Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
91 Cards in this Set
- Front
- Back
|
•Brief abrupt loss of consciousness
•Early onset (3-5 years of age) •Staring / rapid eye blinking (3-5 second duration) •Distinct EEG (3 /second spike and wave discharge) |
Absence seizures
|
|
|
•Short episodes of muscle contractions
•More common on awakening •Brief jerks of limbs |
Myoclonic Seizures
|
|
|
•Loss of muscle tone
•Relatively short lived (10-15 s) •Can result in serious injuries following a fall |
Atonic Seizures
|
|
|
•Common in young children in conjunction with high fever
•Generalized tonic-clonic |
Febrile Seizures
|
|
|
I.V. Benzodiazepine (lorazepam/ diazepam /midazolam)
|
primary treatment of status epilepticus
|
|
|
What is the IV regimen for refractory status epilepticus?
|
Phenobarbital / Pentobarbital / Midazolam/ Propofol
May also need to supply respiratory support |
|
|
–
elemental symptomatology – Motor seizures – Sensory seizures |
Simple partial seizures
|
|
|
–
with complex symptomatology – Automatisms – Visceral and autonomic, including olfactory and gustatory –Psychial(illusory, hallucinatory) –Affective symptoms |
Complex Partial seizures
|
|
|
–
Present in: •Convulsive / Partial – Absent in: •Absence, Myoclonic |
Aura
|
|
|
•Absent in absence
|
Post ictus
|
|
|
Inhibition of seizure spread
– Blockade of Ca2+ influx – Enhancement of Cl-mediated inhibitory post synaptic potentials (IPSPs) |
Phenytoin
|
|
|
Suppression of epileptic focus
– Enhanced affinity for inactivated Na+channels at more depolarized membrane potentials – Enhancement of the inhibitory surround via stimulation of Cl-mediated IPSPs |
Phenytoin
|
|
|
Uses:
– Initial drug of choice in all types of epilepsy except absence epilepsy and atonicseizures – Highly effective in the treatment of generalized tonic-clonicseizures, partial and status epilepticus |
Phenytoin
|
|
|
Pharmacokinetics/Chemistry:
– Oral administration (I.V. for Status epilepticus) – Intramuscular injection results in crystallization and possible muscle necrosis at injection site. – Highly protein bound in plasma (~90%) – Phenytoinmetabolism is rate limited and the enzyme system involved is saturablewithin the therapeutic range of plasma concentrations. |
Phenytoin
|
|
|
–
Neurotoxicity is dose related – Nystagmus, ataxia, vertigo, diplopia, slurred speech Hyperglycemia, osteomalacia, lymphadenopathy, – rashes (Stevens-Johnson syndrome (erythemamultiformebullosum)), – hematological reactions (leukopenia, megaloblasticanemia, thrombocytopenia, agranulocytosis, aplasticanemia). • These allergic reactions require stopping treatment |
Phenytoin
|
|
|
•
Fetal abnormalities • After IV .............→Cardiovascular collapse – Only seen with too large a bolus dose |
phenytoin
|
|
|
Metabolism of ............can be enhanced (Carbamazepine)/decreased via microsomal enzymes.
|
phenytoin
|
|
|
.............. induces CYP3A4 / CYP2C / UDP-glucoronsyltransferase(UGT)
– May reduce levels of Digoxin, steroids, vitamin K, oral contraceptives. |
Phenytoin
|
|
|
•
Patients should be treated with vitamin K supplements to prevent hypoprothrombinemiaand bleeding. |
phenytoin
|
|
|
Highly water soluble
• Can be administered IM • Side effect profile improved compared to parenteral phenytoin |
Fosphenytoin
|
|
|
Mechanism of Action:
– Unknown, but seems similar to phenytoin(decrease Na+conductance) |
Carbamazepine
|
|
|
Uses:
2nd Line – Generalized tonic-clonicseizures – Complex partial seizures – Trigeminal neuralgia – Ineffective in absence seizures – Not well tolerated in the elderly |
Carbamazapine
|
|
|
Pharmacokinetics/Chemistry:
– Almost completely metabolized to the 10,11-epoxide, which is pharmacologically active – Autoinductionof metabolism • CYP1A2 / CYP2C / CYP3A / UGT • induces its own metabolism, with the rate of metabolism increasing in the first 4-6 weeks of therapy – Naïve patient t1/2= 30 h – After a few weeks t1/2= 0-20 h • Process stabilizes at about 1 month |
Carbamazepine
|
|
|
Side Effects:
– G.I. upset – Vertigo, diplopia, blurred vision, ataxia – Hematological disorders –aplasticanemia (rare), thrombocytopenia, hyponatremia, agranulocytosis, leucopenia – Hepatotoxicity • Routine liver panels |
Carbamazepine
|
|
|
Mechanism of action:
– Enhances the GABA-mediated chloride flux that causes membrane hyperpolarization. – Increases threshold for firing and inhibits spread of activity from focus |
Phenobarbital
|
|
|
Uses:
– Generalized tonic-clonicepilepsy – Partial seizures – Prophylaxis or treatment of febrile convulsions – Should only be used in drug refractory patients |
Phenobarbital
|
|
|
Pharmacokinetics:
– Induces hepatic enzymes • Reduces levels of oral contraceptives |
Phenobarbital
|
|
|
Side effects:
– Sedation –tolerance develops – Interference with cognitive function – In children may cause motor hyperactivity, irritability, decreased attention and mental slowing – Concerns about addiction – Potential for withdrawal seizures – Rashes in 1-2% -scarlatiniformor morbilliform. Symptomatic of allergic reaction. – Ataxia, nystagmusat excessive doses |
Phenobarbital
|
|
|
Drug Interactions:
– Additive with other CNS depressants – Valproicacid increases Phenobarbital blood levels – As a P450 inducer can increase levels of many drugs |
Phenobarbital
|
|
|
Mechanism of Action
– Blockade of sodium channels and preventing membrane depolarization – May potentiate GABA via formation of Phenobarbital |
Primidone
|
|
|
Uses:
– Complex partial seizures –more effective than Phenobarbital – Generalized tonic-clonicseizures – Simple Partial seizures • Frequently combined with phenytoin |
Primidone
|
|
|
Pharmacokinetics/Chemistry:
– Metabolized in liver to phenobarbitaland phenylethylmalonamide(PEMA) – Parent and metabolites have anticonvulsant activity |
Primidone
|
|
|
Side Effects:
– Similar to phenobarbital |
Primidone
|
|
|
Mechanism of Action:
– Interacts with GABAergicneurons-potentiating inhibitory effects • Inhibits GABA metabolism – Induces blockage of both Na+and K+channels. – Inhibits T-type calcium channels • Gives a BROAD spectrum of action |
Valproic Acid/Divalproex
|
|
|
Mechanism of Action:
– Interacts with GABAergicneurons-potentiating inhibitory effects • Inhibits GABA metabolism – Induces blockage of both Na+and K+channels. – Inhibits T-type calcium channels • Gives a BROAD spectrum of action |
Valproic Acid/Divalproex
|
|
|
Uses:
– Absence seizures refractory to ethosuximide – Myoclonicseizures – Reflex epilepsies (especially photosensitive) – Generalized tonic clonicseizures-used as combination therapy – Complex partial seizures-used as combination therapy – Bipolar disorder – Potential for birth defects, not recommended for women of child bearing age |
Valproic acid/Divalproex
|
|
|
Pharmacokinetics/Chemistry:
– Low molecular weight fatty acid – Well absorbed from gut and is metabolized to active metabolites and inactive conjugates before excretion |
Valproic Acid/Divalproex
|
|
|
Side Effects:
– Alopecia (5%) – Transient GI effects (16%); nausea and vomiting – CNS-mild behavioral effects, ataxia, tremor, not a CNS depressant – Hepatic failure (rare); elevated liver enzymes (dose dependent). Patients under 2 years of age are at the greatest risk of liver failure. – Possible decrease in platelet and clotting function, • avoid in patients with bleeding disorders |
Valproic Acid/Divalproex
|
|
|
Drug Interactions:
– Inhibits P450s – Increases lamotrigine, phenobarbital and primidone levels by increasing t1/2of elimination – Displaces phenytoin form plasma proteins – Decrease elimintaion of phenytoin |
Valproic Acid/Divalproex
|
|
|
Mechanism of Action:
– Blocks t-type Ca2+channels of thalamic interneurons that appears to interrupt the neuronal hypersynchrony of thalmocortical pathways seen in absence seizures |
Ethosuximide
|
|
|
Uses:
– Absence seizures |
Ethosuximide
|
|
|
Side Effects:
– GI irritation: nausea, vomiting, anorexia – CNS depression –drowsiness, lethargy, euphoria, dizziness, headache, hiccough – Rashes –urticaria, Stevens-Johnson syndrome – Blood dyscrasia have occurred |
Ethosuximide
|
|
|
Mechanism of Action:
– Agonist action on benzodiazepine binding site of GABA A receptor complex – Use and voltage-dependent blockage of Na+ channels – Blocks neuronal Ca2+ channels at sedating doses |
Lorazepam
|
|
|
Uses:
– IV agent in status epilepticus – Adjunct therapy in atonicand myoclonic • Clonazepam |
Lorazepam
|
|
|
Fewer side effects
• Little or no need for serum monitoring • 1-2x/day dosing for some • Fewer drug interactions |
Second Generation Antiepileptics
|
|
|
Adults, kids
• Decreased side effects: gingivialhyperplasia • Adjunct treatment • Similar to phenytoinwith shorter half life |
Ethotoin
|
|
|
Uses:
– Tonic-clonic – Partial seizures |
Ethotoin
|
|
|
Only in refractory patients
• Decreased gingival hyperplasia, hirsuitism • Greater risk for hepatotoxicity, blood disorders |
Mephenytoin
|
|
|
Mechanisms of Action:
– Blocks glycine activation of NMDA receptors and may thereby inhibit processes responsible for the initiation of seizures – Inhibits Ca2+channels; may have some effect on Na+ channels |
Felbamate
|
|
|
Uses: Use has declined
– limited to the treatment of Partial Seizures that are refractory to other drugs. – Lennox-Gastaut syndrome in children. • Multiple seizure types, particularly tonic and atonic seizures, but also including absence seizures ("typical" petit mal) and myoclonic seizures ("atypical" petit mal) as well as nonconvulsive status epilepticus |
Felbamate
|
|
|
Side Effects
– Gastrointestinal: anorexia, vomiting, nausea – CNS: insomnia, headache – Allergic reactions: hematological and dermatological reactions – Acute liver failure – AplasticAnemia |
Felbamate
|
|
|
Drug Interactions
– May alter concentrations of other anticonvulsants – Inhibits CYP2C19, induces CYP3A4 |
Felbamate
|
|
|
Mechanisms of Action
– Unknown: – Chemically related to GABA, but does not work through the GABA system – Increases release of GABA from central neurons – No direct effect on GABA receptors |
Gabapentin
|
|
|
Uses
– Partial seizures –adjunctive to other anticonvulsants – Adjunctive therapy for partial seizures-Pediatric patients (3-12 y.o.) – Well tolerated in elderly – Postherpetic neuralgia – Add-on in refractory patients = improvement |
Gabapentin
|
|
|
As monotherapy: as good as carbamazepine
|
Gabapentin
|
|
|
As monotherapy: as good as carbamazepine
|
Gabapentin
|
|
|
Side Effects
– CNS: ataxia, dizziness, drowsiness, nystagmus, tremor – Weight gain – Dyspepsia, constipation |
Gabapentin
|
|
|
Drug Interactions
– Does not alter serum concentration of other anticonvulsants – Bioavailability is reduced with concurrent use of antacids |
Gabapentin
|
|
|
Mechanisms of Action
– Inhibits voltage-sensitive Na+channels of presynaptic membrane, similar to phenytoin and carbamazepine – Inhibits glutamate and aspartate release – May inhibit Ca2+channels |
Lamotrigine
|
|
|
Uses
– Adjunct in treatment of partial seizures – Generalized tonic-clonic – Atonic – Absence seizures – Add-on therapy for Lennox-Gastaut syndrome (adult/pediatrics) – Well tolerated in elderly |
Lamotrigine
|
|
|
Equivalent to CBZ, phenytoin in treatment of partial and generalized tonic/clonic seizures
|
Lamotrigine
|
|
|
Side Effects
– Dizziness, headache, diplopia, ataxia, somnolence – Skin rash (10%)-severe (Stevens-Johnson) and potentially life threatening; – Higher risk in children-use not indicated if less than 16 years old. |
Lamotrigine
|
|
|
Drug Interactions
– Metabolism induced by phenytoin, carbamazepine; inhibited by valproic acid. – Serum levels of valproic acid are decreased by lamotrigine. – Lamotrigine can induce its own metabolism |
Lamotrigine
|
|
|
Mechanisms of action
– Inhibits voltage-dependent sodium channels of presynaptic membrane – Potentiates the action of GABA by binding to a novel modulatory site on the GABA A receptor – Blocks excitatory amino acid receptors (kainate/AMPA |
Topamirate
|
|
|
Uses
– Adjunctive therapy in partial seizures – Adjunctive therapy in primary generalized seizures – Lennox-Gastaut syndrome in patients > 2 years of age |
Topamirate
|
|
|
GOOD MONOTHERAPY in PATIENTS WITH REFRACTORY PARTIAL AND GENERALIZED TONIC/CLONIC SEIZURES
|
Topamirate
|
|
|
Mechanism of Action
– GABA reuptake inhibitor |
Tiagabine
|
|
|
Uses
– Adjunctive therapy in partial seizures (> 12 years of age) |
Tiagabine
|
|
|
Uses
– Adjunctive therapy in partial seizures (> 12 years of age) |
Tiagabine
|
|
|
Side Effects
– CNS depression-fatigue, dizziness, ataxia, decreased cognition – GI (abdominal pain, nausea, vomiting, diarrhea) – Stevens Johnson rash |
Tiagabine
|
|
|
Mechanism of Action
– Unknown |
Levetiracetam
|
|
|
Uses
– Adjunct therapy for partial seizures – Useful in patients with medical illnesses involving the liver and on hepatically metabolized drugs with potentially serious side effects (e.g., coumarin, cyclophosphamide) |
Levetiracetam
|
|
|
Side Effects
– CNS: somnolence, dizziness, headache |
Levetiracetam
|
|
|
Mechanism of Action
– Blocks voltage dependent Na+ channels resulting in stabilization of hyperexcited neural membranes |
Oxcarbazepine
|
|
|
Uses
– Monotherapy or adjunct therapy for partial seizures – Effective for medication resistant epilepsy |
Oxcarbazepine
|
|
|
Pharmacokinetics/Chemistry
– Metabolized to active 10-hydroxycarbamazepine metabolite – Does not undergo autoinduction |
Oxycarbamazepine
|
|
|
Side effects:
– CNS: Headache, dizziness, somnolence, ataxia, nystagmus – GI: nausea, vomiting, abdominal pain |
Oxycarbazepine
|
|
|
Mechanism of Action
– Modulates calcium and glutamate flux – Structural similarity to gabapentin |
Pregabalin
|
|
|
Uses
– Adjunctive treatment of partial onset seizures – Neuropathic pain – Diabetic peripheral neuropathy |
Pregabalin
|
|
|
Mechanism of Action
– May block Na+ channels and reduce T-type Ca2+ currents resulting in stabilization of neuronal membranes |
Zonisamide
|
|
|
Uses:
– Adjunct therapy for partial seizures (patients 16 y.o. and older) |
Zonisamide
|
|
|
Side effects:
– CNS: dizziness, somnolence, headache, ataxia – Anorexia; appetite loss – Skin reactions –Stevens Johnson syndrome – Fulminant hepatic necrosis – Kidney stones – Agranulocytosis, aplastic anemia – Cognitive side effects: psychomotor slowing, difficulty with concentration, psychosis, mania, depression |
zonisamide
|
|
|
Mechanism of Action
– increase GABA by inhibition of GABA Transaminase |
Vigabatrin
|
|
|
Uses:
– Partial Seizures – Refractory patients |
Vigabatrin
|
|
|
Uses:
– Partial Seizures – Refractory patients |
Zonisamide
|
|
|
How do anticonvulsants alter metabolism of oral contraceptives?
|
The effective levels of contraceptives are altered by anticonvulsants.
– Hepatic metabolism – Plasma protein binding |
|
|
How should anti convulsants be handled prior to preganancy?
|
Switch from barbiturates and phenytoin and stabilize on new drug
|
|
|
What is the danger of phenytoin in pregnancy?
|
“Fetal HydantoinSyndrome”: Characteristics: cleft lip, cleft palate, congenital heart disease, slowed growth, mental deficiency
|
|
|
What is the basic strategy with anti convulsants in pregnancy?
|
More frequent lab values
• Optimal therapy: Monotherapyat lowest possible dose to control seizures • Do not completely remove anticonvulsant • Do not switch anticonvulsant if pregnancy was unplanned |
|
|
What is important in the last trimester?
|
To detect alterations in metabolism—especially important during last trimester when increased drug clearance may require dosage adjustment
|
|
|
Uses
– Partial onset seizures – Refractory patients for multiple drugs – Depression |
Vagal Nerve Stim.
|
