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Anti-convulsants
N/A
64
Pharmacology
Graduate
11/05/2010

Additional Pharmacology Flashcards

 


 

Cards

Term
Phenobarbital-- use
Definition
Generalized tonic clonic seizures
Term
Phenobarbital-- mechanisms of action
Definition

1.  **binds to GABA (A) receptors and prolongs amount of time chloride can flow into neuron (hyperpolarization)

2.  decrease release of excitatory NT (glutamate)

3.  decrease calcium channel activity

Term
Phenobarbital--kinetics issues
Definition

Best documented liver enxymes inducer; leads to drug-drug interactions

 

Causes decreased levels of other drugs that are metabolized by the liver enzymes

Term
Primidone
Definition
Metabolized into phenobarbital and PEMA (both act as anti-convulsants)
Term
Phenytoin-- MOA
Definition
1.  ** decrease sodium permability across neuron membrane
Term
Phenytoin- side effects at therapeutic doses
Definition

gingival hyperplasia

hypertrichosis

thickened facial features

folate deficiency

peripheral neuropathy

Term
Phenytoin- dose-dependent SE
Definition

20 mg/L--> nystagmus

30mg/L--> nystagmus, ataxia

40mg/L--> ataxia, lethargy and decreased cognitive function

Term
Phenytoin-- kinetics issues
Definition

exhibits MM (linear) kinetics--> small dose can result in large increase in plasma levels

 

IV incompatabilities.

Term
Carbamazepine-- uses
Definition

GTCS

 

partial epilepsy

 

trigeminal neuralgia

 

bipolar disease

Term
Carbamzepine-- MOA
Definition
Enhances voltage gated sodium channel inactiavtion (increased recovery time after AP)
Term
Carbamazepine-- kinetics issues
Definition

autoinduction--> starts enhancing its own metabolism in the liver; takes 3-4 weeks to stabalize.

 

 

Levels should be monitored for the first ~28 days, followed by a dose adjustment

 

10, 11 epoxide metabolite (active and can be increased by valproate)

Term
Oxcarbamazepine
Definition

Keto-analog of CBZ

 

Less side effects but less potent

 

Approved for monotherapy for newly diagnosed patients and refractory partial epilepsy

Term
Carbamazepine-- adverse effects
Definition

GI

 

vision effects (diplopia)

 

hematologic effects (leukopenia--> usually transient; drug should be stopped is under 2500.)

 

thrombocytopenia

 

rash

Term
Valproate (Divalproex)-- MOA
Definition

1.Inhibits GABA metabolism (GABA transaminase and sicinic semialdehyde DH)

2.prevents GABA reuptake

3.stimulates GABA synthetic enzymes (from glutamate)

4.  enhances sodium channel inactiavation (prolonged recorvery after AP)

5.  Some effect on T-type calcium channels

Term
Valproate (Divalproex)-- uses
Definition
Most major seizure types (including absence)
Term
Valproate-- adverse effects
Definition

GI--common

alopecia (usually temp)

weight gain

hepatotoxicity (particularly of concern in patient under 2 yo on multi drugs)

metabolic effects

thrombocytopenia (increased ammonia, glucose, urea)

Term
Ethosuxamide-- use
Definition
Absence seizures
Term
Ethuxamide-- MOA
Definition
Blocks T-type calcium channels in thalamic neurons
Term
Benzodiazapines-- individual agents and indications
Definition

Diazepam (status and alcohol withdrawal)

 

Lorazepam (status and alcohol withdrawal)

 

Clonazepam (akinetic seizures, myoclonic seizures, lennox-gastaut)

Term
Benzodiazapines-- MOA
Definition
Binds GABA receptors and increases frequency of chloride channel openings
Term
Benzodiazapines-- adverse effects
Definition

abuse potential

 

tolerance (longterm use)

 

relatively safe unless combined with ethanol

Term
Felbamate-- use
Definition

adjunct for complex partial

 

Lennox-Gastaut (MR and mutliple seizure types)

Term
Falbamate-- MOA
Definition
antagonist of NMDA receptor (glutamate receptor)
Term
Falbamate-- adverse effects
Definition

**aplastic enemia and deadly hepatotoxicity

 

Rarely used; never first-line

Term
Lamotrigine--use
Definition

complex partial seizures

 

monotherapy for refractory partial seizures

Term
Lamotrigine-- MOA
Definition
inhibits sustained repetitive sodium channel firing
Term
Lamotrigine-- adverse effects
Definition
rashes (Steven-Johnson), N and V, dizziness, diplopia, ataxia
Term
Gabapentin-- use
Definition
adjunct in complex partial
Term
Gabapentin-- MOA
Definition

binds to alpha2delta subunit of calcium channels and decreases calcium influx (decreases release of several NT)

 

inhibits Na currents

 

stimulates GABA release

 

 

Term
Gabapentin-- adverse effects
Definition

it is eliminated by kidneys and water soluble, so not many drug interactions

 

 

reduced absorption with antacids

Term
Pregabalin-- use
Definition
adjunct for complex partial
Term
Pregabalin-- MOA
Definition
binds alpha2delta subunit of calcium channel and decreases calcium influx (decreases release of several NT)
Term
Pregabalin-- adverse effects
Definition

eliminated by kidneys and water soluble, not many drug interactions

 

blurred vision, peripheral edema, dry mout, weight gain

Term
Topiramate-- use
Definition
complex partial, GTCS, Lennox-Gastaut
Term
Topiramate-- MOA
Definition

inhibits sodium channels

 

enhances GABA

 

attenuates kainate-induced seizures

 

AMPA antag?

Term
Topiramate-- adverse effects
Definition
kidney stones, ataxia, GI, tremors
Term
Tiagabine-use
Definition
adjunct for complex partial
Term
Tiagabine- MOA
Definition
inhibition of GABA reuptake
Term
Tiagabine-adverse effects
Definition

nervousness, tremor

 

spike-wave stupor--> do not use off-label

Term
Levetiracetam-- use
Definition
adjunct for complex partial
Term
Levetiracetam-- MOA
Definition

binds selectively to SV2A

 

(which may be modifying synaptic release of glutamate and GABA)

Term
Zonisamide- use
Definition
adjunct complex partial epilepsy
Term
Zonisamide-- MOA
Definition

poorly understood; inhibits voltage gated sodium currents adn T-type calcium channels (in vitro)

 

Term
Zonisamide-- adverse effects
Definition
kidney stones, rash, ataxia
Term
Vigabatrin- use
Definition

infantile spasms

 

refractory epilepsy (last line)

Term
Vigabatrin- MOA
Definition

GABA transaminase inhibitor

 

inhibition of GABA reuptake

Term
Vigabatrin--adverse
Definition
blindness (30%)-- only used because one of few things that can treat infantile spasms
Term
Lacosamide- use
Definition
adjunct complex partial
Term
Lacosamide-- MOA
Definition

enhances slow actiavtion of sodium channels

 

100% bioavailable

Term
Lacosamide-- adverse
Definition

no significant drug interaction

 

PR-interval prolongation (caution when using with other drugs causing prolonged PR or people with cardiac disease)

Term
Rufinamide-- use
Definition
adjunct for Lennox-Gastautover 4yo
Term
Rufinamide- MOA
Definition
prolonged inactiavtion of sodium channels
Term
Rufinamide-adverse
Definition

shortened QT interval, hypersensetivity (rash)

 

(caution when using other drugs that shorten QT interval like digoxin and lamotrigine)

 

EUPHORIA-- Schedule V controlled substnace

Term
teratogenic effects of anticonvulsants
Definition

fetal anticonvulsant syndrome

 

neural tube defects (cleft lip, cleft palte, spinal cord like myelomeningocele)

 

poor cognitive outcome (especially Valproate)

Term
common cause of cleft lip and cleft palate
Definition
phenytoin and phenobarbital
Term
common cause of spinal column defects
Definition
carbamazepine and valproate
Term
fetal anticonvlsant syndrome
Definition

thin upper lip

small, upturned nose

long, flat nasal bridge

mild to moderate MR

ptosis

occular hypertelorism

long philtrum

hypoplasia of distal phalanges

small nails

 

Might be caused by folate deficiency or interruption of hyaluronic acid metabolism

Term
poor cognitive outcome
Definition
valproate, phenytoin and phenobarbital
Term
Steven-Johnson Syndrome
Definition

-caused by various anticonvulsants like lamotrigine, carbemazepine, barbiruates, phenytoin, ethosuxamide

-severe febrile hypersensitivity reaction

-array of macules, papules, vesicles, and cytotoxicty

-remove causative agent and admin IV steroids and antibiotics

Term
thrombocytopenia
Definition

- SE of ethosuxamide, phenytoin and phenobarbital and other anticonvulsants

-under 20,000 platelets

-echymoses, petechial hemorrhages in skin and MM

-might be due to drug-induced folate deficiency

Term
major side effects of anticonvulsants
Definition

-teratogenic effects

-steven-johnson syndrome

-thrombocytopenia

-hepatic failure

-aplastic anemia and bone marrow suppression

-lupus-like sydrome

Term
less severe side effects of anti-convulsants
Definition

-rashes (urticaria, 'fixed drug eruption,' etc)

-gingival hyperplasia (phenytoin)

-angioedema

-cystic acne (phenytoin)

-hirsutism (phenytoin)

-thickened facial features (phenytoin)

-alopecia (valproate)

Term
Lennox-Gastaut treatments
Definition

rufinamide

topiramate

felbemate

clonazepam

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