416 Exam 4 PD, MS, Epilepsy Flashcards
MOA carbidopa/levodopa (PD)
Dopamine replacement
Carbidopa/Levodopa AE
Dyskinesia N/V Insomnia Hallucinations Confusion Hypotension
Carbidopa/Levodopa
Sinemet (25/100) Sinemet CR (50/200)
Dopamine agonists (PD)
Bromocriptine (rare) Pramipexole Ropinirole Rotigotine Apomorphine
Dopamine agonists AE
Hallucinations Fatigue/somnolence Edema Nausea Hypotension Pleuropulmonary fibrosis Impulsivity
MOA of MAOI (PD)
Inhibition of DA metabolism- specific for MAO-B receptors
Irreversible MAO-I agents (PD)
Selegiline
Rasagiline (monotherapy)
Reversible MAO-I agents (PD)
Safinamide
MOA of COMT-I (PD)
Inhibition of DA and levodopa metabolism
COMT-I agents (PD)
Entacapone (peripherally only)
Tolcapone (BBB)
MOA anticholinergics (PD)
Decreases excessive cholinergic activity
Anticholinergic agents for PD
Trihexyphenidyl
Benztropine (Cogentin)
Diphenhydramine
MOA of Amantadine for PD
Mild increase in DA concentrations
Amantadine SE
Anticholinergic Nightmares Insomnia Confusion Levido reticularis (discoloration) Withdrawal encephalopathy
Amantadine (Symmetrel) immediate release approved for
PD motor symptoms but NOT dyskinesia
Amantadine (Gocovri) extended release approved for
Levodopa-induced dyskinesia but NOT motor symptoms
Trt depression in PD
Pramipexole (D3 receptors)
SSRIs, SNRIs, TCAs
Trt psychosis in PD
Quetiapine
Primavanserin
Trt dementia in PD
Rivastigmine (approved)
Trt restless leg syndrome in PD
Ropinirole
Pramipexole
Levodopa
Trt REM behavior disorder in PD
Clonazepam (Klonopin)
Injectable agents for MS
IFN B-1a (Betaseron, Extavia)
IFN B-1b (Avonex, Rebif, Plegridy)
Glatiramer acetate (Copaxone)
Daclizumab (Zinbryta)
Oral agents for MS
Fingolimod (Gilenya)
Teriflunomide (Aubagio)
Dimethyl Fumarate (Tecfidera)
Infusion agents for MS
Natalizumab (Tysabri)
Alemtuxumab (Lemtrada)
Mitoxantrone (Novantrone)
Ocrelizumab (Ocrevus)
IFN approved for
RRMS CIS (except Plegridy)
IFN SE
- flu like symptoms
- injection site pain
- leukopenia
- hepatic injury
- worsening of CHF
- hyperthyroidism/thyrotoxicosis
- depression
Glatiramer acetate approved for
RRMS
CIS
MOA of Glatiramer acetate (MS)
Glatiramer cells secrete anti-inflammatory IL-10 cytokines in CNS
Glatiramer acetate SE
Flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, urticaria
Lipoatrophy (permanent)
Natalizuman approved for
RRMS
MOA of Natalizumab (MS)
Block alpha-4 integrin preventing linkage to VCAM-1 ultimately preventing the lymphocyte from stopping to be recruited across the BBB
Natalizumab AE
Progressive multifocal leukoencephalopathy (PML)
>2yrs of Natalizumab exposure
Fingolimod approved for
RRMS
MOA of Fingolimod (MS)
Binds to S1P1 receptors on lymphocytes blocking their capacity to egret from lymph nodes and reducing number of lymphocytes in peripheral blood
Fingolimod SE
Bradyarrythmia AV block -risk of injection -macular edema -hepatic injury -PML
Terifluonomide approved for
RRMS
MOA of Teriflunomide (MS)
Blocks DHODH
-ultimately exhibits a cytostatic effect on activated lymphocytes in periphery decreasing overreactive immune response
Teriflunomide SE
Teratogenic (rapid elimination if pregnant)
-hepatotoxicity
Dimethyl fumarate approved for
RRMS
MOA of Dimethyl fumarate (MS)
Activates Nrf2 which is unregulated in response to oxidative stress but perhaps not sufficiently
Dimethyl fumarate SE
- decreased lymphocyte counts by 30%
- PML
- flushing
- diarrhea and stomach upset
- hepatic injury
Alemutuzumab approved for
RRMS
MOA of Alemutuzumab (MS)
Targets CD52 and targets cells for lysis
-decreases number of new lesions
Alemutuzumab SE
Infusion causes cytokine release
- fever, shaking chills
- flushing and itching
- alterations of HR and BP
- dyspnea or chest discomfort
Premeditated with 1GM of methylprednisolone for 3 days prior to infusion
Alemtuzumab AE
- autoimmune thyroid disorder
- immune thrombocytopenia
- antiglomerular basement membrane disease
- thyroid cancer
- melanoma
- lymphoma
Ocrelizumab approved for
RRMS
PPMS
MOA of Ocrelizumab (MS)
Directed against CD20 expressing pre-B and mature B lymphocytes
-cell surface binding results in antibody dependent cellular cytolysis and complement mediated lysis
Ocrelizumab SE
- pruritus
- rash or erythema
- bronchospasm or dyspnea
- throat irritation or oropharyngeal pain
- flushing or hypotension
- pyrexia
- nausea
- tachycardia
Premeditate with 100mg methylprednisolone and antihistamine
Ocrelizumab CI
Active hep B infection
Daclizumab approved for
RRMS
MOA of Daclizumab (MS)
Specific for CD25
Selectivity inhibits signaling through the high-affinity receptor inhibiting lymphocyte activation
Daclizumab SE
- skin reaction
- swollen lymph nodes
- non-infectious colitis
Mitoxantrone approved for
RRMS (refractory only)
SPMS
PRMS
Mitoxantrone MOA (MS)
Suppresses proliferation of T and B cells and macrophages
- enhances T cell suppressor function
- decrease secretion or pro-inflammatory cytokines
Mitoxantrone CI
Liver dysfunction
Pregnancy
Mitoxantrone SE
- cardiotoxicity
- secondary acute myelogenous leukemia (AML)
- nausea
- alopecia
- amenorrhea
First generation trt of epilepsy
Carbamazepine Ethosuximide Phenobarbital Phenytoin Primidone Valproic acid
Second generation trt for epilepsy
Eslicarbazepine acetate Felbamate Lacosamide Levetiracetam Pregabalin Tiagabine Vigabatrin Gabapentin Lamotrigine Oxycarbazepine Perampanel Topiramate Zonisamide
Drugs with MOA of sodium channel inhibition
Carbamazepine Eslicarbazepine Lacosamide Lamotrigine Oxcarbazepine Phenytoin/Fosphenytoin Rufinamide
Carbamazepine approved for
Partial seizures
Primarily generalized tonic-clonic seizures
- may make absence seizures worse
- may make myoclonic seizure worse
Genetic sequence that identifies SJS with carbamazepine
HLA-B 1502
Eslicarbazepine approved for
Partial seizures (monotherapy)
Lacosamide approved for
Partial seizures (monotherapy)
AE of Lacosamide
- dizziness
- ataxia
- somnolence
- nausea
- PR interval prolongation
- atrial fibrillation
Lamotrigine approved for
- partial seizures
- primary generalized tonic-clonic (adjunct)
- Lennox-gastaut syndrome (adjunct)
AE of Lamotrigine
- dizziness
- HA
- diplopia
- nausea
- rash
- hypersensitivity (SJS/TEN)
- aseptic meningitis
Oxcarbazepine approved for
Partial seizures
- may make absence seizures worse
- may make myoclonic seizures worse
AE of oxcarbazepine
- hyponatremia (<125)
- dizziness
- HA
- somnolence
- diplopia
- nausea
- hypersensitivity (SJS/TEN)
- HLA-B 1502 positive status
Phenytoin/Fosphenytoin approved for
Partial seizures
- primarily generalized tonic-clonic seizures
- may make absence and myoclonic seizures worse
AE of phenytoin
- CNS dose related (dizziness, confusion, ataxia)
- long term use (coarsening of facial features, neuropathy, vit D and folic acid deficiency)
- CV with IV preps
- SJS/TEN
- lupus
- bone marrow suppression
- injection site necrosis
Rufinamide approved for
Lennox-Gastaut syndrome (adjunct)
AE of Rufinamide
- dizziness
- HA
- fatigue
- somnolence
- nausea
- QT interval shortening
Calcium channel inhibition MOA
Ethosuximide
Gabapentin
Pregabalin
Ethosuximide approved for
Absence seizures only (DOC)
AE of Ethosuximide
- nausea
- HA
- dizziness
- bone marrow suppression
- SJS/TEN
- psychiatric manifestations
Gabapentin approved for
Partial seizures (adjunct)
-may make myoclonic seizures worse
AE of Gabapentin
- dizziness
- somnolence
- ataxia
- weight gain
- emotional liability
- hyperkinesis
- angioedema
Pregabalin approved for
Partial seizures (adjunct)
-may make myoclonic seizures worse
AE of Pregabalin
- dizziness
- somnolence
- ataxia
- weight gain
- angioedema
Potentiation of GABA activity MOA
Clobazam
Phenobarbital
Tiagabine
Vigabatrin
Clobazam approved for
Lennox-Gastaut syndrome (adjunct)
AE of Clobazam
- somnolence
- drooling
- aggression (high dose)
- SJS/TEN
Phenobarbital/Primidone approved for
- partial seizures
- primarily generalized tonic-clinic
- not generally considered primary therapy for any seizure disorder
- may make absence seizures worse
AE of phenobarbital/primidone
- dependence
- paradoxical hyperactivity in children
- dizziness
- sedation
- respiratory depression
- SJS/TEN
- necrosis
Tiagabine approved for
Partial seizures (adjunct)
- may make absence seizures worse
- may make myoclonic seizures worse
AE of Tiagabine
- dizziness
- asthenia
- tremor
- somnolence
- new onset seizures in pts w/o epilepsy
Vigabatrin approved for
Complex partial seizure (adjunct)
-very refractor seizures ONLY
AE for Vigabatrin
- somnolence
- dizziness
- fatigue
- weight gain
- permanent loss of peripheral visual field
- anemia
Glutamate inhibition MOA
Perampanel
Perampanel approved for
- partial seizures in pts >12ys
- primarily generalized tonic-clonic seizures (adjunct)
AE of perampanel
- somnolence
- dizziness
- fatigue
- gait disturbances
- hostility/aggression