Neuro

phenytoin (Dilantin)

MOA: Na channel blocker, prolongs refractory period, stabilizes threshold

In: 1st line for tonic-clonic, simple partial, and partial complex

phenytoin adrs

__ ADRs

• Exfoliative dermatitis

• SJS

• Toxic epidermal necrolysis

• Gingival hyperplasia

• Pancytopenia

• Agranulocytosis

• Macrocytic anemia

phenytoin considerations

__ considerations

• Pregnancy category D

• Monitor: CBC, LFTs, BUN/Cr, peak and trough levels, TSH, BG

• Edu: compliance, diabetes, oral hygiene, folic acid supplement

carbamazepine (Tegretol)

R/t tricyclics

MOA: Na channel blocker, limits seizure propagation

In: partial seizures and generalized TC, bipolar - mood stabilizer, trigeminal neuralgia, behaviors in dementia

Monitoring: CBC, BMP, LFTs, TSH - baseline and pharmacogenomics prior

Long half life

carbamazepine adrs

__ ADRs

• Liver damage

• Impairs thyroid function

• Drowsiness

• Dizziness

• Blurred vision

• N/V

• Dry mouth

• Diplopia

• HA

UBSW - blood dyscrasias; dermatologic toxicity (SJS, TEN) - higher risk in Asian descent

ethosuzimide (Zarontin)

MOA: Delays influx of calcium into neurons, increases seizure threshold and suppresses spike-and-wave pattern in absence seizures

In: absence seizures

Therapeutic lvls 40-100

ethosuximide adrs

__ ADRs

• GI upset

• Somnolence

• Fatigue

• Ataxia

• Agranulocytosis

• Aplastic anemia

• Granulocytopenia

GABA analogs

Ex: topiramate (Topamax), valproate (Depakote), and lamotrigine (Lamictal)

PD: inhibit voltage gated Na channels

In: neuropathic pain, partial/focal seizures, TC seizures, absence seizures, myoclonic seizures, mood stabilization - lamictal

lamotrigine considerations

__ considerations

• Levels decreased by barbiturates, estrogens, phenytoin, and mefloquine

• Levels increased by alcohol, carbamazepine, CNS depressant, valproic acid

• Pregnancy category C

lamotrigine adrs

__ adrs (of a specific GABA analog)

• N/V

• Constipation

• Chest pain

• Peripheral edema

• Somnolence

• Fatigue

• Dizziness

• Anxiety

• Insomnia

• HA

• amblyopia

• Nystagmus

• Rashes

USBW - serious rashes (risk increased when co-admin w/ valproic acid)

lamotrigine edu

__ edu

• adherence

• avoiding ETOH

• avoid certain OTC meds

• Adequate hydration

• Report new drugs

• Report ADRs - esp skin rashes

GABA analogs adrs

__ ADRs

topiramate - monitor for?

• mental fogginess

• metabolic acidosis

• glaucoma

• hyperthermia

• suicide risk

valproate

• wt gain

• hair loss

• pancreatitis

• hepatotox

Both pregnancy category D

50-100 (mcg/ml)

Therapeutic window for valproate

levetiracetam (Keppra)

MOA: unknown, may inhibit burst firing

In: partial seizures, myoclonic seizures, general seizures

ADRs: somnolence, fatigue

Pregnancy category C

phenobarbital

MOA: increases threshold for electrical stimulation of motor cortex, inhibits depolarization, enhances transmission of chloride ions

10-40 (µg/ml)

therapeutic window for phenobarbital

benzos

Ex: diazepam or lorazepam

MOA: increase number of chloride channels, suppressing spread of seizure activity

In: terminating status epilepticus or acute seizure episodes

2 (yrs)

Discontinuation of AEDs can be considered in patients who have been seizure free for…

birth defects

All AEDs are associated with __ when used in pregnancy

Caffeine

Blocks adenosine receptors

Potent CNS stimulant

modafinil (Provigil)

Inhibits reuptake of dopamine

Activate glutaminergic circuits, inhibits GABA

In: short-acting psychostimulant for shift work sleep disorders, sleep apnea, narcolepsy, and excessive daytime sleepiness

amphetamines

Ex: Dexamphetamine/amphetamine (Adderall), methamphetamine (Desoxyn), and dextroamphetamine (Dexedrine)

MOA: CNS stimulation of reward centers

Contra: heart dx, HTN, pregnancy

USBW - misuse may cause sudden death and serious CV adverse events

amphetamine like drugs

Ex: Methylphenidate (Ritalin), dexmethylphenidate (Focalin)

MOA: inhibit reuptake of NE and DA, act on NTs in the brain to modify behaviors - CNS stimulation

Contra: heart dx, HTN, pregnancy

Schedule II

amphetamines (and amphetamine like drugs) ADRs

__ ADRs

• Appetite suppression

• Tachycardia

• Dizziness

• HA

• Insomnia

• Growth suppression

norepi reuptake inhibitors

Ex: atomoxetine (Strattera), bupropion (Wellbutrin)

MOA: selective reuptake of presynaptic NE

In: inability to tolerate stimulates; comorbid mood disoder

ADRs: HTN, tachycardia, HA, insomnia, anorexia, growth suppression, prolonged QTc

bp and hr

What should be checked at every visit for someone on ADHD meds?

cholinesterase inhibitors

Ex: donepezil (Aricept), galantamine (Razadyne), rivastigmine(Exelon), neostigmine (Prosttigmin), and pyridostigmine (Mestinon)

PD: block the enzyme that degrades ACH in the brain, enhances cholinergic transmission

1 (yr)

How long are cholinesterase inhibitors thought to be effective for?

nmda receptor antagonists

Ex: memantine hydrochloride

PD: block NMDA receptor (excessive stim leads to excitotoxi), thought to be neuroprotective

dementia monitoring

__ monitoring

• Functional ability/staging (MMSE, GDS, Katz assessment)

• Family observation

• LFTs

• CBC

• BMP

dopamine precursors

1st line for parkinsons

Ex: Carbidopa-levodopa (Sinemet)

PD: cross BBB and converted into DA

Long term issues: choreiform dyskinesia (rapidly flowing, dance-like), toxicity, loss of efficacy

dopamine precursors edu

__ edu

• Full effect observed 2-3wks after starting, may require up to 6mo before maximal response is seen

• High protein diet may delay or impair absorption

• Not to be given with NONSELECTIVE MAOIs

dopamine agonists

Ex: pramipexole (Mirapex) and ropinirole (Requip)

PD: lengthen duration of dopamine in CNS, essentially a PKE

COMT (Catechol-O-Methyltransferase) inhibitors

Ex: entacapone (Comtan) and Tolcapone (Tasmar)

PD: prevents the breakdown of levodopa, prolonging effectiveness, a PKE basically

COMT inhibitors adrs

__ adrs

• diarrhea

• vivid dreams

• visual hallucinations

• drowsiness

• urine discoloration (orange)

• dyskinesias

glutamine antagonists

Ex: amantadine

PD: uncompetitive antagonist of NMDA receptor, direct or indirect effects on DA neuros, may release DA and NE and inhibit reuptake

In: PD, dyskinesia associated w/ PD, and EPS

glutamine antagonists adrs

__ ADRs

• Increased seizure activity

• HF

• Orthostatic HoTN

• Peripheral edema

• Syncope

MAO B inhibitors

Ex: selegiline (Eldepryl) and rasagiline (Azalect)

PD: inhibits breakdown of dopamine

In: depression in PD

Avoid tyramine rich foods

tension

Type of HA

Feels like a hand squeezing around the head

cluster

Type of HA

Pain is in/around 1 eye, typically happen in a group

sinus

type of HA

Pain usually behind the forehead and or cheekbones

migraine

Type of HA

pain, nausea, visual changes are typical

serotonin receptor agonists

“triptan”

PD: abort migraines by stimulating inhibitory serotonin receptors (5-HT1, 5-HT1D)

In: acute migraine treatment w/ or w/o aura and cluster HA, take at onset

Interactions: ergotamines, MAOIs, and SSRIs

triptan contraindications

__ contraindications

• CAD

• uncontrolled HTN

Can lead to MI, dysrhythmias, and death

ergotamine

PD: reduces extracrainial blood flow, decreases amplitude of pulsations, also works on serotonin receptors

ADRs: rebound HA, toxicity (ABD pain, anxiety, chest pain, myalgia, severe N/V, numbness, tingling, vision changes

USBW - coadmin w/ potent CYP3A4 inhibits - increases toxicity risk

ergotamine considerations

__ considerations

• vasoconstrictor effects - avoid w/ angina, arteriosclerosis, CAD, tobacco smoking

• pregnancy category X

• caffeine increases speed of absorption and efficacy

• contraindicated in kidney and liver dx

dihydroergotamine (Migranal, DHE-45)

An ergotamine derivative

• Thought to be safer than ergot, no CYP450 involvement

• Pregnancy category X

• Take at 1st sign of attack

• Contra: kidney and liver dx

ADRs: ergot tox

ergoloid (Hydergine)

An ergot derivative

• Adjunct therapy to treat sx of age-related or idiopathic decline in mental capacity associated w/ dementia

ADRs: bradycardia, HoTN, orthostatic HoTN

HA treatment

__ treatment

• Abortive treatment

• O2 100% x15-30min - cluster

• Corticosteroid burst then taper - cluster

• Mild analgesics - NSAIDs, tylenol - tension and migraine

• Combo meds - often w/ caffeine

• Prophylaxis - CCB, ACEi/ARBs, mag, riboflavin, and botulin toxin

• AEDs - depakote and topiramte

• NSSRIs - nortriptyline and amtriptyline

• BB - propranolol

• Antiemetics

pharmacogenomics

Branch of pharmacology that deals with influence of genetic variations on drug response d/t gene expression r/t efficacy or toxicity