L11- Anti-epileptics (background, therapies)

Question 1

define seizures and epilepsy

Answer 1

Seizures- finite episodes of brain dysfunction via abnormal discharge of cerebral neurons

Epilepsy- recurrent seizures

Question 2

list and categorize the classifications of seizures

Answer 2

Partial seizures (part of brain):

• simple partial
• complex partial
• partial w/ secondarily generalized tonic-clonic seizures

Generalized seizures (whole brain):

• tonic-clonic
• absence

Question 3

define the types of Partial Seizures

Answer 3

Simple partial seizure: no LOC, often characterized by abnormal activity of one limb, lasts 20-60s

Complex partial seizure: LOC, sensory hallucinations, mental distortion, motor dysfunction (chewing movements, diarrhea, urination), lasts 30-120s [mostly temporal lobe]

Partial w/ secondarily generalized tonic-clonic seizure: partial seizure progresses to tonic clonic seizures w/ LOC, lasts 1-2min

Question 4

define the main two types of Generalized Seizures

Answer 4

For all: immediate LOC, can be convulsive or non-convulsive, no evidence of localized onset

Tonic-Clonic (grand mal): LOC, tonic and clonic phases + period following seizure of confusion, exhaustion

Absence (petit mal): brief, abrupt, self-limiting LOC presenting as staring, rapid eye-blinking, tongue rolling, lip smacking (affects children until puberty), lasts <10-45s

Question 5

______ is the main sign or test that confirms an absent seizure

Answer 5

EEG: 3Hz spike-and-wave pattern emerges abruptly and ceases after a few seconds

Question 6

list the ‘other’ types of generalized seizures

Answer 6

• atonic: sudden loss of postural tone (children)
• tonic: muscle contraction and altered consciousness, 10s
• clonic: very rare, children, muscle spasms (no tonic rigidity)
• myoclonic: rare, repeated episodes of muscle contractions
• febrile: young children with high fever (tonic-clonic features)
• status epilepticus: seizures >5min or repeated seizures w/o recovery of consciousness

Question 7

what are the theorized mechanisms of seizures in general

Answer 7

-dec in inhibitory synaptic activity (dec GABA)
OR
-inc in excitatory activity (inc Glutamate)

Question 8

list the 4 types of drugs/agents used experimentally to trigger and or inhibit seizures

Answer 8

Trigger:

• GABA(a) antagonists
• Glutamate agonists

Inhibits:

• agents that enhance GABA transmission
• Glutamate receptor antagonists

Question 9

Partial Seizures, drugs of choice

Answer 9

(simple, complex, secondarily generalized tonic-clonic)
NOTE- all at least have Na+ V-gated channel blocker activity
-carbamazepine, oxcarbemazepine
-levetiracetam
-zonisamide
-phenytoin
-valproate
-lamotrigne
-topiramate
-phenobarbital

Question 10

Tonic-Clonic Seizures, drugs of choice

Answer 10

• carbamaxepine, oxcarbemaxepine
• valproate
• lamotrigine
• phenytoin
• topiramate

Question 11

Absence Seizures, drugs of choice

• (1) uncomplicated
• (2) also with tonic-clonic seizures
• (3) atypical absence seizures
• (4) can also be effected

Answer 11

Note- all have T-type Ca channel blocker activity
1- valproate, ethosuximide
2- valproate
3- valproate
4- lamotrigine

Question 12

Myoclonic seizures:

• (1) drug of choice
• (2) alternate
• (3) in adjunct therapy

Answer 12

1- valproate
2- topiramate
3- levetiracetam

Question 13

Atonic seizures, drugs of choice

Answer 13

valproate, lamotrigine

Note- all drugs can be effective

Question 14

describe treatment for Febrile Seizures

Answer 14

if <15 mins: supportive Tx

if >15 mins: diazepam IV or rectal admin (to prevent brain damage)

Question 15

define status epilepticus and some of its features

Answer 15

i) single seizure >5mins
ii) two or more seizures w/o recovery of consciousness

• convulsive or non-convulsive
• *most common type: generalized tonic-clonic status epilepticus –> life-threatening (or at minimum causes permanent brain damage)

Question 16

describe treatment for epilepticus

Answer 16

Initial phase: (benzodiazepines) IM midalozam, IV lorazepam, or IV diazepam

Second phase: (Na channel blockers) IV fosphenytoin, IV valproic acid, IV levetiracetam

Third phase: (to induce comatose state) repeat 2nd phase OR IV midalozam, pentobarbital, propofol

Question 17

______ are used to control drug-induced seizures (non-epileptic patients)

Answer 17

diazepam
lorazepam
phenobarbital

Question 18

Successful control of seizures without significant adverse effects can be achieved in (1) portion of patients. (2) are some of the treatment principles.

Answer 18

2/3 of Pts

• start with 1 drug at time – titrate up to max / optimal dose
• monitor Tx regularly
• combination therapy is attempted if two trials of single drug therapy has failed

Question 19

list the non-pharmacological methods of treating epilepsy

Answer 19

Surgery- resect area of epileptic focus

Ketogenic Diet (unclear mechanism)

Vagus Nerve Stimulation- L vagus with implanted pacemaker-like device –> activate device when Pt feels imminent seizure