epilepsy/neuro degen

• Sodium Channel Blockers


  Action potential generation is mediated by voltage sensitive Na channels (Na channels open during action potential firing and close in repolarization), binds to/stabilizes Na channels that are inactivated (open)
• Carbamazepine (Tegretol)


  Adverse effects: dizzy, diplopia, leukopenia, hyponatremia, Contraindicated: worsens absence seizures, bad for elderly
• Oxcarbazepine (Trileptal)


  Mechanism of action: Na channel inactive, modulate Ca channel, Adverse effects: dizzy, diplopia, ataxia, hyponatremia, visual disturbances, N/V, Pearls: monitor Na, dec contraceptive effectiveness
• Lamotrigine (Lamictal)


  Also decreases glutamate release, Adverse effects: sedation, diplopia, ataxia, rash (SJS), Pearls: taper slow, use in preg
• Phenytoin (Dilantin)


  Adverse effects: nystagmus, ataxia, gingival hyperplasia, osteomalacia
• Fosphenytoin (Cerebyx)


  Prodrug of phenytoin, do IV/IM
• Topiramate (Topamax)


  Also acts as an agonist at GABA-A receptors, Also acts as a glutamate antagonist, Adverse effects: difficulty concentration, can't find words, kidney stones, WL, Pearls: adequate hydration, dec effectiveness of contraceptives
• Drugs that Enhance GABA Inhibitory Transmission

  Mechanism of action: stim release/syn of GABA, inhib GABA transporters so action is prolonged, inhib GABA metabolism, enhance effect of GABA on its receptor
• Benzodiazepines


  Mechanism of action: binds to GABA inhib receptors and potentiate effects of GABA, Adverse effects: somnolence, dizzy, unsteady, Pearls: caution in elders (cognitive impairment)
• Phenobarbital


  Mechanism of action: promotes GABA binding to GABA-A receptor and inc amt of time chloride channel is open, Adverse effects: sedation, paradoxical hyperactivity in peds, osteomalacia
• Valproic Acid (Depakene, Stavzor)

  Mechanism of action: Inc brain conc GABA, kinda impacts Na channel, also blocks calcium channels, Adverse effects: sedation, WG, hair loss, N/V, thrombocytopenia, Contraindicated: NO PREG
• Calcium Channel Blockers


  Valproic Acid (Depakote) mechanism of action: absence seizure tx involving thalamus/cortex circuitry, blocks T-type Ca channel that's involved in neuronal firing occuring during the absence seizures
• Gabapentin (Neurontin)/Pregabalin (Lyrica)


  Mechanism of action: GABA analog that does NOT act at GABA receptors, maybe dec Ca dependent release of neurotransmitters, Adverse effects: G= fatigue/ataxia/dizzy; P=drowsy/blurred vision/WG, Pearls: renal dosage adjustments needed, less significant drug interactions bc not metabolized by liver, G=space from antacids
• Levetiracetam (Keppra)


  Mechanism of action: dec inhib of GABA channels, block Ca channels, binds w high affinity SV2A, Adverse effects: somnolence, dizzy, HA, behavioral changes, Pearls: pt mood, adjust dosage in renal dysf, low drug interaction potential
• Acetylcholinesterase Inhibitors


  Mechanism of action: inhib acetylcholinesterase (enzyme responsible for the destruction of acetylcholine) and improve availability of acetylcholine, Adverse effects: Nausea, diarrhea, vomiting, anorexia, tremors, bradycardia, muscle cramps, Interactions: d/g= cytochrome P450 substrates, caution w BB/CCB/NSAIDs
• Donepezil (Aricept)


  Long half life (70hrs)
• Rivastigmine (Exelon)


  Tablet or 24hr transdermal patch
• Memantine (Namenda)


  Mechanism of action: antagonist w low affinity at NMDA receptor; blockade of NMDA receptors slows the intracellular calcium accumulation and helps prevent further nerve damage; Low affinity antagonism to NMDA-type receptors may prevent excitatory amino acid neurotoxicity w/o interfering with the physiological actions of glutamate required for memory and learning, Clinical use: mod/severs disease, monotherapy/add-on to acetylcholine inhibitor; added when pt progresses to mod disease/continue to decline despite tx w cholinesterase inhib (Memantine/Donepezil (Namzaric)), Adverse effects: well tolerated; Confusion, agitation, restlessness, constipation, dizziness, HA, Caution: pts w seizure disorder/hepatic impairment, need renal dosage if CrCl<30 mL/min
• Levodopa


  Mechanism of action: levodopa's immediate precursor to dopamine so its converted to dopamine, crosses BBB extensively metabolized in GI tract and periph tissues
• Carbidopa (Lodosyn)


  Mechanism of action: prevents conversion of levodopa to dopamine in GI tract/periph tissues, reduces levodopa dose requirements and improves tolerability
• Levodopa/Carbidopa (Sinemet, Parcopa, Rytary, Duopa)


  Adverse effects: periph effects: anorexia, nausea, vomiting, tachycardia, ventricular extrasystoles, hypotension, discoloration of saliva and urine; CNS effects: visual and auditory hallucinations, abnormal involuntary movements (dyskinesias), depression, psychosis, anxiety, Pearls: effective for all 3 cardinal sx (resting tremor, bradykinesia, rigidity); pts will develop motor complications from using this drug for several years, Contraindicated: closed-angle glaucoma, hypersensitivity, no if also on MAOI, careful if melanoma hx, Interactions: MAOIs,antipsychotic drugs, vitamin B6, abs impacted by drugs that delay/promote gastric emptying
• Entacapone (Comtan)


  Mechanism of action: inhib conversion of levodopa to 3-O-methyldopa in both periphery/CNS→allowing higher conc of levodopa, Adverse effects: Diarrhea, nausea, anorexia, Dyskinesias, Hallucinations, Sleep disorder, Pearls: not useful as monotherapy (only in combo w levodopa), help wearing off in levodopa-carbidopa; may need to dec levodopa dose when added to avoid avoid adverse dopaminergic effects
• Monoamine oxidase inhibitors


  Mechanism of action: block oxidative degradation of dopamine thru MAO-B inhib, Adverse effects: Confusion, Dyskinesias, Hallucinations, Hypotension, Insomnia. Nausea, Hypertensive crisis, Pearls: slow disease progression from reduced oxidative stress; used as initial therapy or adjunctive w levodopa, Interactions: SRIs, SNRIs, tricyclic antidepressants, MAOIs, meperidine
• Rasagiline (Azilect)


  Pharmacology: irreversible selective inhib of MAO-B
• Selegiline (Eldepryl)


  Pharmacology: can cause HTN/insomnia
• Amantadine (Symmetrel)


  Mechanism of action: antiviral drug w anti-parkinson action; inc release of dopamine, blocks cholinergic receptors, inhib N-methyl-D-aspartate (NMDA) type of glutamate receptors, Clinical use: monotherapy for mild/mod disease or as adjunctive therapy w levodopa in adv disease, improve rigidity, bradykinesia, less efficacy for tremor and useful for treating dyskinesias associated w long-term dopaminergic tx, Adverse effects: dry mouth, hypotension, livedo reticularis, nausea, restlessness, sedation, vivid dreams
• Dopamine Receptor Agonists


  Mechanism of action: directly stim dopamine receptors, Clinical use: initial monotherapy/adjunctive therapy levodopa; not great but has less long-term motor complications; non ergot derivatives>ergot derivatives bc pulm/retroperitoneal fibrosis; may need to dec levodopa dose to lessen risk of dopaminergic ad effects, longer duration than levodopa and is good in pts having fluctuations in levodopa response; initial therapy w newer agents→less risk of developing dyskinesias/motor fluctuations compared to pts starting on levodopa
• Pramipexole (Mirapex)/Ropinirole (Requip)


  Non-ergot derivatives, Clinical use: also RLS, Adverse effects: nausea, hallucinations, insomnia, dizzy, constipation, hypoTN, Do not cause fibrosis or peripheral vasospasm as seen with ergot derivatives
• Cholinergic Receptor Antagonists (Anticholinergic Agents)

  Benztropine (Cogentin) mechanism of action: compete with acetylcholine at muscarinic receptors in the CNS, Pearls: less effective than dopaminergic drugs but maybe helpful as adjunctive therapy, tremor sx reduced most, Adverse effects: Mood changes, Dry mouth, Visual problems, Confusion, Hallucinations, Urinary retention, Constipation, Contraindicated: Glaucoma, Prostatic hyperplasia, Pyloric stenosis, Dementia
• Brand/Generics for Exam: Gabapentin (Neurontin), Pregabalin (Lyrica), Levetiracetam (Keppra), Topirimate (Topamax), Lamotrigine (Lamictal), Phenytoin (Dilantin), Levodopa/Carbidopa (Sinemet), Donepezil (Aricept), Memantine (Namenda), Ropinirole (Requip)
• Medications used for the treatment of epilepsy that also exhibit antianxiety effects

  • benzodiazepine ??
• Medications used for the treatment of epilepsy that are associated with risks when used in the elderly population

  • Carbamazepine (Tegretol)
  • Benzodiazepines
• Complications that can arise with prolonged use of levodopa/carbidopa therapy

  1. Motor complications after several years

  2. Wearing off- loss of clinical effect towards end of dosing interval

  3. Dyskinesias- involuntary movements involving face, neck, trunk, and upper extremities

  4. On-off phenomenon- rapid transformations from normal or controlled motor activity to bradykinetic or uncontrolled motor activity

  5. Freezing- drug-resistant off period or inability to initiate motor function; starting hesitation
• Methods to help decrease complications with prolonged use of levodopa/carbidopa therapy


  Most oral forms should be administered on an empty stomach (at least 30 minutes before a meal or 1 hour after meal), Amino acids (such as in high protein meals) or high fatty meals can compete with levodopa for absorption, take with non-protein snack to decrease nausea
• Clinical pearls regarding the use of acetylcholinesterase inhibitors

  Start therapy early to max clinical benefits, donepezil is preferred, retitrate if therapy is stopped for a day or so
• Precautions surrounding the use of acetylcholinesterase inhibitors in patients with certain comorbidities

  • COPD or asthma- cholinergic effects can increase bronchoconstriction and secretions
  • Bradycardia can be worsened by cholinergic agents-hypotension or syncope
  • PUD/GERD- cholinergic effects can increase gastric acid production
• Factors that indicate initiation of anti-seizure medications

  Decide the cause of seizure, risk of recurrence, benefit to starting med immediately vs risk of recurrent seizure, side effect profile, patient profile (driving/employment)
• Factors to consider when selecting medications to treat seizure

  • Efficacy, pharmacokinetics (frequency, interactions, aging), adverse effects, cost, contraceptive impact, lots of interactions of anti-seizure meds with hepatic enzyme induction/inhibition properties
• Factors that will influence treatment compliance

  Taking medication less times per day, drugs that interfere with hepatic enzyme inducers
• Medication choices for special populations (pregnant, pediatric and geriatric)

  • Pregnant women get folate while on anti-seizure meds, counseled on teratogenic effects of anti-seizure meds, plan pregnancy after discussion with neurologist. Do NOT take valproate (depakote) and DO take Levetiracetam (Keppra), Lamotrigine (Lamictal) or Oxcarbazepine (Trileptal). Aging problems: age related alterations in protein binding, reduces hepatic metabolism, diminish renal clearance, polypharmacy, neurologic drug side effects