Anticonvulsants Flashcards
True or false: All epileptic episodes are accompanied by convulsions.
False. Not all, but majority. Some just involve loss of consciousness
What is the difference between primary and secondar epilepsy? Which is more common? How does treatment duration for each differ?
Primary (70%) - No specific cause. chronic drug treatment
Secondary (30%) - Known cause for seizure (e.g. stroke, illness), treat till underlying cause is gone
What are the 2 types of partial seizures?
Simple
Complex
What are the 5 types of generalized seizures?
Tonic Clonic Absence Myoclonic Febrile Seizures Status Epilepticus
Partial epilepsy originates from _ within the cortex. If the electrical activity spreads throughout the cortex, then you have a _
Small group of neurons (seizure focus)
Generalized tonic clonic seizure
A seizure characterized by no impairment of consciousness, non-spreading focal motor, sensory, autonomic or psychic disturbances is a _
Simple Partial seizure
A seizure characterized by impaired consciousness, dream-like state with/without automated movement and electrical activity that can spread through out the cortex is _
Complex partial seizure
A seizure that spreads through out both hemispheres of the brain, accompanied by immediate loss of consciousness and may or may not be convulsive is a _
Generalized seizure
A seizure characterized by a period of rigid extension of trunk and limbs accompanied by a loss of consciousness, followed by a period of rhythmic contraction of limbs is a _. This is also known as _
Tonic clonic seizure
Grand mal
A seizure characterized by a brief loss of consciousness, patient staring followed by rapid eye blinking, usually in patients aged 3 - puberty is a _. This is also known as _
Absence seizure
Petit mal
A seizure characterized by short episodes of muscle contractions that may reoccur over several minutes is _. The major cause of this type of seizure is _
Myoclonic
Permanent neurological damage
A seizure characterized by tonic clonic convulsions in young (up to 5 years) feverish children is _
Febrile seizures
A seizure characterized by repeated seizures without recovery of consciousness between them, with seizures lasting up to 30 minutes is _.
Status epilepticus
A type of seizure characterized as a medical emergency and carries risk of cardiovascular collapse and permanent brain damage is _
Status epilepticus
Would you expect more/less blood flow to an area of the brain involved with the onset of a seizure?
More blood flow
Three main objectives of antiepileptic drugs are _
Block origin of seizure activity
Block spread
Block syncronization of neuronal activity
4 antiepileptic drugs that work by inhibiting voltage gated sodium channels, thus extending the refractory period of neurons are _
Carbamazepine
Phenytoin
Lamotrigine
Valproic acid
2 antiepileptic drugs that work by inhibiting voltage gated calcium channels, thus inhibiting rhythmic activity of neurons are _
Ethosuxamide
Valproic acid
2 classes of antiepileptic drugs that enhance GABAergic inhibitory neurotransmission are _. What 2 other “individual” drugs have the same effect?
Benzodiazepine
Barbiturates
Valproic acid
Gabapentin
What type of calcium channels are responsible for the rhythmic firing activity of neurons and are thus the targets of valproic acid and ethosuxamide?
T-type calcium channels
What is the way to treat status epilepticus?
- Begin IV rapid acting antiepileptics (e.g. diazepam)
- support CV and repiratory function
- Follow with IV long acting antiepileptic (e.g. phenytoin)
What is the drug of choice for treating epilepsy in adult? What types of seizures is it good for? What types of seizures is it not good for?
Phenytoin
Good - Partial simple, partial complex, tonic clonic
Bad - Absence
What is the mechanism by which phenytoin works?
Blocks voltage gated sodium channels, blocks repeated firing
Under what conditions is phenytoin administered orally? IV? Does it bind plasma proteins? What are the 2 CYP enzymes that metabolize it? What is a prodrug for phenytoin that is used IM and IV?
Orally (chronic), IV (emergency)
Binds highly (90%) to plasma proteins
CYP2C9 and CYP2C19
Fosphenytoin
Phenytoin increases the metabolism of what other 2 drugs? What drug stimulates phenytoin’s metabolism? What 2 inhibit phenytoin metabolism?
Doxycycline and cyclosporine
Carbamazepine
Chloramphenicol and Sulfonamide
In addition to phenytoin, what is another drug of choice for simple partial, simple complex and tonic clonic seizures? What is the mechanism
Carbamazepine
Blocks voltage gated sodium channels, blocks action potential propagation
While slowly absorbed orally, why is carbamazepine able to rapidly penetrate the brain? What is unique about its interaction with CYP450 enzymes?
Highly lipid soluble
Induces its own metabolism with chronic use
In addition to its own metabolism, what other drug’s metabolism does carbamazepine enhance?
Phenytoin
What is the drug of choice for myoclonic seizures? How does it work? (3)
Valproic acid
Blocks Na, Ca and facilitates GABA transmission
What is a drug that combines sodium valproate and valproic acid? What is the reason for this combination?
Divalproex
Improves GI tolerance
What is the drug of choice for treating absence seizures? What is the mechanism?
Ethosuximide
Blocks T-type calcium channels, reduces rhythmicity
Regarding ethosuxamide, how well does it bind plasma proteins? What percentage is excreted unchanged in urine? What percentage is metabolized by CYP enzymes?
Doesn’t bind plasma proteins
25 percent excreted unchanges
75 percent metabolized
What barbiturates are used to treat seizures (2)? What are the 3 types of seizures they are used to treat? How can you acheive dose sparing with these barbiturates?
Phenobarbital, Primidone
Febrile, Tonic clonic, Simple Partial
Combine with carbamazepine or phenytoin
What is the metabolic product of primidone? What is the effect / mechanism of barbiturates?
Phenobarbital
Increase GABA inhibitory transmission
What is the drug class of choice for the treatment of status epilepticus? What are 2 examples provided? What other types of seizure can be treated with this drug (2)? What is a drawback of long term use?
Benzodiazepines
Diazepam and lorazepam
Myoclonic and absence seizures
Tolerance develops in 1-6 months
In addition to phenytoin and carbamazepine, what is a newer type of drug used to treat simple partial, complex partial and tonic clonic seizures? What is the mechanism?
Lamotrigine
Suppresses glutamate release, prevents Na+ firing
Regarding lamotrigine, what antiepileptic drugs decrease its half life? Increase its half life?
Decrease - Phenytoin and carbamazepine
Increase - Valproic acid
Besides lamotrigine, what is another new type of drug used to treat simple partial, complex partial and tonic clonic seizures? What is the mechanism?
Gabapentin
Blocks Ca++ channels, blocks glutamate release
What is unique about gabapentine metabolism? Does it bind plasma proteins? What drugs does it interact with?
It is not metabolized, excreted by kidneys
No plasma protein binding
No drug interactions
What types of seizures is topiramate used to treat? How does it work?
simple partial, complex partial and tonic clonic seizures
Blocks Na+ channels, increases postsynaptic GABA-A activity
What types if seizures is pregabalin used to treat? How does it work? This mechanism is similar to what other newer antiepileptic?
Blocks Ca++ channels, blocks glutamate release
Gabapentin
What drug is considered an adjunct for the treatment of simple partial, complex partial and tonic clonic seizures? How does it work?
Levetiracetam
Binds synaptic SV2A, modifying GABA and glutamate release
What are 5 common side effects of antiepileptics?
Drowsiness/sedation Ataxia Nausea/vomiting Skin rash Metabolic changes
An antiepileptic associated with gingival hyperplasia, megaloblastic anemia, and teratogenic effects is _
Phenytoin
An antiepileptic associated with hepatotoxicity, thrombocytopenia, and teratogenic effects is _
Valproic acid
An antiepileptic associated with hepatotoxicity and teratogenic effects is _
Carbamazepine
An antiepileptic associated with megaloblastic anemia alone is _
Primidone
An antiepileptic associated with thrombocytopenia alone is _
Pregabalin
An antiepileptic associated with teratogenic effects alone is _
Phenobarbital
