Parkinsons, alzheimers, seziures Flashcards
pathophysiology of parkinsons
less dopamine –> less instructions to the brain –> movement problems
TRAP major symptoms
Tremor
Rigidity
Akinesia/bradykinesia
Posture instability
Dopamine blocking medications that can worsen PD
-phenothiazines (prochlorperazine) used for psychosis, nausea, agitation
-butyrophenones (haldol, droperidol) used for psychosis and behavior disorders for nausea
-first and second generation antipsychotics (risperidone at high doses, paliperidone)
-metoclopramide (can accumulate)
primary treatment of PD
-give precursor to dopamine that becomes dopamine in the brain (Sinemet)
-give a dopamine agonist that acts like dopamine to prevent “off” periods
-give other drugs for specific symptoms (benztropine for resting tremor)
Carbidopa/Levodopa (Sinemet)
-precursor of dopamine
-carbidopa inhibits dopa decarboxylase enzyme preventing peripheral metabolism of levodopa
-CI: non-selective MAOi w/in 14 days
-nausea, dizziness, orthostasis, dyskinesia, hallucinations, psychosis, unusual sexual urges, priapism
-can cause brown/black coloring of the urine
-COOMBs test if positive d/c
-7-10 mg/day is required to inhibit dopa decarboxylase
-do not discontinue abruptly
Dopamine agonists
-Pramipexole (Mirapex, Mirapex ER)
-Ropinirole (Requip XL)
-somnolence, orthostasis, hallucinations, dyskinesia
-do not discontinue abruptly
other drugs used to treat PD
-amantidine (blocks dopamine reuptake into presynaptic neurons and increases doapmine release)
-MAO-B inhibitors (block the breakdown of dopamine): Selegiline, Rasagiline
Benztropine (Cogentin)
-used for tremor
-anticholinergic side effects
Drugs that worsen dementia
-antiemetics (promethazine)
-antihistamines (diphenhydramine, doxylamine)
-antipsychotics (chlorpromazine, aripiprazole)
-barbiturates (phenobarbital, butabital)
-BZD (alprazolam, clonazepam)
-central acting anticholinergic (benztropine)
-peripheral anticholinergic (incontinence and IBS drugs)
-skeletal muscle relaxants (baclofen)
-other CNS depressants (opioids, sedative-hypnotics)
natural products for Alzheimers
vitamin E and ginkgo
mild to moderate Alzheimer’s tx
start anticholinesterase inhibitors (donepezil, rivastigmine, galantamine)
moderate to severe Alzheimer’s tx
start anticholinesterase inhibitors (donepezil, rivastigmine, galantamine) +/- memantine
if alzheimers progresses on maintenance medication or stable on donepezil 10 mg
switch to Namzaric (donepezil + memantine)
Anticholinesterase inhibitors
-donepezil (Aricept)
-Rivastigmine (Exelon)
-cardiac: bradycardia, syncope, QT prolongation
-nausea (donepezil dosed QHS to decrease nausea), diarrhea
-patch and ODT have less GI effects
NMDA blocker
-Memantine (Namenda)
-dizziness, confusion, headache
-do not crush or chew - can sprinkle on food
Drugs that lower the seizure threshold
bupropion
clozapine
theophylline
vareniciline
carbapenems
lithium
meperidine
penicillin
quinolones
tramadol
Status epilepticus treatment
-0-5 min (stabilization phase): stabilize with ECG, O2
-5-20 min (initial treatment phase/if seziure continues): IV lorazepam or Midazolam or rectal/buccal/nasal spray midazolam
-20-40 min (if seziure continues): IV fosphenytoin, valproic acid, levetiracetam
Distat Acudial Dispensing
-syringes must be dialed to the right dose and locked before dispensing
1. hold the barrel of the syringe in one hand with the cap facing down and the dose window visible. Do not remove the cap
2. use the other hand to grab the cap firmly and turn and adjust the dose
3. confirm the correct dose shows in the window. hold the locking ring at the bottom of the syringe barrel and push upward to lock both sides of the ring
-once locked the green band should say ready and the syringe cannot be unlocked
AEDs that increase GABA
BZD and valproic acid
AEDs that enhance/potentiate GABA effect
phenobarbital
AEDs that increase GABA and are a CCB
levetiracetam
AEDs that are T-type CCB
ethosuximide
AEDs that are CCB
pregabalin/gabapentin
AEDs that are Na and Ca channel blockers
oxacarbazepine
AEDs that are Na channel blockers
carbamazepine, lamotrigine, phenytoin/fosphenytoin, topiramate
Carbamazepine, Oxcarbazepine, Eslicarbazepine
hyponatremia, rash, enzyme induction
Gabapentin and pregabalin
weight gain, peripheral edema, mild euphoria
Phenobarbital and Primedone
sedation, dependence/tolerance/OD risk, enzyme induction
Topiramate and zonisamide
weight loss, metabolic acidosis
-nephrolithiasis and oligohidrosis/hyperthermia
Supplementation with AEDs
-ALL AEDS: calcium and vitamin D
-women of bearing age: folate
-valproic acid: possibly carnitine
-lamotrigine and valproic acid: selenium and zinc (if alopecia develops)
Lamotrigine (Lamictal, Lamictal ODT, Lamictal starter kit, lamictal XR)
-doses need to be just right and titrated slowly to prevent serious skin infection
-SJS/TEN
-alopecia (selenium/zinc)
-valproic acid increases lamotrigine more than 2 fold
-carbamazepine, phenytoin, phenobarb decrease lamotrigine levels by 40%
Lamotrigine dosing
week 1-2: 25 mg daily
week 3-4: 50 mg daily
week 5 and on: can increase by 50 every 1-2 weeks
-start with the standard dose if no interacting medications
-start with a lower dose if using valproic acid
-start with a higher dose if taking carbamazepine, phenytoin, phenobarb and not taking valproic acid.
Levetiracetam (Keppra)
-maximum: 3 g/day
-CrCl <80 mL/min
-IV:PO 1:1
-psychiatric reactions, including psychotic symptoms, somnolence, fatigue
Topiramate (Topamax)
-titrate doses over 5 weeks
-max dose: 400 mg/day
-CrCl < 70 mL/min: decrease dose by 50%
-metabolic acidosis, oligohidrosis (reduced perspiration), nephrolithiasis, angle closure glaucoma, hyperammonemia, visual problems, fetal harm
-somnolence, memory/concentration/attention, weight loss, anorexia
-monitor bicarb
Valproic acid
Divalproex (Depakote, Depakote ER, Depakote sprinkle)
-initial 10-15 mg/kg/day
-max: 60 mg/kg/day
-therapeutic range: 50-100 mcg/mL
-boxed warning: hepatic failure, fetal harm
-hyperammonemia (treat with carnitine), dose-related thrombocytopenia, alopecia
-LFTs, platelets
Carbamazepine (Tegretol, Tegretol XR)
-max: 1600 mg/day
-therapeutic range: 4-12 mcg/mL
-serious skin reactions (test for HLA-B*1502)
-aplastic anemia and agranulocytosis, myelosuppression
Lacosamide (Vimpat)
-max: 400 mg/day
-CrCl < 30 mL/min: max dose 300 mg/day
-IV to PO: 1:1
-prolongs PR interval and increases risk of arrhythmias
Oxcarbazepine (Trileptal)
-max: 2400 mg/day
-carbamazepine to oxcarbazepine dose conversion 1.2-1.5x carbamazepine dose
-serious skin rxns HLA-B*1502
Phenobarbital
-therapeutic range: 20-40 mcg/mL (adults)
-habit-forming, respiratory depression, fetal harm, physiological dependence, tolerance, hangover effect
Phenytoin (Dilatin, Dilatin Infatabs)
fosphenytoin (Cerebyx)
-fosphenytoin is the prodrug of phenytoin
-LD: 15-20 mg/kg
-MD: 300-600 mg/day *fosphenytoin is dosed in PE (fosphenytoin 1.5 mg = 1 mg PE)
IV-PO = 1:1
-total level: 10-20 mcg/mL
-free level: 1-2.5 mcg/mL
-phenytoin IV rate should not exceed 50 mg/min and fosphenytoin should not exceed 150 mg/PE/min (hypotension/cardiac arrhythmias)
-purple glove syndrome if extravasation
IV phenytoin
-do not exceed 50 mg/min
-monitor BP, respiratory function and ECG
-requires a filter
-dilute NS stable for 4 hours, do not refrigerate
NG-tube Phenytoin
-enteral feedings decrease phenytoin absorption
-hold feedings 1-2 hours before and after administration
IV fosphenytoin
-do not exceed 150 mg/PE/min
-monitoring BP, respiratory function, and ECG
-lower risk of purple glove syndrome than phenytoin
ethosuximide (Zarotin)
-used for absence seziures , SJS/TEN, blood dyscrasias
other drugs
-gabapentin (neurotin)
-Pregabalin (Lyrica)
-Primidone (mysoline) - prodrug of phenobarbital
adjusting phenytoin doses
-phenytoin has michaelis-Menten kinetics also called saturable kinetics
-if the enzyme have become saturated, a small increase in dose can cause a large increase in drug level
-if albumin is low (< 3.5) and CrCl > 10 adjust the total level with the formula
-free levels do not require correction
phenytoin correction
total phenytoin measured / (0.2 x albumin) + 0.1
AEDs: enzyme inducers
carbamazepine, oxacarbazepine, phenytoin, fosphenytoin, phenobarbital, primidone
AEDs: enzyme inhibitor
valproic acid
AEDs are CNS depressants
-AEDs DEPRESS electrical activity in the brain; they are CNS-DEPRESSants, and cause dizziness, confusion, sedation, and ataxia/coordination difficulties
-increase the risk for impairment, falls, and injuries
