Antiepileptics Flashcards
1
Q
Epilepsy (2)
A
- manifests by seizures caused by the asynchronous discharge of neurons
- seizures can also be caused by trauma, infections, surgery, tumors
2
Q
Types of epilepsy
A
- Partial - simple or with generalization
- Generalized - tonic-clonic, myoclonic, absence
- Status epilepticus
3
Q
Partial seizures (5)
A
- involves a part of brain (depends on the part affected)
- involuntary muscle contractions
- abnormal sensory experiences
- affects mood and behavior
- simple (with conscious), complex (without consciousness)
4
Q
Generalized seizures (4)
A
- involves the whole brain
- tonic-clonic: strong contraction of whole muscle (1min), rapidly contracts and relaxes (2-4min), still unconscious for a few min (defecation, micturition, salivation is possible), fell “ill” after recovery
- myoclonic: short muscle twitches
- absence: thalamus is responsible, calcium channels are important. Abrupt “disconnection”, patient doesn’t know what happened
5
Q
Status epilepticus (5)
A
- continuous uninterrupted seizures
- lasts for more than 5 min
- several episodes of seizures during this period
- usually tonic-clonic
- life threatening
6
Q
Anti-epileptic drugs mode of action (4)
A
- imbalance between excitatory and inhibitory processes in the brain
- too much excitation or too little inhibition
- main goal: decrease neuronal excitability or increase neuronal inhibition
- main mediators: glutamate (excitation), GABA (inhibition)
7
Q
Anti-epileptics names (9)
A
- Phenytoin
- Carbamazepine
- Valproate
- Ethosuximide
- Phenobarbital
- Benzodiazepines
- Lamotrigine
- Topiramate
- Gabapentin
8
Q
Channels blocked by phenytoin and carbamazepine
-pharmacokinetics of phenytoin
A
Sodium channel in pre-synaptic neuron
-metabolism is non-linear, zero-order at moderate to high doses
9
Q
Channels blocked by valproate
-pharmacokinetics
A
- sodium channel in pre-synaptic neuron
- low voltage calcium channel in post- synaptic neuron (T-type)
- GABA transaminase (GATA-T)
-compete with phenytoin for plasma binding proteins, hepatotoxicity, inhibit –> carbamazepine, phenobarbital, ethosuximide, lamotrigine, phenytoin
10
Q
Channels blocked by ethosuximide
A
-low voltage calcium channels in post-synaptic neuron T-type)
11
Q
Channels blocked by barbiturates and benzodiazepines
A
- they act on GABA A receptors on the post- synaptic neuron
- benzodiazepines - increase the frequency of channel opening
- barbiturates - increase the duration of channel opening
12
Q
Channels blocked by lamotrigine
-pharmacokinetics
A
- sodium channel in pre-synaptic neuron
- high voltage calcium channel in pre-synaptic neuron
-eliminated via hepatic glucuronidation
13
Q
Channels blocked by gabapentin, pregabalin
-pharmacokinetics
A
-high voltage calcium channel in pre-synaptic neuron
- eliminated by the kidneys (uncharged form), no drug-drug interactions
- only used for partial seizures because it partially blocks the calcium channels binding to alpha and delta sub-unit
14
Q
Channels blocked by topiramate
-pharmacokinetics
A
- sodium channel in pre-synaptic neuron
- high voltage calcium channel in pre-synaptic neuron
- block AMPA receptor in post-synaptic neuron
- stimulate GABAA receptor in post-synaptic neuron
-both hepatic and renal elimination (uncharged form)
15
Q
Anti-epileptic drugs choice in:
- Partial Seizures
- Generalized
- Status epilepticus
A
- for both simple and generalized: valproate, topiramate, carbamazepine, phenytoin, gabapentin, lamotrigine
- absence –> ethosuximide, valproate
myoclonic –> valproate, lamotrigine, topiramate
tonic- clonic –> valproate, lamotrigine, topiramate - diazepam
16
Q
Other indications of anti-epileptic drugs
A
- Depression: lamotrigine, topiramate
- Bipolar disorder: valproate, carbamazepine, lamotrigine, topiramate
- Migraine: valproate, topiramate
- Neuropathic pain: carbamazepine, gabapentin
17
Q
Anti-epileptic drugs of choice in pregnancy
A
- Lamotrigine
- Topiramate
***Contraceptives could also affect anti-epileptic drugs and vice-versa
18
Q
Anti-epileptic’s pharmacokinetics (6)
A
- used for long periods of time
- well absorbed, good bio-availability
- many are metabolized by hepatic enzymes
- resistance –> increase expression of transporters at the level of blood-brain barrier
- many of these drugs are strong inducers or inhibitors of liver enzymes that metabolize other drugs –> drug interaction!!!!!
- ex: rifampin –> induce hepatic enzymes and may decrease the anti-epileptic effects of some drugs
19
Q
Anti-epileptic drugs - unwanted effects
-only main ones
A
- Phenytoin –> gum hypertrophy, hirsutism, megaloblastic anemia, fetal malformation
- Carbamazepine –> leucopenia, cardiotoxicity
- Phenobarbital –> sedation, depression
- Benzodiazepines –> sedation, withdrawal syndrome
- Ethosuximide –> may exacerbate tonic-clonic seizures
- Lamotrigine –> Stevens-Johnson syndrome (severe allergic reaction)
- Gabapentin (Pregabalin) –> sedation, ataxia
- Topiramate –> metabolic acidosis, kidney stones
- Valproate –> fetal malformation, liver damage
general: sedation, ataxia
20
Q
Parkinson’s disease
- characteristics (5)
- symptoms
A
- chronic, progressive, neuro-degenerative disorder
- dopamine deficiency
- neurons connecting substantia nigra and striatum progressively degenerate
- affects coordination and movement
- exact cause still unknown
- 4 cardinal symptoms: resting tremor, rigidity, postural instability, bradykinesia
- also cognitive impairment
21
Q
Pathogenesis - Parkinson’s disease (5)
A
- degenerative disease of basal ganglia
- idiopathic –> may follow stroke, virus infection, drug induced
- early degeneration of dopaminergic nigrostriatal neurons, followed by general neurodegeneration
- dopaminergic neurons in substantia nigra –> inhibit GABA neurons in striatum –> less dopamine, more GABA –> increased inhibition of thalamus and less excitation to motor cortex
- dopaminergic neurons in susbtantia nigra –> inhibit excitatory cholinergic neurons in striatum –> increased production of acetylcholine = impaired mobility
22
Q
Diagnosis - Parkinson’s disease (3)
A
- there are no definitive tests
- neurological exams or medical history/ symptoms
- other tests (ex: blood, brain scans…) only made to exclude other causes
23
Q
Treatment - Parkinson’s disease
- drugs act by…
- name of the drugs and their function? (5)
A
-counteracting dopamine deficiency in the basal ganglia or blocking muscarinic receptors
- Levodopa + carbidopa (inhibit peripheral dopa decarboxylase) or entacapone (inhibit cathecol-o-methyltransferase)
- Bromocriptine (dopamine agonist)
- Selegiline (inhibit monoamine oxidase B)
- Amantadine (enhance dopamine release)
- Benztropine (muscarinic receptor antagonist)
24
Q
Why is Levodopa given with another drug?
A
- Levodopa is dopamine’s precursor.
- Dopamine cannot cross the blood-brain barrier, so instead Levodopa is used (it is able to cross it).
- Another drug is necessary to prevent peripheral metabolism of Levodopa.
- After it crosses the blood-brain barrier, it is converted to dopamine
25
Q
Levodopa
- characteristics (2)
- unwanted effects (4)
- benefits of levodopa with carbidopa
A
- “Gold standard”- most effective for motor symptoms
- given 2-4 times daily
- “on-off” effects due to rapid plasma concentration fluctuations, nausea, anorexia, psychological effects (schizophrenia like syndrome), postural hypotension
- reduce dose by about 10-fold and minimize side effects
26
Q
Bromocriptine
- characteristics (4)
- unwanted effects (6)
A
- dopamine agonist, longer duration of action, less tendency to causes “on-off” effects and dyskinesia, inhibits release of prolactin
- nausea, anorexia, confusion, delusions, peritoneal fibrosis, sleep disturbances
27
Q
Benztropine
- characteristics (1)
- unwanted effects (8)
A
- muscarinic receptor antagonist
- dry mouth, urinary retention, constipation, memory and cognitive problems, hallucinations, confusion, sedation, blurred vision
28
Q
Selegiline
- characteristics (3)
- unwanted effects (8)
A
- monoamino oxidase B inhibitor, mild anti-depressant activity, less tendency to cause “cheese reaction”
- nausea, dizziness, confusion, hallucinations, nightmares, headache, heartburn, dry mouth
29
Q
Pathogenesis - Alzheimer’s disease
A
- Cholinergic hypothesis - lack of acetylcholine due to loss of central cholinergic neurons
- Amyloid hypothesis - accumulation of beta-amyloid proteins (induce neuroinflammation)
- Tau hypothesis - abnormal accumulation of tau proteins (form neuro-fibrillary tangles in the brain)
30
Q
Alzheimer’s disease
- risk factors (3)
- protective factors (4)
A
- advancing age, modifiable (mid-life obesity, diabetes, smoking, hypertension, dyslipidemia), non-modifiable (genetics)
- education, diet, exercise, social and cognitive engagement
31
Q
During Alzheimer’s disease, in which part of the brain we have a problem?
A
- cholinergic neurons
- hippo-campus
- frontal cortex
32
Q
Features of Alzheimer’s disease (3)
A
- appear gradually and eventually leads to irreversible ability to reason, remember and learn
- cognitive impairment –> memory loss, inability to learn new things, language impairment, disorientation, difficulty in performing familiar tasks
- non-cognitive impairment –> irritability, agitation, anxiety, aggression, sleep disturbances, depression
33
Q
Diagnosis - Alzheimer’s disease (2)
A
- clinical features and patho-histological confirmation by brain autopsy or biopsy
- 3 key patho-histological features: cortical atrophy, b-amyloid neuritic plaques, neuro-fibrillary tangles
34
Q
Treatment - Alzheimer’s disease (2)
A
- Cholinesterase inhibitors –> inhibit cholinesterase enzymes, increase the levels and duration of acetylcholine
- donepezil, rivastigmine, galantamine - NMDA receptor antagonists –> B-amyloid proteins cause an abnormal rise in glutamate, which bind to NMDA receptors and over stimulate them = excessive influx of Ca2+. Receptors need to be blocked
- memantine
35
Q
Cholinesterase inhibitors and NMDA receptors antagonists - side effects
A
- Cholinesterase inhibitors –> GI effects (nausea, vomiting, diarrhea), bradycardia, loss of appetite, weight loss
- NMDA receptor antagonists –> headache, insomnia, diarrhea
