AntiEpileptics Flashcards Preview

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Flashcards in AntiEpileptics Deck (22):
1

Current pharm of AEDS

-enhance GABA action
-inhibit Na channel function
-inhibit Ca channel function
-inhibit glutamate release
-inhibit glutamate receptors

2

↑GABAergic neurotransmission → ↑inhibition

Phenobarbital, Class: Barbiturate
Diazepam, Lorazepam. Class: Benzodiazepines
Tiagabine, (new drug)
Vigabatrin

3

Barbiturate

Phenobarbital

4

Phenobarbital

-Class: Barbiturate
-MOA: enhance the activation of GABA-A receptors
-increase duration of each channel opening → allosteric modulator
-also antagonizes glutamate receptors and blocks Na channels
-Pharm: Rapid absorption
- Long half life (53-118 hrs)
- Phenobarbital can be given as IV in emergency
-USE: Partial seizures esp. in neonates → 2nd line drug in adults due to severe sedation
→ rarely used in newly diagnosed patients due to sedation
-AE: CNS sedation.
-Tolerance and physical dependence possible
- P450 inducer
Drug Interactions:
- severe sedation if combo w/ alcohol or benzodiazepines
-in OD, produces coma and respiratory and circulatory failure

5

Benzodiazepines

Diazepam, Lorazepam

6

Diazepam, Lorazepam

-Class: Benzodiazepines
-MOA: → allosteric modulator of GABA-A R (increases frequency)
-Pharm: Rapid onset
- Diazepam can be given as a rectal gel for treatment of SE
-USE: Status epilepticus
-AE: CNS sedation, tolerance, dependence
-Drug Interactions: Potentiate other CNS depressants

7

Tiagabine

(new drug)
-MOA: analog of GABA
- inhibits GABA re-uptake
-Pharm: penetrates the BBB
-short half life
-Use: add on therapy for partial seizures
-AE: CNS sedative, drowsiness, confusion
-minimal drug interactions

8

Vigabatrin

-MOA: -inhibits the enzyme GABA transaminase that inactivates GABA in the pre-synaptic terminal

9

decreases Na conductance @hyperactive neurons

Phenytoin, Fosphenytoin (prodrug)
Carbamazepine
Valproate
Lamotrigine
Oxycarbazepine, (new drug)
Zonisamide (new drug)

10

Phenytoin
Fosphenytoin (prodrug)

-MOA: Use-dependent inhibitor of Na channels → block preferentially the excitation of cells that are firing repetitively; the higher the frequency of firing, the greater the block
-does not interfere with normally firing cells!!
-PHARM/ADMIN: Fosphenytoin (prodrug) can be given IM, IV
- Highly bound to plasma proteins
- Half life—22-36 hrs
-zero order kinetics (drug’s elimination independent from it’s concentration) → but the range of plasma concentration over which phenytoin is effective without causing excessive unwanted effects is very narrow
-USE: 1st line drug for Partial seizures, generalized tonic-clonic seizures, status epilepticus
-AE: CNS sedation (drowsiness, ataxia, confusion, insomnia, nystagmus, etc)
-gum hyperplasia, hirsutism, teratogenic, peripheral neuropathy and decreases deep tendon reflexes
- P450 inducer → ↑ metabolism of other drugs so monitor drug levels
Drug Interactions:
- carbamazapine + Phenobarbital will ↓ plasma levels
- Alcohol, Diazepam, Methylphenidate, ↑ plasma levels
- Valproate can displace drug from plasma proteins → ↑ phenytoin toxicity

11

Carbamazepine

-MOA: Use-dependent inhibitor of Na channels → block preferentially the excitation of cells that are firing repetitively; the higher the frequency of firing, the greater the block
-does not interfere with normally firing cells!!
-Pharm/Admin: Half life—6-12 hrs
- have active metabolite
-derived from tricyclic antidepressant drugs
-USE: 1st line drug for Partial seizures, generalized tonic-clonic seizures
-AE: CNS sedation, diplopia, ataxia
- in elderly pts: agranulocytosis + aplastic anemia
- teratogenic
-increase ADH
-stimulates the metabolism of other drugs by inducing microsomal enzymes, stimulates its own metabolism → this may require an increase in dose of this and other drugs patient is taking

12

Valproate

-MOA: simple monocarboxylic acid unrelated to any other class of anti-epileptic drug
→inhibits T-type calcium channels, enhances GABA transmission, and blocks sodium channels (MOA not fully understood)
-USE: inhibits most kinds of experimentally induced convulsions, and is effective in many kinds of epilepsy
-first line drug for generalized seizures, tonic-clonic seizures, myoclonic seizures, treats partial seizures -AE: CNS depressant (esp w/ phenobarbital), anorexia, nausea, vomiting, hair loss, weight gain, elevation of liver enzymes
-hepatoxicity is rare but severe, greatest risk <2 YO
-may cause birth defects
-Drug interactions: may potentiate CNS depressants, displaces phenytoin from plasma proteins, inhibits metabolism of phenobarbital, phenytoin, carbamazepine (p450 inducer)

13

Lamotrigine

-MOA: use-dependent inhibition of Na+ channels
-USE: add-one therapy, monotherapy for refractory partial seizures
-newly diagnosed epilepsy
-effective against generalized seizures
-AE: less CNS sedative effects than classic AEDs
-dermatitis, potentially life-threatening in 1-2% of pediatric patients
-Steven-Johnson syndrome
-Drug interactions: levels increased by valproate, decreased by carbamazepine, phenobarbital, phenytoin

14

Oxycarbazepine

(new drug)
-MOA: activity dependent blockade of Na+ channels
-Pharm: Chemically related to carbamazepine
- Half life—1-2 hrs
- active metabolite with a half life—8-12 hrs → longer half life
- also augments K+ channels
-USE: add on therapy or monotherapy for Partial seizures that are refractory to 1st line AEDs
-AE: Similar to carbamazepine (CNS sedative) but may be less toxic
- cause hyponatremia
- rash
Drug Interactions:
- Stimulates CYP3A → metabolizes steroid hormones so ↓ effectiveness of birth control pills → also ↓ carbamazapine
- Inhibits CYP2C19 → normally metabolizes phenytoin and valproate so ↑ phenytoin, valproate

15

Zonisamide

(new drug)
-MOA: blocks Na channels
-USE: add on therapy for Partial seizures + general seizures
-AE: CNS sedative
-minimal drug interactions

16

↓Ca current → T-type Ca channels

Ethosuximide
Gabapentin (new drug)

17

Ethosuximide

-MOA: blocks T-type Ca++ currents in thalamus.
- USE: absence seizures
-Admin: 2x daily dosing decreases severity of GI effects
-AE: GI distress (pain, nausea, vomiting), lethargy, headache
**less CNS effects**
-transient fatigue, dizziness, headache
-hematoxicity
-Drug interactions: administration with valproate results in inhibition of it’s metabolism

18

Gabapentin

(new drug)
-MOA: Inhibit L-type Ca channel
→ acts presynaptically
→may lead to ↓ glutamate release
→may interfere with GABA uptake
-Pharm: Do not bind plasma proteins
- Eliminated unchanged by kidneys (not metabolized) → so ↓ elimination if renal disease
-USE: add on therapy for Partial seizures
- monotherapy for newly diagnosed partial epilepsies
-AE: less CNS sedation
- no known drug interactions

19

Pleitropic

Felbamate, (new drug)
Topiramate, (new drug)
Levetiracetam, (newer drug)

20

Felbamate

(new drug)
-MOA: modulation of NMDA and GABA receptors
-USE: 3rds line drug for refractory partial seizures due to AE *
-AE: Black box warning → due to Aplastic anemia + Severe hepatitis *
Drug Interactions:
- Stimulates CYP3A → metabolizes steroid hormones so ↓ effectiveness of birth control pills → also ↓ carbamazapine
- Inhibits CYP2C19 → normally metabolizes phenytoin and valproate so ↑ phenytoin, valproate

21

Topiramate

(new drug)
→ MOA is multifunctional
- ↑GABA-A: by ↑ channel opening freq
- use-dependent Na channel blocker
-Inhibit AMPA receptors (blocks glutamate binding site)
-weakling inhibits carbonic anhydrase
-inhibits calcium channels
-USE: add on therapy for Refractory partial or generalized seizures
- monotherapy for partial or generalized seizures
- effective in pts w/ generalized epilepsy that are unsuccessful on other therapies
- it’s a weak carbonic anhydrase inhibitor → cause metabolic acidosis
-AE: CNS sedative, weight loss, kidney stones
Drug Interactions:
- Stimulates CYP3A → metabolizes steroid hormones so ↓ effectiveness of birth control pills + ↓ carbamazapine
- Inhibits CYP2C19 → normally metabolizes phenytoin and valproate so ↑ phenytoin, valproate

22

Levetiracetam

(newer drug)
-MOA: it binds to synaptic vesicle protein SV2A → may regulate NT release
-USE: add on therapy for partial seizures
-AE: CNS depression, behavioral mood swings
-minimal drug interactions