Neurology

*See the seizure medication table for quick reference.

Seizure overview.

Head trauma:

• Early seizure – within first 7 days, prevent with 5/mg/kg day phenytoin (valproate has higher mortality)
• No prophylaxis for late seizures.

Emergent:

For emergent seizures, benzos are the drug of choice to stop seizing.

• Lorazepam – onset 2-3 minutes, 0.1 mg/kg up to 4 mg every 5-10 minutes.
• Diazepam – onset rapid, but duration is short.  0.15/mg/kg up to 10 mg every 5 minutes.
• Midazolam – 0.2 mg/kg up to 10 mg/dose

After benzos, start control med:

• Phenytoin 20 mg/kg
• Fosphenytoin
• Phenobarbital 20 mg/kg
• Valproic Acid 20-40 mg/kg
• Levetiracetam 20-30 mg/kg
• Lacosamide 200-400 over 15 minutes

If refractory to above:

1. Phenobarbital 5-15 mg/kg over 15 minutes then 0.5 mg/kg/hr
2. Thiopental 2-7 mg/kg then 0.5 mg/kg/hr
3. Midazolam 0.2 mg/kg then 0.5 mg/kg/hr
4. Propofol 1-2 mg/kg then 20-200 mcg/kg/min

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

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

Table: 1 – first line drug, 2 – second line drug, 3 – some effect, 4 – adjunctive therapy, 5 – used only when benefits outweigh risks

Here’s a chart from another reference, but I didn’t write it down:

Drugs and states that can induce seizures:

• tramadol
• fluoroquinolones
• bupropion
• imipenem/cilastatin
• benzos when in withdrawal
• alcohol withdrawal
• hyponatremia
• hypernatremia
• hypercalcemia

Risk factors:

• Age: risks double every decade over 55
• Race: more risk in native Americans, second highest risk in African Americans then whites.
• Sex: risk higher in men
• Low birth weight
• Family History
• Diabetes
• Hypertension
• Oral contraceptive use
• Post-menopausal hormone use
• Atrial fibrillation
• Coronary artery disease
• Asymptomatic carotid stenosis
• Dyslipidemia
• Obesity
• Physical inactivity
• Sickle Cell Disease
• Pregnancy
• Peripheral artery disease
• Patent foramen ovale
• Depression
• Alcohol Use
• Smoking

Prevention:

• Treat modifiable risks
• Treat Afib (CHA2D2-VASc)

Acute Stroke:

• TPA within 4.5 hours only: 0.9 mg/kg (up to 90 mg), 10% as a bolus dose, give the rest over 1 hour.  Hold antiplatelets for 24 hours.  DO NOT give in pregnancy.
• Do not give if:
  • History of intracranial bleed
  • Active internal bleeding
  • Intracranial/spine surgery, head trauma or stroke within 3 months, risk of bleeding outweighs benefits
  • GI hemorrhage within 3 weeks or structural GI malignancy
  • Glucose < 6 or >400 until normalized
  • Arterial punch within 1 week
  • BP > 185/110, can be stabilized but must be kept below this for at least 24 hours after the TPA given
  • Intracranial, intraaxial neoplasm or an unruptured aneurysm
  • INR >1.7, APTT > 40, PT >15, platelet <100,000
  • LMWH in the last 24 hours, XA inhibitor in last 48 hours
  • Endocarditis
• If TPA cannot be given, initiate ASA within 48 hours of stroke
  • Aspirin (75-100 mg daily), Aggrenox (200/25 BID) and clopidogrel (75 mg daily) are all options after the first stroke or TIA.  Cilostazol (100 mg BID) is not a preferred agent.  May consider ASA and Clopidogrel in combination for 90 days.
  • Can consider warfarin if patient has atrial fib, rheumatic mitral valve disease, mechanical prosthetic heart valves, bioprosthetic heart valves or left mitral thrombus formation. Target INR 2.5 (3 in mechanical heart valves)

In patients who need to be initiation on dopaminergic agents, either levodopa or dopamine agonists can be used. Levodopa is better at improving motor functions, dopamine agonists are better at lessening motor complications.  May also use a MAOI (rasagiline or selegiline only, they increase extracellular dopamine).

Carbidopa/Levodopa is the mainstay of therapy, but often clinicians will use a dopamine agonist as the first line in a younger patient to save carbidopa/levodopa, which has a limited effective life of 3-4 years.

• Wearing Off Phenomenon: the return of symptoms before the next dose. Add dopamine agonist, MAO-B, COMT inhibitor increase levodopa.
• On-Off Phenomenon: profound, predictable return of symptoms without respect to dosing interval. Add COMT inhibitor (entacapone) or  rasagiline
• Dyskinesias are drug induced.  Decrease levodopa or add amantadine.

Dopamine Agonists:

• Bromocriptine 5-40 mg
• Pramipexole 1.5-4.5
• Ropinirole: 0.75-24
• Rotigotine: 6-8
• Peroglide
• May cause nausea and vomiting, hypotension, hallucinating. hypersexuality and/or compulsive behavior.  Monitor BP while titrating.

Anticholinergics: Trihexyphenidyl and benztropine are both 0.5-1 mg BID and cause dry mouth, urinary retention, dry eyes, constipation (think dry)

Amantadine: may reduce dyskinesia caused by levodopa, 100 mg BID to TID

COMT Inhibitors: Tolcapone is restricted due to hepatotoxicity.  Entacapone must be used with levodopa/carbidopa, increases levodopa to the brain.

Acute:

• Treat with NSAIDS, APAP, 5-HT receptor antagonists (triptans).
• Prophylaxis: Avoid precipitants, TCAs, propranolol, topiramate, verapamil, valproic acid, NSAIDs, Botox, Magnesium, Vitamin B12, CoQ10, feverfew

Migraine:

• If they are recurrent, interfere with daily activities or patient prefers prophylactic therapy, prophylaxis should be considered. Use lowest effective dose, give 2 – 3-month trial, consider a choice that also helps with comorbidity
• Possibilities: Frovatriptan for menstrual migraines, metoprolol (not in asthma, but may help in HTN), Botox, petasites/butterbur, propranolol, timolol, topiramate, valproic acid
• Triptans are good for an acute migraine.
• Butorphanol has an intranasal route, good for nausea and vomiting

Tension Headaches:

Treatment: APAP, NSAID, ASA, treat depression and anxiety
Prophylaxis: Tricylic antidepressants, Botox

Cluster Headaches:

Treatment: triptans, oxygen, intranasal lidocaine, octreotide and 10% cocaine
Prophylaxis: verapamil, melatonin, suboccipital injection of betametasone, lithium (~0. 3 mmol/L, subtherapeutic, dose for bipolar = 0.8 – 12)