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155 Cards in this Set
- Front
- Back
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what is a partial seizure?
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a. Partial seizures: focal in nature because they initiate in localized regions of the cortex;
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what are some common causes/sites of origin in partial seizures?
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often originate in the region of an anatomic abnormality such as a brain tumor, AV malformation, trauma, or stroke.
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what are the three types of partial seizures?
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simple
complex partial with secondarily generalized |
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what is a simple partial seizure?
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i. Simple partial: no loss of consciousness
1. Sensory or motor 2. Last less than one minute |
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what is a complex partial seizure?
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ii. Complex partial: impaired or loss of consciousness
1. Last less than two minutes |
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what is a partial seizure with secondarily generalized
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iii. Partial with secondarily generalized
1. Simple partial or complex partial seizure that progresses to a generalized seizure. 2. Entire episode lasts less than two minutes. |
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what are generalized seizures
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b. Generalized seizures: global neocortical discharges
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what is the usual origin of generalized seizures?
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discharges that synchronize with discharges in the thalamus
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what is the most common cause of generalized seizures?
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congenital
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what are the 4 types of general seizures?
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absense
myoclonic tonic tonic-clonic |
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describe absence generalized seizure(petit-mal)
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i. Absense (petit-mal): abrupt onset of impaired consciousness
1. Lasts less than 30 seconds |
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describe myoclonic generalized seizures
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ii. Myoclonic: shock-like contraction of muscles; may be generalized or localized
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describe tonic generalized seizures?
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The person will quickly lose consciousness, and the skeletal muscles will suddenly tense, often causing the extremities to be pulled towards the body or rigidly pushed away from it, which will cause the person to fall if standing. The tonic phase is usually the shortest part of the seizure, usually lasting only a few seconds. The person may also express vocalizations like a loud moan or scream during the tonic stage, due to air forcefully expelled from the lungs.
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describe the tonic clonic generalized seizure(grandmal)
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tonic phase followed by clonic phase consisting of convulsive spasms and jerks
not preceeded by partial siezure |
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what is a generalized MOA for antiseizure drugs?
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a. The antiseizure drugs work by suppressing repetitive action potentials in epileptic foci in the brain. Different mechanisms are involved in achieving this effect, and some drugs use multiple mechanisms.
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which antisiezure drugs work by inhibition of voltage gated sodium channels
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i. Phenytoin, carbamazepine, and lamotrigine (these are the main ones).
ii. Valproate and Phenobarbital may do so at high doses iii. Others: topiramate, zonisamide |
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which antiseizure drusg work by enhanceing GABA mediated Cl flux:
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benzodiazepines
phenobarbital and other barbiturates vigabatrin tigabine gabapentin valproic acid |
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what is the resulting effects of the GABA acting antisiezure meds
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these drugs all result in increased Cl- flux and increased inhibitory effects of GABA.
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what is the drugs target of benzodiazepines?
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1. The drug target is the specific GABA-A receptor-chloride ion channel macromolecular complex.
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what is the effect of benzodiazepines on the GABA-A receptor complex
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Interaction with the complex increases the frequency of chloride ion channel opening.
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what is target of phenobarbital and other barbiturates in reference to GABA?
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1. Interact with different receptor sites on GABA chloride ion channel
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what is the effect of phenobarbital on the GABA chloride ion channel?
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increase the duration of chloride ion channel opening.
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what is the target and effect of vigabatrin?
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1. Irreversibly inactivates GABA transaminase
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what is the purpose of GABA transaminase?
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an important enzyme in the termination of action of GABA. Effect is to increase duration of GABA signaling.
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what is the effect of Tigabine?
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1. Inhibits the reuptake of GABA transporters in neurons and glia.
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what is the effect of gabapentin?
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1. Structural analogue of GABA, but does not activate the receptors and the mechanism is unclear.
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what is the effect of valproic acid on GABA?
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`Inhibits GABA transaminase at very high concentrations.
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what is the MOA of ethosuximide?
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d. Blockade of thalamic calcium channels
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what is the total effects of valproic acid?
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i. Valproic acid: neuronal membrane hyperpolarization enhancing K+ channel permeability (in addition to its major effect of blocking sodium channels and minor effects of inhibiting GABA and blocking thalamic calcium channels).
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what are the total effects of phenobarbital?
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ii. Phenobarbital: antagonist at some glutamate receptors (in addition to its enhancing effect of GABA signaling).
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what is the effect of topiramate?
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iii. Topiramate: blocks sodium channels, potentiates the action of GABA, and may also block glutamate receptors.
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what is the effect of felbamate?
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iv. Felbamate: blocks glutamate NMDA receptors
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what is MOA of levetiracetam?
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unknown
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what are the drugs of choice for treating simple and complex partial seizures?
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i. Drugs of choice: Carbamazepine, Phenytoin, Valproate
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what are some alternative drugs for treating simple and complex seizures?
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ii. Alternatives:
1. Lamotrigine: usefulness is limited by its toxic potential. 2. Gabapentin: used adjunctively in refractory cases. 3. Topiramate: adjunctive drug. 4. Vigabatrin: back up drug. 5. Levetiracetam, tigabine, and zonisamide |
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what is the drug of choice for treatment of partial with secondary generalized siezures
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i. Drugs of choice: Carbamazepine, Phenytoin, Valproate
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what are the alternative drugs for treatment of partial with secondary generalized siezures
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1. Phenobarbital
2. Primidone: metabolized to Phenobarbital, is an alternative agent in adults and a primary drug in infants. 3. Lamotrigine: usefulness is limited by its toxic potential. 4. Gabapentin: used adjunctively in refractory cases. 5. Topiramate: adjunctive drug. 6. Vigabatrin: back up drug. 7. Levetiracetam, tigabine, and zonisamide |
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what is the drugs of choice for treatment of tonic clonic seizures?
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i. Drugs of choice: Carbamazepine, Phenytoin, Valproate
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what are some alternative treatment of tonic clonic seizures?
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1. Phenobarbital
2. Primidone: metabolized to Phenobarbital, is an alternative agent in adults and a primary drug in infants. 3. Lamotrigine: usefulness is limited by its toxic potential. 4. Topiramate: adjunctive drug. |
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what is the drugs of choice for treating generalized absence seizures
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i. Drugs of choice: Ethosuximide and valproic acid
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why are Ethosuximide and valproic acid the drugs of choice in generalized absence siezures?
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1. These drugs are preferred because they cause minimal sedation.
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when should ethosuximide be used in generalized absence siezures?
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2. Ethosuximide should be used in uncomplicated absence seizures if the patient can tolerate its GI side effects.
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when should valproic acid be used in generalized absence siezures?
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3. Valproic acid should be used in patients with concomitant generalized tonic-clonic or myoclonic seizures.
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what are the alternative drugs for treatment of generalized absence siezures?
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1. Lamotrigine
2. Clonazepam: causes sedation and tolerance 3. Topiramate |
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what is the drug of choice in myoclonic seizures
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i. Drug of choice: Valproic acid
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what are some alternative drug choices in myoclonic seizures?
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1. Clonazepam
2. Levetiracetam, lamotrigine, and zonisamide are back up drugs. 3. Felbamate: adjunct drug a. Hematotoxic and hepatotoxic |
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what is status epilepticus?
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: series of seizures that are usually tonic-clonic, without recovery of consciousness between attacks; is a life-threatening emergency.
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how should status epilecpticus be treated?
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i. For short-term control IV diazepam or lorazepam can be used.
ii. IV phenytoin can be used for prolonged therapy. iii. Phenobarbital can be used especially in children. iv. General anesthesia can be used in very severe status epilepticus in patients who do not respond to other therapies. |
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what is the main MOA of phenytoin?
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a. Phenytoin inhibits depolarization by blocking sodium channels.
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what are drug interactions of phenytoin that increase its free state in the blood without affecting metabolism?
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b. Drug interactions
i. Phenytoin binds extensively to plasma proteins, so drugs that compete for binding increase free (unbound) levels in the plasma transiently. 1. Sulfonamides 2. Valproic acid. |
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how is metabolism of phenytoin enhanced? and by what
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ii. Metabolism of phenytoin is enhanced in the presence of inducers of liver metabolism.
1. Phenobarbital 2. Rifampicin 3. Carbamazepine |
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what inhibits metabolism of phenytoin?
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iii. Metabolism of phenytoin is also inhibited by other drugs.
1. Cimetidine 2. Isoniazid. |
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what are the toxic effects of phenytoin?
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c. Toxic effects
i. Diplopia, nystagmus ii. Ataxia iii. Hirsutism iv. Gingival hyperplasia v. Idiosyncratic reactions like rashes vi. Hematologic complications, anemia vii. Teratogenicity: fetal hydantoin syndrome |
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what are the uses of phenytoin and contraindications?
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d. Use: Effective in partial and generalized tonic-clonic seizures. May exacerbate absence seizures.
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what is the main MOA for carbamazepine?
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a. Carbamazepine inhibits depolarization by blocking sodium channels. It may also potentiate GABA-A post synaptic receptors (inhibitory).
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what are the drug interactions for carbamazepine?
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b. Drug interactions
i. Carbamazepine induces the synthesis of liver drug-metabolizing enzymes, which increased the metabolism of carbamazepine itself. This may also increase the clearance of many other anticonvulsant drugs. |
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what inhibits the metabolism of carbamazepine?
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ii. Metabolism is inhibited by other drugs:
1. Propoxyphene 2. Valproic acid |
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what are the toxic effects of carbamazepine?
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c. Toxic effects
i. Diplopia ii. Ataxia iii. Rashes iv. Idiosyncratic blood dyscrasias – mild leucopenia is common but usually not a problem. The most serious side effect is aplastic anemia, which is rare but potentially fatal. v. Teratogenicity |
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what is the main use for carbamazepine?
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d. Use: drug of choice for partial seizures; also effective for tonic-clonic seizures and for mood stabilization in bipolar disease.
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what is the main MOA for valproic acid?
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a. Its main mechanism involves activation of potassium channels and inhibition of sodium channels. It also increases presynaptic GABA and inhibits voltage-gated calcium channels in the thalamus.
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what are the drug interactions of valproic acid?
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b. Drug interactions
i. Valproic acid is highly protein bound and may displace other drugs. ii. Inhibits the metabolism of phenytoin, Phenobarbital, and lamotrigine. |
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what are the toxic effects of valproic acid?
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c. Toxic effects
i. Hepatotoxicity, especially in children < 2 y/o 1. This is due to the formation of a toxic metabolite during hepatic biotransformation. 2. Liver function tests should be performed. ii. Nausea and epigastric distress iii. Teratogenicity: neural tube defects |
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what are the uses of valproic acid?
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d. Usu: Effective in generalized seizures of all types, especially myoclonic. Also effective as a mood stabilizer and in migraine prophylaxis.
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what is the MOA of lamotrigine?
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a. Inhibits Na channel, also voltage-gated calcium channels in the thalamus.
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what are the toxic effects of lamotrigine?
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b. Toxic effects
i. Rashes are common ii. Stevens-Johnson syndrome reason for contraindication in children. |
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what are the uses of lamotrigine?
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c. Use: general and partial seizures
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what is the MOA of topiramate?
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a. Inhibits sodium channels and potentiates GABA activity. May also block glutamate receptors.
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what is the toxic effects of topiramate?
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b. Toxic effects
i. Neurologic: fatigue, decreased mental acuity, anxiety, confusion, paresthesias ii. Eye: glaucoma |
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what is the MOA of zonisamide?
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a. Inhibition of sodium and calcium channels.
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what are the tox effects of zonisamide?
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a. Somnolence and fatigue are common with use. Depression and psychosis are less common but have been reported.
i. Skin rashes are common. May be severe and life-threatening. ii. Renal calculi in 4%. |
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what are the uses of zonisamide?
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d. Use: Adjunct in refractory partial seizures.
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what is the MOA of primidone?
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a. Primidone is metabolized to Phenobarbital.
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what is the MOA of phenobarbital
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b. Mechanism includes enhancement of GABA mediated chloride flux by binding to the chloride channel and increasing the duration of chloride ion channel opening. Phenobarbital is also an antagonist at some glutamate receptors (blocks excitatory effects of glutamate. '
c. Has prominent sedative activity probably main antiseizure mech. |
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what is the toxic effects of phenobarbital
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d. Toxic effects:
i. Sedation ii. Tolerance dependence |
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what is the use of phenobarbital
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e. Use: often used as a first-line drug in most kinds of seizures; highly effective against partial and generalized.
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what is the MOA of tigabine?
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a. Inhibits the reuptake of GABA transporters in neurons and glia.
b. Sedation may occur with dose escalation. Cases of psychosis have been reported. |
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what are toxic effects of tigabine?
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c. Toxic effects
i. Is a generally well tolerated drug. ii. Major side effect is a tremor. iii. Anxiety and depression may occur. iv. Psychosis requires withdrawal of the drug. |
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what is the use of tigabine?
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d. Use: Adjunct in partial seizures.
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what is the MOA of gabapentin?
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a. Is a structural analogue of GABA and enhances the concentration of presynaptic GABA, but the exact mechanism is unclear. It does not activate the receptors itself.
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what is the elimination of gabapentin?
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b. Is eliminated by the kidneys (not the liver like most of the antiseizure drugs).
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what is the use of gabapentin?
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d. Use: partial seizures; also neuropathic pain, especially postherpetic neuralgia
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what is the MOA of ethosuximide?
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a. Inhibits voltage-gated calcium channels in the thalamus. This is the only drug that is thought to act exclusively by this mechanism.
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what is the drug interactions of ethosuximide
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b. Drug interactions
i. Valproic acid increases ethosuximide levels |
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what are the toxic effect of ethosuximide
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c. Toxic effects
i. Well tolerated drug ii. Gastric and hematological abnormalities iii. Skin rashes |
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what is the use of ethosuximide
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d. Use: first-line for absence seizures.
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what is the MOA of felbamate?
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a. Blocks glutamate NMDA receptors.
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what are the toxic effects of felbamate?
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b. Toxic effects
i. Aplastic anemia ii. Hepatitis, acute hepatic failure |
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what is the use of felbamate?
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c. Use: third line drug for refractory partial seizures
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what are the toxic effects of levetriacetam?
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b. Toxic effects:
i. Sedation and dizziness |
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what is the use of levetiracetam?
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c. Use: adjunct for partial seizures.
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what are the drugs that are always used as backup drugs?
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felebamate
gabapentin lamotrigine levetiracetam tiagabine topiramate vigabatrin zonisamide |
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what are expamples of the benzodiazepine subclass of drugs?
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diazepam
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what is valproic acid prototype drug for what subclass of drugs
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carboxylic acids
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phenytoin is a prototype for what subclass of drugs?
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hydantoins
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ethosuximide is a prototype for what subclass of drugs?
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succinimides
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carbamazepine is a prototype for what subclass of drugs
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tricyclics
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what is epilepsy?
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group of chronic syndromes that involve the recurrence of seizures
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what are the classes withing the antiseizure drugs?
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anticonvulsants
antiepileptics |
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what is the duration of treatment for antiseizure meds?
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long periods of time
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what are some common pharmacokinetic qualites of antiseizure drugs?
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good oral absorption
good bioavailability most drugs metabolized via hepatic enzymes |
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what are some drugs that will inhibtit antiseizure drug metabolism in general?
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H2 blockers like amentadine
proton pump inhibitors |
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what are some drugs that will displace plasma binding sites of antiseizure drugs causing their plasma level to rise to toxic levels?
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albumin? not sure if that is the drug or where its displaced from
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what is a new drug that is replacing phenytoin?
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diphenylhydantoin
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what is a key characteristic of phenytoin metabolism?
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it is flow dependent based on first pass metabolism through the liver.
so elderly people and others with low blood flow to the liver will metabolize phenytoin slower. |
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what is an advantage of phenytoin over other antiseizures
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non sedating
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what is a vital fact about phenytoin metabolism rate order?
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elimination shifts from 1st order to 0 order kinetics at moderate to high doses(shifts from concentration dependent to concentration independent rate bc of saturation of enzymes)
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what is important to note about phenytoin behavior in the blood?
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extensivly binds to plasma proteins(97-98%) so when bound its not actively producing affects
ALSO if you give a drug that displaces phenytoin from the plasma protiens a normal dose you have given for a long time will become highly toxic. |
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where is GABA transaminase found?
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presynaptic nerve terminal
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what is important about phenobarbital elimination in the kidney?
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pH dependent
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which drug enhances GABA efflux?
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benzodiazepine
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what drug decreases GABA breakdown?
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vigabatrin
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what drug inhibits GABA reuptake
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tiagabine
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what antiseizure meds are especially high protein binding?
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phenyltoin
diazapam valproate tiagabine |
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what antiseizure meds are not metabolised and renal excretion is only route of elimination?
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Vigabatrin
gabapentin |
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what antiseizure meds undergo renal excretion either alone
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GABApentin
pregabelin levetiracetam topiramate |
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what can cause irreversible peripheral visual field defects
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vigabatrin
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which drug when used during pregnancy can lead to spina bifida?
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lamotrigine
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what drug can cause fetal fetal hydantoin syndrome
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phenyltoin
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what drug can cause hypospadius defect if taken during pregnancy
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topranimide
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what can cause aplastic anemia and severe hepatitis?
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felebamate
And carbamazepine |
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what is epilepsy?
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gropu of chronic syndromes involving reccurent siezures
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what is a general rule for most antiseizure meds drug reactions with rifampicin?
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inadequate levels of antiseizure meds due to rifamicin induceing hepatic drug metabolizing enzymes which are the major route of elimination for MOST not all seizure meds
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what is a key benifit of phenytoin?
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non-sedating
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how long does it take to reach stead state for low blood concentration of phenytoin?
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5-7days
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how long does it take to reach steady state for high blood conc. of phenytoin?
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4-6 weeks
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what is a watersoluble prodrug form of phenytoin that can be used IV?
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fosphenytoin
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why cant phenytoin be given easily IV?
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not water soluble must add to ethylene glycol with saline to be given IV. ethylene glycol can be cardio toxic
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what drug can cause gingival hyperlasia early?
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phenyltoin
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what is a benifit of carbamazepine over phenytoin?
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carbamazempine does not bind protein as much
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what is a toxic effect seen in carbamazepine but not in phenytoin?
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rashes and blood cell count changes
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what drug has best control for tonic clonic seizures?
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valproic acid is better than ethosuximide
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what is a drug that is known for its effect on the liver in children?
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valproic acid causes hepatotoxicity in kids under 2 y/o
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what is the MOA of valproic acid hepatotoxicity in young children?
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formation of toxic metabolite in liver metabolism, seen in kids bc adults have more liver mass and can handle low doses with out issues
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what drug is unique with its toxic effects in the prodcution of gastic upset with loss of apetite and weight.
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ethosuximide
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what is best drug for treating infant seizures?
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phenobarbitol/barbituates in general
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what is the most effective benzodiazepine?
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lorazapam
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what drug is not metabolized with both hepatic and renal elimination as the means of getting rid of it?
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topiramate
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are absence seizures usually a life long issue?
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no usually start in childhood and cease by the age of 20
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what are the drugs of choices for terminating attacks of status epilepticus short term control
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IV diazepam or Lorazepam
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what is the long term treatment for status epilepticus?
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IV phenytoin
remember though IV phenytoin can't be given alone must be given with propylene glycol which is cardio toxic for this reason FOSPHENYTOIN is probably a better drug for long term care of status epilepticus via IV |
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what is the most common drugs used for the most severe cases of epilepsy?
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phenobarbitol just to sedated them in general
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what drugs display a crushingoid side effect?
crushingoid-ommon symptoms are thinning of the skin, weakness, weight gain, bruising, hypertension, diabetes, thin weak bones (osteoporosis), facial puffiness and, in women, cessation of menstrual periods. |
corticotropin and coticosteroids
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what are corticotropin and corticosteroids used for mainly?
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infantile spasm
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what drug is the drugs of choice in treatment of trigeminal neuralgia?
**** KNOW THIS ITS ON THE TEST |
gabapentin
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what antiseizure med is also used to treat migraine?
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phenytoin
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what are some antisiezure meds used in treatment of bipolar?
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valproic acid, carbamazepine, phenytoin and gabapentin
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what is fetal hydantoin syndrome?
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About one third of children whose mothers are taking this drug during pregnancy typically have children who have intrauterine growth restriction with microcephaly and develop minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects). A smaller population will have growth problems and developmental delay, or mental retardation. Rare side effects include methemoglobinemia.
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what is the drug used to treat benzodiazepine overdose?
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flumazenil
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what is associtated with life threatening steven johnson syndrome and skin rashes?
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lamotrigine
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what is steven johnson syndrome?
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necrotic skin disease
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what are the drugs that can cause rashes?
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ethosuximide
zonisamide carbamazepine phenyltoin lamotrigine |
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what are the general adverse effects of barbiturates and benzodiazepines?
***KNOW THIS |
sedation, tolerance and dependence
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what are the general adverse effects of carbamazepines?
***KNOW THIS |
diplopia, ataxia, anemia
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what are the general adverse effects of the phenytoin drugs?
***KNOW THIS |
diplopia, gingival hyperplasia, ataxia, teratogenic
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what are the general adverse efffects of valproic acid
***KNOW THIS |
GI symptoms, hepatotoxic(especially in less than 2)
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