Anti-epileptic Drugs Flashcards
1
Q
What is epilepsy
A
- Chronic disorder characterized by recurrent seizures
- Sudden, transient disturbances in cerebral excitation
- May remain localized in a specific area or may spread & become generalized
- Physical convulsion due to neuronal activation of motor cortex leading to muscle contractions
2
Q
Describe hyper excitable cerebral neurons
A
- Inciting causes stroke, tumors, toxins, head trauma, CNS infection, & hypoxia
- Congenital abnormalities & genetic factors
3
Q
Describe innovative approaches to treatment of epilepsy
A
- Surgery
- Neuronal stimulation
- Dietary control
4
Q
Classifications of seizures
A
- Focal (partial) seizures
- Generalized seizures
- Outward manifestations depend on the area of brain impacted
5
Q
Describe focal/partial seizures
A
- Older terminology includes terms such as partial
- Only affect one part of the brain/typically one cerebellar hemisphere
- May progress to affect the whole brain
6
Q
Describe generalized seizures
A
- Subclassification include tonic-clonic (grand mal) & absence
- Affects the whole brain
7
Q
Role of AEDs in epilepsy
A
- Individual seizures are usually self-limiting
- Recurrence of seizures may cause further damage to neurons; harmful to healthy cells
- Biochemical changes, harmful proteins, oxidative stress
- Increased susceptibility to additional seizures
- Physical harm from LOC/falls
- Goal is to suppress the excitability of neurons that initiate seizures
8
Q
Lists the first generation AEDs
A
- Barbiturates
- Benzodiazepines
- Hydantoins
- Iminostilbenes
- Succinimides
- Valproates
9
Q
Describe barbiturates
A
- Phenobarbital & pentobarbital
- Potentiate inhibitory effects of GABA, decreased the release of excitatory glutamate
- Narrow therapeutic index
- Very effective but mostly last-line
- SE: sedation & ataxia
10
Q
Describe benzodiazepines
A
- Clonazepam & lorazepam
- Potentiate inhibitory effects of GABA
- Great for acute termination of seizures/status epilapticus
- Longterm use limited to specific subtypes
- SE: sedation, ataxia, behavioral changes
11
Q
Describe hydantoins
A
- Phenytoin & fosphenytoin
- Stabilize neurons by blocking sodium channels, may increase concentrations of inhibitory NTs (GABA)
- Narrow therapeutic index
- SE: sedation, dizziness, HA, gastric irritation, hirsutism, skin reactions
12
Q
Describe iminostilbenes
A
- Carbamazepine & oxcarbamazepine
- Stabilize neurons by blocking sodiumchannels; may inhibit presynaptic uptake and release of NE
- SE: dizziness, drowsiness, ataxia, blurred vision, water retention (abnormal ADH release)
13
Q
Describe succinimides
A
- Ethosuximide
- Inhibit spontaneous firing in thalamic neurons by limiting calcium entry
- SE: GI distress, HA, dizziness,lethargy,dyskinesia, bradykinesia, skin rashes
14
Q
Describe valproates
A
- Vampiric acid & divalproex
- May inhibit sodium channels; may hyperpolarize neurons through potassium channels; may increase GABA concentration
-SE: GI distress, hair loss, weight gain/loss, impaired platelet function
15
Q
Lists the 2nd generation AEDs
A
- Gabapentin: sedation, dizziness
- Lacosamide: dizziness, HA, double vision
- Lamotrigine: ataxia, skin reactions
- Levetiracetam: sedation, dizziness
- Pregabalin:peripheral edema, temporary
- Rufinamide: drowsiness, HA, nausea
- Tiagabine: rare depression,anxiety
- Topiramate: sedation, dizziness, ataxia
- Vigabatrin: rare suicidal thoughts, confusion, weight gain
- Zonisamide: sedation, loss of appetite
16
Q
Describe 2nd generation AEDs compared to 1st generation AEDs
A
- Not more effective
- More favorable kinetics
- Yes milder side effects
- Similar ADEs to 1st generation. just less severe& less frequently seen
17
Q
Describe AEDs in pregnancy
A
- Birth defects incidence is generally higher in women who take AEDs compared those w/o exposure
- Risks of stopping AEDs exist
- Individual decision to be discussed with physician & families
- Consideration for narrowing therapy to a single agent at lowest effective dose
18
Q
What is status epilepticus
A
- Series of seizures without appreciable recovery in between
- Untreated SE will result in permanent damage
- IV benzodiazepines followed by additional agents (levetiracetam, phenytoin, valproic acid, lacosamide); General anesthesia (propofol, pentobarbital)
19
Q
Other indications for AEDs
A
- Commonly used for non-epilepsy indications
- Neuropathic pain
- Migraine prophylaxis
- Bipolar disorder
- Restless leg syndrome
- Trigeminal neuralgia
- Seizure prophylaxis following head trauma
- Highlights importance of linking a medication to an indication
20
Q
Special concerns for rehab patients taking AEDs
A
- Epileptic patients, even while on AEDs, are at risk for seizure activity
- Close observation of patients may provide indications of non-compliance and undesirable side effects
- Alert patients and providers of potential toxic effects of medications
- Consider timing of therapy sessions when side effects are least bothersome
- Identify when therapy modalities may be exacerbating conditions: Skin reactions with therapy tools, etc.; HA or nausea inducing activities
-Recognize environmental triggers for seizures: Lighting, sounds, smells
21
Q
What is Parkinson disease
A
- Slow, progressivedegeneration ofdopamine-secretingneurons
- Clinical syndrome may also be precipitated byfactors such as trauma, variousantipsychotic drugs, CV disease, etc.
- Movement disorder characterized byresting tremor, bradykinesia, rigidity,posturalinstability.
- Advanced disease results inpersistently flexed posture; low, soft speaking voice
- Untreated canlead to total incapacitation.
- Nonmotor symptoms: depression,cognitive impairment, fatigue, chronic pain
22
Q
PD pharmacology
A
- Symptom management is priority goal: Motor function > improved physiological and psychological well-being
- Current pharmacology does not cure disease;motor deterioration tends to slowly progress
23
Q
PD pathophysiology
A
- Degeneration of dopamine-producing cells in substantia nigra > loss of dopaminergic input in the corpus striatum
- “Direct” (D1 receptors) and “indirect” (D2 receptors)pathways
- Results in a cascading effect on the cortex
24
Q
Genetic etiology of PD
A
- Mutations resulting in overproduction of certain proteins
- Associated free-radical/reactive oxygen species cellular damage
- “Vicious” cycle of the above results in degeneration & death of neurons
25
Q
Environmental etiology of PD
A
- Designer drug use (MPTP)
- Environmental toxins (herbicides, insecticides, fungicides, industrial agents); possible trigger for genetic pathways
- Role of ‘antioxidants’ in prevention has no definitive evidence to date
26
Q
Describe Levodopa
A
- Primary agent; cornerstone
- Dramatic improvement in all symptoms; bradykinesia and rigidity: Small portion of patients don’t respond or cannot tolerate
- Prolonged use > tolerance vs disease progression > loss of efficacy
- Start with low doses, increase to symptom reduction or until ADEs become problematic
- Levodopa conversion to dopamine in the periphery is a problem > less than 1% reaching the brain
27
Q
Describe Levodopa-carbidopa
A
- Carbidopa is a peripheral decarboxylase inhibitor
- Enables higher amounts of levodopa to reach the brain
- Fixed C:L ratio at 1:4 or 1:10
- Available in a controlled-release formulation to slow absorption, prolong benefits, and allow fewer doses per day
28
Q
Adverse drug reactions to Levodopa
A
- Gastrointestinal is common: N/v can be severe at initiation of therapy, sx greatly reduce when given in combo with carbidopa
- Cardiovascular: arrhythmias are minor unless prior Hx, orthostatic hypotension
- Dyskinesias: develop after prolonged use, varies/pt specific, may be a factor of too much drug/dopamine, intricate relationship b/w BG neurons & endo/exo genous dopamine
- Behavioral: psychotic sx are more prevalent, atypical antipsychotics may help reduce sx w/o worsening parkinsonism
29
Q
Describe the diminished and fluctuations of Levodopa
A
- Tolerance to therapy can make it ineffective over time unless doses are increased
- End of dose akinesia: drug effect wears off; resolved with adjustment in dose/timing
- On-off phenomenon: unpredictable change in response to therapy, freezing can lead to falls/injury
30
Q
What are Levodopa drug holidays
A
- Refractory response may be overcome w/ a holiday lasting 3 days to 3 wks
- Goal is to be able to restart levodopa therapy at lower doses with better results
- Risks of not taking therapy: severe immobility, VTE, pneumonia
- Employed on limited basis
31
Q
Parkinson therapies other than Levodopa
A
- Dopamine agonists
- Anticholinergics
- Amantadine
- Monoamine Oxidate B inhibitors (MAO-B inhibitors)
- Catechol-O-methyltransferase inhibitors (COM inhibitors)
32
Q
Describe dopamine agonists for PD therapy
A
- Bromocriptine, cabergoline, pramipexole, rotigotine, ropinirole
- Employed in those experiencingdecrease responsiveness
- May be helpful for end-of-dose akinesia and on-off phenomenon
- May normalize endogenous dopamine activity; neuroprotective
- SE: N/V, orthostatic hypotension
33
Q
Describe anticholinergics for PD therapy
A
- Limiting acetylcholine transmission may alleviate PD symptoms
- SE limit use: sedation, mood change, confusion,blurred vision
34
Q
Describe amantadine for PD therapy
A
- Helpful for reducing dyskinesias
- SE: Orthostatic hypotension, confusion
35
Q
Describe MAO-B inhibitors for PD therapy
A
- MAO-B enzyme breaks down dopamine
- Inhibition leads to prolonged effects at CNS synapses
- Selegiline/rasagiline are often used in early treatment to delay levodopa therapy then used in combination
- SE: sleep and mood disturbances (S>R); dizziness, sedation, GI distress
36
Q
Describe COM inhibitors for PD therapy
A
- Enzyme that converts levodopa to an inactive metabolite
- Preventing metabolism of levodopa increases drug available in CNS
- Used in combo with levodopa and carbidopa
- SE: increase in dyskinesia with therapy initiation; N/V, muscle pains
37
Q
Describe the clinical course of PD
A
- Early arguments to wait until advances staged to prescribe Levodopa
- Use of dopamine agonists or MAO-B inhibitors might be suitable initial agents: Levodopa with significant motor sx
- No consensus; patient & provides decisions
38
Q
Special considerations for. rehab for PD patients
A
- Coordinate therapies with peak drug effects (Levodopa ~1hr post-dose)
- Morning hrs may be ideal given late day fatigue
- May encounter ‘drug holiday’ patients in inpatient: need to maintain as much mobility as possible
- Monitor BP: orthostatic hypotension, dizziness, or syncope
- Careful guarding given fall risk
- Gait training, balance activities are essential to QOL
