Term
| what are the 3 major classes of anticonvulsants? |
|
Definition
1. Na channel inactivators
2. GABAergic agents
3. Ca channel blockers |
|
|
Term
| how do Na channel inactivators work to treat epilepsy? |
|
Definition
| prolong Na channel refractory period |
|
|
Term
| indications for Na channel inactivators? |
|
Definition
1. generalized tonic-clonic
2. focal (partial) |
|
|
Term
| Na channel inactivators used to treat epilepsy (6) |
|
Definition
1. carbamazepine
2. phenytoin
3. valproic acid
4. lamotrigine
5. topiramate
6. zonisamide |
|
|
Term
| Na channel inactivators are also used to treat migraine (2) |
|
Definition
1. topiramate
2. zonisamide |
|
|
Term
| *mechanism of action for carbamazepine? |
|
Definition
| prolongation of Na channel inactivation |
|
|
Term
| what is the drug of choice for focal onset (partial) seizures? |
|
Definition
|
|
Term
| *indications for carbamazepine? |
|
Definition
*drug of choice for focal onset (partial) seizures
generalized tonic-clonic |
|
|
Term
| original use of carbamazepine? |
|
Definition
| trigeminal neuralgia (tic doloureaux) |
|
|
Term
| other effects of carbamazepine (5) |
|
Definition
1. anticholinergic, neuromuscular-blocking, muscle relaxant
2. central anti-diuretic
3. anti-arrhythmic
4. antidepressant
5. sedative |
|
|
Term
| adverse effects of carbamazepine (4) |
|
Definition
1. resp depression
2. CNS - nystagmus, diplopia, tiredness, drowsiness, vertigo, headache
3. hepatotoxicity
4. agranulocytosis |
|
|
Term
| mechanism of action of phenytoin? |
|
Definition
| *prolongation of Na channel inactivation |
|
|
Term
| indications for phenytoin? |
|
Definition
generalized tonic-clonic and focal (partial) seizures
*NOT absence seizures |
|
|
Term
| pharmacokinetics of phenytoin? |
|
Definition
zero order kinetics
one of the few drugs for which a constant amount of drug is eliminated per unit time |
|
|
Term
| does phenytoin have a sedative effect? |
|
Definition
|
|
Term
| *contraindications for phenytoin |
|
Definition
1. sinus bradycardia, heart block (complete or partial)
2. hypoglycemic seizures |
|
|
Term
| what is fosphenytoin sodium? |
|
Definition
water soluble phosphorylated form of phenytoin
converted to phenytoin by phosphatases |
|
|
Term
|
Definition
|
|
Term
| why is fosphenytoin sodium preferred over phenytoin? |
|
Definition
*no phlebitis
can cause arrhythmia |
|
|
Term
| fosphenytoin sodium administration? |
|
Definition
|
|
Term
| what type of seizures can phenytoin not be used for? |
|
Definition
|
|
Term
| is phenytoin water soluble? |
|
Definition
NO
precipitates in dextrose and saline |
|
|
Term
|
Definition
| inflammation at the injection site |
|
|
Term
| what drug can be used in place of phenytoin to reduce the phlebitis? |
|
Definition
|
|
Term
| *phenytoin adverse effects (8) |
|
Definition
1. painful phlebitis
2. gingival hyperplasia
3. excessive hair growth
4. double vision
5. accelerates hepatic degradation of glucocorticoids
6. megaloblastic anemia
7. ataxia and nystagmus
8. osteomalacia |
|
|
Term
| what is an adverse effect of phenytoin when give IV? |
|
Definition
|
|
Term
| how does phenytoin cause gingival hyperplasia? |
|
Definition
| altered collagen metabolism leads to thickened, inflamed gums in 20% of patients; can't eat properly |
|
|
Term
| what is hypertrichosis seen with phenytoin use? |
|
Definition
| excessive hair growth where hair is normally present |
|
|
Term
| what is hirsutism associated with phenytoin use? |
|
Definition
| excessive hair growth in places there is usually no hair |
|
|
Term
| what drug causes alopecia? |
|
Definition
|
|
Term
| why does phenytoin lead to double vision? |
|
Definition
|
|
Term
| a patient taking glucocorticoids is started on phenytoin. the effect of the glucocorticoid is diminished. why? |
|
Definition
| *phenytoin accelerated hepatic degradation of glucocorticoids |
|
|
Term
| how does phenytoin lead to osteomalacia? |
|
Definition
1. inhibition of intestinal absorption of Ca
2. catabolism of vitamin K and reduction in vitamin K-dependent proteins for normal Ca metabolism in bone |
|
|
Term
|
Definition
| hypocalcemia + elevated alkaline phosphatase activity |
|
|
Term
| why is phenytoin-induced osteomalacia not always ameliorated by the administration of vitamin D? |
|
Definition
| due to the catabolism of vitamin K and reduction in vitamin K-dependent proteins for normal Ca metabolism in bone |
|
|
Term
| why would a patient taking phenytoin be more likely to undergo a fracture? |
|
Definition
| osteomalacia is an adverse effect |
|
|
Term
| *mechanism of action of valproic acid/valproate sodium? |
|
Definition
1. prolongation of Na channel inactivation
2. increase GABA synthesis; decrease GABA breakdown
3. blocks T type Ca channels |
|
|
Term
| valproic acid/valproate sodium indications? |
|
Definition
*very broad spectrum of action
*focal (partial), generalized tonic-clonic, absence, myoclonic |
|
|
Term
| valproic acid/valproate sodium side effects (4) |
|
Definition
1. thrombocytopenia
*2. alopecia
3. hepatotoxicity
*4. acute pancreatitis |
|
|
Term
| valproic acid/valproate sodium contraindications |
|
Definition
1. bleeding disorders
2. hepatic disease/dysfunction
3. pregnancy - possible teratogen |
|
|
Term
| receptor type of GABAa receptor? |
|
Definition
| ligand gated chloride channel |
|
|
Term
| subunits of GABAa receptor? |
|
Definition
|
|
Term
| where does GABA bind the GABAa receptor? |
|
Definition
| between the alpha and beta subunits |
|
|
Term
| what happens after GABA binds to the GABAa receptor? |
|
Definition
| channel opens --> Cl influx into the neuron --> hyperpolarizes neuron --> inhibits propagation and generation of AP |
|
|
Term
|
Definition
| metabotropic - G protein coupled receptor |
|
|
Term
| what 2 types of drugs also bind to the GABAa receptor? |
|
Definition
| benzodiazepines and barbiturates |
|
|
Term
| mechanism of action of benzodiazepines and barbiturates? |
|
Definition
| similar to GABA - bind and directly activate GABAa channel --> hyperpolarize neuron |
|
|
Term
| where do benzodiazepines bind on the GABAa receptor? |
|
Definition
|
|
Term
| where do barbiturates bind on the GABAa receptor? |
|
Definition
|
|
Term
| what enzyme produces GABA from glutamic acid? |
|
Definition
| glutamic acid decarboxylase |
|
|
Term
| what is the co-enzyme for glutamic acid decarboxylase? |
|
Definition
|
|
Term
| what drug can deplete pyridoxal phosphate? |
|
Definition
|
|
Term
GABA is degraded to what?
what is the importance of this degradation product? |
|
Definition
succinic acid
it has a negative feedback on the rate-limiting enzyme in GABA synthesis (glutamic acid decarboxylase) |
|
|
Term
| the date rape drug acts like what NT to cause retrograde amnesia? |
|
Definition
|
|
Term
patient has a head injury and loses consciousness. when they regain consciousness, they don't remember anything about the event.
this is known as ____ and is due to what? |
|
Definition
retrograde amnesia
due to GABA activation |
|
|
Term
| what are the 3 effects of GABA? |
|
Definition
1. anticonvulsive
2. anxiolytic
3. amnestic (retro and anterograde) |
|
|
Term
| how does valproic acid stop GABA synthesis? |
|
Definition
inhibits succinic semialdehyde dehydrogenase
succinic acid can't be produced --> can't negatively feedback on glutamic acid decarboxylase --> more GABA is produced |
|
|
Term
| how does GABA work to cause hyperpolarization? |
|
Definition
at the pre-synaptic axon, Na influx leads to GABA release
GABA binds receptor on post-synaptic neuron --> Cl ions influx --> hyperpolarize the neuron --> an AP can't be generated |
|
|
Term
| where are GABAa receptors located? |
|
Definition
| cerebral cortex > limbic system > cerebellum, spinal cord |
|
|
Term
| what drugs work to increase GABA synthesis? |
|
Definition
*valproic acid
vigabatrin |
|
|
Term
| what drug works to increase GABA release? |
|
Definition
|
|
Term
| what drug works to block GABA reuptake? |
|
Definition
|
|
Term
| what drug works to decrease GABA breakdown? |
|
Definition
|
|
Term
| what drugs are GABA receptor agonists? |
|
Definition
*lorazepam, diazepam
clonazepam
*phenobarbital
topiramate |
|
|
Term
| what are the 2 ways to terminate the action of GABA? |
|
Definition
| degrade it or take it back up into the cell that released it |
|
|
Term
| what are the prototype GABA agonists? |
|
Definition
|
|
Term
| mechanism of action of phenobarbital? |
|
Definition
| *GABA receptor stimulation; Ca channel inhibition |
|
|
Term
| indications for phenobarbital? |
|
Definition
| *generalized tonic-clonic, focal (partial), myoclonic, neonatal, status epilepticus |
|
|
Term
| why is phenobarbital the most widely used anti-epileptic? |
|
Definition
| because of efficacy, low toxicity, and low cost |
|
|
Term
| what anti-epileptic can be used in children <2 years of age? |
|
Definition
|
|
Term
| adverse effects of phenobarbital? |
|
Definition
*sedation
nystagmus, ataxia
*respiratory depression
megaloblastic anemia
hypoprothrombinemia with hemorrhage in neonates with maternal treatment |
|
|
Term
| how do you treat phenobarbital-induced megaloblastic anemia? |
|
Definition
|
|
Term
| how do you treat phenobarbital-induced hypoprothrombinemia with hemorrhage in neonates with maternal treatment? |
|
Definition
|
|
Term
| what 2 side effects of phenobarbital stop its widespread use? |
|
Definition
*sedation
resp depression |
|
|
Term
| what is the only type of seizure that phenobarbital can not be used to treat? |
|
Definition
|
|
Term
| primidone is metabolized to what? |
|
Definition
|
|
Term
|
Definition
anticonvulsant and sedative
like phenobarbital |
|
|
Term
|
Definition
| *effective in all types of seizures EXCEPT ABSENCE |
|
|
Term
| adverse effects of primidone? |
|
Definition
| same as phenobarbital - sedation, resp depression |
|
|
Term
| how do Ca channel blockers work in treatment of seizures? |
|
Definition
| reduce pacemaker Ca currents in thalamic neurons |
|
|
Term
| what is the unique drug for absence epilepsy? |
|
Definition
|
|
Term
| patient has epilepsy with no convulsions, very brief loss of consciousness following it. what is the treatment? |
|
Definition
|
|
Term
| what 2 drugs block T type voltage gated Ca channels? |
|
Definition
1. valproate sodium
2. ethosuximide |
|
|
Term
| mechanism of action of ethosuximide? |
|
Definition
| *reduction of T-type Ca currents in the thalamus |
|
|
Term
| ethosuximide indications? |
|
Definition
| *drug of choice for absence epilepsy |
|
|
Term
| what is the drug of choice for absence epilepsy? |
|
Definition
|
|
Term
| ethosuximide adverse effects? |
|
Definition
blood - leukopenia, thrombocytopenia, aplastic anemia due to BM depression
skin - reactions, SLE, urticaria, pruritis |
|
|
Term
| ethosuximide contraindications? |
|
Definition
hepatic or renal disease
safety in pregnancy or children <3 years had not been established |
|
|
Term
| top 3 first line drugs used for all different types of focal onset seizures? |
|
Definition
1. carbamazepine
2. phenytoin
3. valproate |
|
|
Term
| 3 antiepileptics also used to treat migraines? |
|
Definition
1. lamotrigine
2. topiramate
3. zonisamide |
|
|
Term
| 3 drugs used to treat absence seizure? |
|
Definition
1. ethosuximide
2. valproate
3. lamotrigine - newer |
|
|
Term
what is a newer drug used in all forms of generalized epilepsy?
what is important about it's administration? |
|
Definition
lamotrigine
not effective alone; has to be administered as an adjunct drug |
|
|
Term
| what is the first line drug for myoclonic seizures? |
|
Definition
|
|
Term
| side effects of lamotrigine (5) |
|
Definition
*1. visual disturbance
2. sedation
3. ataxia
4. skin rash
5. dyspepsia |
|
|
Term
| side effects of topiramate? |
|
Definition
*1. diplopia
*2. renal calculi
*3. weight loss
*4. neuropathy
somnolence, dizziness, ataxia, nystagmus, irritability, nausea, dyspepsia, hypohydrosis, hyperthermia |
|
|
Term
| side effects of zonisamide? |
|
Definition
| somnolence, confusion, ataxia, anorexia, nausea, vomiting, rash, *renal calculi |
|
|
Term
| how does status epilepticus manifest? |
|
Definition
| *multiple grand mals in succession or prolonged grand mal with no recovery of consciousness |
|
|
Term
| how long can status epilepticus last? |
|
Definition
|
|
Term
| treating status epilepticus is important because? |
|
Definition
| it is a medical emergency |
|
|
Term
| what is the first step in treating status epilepticus? |
|
Definition
|
|
Term
| what is the first thing given to a patient with status epilepticus? |
|
Definition
| 'coma cocktail' with 50% dextrose and 100 mg thiamine |
|
|
Term
| why is dextrose given to a patient with status epilepticus? |
|
Definition
| to replenish glucose for neurons and to rule out hypoglycemia as a cause of seizure |
|
|
Term
| why is thiamine given to a patient with status epilepticus? |
|
Definition
to prevent encephalopathies
especially in malnourished patients like alcoholics |
|
|
Term
| if seizures in status epilepticus continue despite IV dextrose, what can be concluded? |
|
Definition
| seizure is not due to hypoglycemia |
|
|
Term
| if a patient with status epilepticus continues to seize despite IV dextrose, what is the drug of choice next? |
|
Definition
lorazepam or diazepam (a benzodiaziapine)
used before/over phenytoin to avoid side effects |
|
|
Term
| why would lorazepam be chosen over diazepam to treat status epilepticus? |
|
Definition
| because it has a slightly longer duration |
|
|
Term
| if a patient with status epilepticus doesn't respond to the first dose of lorazepam (or diazepam) what should you do next? |
|
Definition
| give another dose after 10 min |
|
|
Term
| when do you give fosphenytoin or phenytoin to a patient with status epilepticus? |
|
Definition
| REGARDLESS of response of patient to lorazepam (or diazepam) |
|
|
Term
| why would you give fosphenytoin rather than phenytoin in status epilepticus? |
|
Definition
| phenytoin precipitates in dextrose-saline and causes phlebitis |
|
|
Term
| if convulsions continue in a patient with status epilepticus despite fosphenytoin what does the patient have? |
|
Definition
| refractory status epilepticus |
|
|
Term
| treatment for refractory status epilepticus? |
|
Definition
intubation and artificial ventilation
followed by a general anesthetic (midazolam or propofol) + phenobarbital |
|
|
Term
| what 4 drugs given for refractory status epilepticus require intubation? |
|
Definition
1. phenobarbital
2. midazolam
3. propofol
4. pentobarbital |
|
|
Term
| treating a patient for refractory status epilepticus requires what? |
|
Definition
|
|
Term
| what is the definitive antiepileptic drug for status epilepticus? |
|
Definition
fosphenytoin
can't treat immediately due to side effects |
|
|
Term
| what are the goals of pharmacotherapy of epilepsy? |
|
Definition
1. prevent further attacks
2. achieve 3 seizure-free years
3. then gradually withdraw drugs, one by one |
|
|
Term
| what is the risk of drug reaction compared to the risk of a second seizure in a patient with a history of a solitary seizure? |
|
Definition
the same - 15%
don't start treatment right away - if they have another one then it's definitely epilepsy |
|
|
Term
| when do you not initiate anti-seizure therapy for a patient that presents with a history of a solitary seizure? |
|
Definition
1. healthy young adult
2. no family history of epilepsy
3. normal neuro exam
4. normal EEG
5. normal brain MRI scan |
|
|
Term
| when do you consider anti-convulsant therapy for a patient that presents with a history of a solitary seizure? |
|
Definition
1. positive family history of epilepsy
2. abnormal neuro exam
3. abnormal EEG
4. abnormal MRI |
|
|
Term
| if a patient that presents with a history of a solitary seizure has any risk factors or symptoms for epilepsy, what is the risk of seizure recurrence? |
|
Definition
|
|
Term
| what are the first line drugs for focal or generalized onset tonic-clonic seizure? |
|
Definition
carbamazepine
phenytoin
valproic acid |
|
|
Term
| how are the different drugs used in treating focal or generalized onset tonic-clonic seizures? |
|
Definition
1. use a first line drug
2. if seizures continue despite max tolerated dose - add second drug
3. gradually withdrawal the first
4. use new drugs as adjunctive therapy |
|
|
Term
| what is the drug of choice for absence seizures? |
|
Definition
|
|
Term
| what is the drug of choice for myoclonic seizures? |
|
Definition
|
|
Term
| should dosing for antiepileptics be based on serum levels? why or why not? |
|
Definition
NO
many patients require and tolerate 'toxic' levels for therapeutic effect |
|
|
Term
| what must you monitor with anti-epileptic therapy? |
|
Definition
1. CBC at least annually
2. liver function tests - carbamazepine, valproic acid
3. serial blood counts - carbamazepine, ethosuximide |
|
|
Term
| how can drug therapy for epilepsy affect chances of getting status epilepticus? |
|
Definition
| poor compliance may precipitate status epilepticus |
|
|
