1. Determine minimal efficacious level (minimize side effects)
2. Determine level at in which signs of toxicity occur
3. Confirm compliance in apparently ineffective therapy

Phenytoin, phenobarbital, carbamazepine, valproic acid

1. Monotherapy
2. Maintain lowest dose levels
3. Folate supplementation
4. Vitamin K supplementation for enzyme inducers (phenytoin and phenobarbital)

• Used for:
  • Generalized tonic-clonic seizures and partial seizures (oral)
  • Status epilepticcus
  • Neuropathic pain
• Acts as membrane stabilizer by inactinating Na⁺ channels
• Enzyme inducer: will metabolize oral contraceptive more quickly

• Phenytoin (dilantin)
• Acutely causes ataxia, sedation and GI disturbance. Therapeutic levels will cause nystagmus
• Hypoalbuminemia (90% protein bound)

IV administration of prodrug (phenytoin requires slow oral absorption)

Equip patient with heart monitor for bradycardia and hypotension from propylene glycol

• Used for:
  • Generalized tonic-clonic seizures and partial seizures
  • Partial epilepticus (especially when phenytoin fails)
  • Essential tremors
• Induces GABA_A inhibition
• Hyperactivity (in kids), sedation, cognitive dysfunction 

• Metabolized into two AED (phenobarbital and PEMA), each active and with long half-life
• Enzyme inducer
• 96 hr t_1/2

• Used for:
  • Tonic clonic seizures, patial seizures
  • Trigeminal neuralgia
  • Bipolar disorder, schizoaffective disorders, neuropathic pain
• Membrane stabilizer (possible action on NMDA receptor, GAB receptor, adenosine receptor)
• Autoinduces hepatic enzymes (shortens its own half-life with chronic use)

• Short half-life (12 hours), required BID or TID dosing
• Predisposing HLA's in Asian population can predict Steve Johnson Syndrome
• Monitor CBC for pancytopenia, Na⁺ for SIADH

• Used for
  • All seizure types
  • Bipolar disorder
  • Migraine prophylaxis
• Augments GABAergic inhibition through multiple mecahnisms (may also block calcium T channels)
• Short half-life (required BID or TID), enzyme inhibitor (increases levels of other agents)

• Dose dependent: GI, thrombocytopenia, neural tube defects in fetus
• Idiosyncratic: alopecia, weight gain, pancreatitis and hepatic failure (in young children)

• Phenytoin, barbiturates, carbamazpine = inducers (decreases levels of other drugs)
• Valproic acid = inhibitor (increases levels of other drugs)

• Ethosuximide
• T_1/2 > 24 hours (take once daily)
• Blockage of calcium T channels

• Drugs ending with -azepam = benzodiazepines
• Enhances GABA action at the GABA_A receptor
• IV forms used for status epilepticus; induces tolerances, limiting use as AED

Which AED...

1. Is a selective inhibitor of GABA reuptake?
2. Offers complete bioavailabality?
3. Has side effects similar to topiramate?
4. Is used for diabetic neuropathy, fibromylagia, and postherpatic neuralgia  

1. Tiagabine
2. Levetiracetam
3. Zonisamide
4. Pregabalin

• Cytosolic metabolization
• Does not form epoxides (decreases incidence of skin rash and blood dycrasias)
• Not an enzyme inducer
• No autoinduction

Sleepiness, hypotension, anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention especially with BPH). Elderly patients may become confused.

Elevation of mood generally occurs in three weeks, and tolerance develops against the unpleasant effects of drugs.

Tertiary selectively block 5-HT reuptake, secondary blocks NE selectively

Secondary generally less sedative

• Alpha 1 blockade leads to postural hypotension
• NE reuptake blockade and muscarinic block leads to tachcardia
• QT prolongation can lead to arrhythmia

• Potentiates directly acting monoamines, MAOI, alcohol and other sedatives
• Blocks tyramine, guanethidine
• FDA warning against use of migraine drugs with certain antidepressants

Irreversible inhibitors of MAO-A (metabolizes 5-HT) and MAO-B (metabolizes NE and EPH), causing rapid release of monoamines into nerve terminal.

Given once a day despite irreversible nature. 

• Side effects
  • Agitation, hallucination, hyperreflexia, convulsions, unstable blood pressure (serotonin syndrome); orthotic hypotension
• Drug interactions
  • With levodopa --> severe hypertension
  • Potentiation of tyramine
  • Meperidine leads to hyperpyrexia
  • When switching drugs, wait at least 2 weeks for the enzyme to recover

What is...

• The Biogenic Amine Theory of depression?
• The Neurotransmitter Receptor Hypothesis of depression?
• The Neurotrophic Theory?
• The effect of parachlorophenylalanine (PCPA)?

• Depression is caused by a deficiency in monoamine, mania is caused by excess
• Depression is caused by down regulation of receptor response and number
• Antidepressants have mitogenic activity on hippocampus (serotonin increases neurogenesis)
• Depletes brain of serotonin; antidepressant effects of tricyclics and MAOI are blocked by this drug.

• No muscarinic blocking activity, so less adverse effects without change in efficacy
• SARI blocks 5-HT2 receptor; too sedative for use, however. Causes priapism
• SSRI = fluoxetine, SARI = trazodone

Anxiety (treat with benzodiazapene)

Sexual dysfunction

Suicidal behavior

Nausea

The long/long genotype for the serotonin transporter gene (5-HTT).

This genotype generally makes upregulates 5-HTT productions. Patients are more resilient to depression to begin with.

Lithium carbonate (theorized to inhibit inositol hydrolysis/signaling).

AEDs, such as lamotrigine (risk of SJD) or valproate (teratogenic).

Combination of levodopa (L-DOPA) and carbidopa.

L-DOPA can cross the blood-brain barrier (dopamine cannot), where it is converted to dopamine. Carbidopa (which cannot cross the BBB), prevents peripheral decarboxylation of L-DOPA, preserving it for the CNS

• 0-5 minutes: ABC's, IV access, blood work (Ca²⁺, Mg²⁺, glucose, EtOH, AED levels, LFTs, ABG)
• 5-8 minutes: IV lorazepam or diazepam (dosing in notes); IV thiamine followed by glucose; fosphenytoin
• 10-20 minutes: repeat benzodiazepine 
• 20-30 minutes: fosphenytoin if needed
• >30 minutes: intubate and ventilate; IV phenobarbital

Occurs if the patient develops withdrawal symptoms if substance is rapidly taken away or if antagonist is given

Note: NOT synonymous with addiction

• Constipation = stimulatory laxative with or without stool softener. Do not use bulk laxative
• Sedation = typically resolves by itself within 2-3 weeks. Decrease dose and titrate slowly
• Nausea and vomiting = Reglan TID or BID, with dexomethasone
• Respiration = proper titration

• Morphine
• Intensol morphine / rocksol

• The patch form requires 20 hours to achieve adequate serum levels, so prescribe oral form for break-out pain
• It takes a long time to eliminate
• Drug is absorbed through skin, not subcutaneous fat

• Composed of racemic mixture
• Bimodal elimination phase (fast elimination followed by long slow elimination), so fast titration can lead to over sedation
• Cheap (1/10 the cost of morphine)
• Effective against neuropathic pain (NMDA receptor mediated)

Encephalin, endorphins and dynorphins are typically secreted by the CNS and travel retrograde, where they inhibit pain. This system is inhibited in CRPS.

Examples include phantom limb pain (Type I), as well as fibromyalgia and Charcot-Marie-Tooth (Type II)