573 - Block Exam 1 (Neuro)

Migraine TX (Abortive)

mild cases:

-acetaminophen

-NSAIDS

moderate cases:

ADD

-triptans OR -gepants

severe/refractory cases:

-DHE

Migraine Prophylaxis

-consider if > 2 migraines/month

-takes up to 4 weeks (minimum) to work

moderate:

atogepant

topiramate

propanolol

diltiazem

severe:

-monoclonal aBs

agents:

-Topiramate (Topamax)

-Amitriptyline

-Propanolol

-Diltiazem

-Atogepant

-monoclonal aBs

(Serotonin analogues)

-Triptans

tx:

moderate migraines

MOA:

abortive agent; activates 5-HT1 → vasconstriction

dose:

-SQ; fastest, relief in 1 hr

-PO; relief in 2 hrs

caution/CI:

-vasoconstriction; chest tightness***

-CI in pts w/ cardiac hx

-serotonin syndrome***; when combined w/ meds that target serotonin

-NOT to use w/ MAOI

agents:

-rizatriptan (also for peds 6+)

-almotriptan (also for peds 12+)

-sumatriptan (also for peds 12+)

-Gepants

tx:

moderate migraines

MOA:

-abortive or prophylaxis

-best taken during aura

dose:

-prophylaxis: 75mg QD

-abortive: 1 tab PO PRN

caution/CI:

-NOT approved for uses > 18x/month

agents:

-Atogepant (prophylaxis only)

-Ubrogepant (Ubrelvy); abortive ONLY, no more than 8 doses/month

-Rimegepant (Nurtec; prophylaxis and abortive; one or the other)

Ergotamine

tx:

severe migraines

caution/CI:

-causes nausea***

-pregnancy

-vasoconstriction

Dihydroergotamine (DHE)

tx:

severe/refractory migraines

MOA:

-safer than ergotamine; not as much vasoconstriction

dose:

-IM

-intranasal

caution/CI:

-vasoconstriction; can't give w/ cardiac hx

Tramadol

tx:

severe migraines

Fioricet (acetaminophen/ caffeine/butalbital)

tx:

migraines

Anti-epileptic

Topiramate (Topamax)

tx:

-migraine PROPHYLAXIS

-ADJUNCT in Lennox-Gastaut syndrome

dose:

-must taper up & down

MOA:

-enhances Na+ channel inactivation

-may cause weight loss

caution/CI:

-Stevens-Johnson syndrome**

-Sudden stop = seizures**

-stupor

-suicidality/psychosis

Amitriptyline

tx:

migraine PROPHYLAXIS

MOA:

anticholinergic properties

caution/CI:

-STRONG anti-SLUDGE effects

↳drowsiness fatigue**

Propanolol

tx:

migraine PROPHYLAXIS

MOA:

-very lipophilic; crosses BBB

caution/CI:

-may have profound effect on HR

Diltiazem

tx:

migraine PROPHYLAXIS

MOA:

-may have more profound effect on BP

Atogepant (Qulipta)

tx:

migraine PROPHYLAXIS ONLY

MOA:

reduces # of migraine days by ~50%

Monoclonal Antibodies

tx:

severe migraine PROPHYLAXIS

MOA:

binds to CGRP

caution/CI:

-cannot be used with -gepants

agents:

-Galcanezumab; Q monthly humanized, can build tolerance

-Erenumab Q monthly

-Fremanezumab; Q monthly or Q3mo

Antipsychotic

Haloperidol

tx:

sx associated w/ Huntington's disease

↳excessive agitation

↳aggression

MOA:

very strong antipsychotic

Diazepam

tx:

sx associated w/ Huntington's Disease

↳excessive agitation

↳aggression

MOA:

-stimulates GABA receptors

-lipophilic

Multiple Sclerosis TX

-No cure, tx based on minimizing sx

agents:

-interferon

-steroids; MUST TAPER if used > 7 days

-mitoxantrone

-glatiramer acetate

-natalizumab

-baclofen

-tizandine

Interferon beta 1-b (Betaseron, Extavia)

tx:

MS

MOA:

-reduces frequency of relapses

dose:

SQ

caution/CI:

-causes flu like sx

↑ LFTs

Mitoxantrone

tx:

MS

MOA:

antineoplastic; supresses T, B cells and macrophages

Glatiramer acetate (Copaxone)

tx:

MS

MOA:

-mimics myelin sheath; distracts immune system (decoy)

-immune system attacks decoy; preserves natural myelin sheath

Natalizumab (Tysabri)

tx:

SEVERE MS

MOA:

-prevents lymphocytes from entering CNS

↳slows progression; keeps pts in remission longer

caution/CI:

↑ risk of TB and other serious infections/disease

Baclofen (Lioresal)

tx:

SEVERE MS

MOA:

helps w/ spasticity sx

Tizanidine (Zanaflex)

tx:

MS

MOA:

helps w/ spasticity sx

dose:

-mild: PO

-severe: parenterally

Gabapentin (Neurotonin)

tx:

-ALS (Lou Gehrig's)

-adjunct for seizures

MOA:

-slows decline of muscle strength (for a few months)

caution/CI:

-weight gain potential

-fluid retention potential

Riluzole (Rilutek)

tx:

ALS (Lou Gehrig's)

MOA:

-prolongs time before pts require tracheotomy

-prolongs life ~3 months

Cholinesterase inhibitor

Donepezil

tx:

Alzheimer's Disease

MOA:

-reversible cholinesterase inhibitor

increases Ach in cerebral cortex

↳slows cognitive loss; helps w/ sundowning

-long acting; half life of 70 hrs

dose:

5mg PO QD starting dose

caution/CI:

-D/N/V***

Tacrine (Cognex)

tx:

Alzheimer's Disease

caution/CI:

-pulled from market; HEPATOTOXICITY***

Cholinesterase inhibitor

Rivastigmine

tx:

-Alzheimer's Disease

-dementia

dose:

-PO BID

-4.6 mg transdermal QD; doesn't go thru GI tract

↳doesn't enter GI tract; less GI SE

↳4.6 mg only to mitigate SE, not help treat Alzheimer's

↳give 4.6 mg for 30 days, then ↑ to 9.5 mg

MOA:

-reversible cholinesterase inhibitor

caution/CI:

-short acting; more SE

-bradycardia

-QT prolongation

Cholinesterase inhibitor

Galantamine

tx:

-Alzheimer's Disease

-dementia

dose:

-PO BID

caution/CI:

-short acting; more SE

-bradycardia

-QT prolongation

Memantine (Namenda)

tx:

-Alzheimer's Disease

-moderate-severe dementia

MOA:

-noncompetitive antagonist at NMDA receptor

-can be combined w/ cholinesterase inhibitors (add on)

-not much cholinergic activity; no GI SEs

caution/CI:

-renally eliminated

Brexpiprazole (Rexulti)

tx:

agitation associated dementia due to Alzheimer's

Aducanumab (Aduhelm)

tx:

-Alzheimer's Disease

MOA:

-may halt progression of Alzheimer's Disease

dose:

-IV Q 4 weeks

-starting dose: 1mg/kg

-maintenance: 10mg/kg

caution/CI:

-must confirm B-amyloid pathology before starting

-micro-hemorrhage

-causes brain edema, CVA in pts w/ ApoE4

Lacanumab (Leqembi)

tx:

-Alzheimer's Disease

-mild/early dementia

-mild cognitive impairment

caution/CI:

-must confirm B-amyloid pathology before starting

-micro-hemorrhage

-causes brain edema, CVA in pts w/ ApoE4

-infusion reaction/HA

Levodopa

tx:

Parkinson's disease

↳Let's PARK the Car

dose:

w/ meal QHS

MOA:

-crosses BBB easily; converted into dopamine in CNS

-should always be used with carbidopa to prevent breakdown and reduce SE

-lasts only 4-6 hrs

caution/CI:

-major SE when taken alone

↳N/V

↳orthostatic hypotension

↳cardiac arrhythmias

-too much dopamine causes vasodilation

Carbidopa

tx:

adjunct w/ levodopa for Parkinson's disease

↳Let's PARK the Car

dose:

w/ meal QHS

MOA:

-does not cross BBB

-used with levodopa to inhibit breakdown before it reaches brain

caution/CI:

-has no effect without levodopa

Amantadine

tx:

early/mild Parkinson's

MOA:

-forces release of dopamine

-may inhibit reuptake of dopamine

-dead neurons can't release neurotransmitters; thus, amantadine best in early stages

-in later stages, used as adjunct, not primary

caution/CI

-anti-SLUDGE; drowsiness**

-livedo reticularis**

MAOi (Monoamine oxidase inhibitors)

tx:

-Parkinson's

-depression

MOA:

-prevents breakdown of dopamine

-only used in early stages or to boost Levodopa+Carbidopa therapy

caution/CI:

-foods containing tyramine; can spike BP

-CI w/ meperdine

-CI w/ SSRI

agents:

-selegiline

-rasagiline

MAOB inhibitor

Selegiline (Eldepryl)

tx:

-Parkinson's mainly

-sometimes depression

MOA:

-prevents breakdown of dopamine

-only used in early stages or to boost Levodopa+Carbidopa therapy

caution/CI:

-foods containing tyramine

-CI w/ triptans**

MAOB inhibitor

Rasagiline (Azilect)

tx:

-Parkinson's

MOA:

-monotherapy or adjunct tx for Parkinson's

-prevents breakdown of dopamine

-only used in early stages or to boost Levodopa+Carbidopa therapy

caution/CI:

-foods containing tyramine

-CI w/ triptans**

COMT inhibitors (-capone)

Tolcapone (Tasmar)

tx:

-Parkinson's

MOA:

-adjunct tx for Parkinson's

-COMT inhibitor in breakdown of levodopa

caution/CI:

-Severe hepatotoxicity**

-MUST be given w/ levodopa+carbidopa**

COMT inhibitors (-capone)

Entacapone (Comtan)

tx:

-Parkinson's

MOA:

-COMT inhibitor in breakdown of levodopa

-safer than tolcapone; no hepatotoxicity

-short acting (half-life < 1hr)

COMT inhibitors (-capone)

Opicapone (Ongentys)

tx:

-Parkinson's

dose:

QD

MOA:

-COMT inhibitor in breakdown of levodopa

Dopamine agonist

Ergot Alkaloid

tx:

-Parkinson's

MOA:

activate dopamine receptors throughout body

caution/CI:

-excessive doses may mimic acid trip

↳hallucinations

↳vivid dreams

Dopamine agonist

Bromocriptine

tx:

-mild Parkinson's

MOA:

-D2 receptor agonist, D1 antagonist

caution/CI:

-may mimic LSD/acid trip

↳hallucinations

↳vivid dreams

-SE/risks may outweigh benefits

Dopamine agonist

Pramipexole (Mirapex)

Ropinerole (Requip)

tx:

-early Parkinson's; largely 1st line

-restless leg syndrome (RLS)

MOA:

-D2 receptor agonist

-may be used with levodopa+carbidopa

↳more benefits during "off" periods, and can lower levodopa dose requirement

caution/CI:

-N/V

-behavioral changes

Dopamine agonist

Apomorphine (Apokyn)

tx:

hypomobility/freezing episodes from Parkinson's

MOA:

-fast on/off dopamine receptor agonist

-does NOT bind to opioid receptor

dose:

SQ

Pimavanserin (Nuplazid)

tx:

-visual hallucinations in Parkinson's

MOA:

-no dopamine activity; inverse agonist

dose:

QD

caution/CI:

-causes QT prolongation

Istradefylline (Nourianz)

tx:

-hypomobility/freezing episodes from Parkinson's

MOA:

-works on adenosine pathway; helps balance movements

caution/CI:

-smoking INDUCES metabolism

-insomnia

-hallucinations

Anticholinergics

Benztropine (Cogentin)

tx:

-Parkinson's w/ significant tremors

-pseudoparkinsonism

MOA:

↓ Ach to establish balance

-inhibits reuptake of dopamine

-prolongs action of dopamine

caution/CI:

-anti-SLUDGE SE

-drowsiness

Anticholinergics

Trihexyphenidyl (Artane)

tx:

-Parkinson's w/ significant tremors

-pseudoparkinsonism

MOA:

↓ Ach to establish balance

-stronger than Benztropine

caution/CI:

-anti-SLUDGE SE

-drowsiness

Parkinson's TX strategy

1st line:

dopamine agonists or MAOB-i

↳pramipexole or ropinirole

↳selegiline or rasagiline

2nd line:

add Levodopa + Carbidopa (100/25)

3rd line:

add adjunctive meds to ↓ levo dose

↳COMT-i: entacapone or opicapone

4th line:

add anticholinergics for tremors

↳benzotriptine or trihexyphenidyl

Add ons:

-dementia sx: cholinesterase inhibitors (e.g. rivastigmine)

-hypotension: fludrocortisone or midodrine

-advanced tremor: anticholinergics (e.g. benztropine)

Seizure TX:

partial & generalized tonic-clonic seizures:

1st lines (prophylaxis):

-carbamazepine

-oxcarbazepine

-phenytoin

-valproate (peds ok)

-levetiracetam (peds ok)

absence seizures (prophylaxis):

-1st line: valproic acid

-alternative: ethosuximide

Levetiracetam (Keppra)

tx:

-tonic-clonic seizures (controller)

dose:

BID PO

MOA:

-don't have to monitor as closely as carbamazepine and others

-no known drug interactions

caution/CI:

-CNS depression

-can cause anxiety/agitation/aggressiveness

Brivaracetam (Briviact)

tx:

tonic/clonic seizures

dose:

QD

MOA:

alternative to levetiracetam

caution/CI:

-not to use with keppra or Na channel inhibitors

Carbamazepine

tx:

-tonic-clonic seizures (controller)

-trigeminal neuralgia

dose:

200mg BID; max 1,200 mg/day

MOA:

-Na+ channel blocking only

caution/CI:

-can only use ONE Na+ channel drug at a time

-CNS depression/sedation***

-respiratory depression*

-SIADH

-aplastic anemia**

↳check CBCs

-rash in Asians/Indians → SJS**

-N/V; higher dose = more SE

Oxcarbazepine (Triletpal)

tx:

-tonic-clonic seizures (controller)

MOA:

-enhances fast Na+ channel inactivation, just like carbamazepine

-not as strong as carbamazepine

caution/CI:

-can only use ONE Na+ channel drug at a time

-CNS depression/sedation***

-respiratory depression*

-SIADH**

-aplastic anemia**

↳check CBCs

-rash in Asians/Indians → SJS**

-N/V; higher dose = more SE

Phenytoin/Fosphenytoin

tx:

-tonic-clonic seizures (controller)

-status epilepticus

dose:

initial loading dose (for status epilepticus, use Fosphenytoin): 15-20mg/kg

↳NTE 50mg/min; causes irreversible demyelination of neurons

MOA:

-strongest Na+ channel (only) blocking drug

-prodrug form: Fosphenytoin

-follows non-linear kinetics; doubling dose = quadruples blood level

caution/CI:

-NEVER double phenytoin dose***

-causes birth defects**

-can only use ONE Na+ channel drug at a time

-SJS***

-nystagmus

-gingival hyperplasia

-hirsutism

-INDUCER of metabolism; narrow therapeutic range

↳change dose every 7 days

Phenobarbital

tx:

2nd line for general tonic clonic seizures

MOA:

-increase GABA-mediated chloride influx

caution/CI:

-ataxia

-dizziness

-respiratory depression**

-inducer of metabolism

-should NOT be used alone

Primidone

tx:

2nd line for general tonic clonic seizures

MOA:

metabolized to phenobarbital

caution/CI:

not the greatest choice

Valproate/Valproic acid (Depakote)

tx:

-DOC for absence seizures (monotherapy)

↳also good for peds

-bipolar disorders

-migraine prophylaxis

MOA:

-changes absorption rate; more stable blood levels

-most MOA out of all anti-epileptics

caution/CI:

-can cause SJS ESPECIALLY w/ Lamotrigine

-GI upset***

-hepatic toxicity***

↳monitor LFTs every 6mo

-weight gain***

-INHIBITS metabolism of other drugs; can ↑ serum levels of other drugs

Lamotrigine (Lamictal)

tx:

-ADJUNCT therapy for seizures

-1st line for Lennox-Gastaut syndrome

dose:

starting dose: 25mg QHS; ↑ x2 Q2weeks

↳never start high dose

caution/CI:

-rash that can progress to Stevens-Johnson syndrome ESPECIALLY w/ valproic acid

↳start dose low, go slow

Rufinamide

tx:

-ADJUNCT therapy for seizures

-ADJUNCT in Lennox-Gastaut

caution/CI:

-CI in pts w/ cardiac issues

Lacosamide

tx:

-ADJUNCT therapy for seizures

MOA:

controlled substance

caution/CI:

-in higher doses, can lead to euphoria

↳avoid in addicts

Felbamate

tx:

-ADJUNCT therapy for REFRACTORY seizures

caution/CI:

hepatotoxicity

Pregabalin

tx:

-ADJUNCT therapy for seizures

-chronic pain

dose:

QD or BID

MOA:

controlled substance

caution/CI:

-in higher doses, can lead to euphoria

↳avoid in addicts

-fluid retention

-weight gain

Tiagabine

tx:

-ADJUNCT therapy for REFRACTORY seizures

MOA:

works on GABA receptor:

Ethosuximide

tx:

DOC for absence seizures (valproic acid alternative)

MOA:

-long half life; stable drug levels

↳reduces breakthrough seizures

-safe; good for peds

Zonisamide

tx:

-ADJUNCT therapy for seizures

MOA:

-T-type calcium channel activity

caution/CI:

-sulfa allergy in hypersensitive pts

Benzodiazepines (-pams)

tx:

-seizure abortive***

MOA:

-augments GABA-mediated chloride influx

caution/CI:

-NEVER to be given alone for seizure prevention

↳can develop tolerance, requiring higher doses

agents:

-lorazepam (DOC to stop seizures)

-diazepam (DOC to stop seizures)

-clonazepam (tx absence, myoclonic, atonic)

Canabinoid

Canabidiol (Epidiolex)

tx:

-seizure prophylaxis

MOA:

can be used in children 2 YO+

Status epilepticus tx

1st line:

lorazepam 2-4 mg IV

or

diazepam 5-10 mg IV

then add controller:

Fosphenytoin 20 mg/kg IV single loading dose

↳NTE 1500 mg/kg

non-healthcare professional:

diazepam rectal gel 0.2mg/kg

↳round to nearest 2.5 mg

↳NTE 20 mg