMS programs.

• Benzos can be used as adjunctive, short-term therapy (clorazepate, clonazepam, diazepam or lorazepam)
• Brivaracetam
• Carbamazepine – Beware of Stevens Johnsons syndrome with carbamazepine, induced its own metabolism, pharmacogenomic considerations (HLA-B testing in Asians), blood disorders
• Eslicarbazepine
• Ethosuximide – Absence seizures
• Felbamate in severe, refractory seizures.  Severe side effects: aplastic anemia, liver damage.  Adjunct for Lennox-Gestault
• Fosphenytoin
• Gabapentin – Also for peripheral neuropathy
• Lacosamide – partial onset seizure, increases suicidal ideation
• Lamotrigine – Adjunct for partial, bipolar, Lennox-Gestault. Valproate inhibits the metabolism (must lower dose).  Carbamazepine induces metabolism.  Titrate to avoid Stephen-Johnson’s syndrome.  Estrogen induces metabolism (increase dose).  Good for patients with sexual dysfunction
• Levetiracetam – partial and myoclonic, traumatic brain injury, adjust in renal dysfunction
• Oxcarbazepine – no auto-induction, partial, bipolar, causes hyponatremia, some cross sensitivity with carbamazepine. Good for sexual dysfunction.
• Perampanel – neuropsychiatric effects
• Phenobarbital – partial and generalized, not for absence seizures, used for anxiety too.
• Phenytoin – Dose-related effects include nystagmus, ataxia, drowsiness, cognitive impairment. Non-dose related effects include gingival hyperplasia, hirsutism, acne, rash, hepatotoxicity, coarsening of facial features. Therapeutic range: 10-20 mg/ml.   Michaelis–Menten saturable kinetics, so dose accordingly.
  • Dose titration:
  • < 7 mg – increase 100 mg daily
  • 7-12 increase 50 mg daily
  • > 12 increase by 30 mg or less
• Pregabalin: reduce dose in renal dysfunction
• Valproate: good for absence seizures, migraine and partial complex seizures.  Causes neural tube defects, beware in women of childbearing age.  Can increase anemia.
• Primidone: Metabolized to phenobarbital.  Also used for tremor.
• Tigabin: Use as an adjunct in partial seizures, may cause seizures
• Topiramate: Adjunct for partial seizures or Lennox-Gestault. Warning in open-angle glaucoma.
• Vigabatin: SHARE Rems program.  Causes retinal dysfunction.
• Zonisamide: Avoid in sulfa allergy, decreases the ability to sweat, increases kidney stones.

*******No Valproic Acid in potentially pregnant patients***********

Also avoid: phenytoin, carbamazepine, and phenobarbital, but not as severely.  Try to use a single agent.

May DC epilepsy meds if:

1. Seizure free for at least 2 years on medication
2. Single type of partial or primary seizure
3. Normal neurological exam and normal IQ
4. EGG normal

Drugs that can induce seizures: tramadol, FQs, bupropion, imipenem/cilastatin, benzo withdrawal

Electrolytes that can induce seizures: hyponatremia, hypernatremia, hypercalcemia.

Acute Relapses:

• Methylprednisone 1g/day in divided doses for 3-5 days.
• Oral prednisone 1250 mg every other day for 5 days
• Intravenous adrenocortical hormones.

DMARDs-

1. Alemtuzumab – Can cause thyroid disorder, infusion reactions, increased infections (screen for herpes and TB before giving), may risk some cancers, vaccinate 6 weeks prior to therapy, avoid live vaccines during treatment.
2. B – interferon – flu-like symptoms, injection site problems
3. Dimethyl fumarate – GI and skin reactions
4. Glatiramer acetate – injection site reactions, chest pain, shortness of breath,
5. Fingolimod – Contraindicated in mi, unstable angina and stroke, heart failure class III/ IV monitor for bradycardia, avoid he vaccines.
6. mitoxantrone – only second line due to toxicity. Can cause leukemia-like disease
7. Natalizumab – relapsing forms, only through special program due to leukoencephalopathy risk.
8. Teriflunomide – Secondary, hepatotoxicity, neutropenia, increased infection risk.

Fatigue: non-pharmacologic (rest, sleep management, cooling) or amantadine or methylphenidate
Spasticity: Baclofen or tizanidine
Walking Impairment: Dalfampridine (K+ Channel Blocker): may cause seizures, UTI, insomnia
Pseudobulbar affect: Dextromethorphan/Quinidine

Diagnosis:

• Brief Psychiatric Rating Scale (BPRS)
• Positive and Negative Symptom Scale (PANSS) – 7-point, 30 item scale.  Requires a 45-minute interview
• Positive Symptom Rating Scale (PSRS) – 1-7 scale
• Brief Negative Symptoms Assessment (BNSA) 1-6 scale

Treatment:

• Antipsychotics are the first line
• The Joint Commission recommends 1 antipsychotic unless:
  • 3 failed attempts at monotherapy
  • A plan to taper to monotherapy
  • Augmentation of clozapine
  • Other documentation

Antipsychotics:

• First-generation:
  • Mostly treat positive symptoms (hallucinations, delusions, disorganized behavior)
  • All lower seizure threshold, cause weight gain, liver toxicity, QT prolongation
  • Low potency (anticholinergic > EPS)
    • Chlorpromazine (blue-grey skin, also treats hiccups, N/V, RLS) and thioridazine
  • High potency (EPS>>anticholinergic)
    • Fluphenazine (comes in depot shot), haloperidol (depot too), loxapine (bronchospasm risk), perphenazine, trifluoperazine (don’t give greater than 6 mg/day longer than 12 weeks)
  • Smoking may increase metabolism, so may need to decrease dose if patients quits, especially olanzapine and clozapine
• Second Generation (aka atypical):
  • Treats mostly positive symptoms, but can improve negative symptoms as well.  Cause less extrapyramidal symptoms and tardive dyskinesia. Overall, 2nd generations are better tolerated.
  • Some seizure threshold lowering, risk for diabetes and hyperlipidemia, some QT prolongation, hyperprolactinemia, antihistamine effects
  • Weight gain worst to least: clozapine > olanzapine > risperidone, paliperidone, iloperidone, quetiapine > ziprasidone, aripiprazole, lurasidone
  • Clozapine only for refractory cases due to agranulocytosis risk.  Monitor ANC.  If <1000, interrupt therapy, if <500 stop.
    • May add lamotrigine to clozapine. No data for other anticonvulsants
  • Olanzapine should never be taken with lorazepam.
  • Risperidone has greater EPS and TD with 6mg or more dosing.
  • Ziprasidone has more QT prolongation than others.
  • Aripiprazole has more akathisia, low EPS and TD
  • Iloperidone causes orthostasis if not properly titrated
  • Paliperidone s the active metabolite of risperidone.
  • All patients prescribed second-generation antipsychotics should be monitored for weight, blood pressure, fasting, glucose, lipids and waist circumference.
  • Benzos may be useful during the acute phase
• Neuroleptic malignant syndrome:
  • Can occur with any agent, but more common with high potency first-generation antipsychotics
  • Manifested by agitation, confusion, changing levels of consciousness, fever, tachycardia, labile blood pressure, sweating.
  • High mortality rate.
  • Treatment: Discontinue agent, give supportive therapy including fluids and cooling.  Bromocriptine and dantrolene can be used.