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100 Cards in this Set
- Front
- Back
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Convulsion def
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involuntary contraction or series of contractions by voluntary muscles
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Seizure def
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excessive discharge of nerurons and is characterized by changes in electrical activity measured by EEG
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Epilepsy def
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periordic recurrence of seizures with and w/o convulsion
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First 5 etiologies of Epilepsy
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1)genetic predisposition
2)mental retardation/palsy 3)some pediatric neurologic conditions associated w/ seizure may influence/determine appearance of epileptic disorder later in life 4)Trauma to head (including stroke, infexn, tumor) 5)sleep deprivation |
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Second 6 etiologies of Epilepsy
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6)Hormones from menses, puberty, pregnancy
7)sensory stimuli 8)emotional stress 9)hyperventilation (absence seizures) 10)withdrawal from CNS meds, alcohol, abused drugs 11)toxic []s of antiepileptic meds |
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2 types of Generalized seizures and desc (3)
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1)Generalized Tonic-Clonic seizures
2)Absence seizures 1)no detectable focal point of origin 2)may originate from single/several foci 3)NO WARNING |
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Generalized Tonic-Clonic Seizure
a)characteristics (3) b)tonic phase? c)clonic phase? d)therapy (5) |
a1)LOSS OF CONSCIOUSNESS AND PT FALLS TO GROUND
a2)POSTICTAL, regain conscious slowly and remains confused/lethargic for a while a3)lasts 2-5min b)generalized bilateral contraction c)generalized bilateral repetitious rhythmic jerking, incontinent of urine/stool d1)VPA d2)CBZ d3)dilantin d4)primidone d5)phenobarbital |
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Absence Seizures
a)characteristics (3) b)TYPICAL TYPE (4) c)ATYPICAL TYPE (3) d)tx (2) |
a1)ALMOST EXCLUSIVELY IN KIDS
a2)ABRUPT LASPE IN MENTAL FXN LAST ONLY A FEW SEC a3)staring/smacking of lips b1)sudden onset b2)3cycles/sec b3)spike and wave EEG b4)disappears in adulthood c1)onset/cessation may NOT be abrupt c2)EEG 2 to 2.5 cycles/sec (spike and wave) c3)do NOT necessarily disappear in adult hood d1)ethosuccamide d2)VPA |
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3 types Partial seizures and desc (2)
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1)simple partial seizures
2)complex partial seizures 3)secondarily generalized 1)localized focus of abnormal neural activity 2)characteristics depend on location of foci and ability of abnormal impulses to spread |
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Simple partial seizures
a)characteristics (2) b)symptoms (4) c)tx (3) |
a1)focal, motor, sensory partial seizures
a2)characteristics depend on location of foci b1)PT CONSCIOUS and able to respond to surroundings b2)last several sec to min b3)NOT CONFUSED after seizure b4)affected limb may be weak or paralyzed (Todd's paralysis) c1)CBZ c2)phenytoin c3)phenobarbital |
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Complex partial seizures
a)characterictics (2) b)examples of activity (4) c)symptoms (2) d)tx (3) |
a1)psychomotor, temporal lobe seizures
a2)localized focus but often affects many different systems b1)walking b2)removing clothes b3)moving items on desk b4)lip smacking/chewing c1)IMPAIRED CONSCIOUSNESS c2)PT DISORIENTED AND CONFUSED AFTER SEIZURE (postictal) d1)CBZ d2)phenytoin d3)phenobarbital |
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Secondary Generalized seizure
a)characteristics b)diff b/w GTCS and partial seizures that have secondary generalized c)tx |
a1)partial seizures can spread and become tonic-clonic seizures
b1)IF PRECEDED BY AURA (pt can predict it or feel it coming) IT IS PARTIAL c)drugs have limited ability to control this disorder |
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Hyperexcitability?
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unstable cell membrance or surrounding supportive cells in the gray matter of cortical/subcortical area of the brain develop intrinsic burst discharges
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Hypersynchronicity?
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excitability spreads by paroxysmal discharges occurring synchronously in a large population of cortical neurons
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Seizure activity is 3 things
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1)hyperexcitability
2)hypersynchronicity 3)failure of inhibitory activty |
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NT's involved in seizures (4)
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1)major excitatory is glutamate and asparatate
2)major inhibitory is GABA and dopamine |
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Ions involved in seizures (2)
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1)neuronal hyperexcitability (neuronal firing--Na)
2)neuronal hypersynchronicity (pacemaker potentials--Ca) |
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Na channel drugs act how? and ex of some (6)
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Prolong the inactivation of Na channels reducing the ability of neurons to fire @ high frequencies
1)tegretol 2)phenytoin 3)valproate 4)lamictal 5)zonisamide 6)topamax |
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Ca channel drugs act how and ex of some (4)
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inhibit flow of Ca thru T-type channels = reduces the pacemaker current the underlies the thalamic rhythm in spikes/waves seen in generalized and absence seizures
1)ethosuccimide 2)valproate 3)trimetadione 4)zonisamide |
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Enhance GABA mediated inhibition drugs act how? and ex of some/submechanism (5)
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GABA(a) receptors are responsible for fast synaptic inhibition. Activation of GABA(a) receptors opens a Cl channel causing hyperpolarization
1)NEURONTIN substitutes for GABA 2)VIGABATRIN irreversibly inhibits GABA aminotransferase (which normally metabolizes GABA) 3)PHENOBARBITAL binds barbituate site of GABA(a) receptor extending open time of Cl channel 4)BZD's bind bzd site of GABA(a) receptor opening Cl channel more often 5)TIAGABINE blocks GABA reuptake |
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Drugs that decr glutatmate-mediated excitation (2 w/ submechanism)
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1)TOPAMAX antagonize AMPA and Kainate to do so
2)FELBAMATE antagonize NMDA to do so |
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AMPA receptor channels are responsible for... (3)
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1)for fast excitatory neurotransmission by Na-K channel and coexist w/ NMDA receptors in all synapses
2)opening AMPA channel releases the Mg block present in the resting stage 3)so blocking it keeps this Mg block and thus in resting stage |
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NMDA receptor channels
a)unique why b)fxn (2) |
1)unique among glutatmate receptors b/c of their voltage dependence and high permeability to Ca
2)they open to Ca entry and provide the prolonged phase of the excitatory neurotransmission 3)so blocking them would prevent this |
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Antiepileptic w/ UNKNOWN mechanism
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Levetiracetma (KEPPRA)
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Non-pharma tx of epilepsy (3)
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1)temporal lobectomy (remove just one of em)
2)Corpus colosotomies and hemispherectomies (BUT HIGHER MORBIDITY AND MORTALITY) 3)Vagal Nerve stimulation |
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Dx of seizure involves... (5)
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1)hx
2)PE 3)EEG 4)scans (CT, MRI, PET, SPECT) 5)video/EEG monitoring |
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EEG?
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graphic representation of alternating electrical potentials on scalp surface
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2 peaks in incidence/prevalence of Epilepsy
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1)children under 16
2)over 64yo |
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Simple partial seizures have 4 types of symptoms and 2 other things
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1)motor (foci in motor cortex)
2)somatosensory or special sensory (foci in sensory cortex) 3)autonomic symptoms (like sweating) 4)psychic symptoms (doom, euphoria, pleasure) 1)NO LOSS OF CONSCIOUSNESS**** 2)IN JUST 1 PART OF THE BRAIN*** |
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2 types of complex partial seizures
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1)begin as simple partial seizure and progress to impairment of consciousness
2)impairment of consciousness right off |
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Partial seizures EVOLVING TO SECONDARY GENERALIZED SEIZURES (3 ways)***** and meaning
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1)simple parital seizures evolving to generalized seizures
2)complex partial seizures evolving to generalized seizures 3)simple parital seizures evolving to complex partial seizure to generalized seizures 1)seizure starts in one part of brain and spreads |
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Generalized seizure types (6)
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1)absence (or atypical absence)
2)myoclonic 3)clonic 4)tonic 5)tonic-clonic 6)atonic (astatic) |
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Status epilepticus (2)
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1)seizure starts and does NOT stop for about 30min
2)50% mortality rate |
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Seizure def from Oommen
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Subjective or objective behavioral manifestation of an abnormal and excessive electrical discharge from the brain
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Normal values OUTSIDE CELL MEMBRANE
a)Na b)K c)Ca d)Mg e)Cl f)A- (anions) g)Net+ |
a)145
b)4 c)0 d)0 e)114 f)0 g)35 |
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Normal values INSIDE CELL MEMBRANE
a)Na b)K c)Ca d)Mg e)Cl f)A- (anions) g)Net+ |
a)12
b)155 c)3 d)26 e)2 f)123 g)16 |
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Paroxysmal Depolarization Shift****** (3)
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1)fundamental defect in epileptogenic state is this (PDS)
2)an unexplained tendency of epileptic neuron to repeatedly depolarize 3)is result of unregulated release of excitatory NT's (glycine) |
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Lowering the Seizure Threshold (5)****
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1)misnomer!!! base membrane potential is actually raised
2)repeated small EPSPs cause persistent elevation of membrane potential 3)result is that small EPSP causes AP to trigger 4)partial depo state in cell membrane 5)greater excitability of the membrane |
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If Excitation is increased (as the cause of epilepsy); how to tx? (3)
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1)Na channel antagonists
2)Ca channel antagonists 3)Glutamate receptor antagonist |
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If Inhibition is decreased (as the cause of epilepsy); how to tx? (3)
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1)GABA(a) agonist
2)Enhanced GABA levels 3)K+ channel agonists |
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A ____ part of the brain can also cause seizure and afterwards...
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hypoperfused/hypometabolic parts of the brain cause seizure; this part becomes hypermetabolic/perfused after seizure
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Big qualification of Epilepsy
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RECURRENT seizures
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Invasive Localization of seizure (3)
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1)using sub-dural strips/grids
2)records electrical activity for localizing epileptogenic areas in the brain 3)also used for cortical mapping of cortex prior to surgical ablation of abnormal areas |
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Intra-Operative ECoG (2)
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1)grid electrodes used for intra-operative electro-corticography (ECoG)
2)lets EEGer direct the extent of surgical resection during temporal lobectomy |
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Cortical Mapping
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1)40 electrode grid surgically placed for seizure localization and cortical mapping
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Vagal Nerve Stimulation (VNS) therapy (3)
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1)packmaker like pulse generator
2)reduces seizure freq (not a cure) 3)pt can abort the seizures using magnets when they happen |
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Deep Brain Stimulation Therapy (3)
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1)named Kinetra
2)implanted in chest wall and used to stimulate the anterior nucleus of the thalamus 3)only FDA approved for Parkinson's right now |
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Address Remedial Causes of Seizure therapy (5)
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1)mechanical (trauma, tumor, vascular)
2)metabolic 3)sudden withdrawal of CNS meds 4)fever, infexn 5)psychiatric (anxiety/depression) |
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Best tolerated antiepileptic drug selection (2)
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1)phenytoin
2)CBZ |
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Dose titration of anti-epileptic drugs (2)
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1)doing so minimizes CNS depression
2)start w/ 1/4 to 1/3 of anticipated maintenance dose and incr over 3-4wks |
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In drug monitoring the Evaluation of durg []s must consider (4)
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1)pt adherence
2)time of last dosage adjustment 3)time when last dose was administered 4)clinical picture (efficacy/toxicities--if drug is efficacious and pt shows no sign of toxicity then no need to monitor) |
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Indications for monitoring drug []s (6)
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1)continued seizure on "therapeutic dose" (may need above "td")
2)seizure recurrence after control achieved 3)pt appears toxic (but may NOT be outside usual therapeutic range) 4)document therapeutic level after dosage change 5)assess therapy in pt w/ infrequent seizures 6)TREAT PT, NOT DRUG LEVEL |
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Free []s of AED (antieleptic drug) (4)
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1)many AEDs are highly protein bound (vpa, pheny)
2)free drug is active 3)numerous drugs and disease states alter protein binding 4)altered protein binding alters CL and total drug []s for some drugs |
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Consider free []s for VPA and Phenytoin in what conditions (7)
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1)chronic liver/renal failure
2)hypoalbuminemia 3)burns 4)pregnancy 5)malnutrition 6)displacing drugs (other highly protein bound meds0 7)neonates/elderly |
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Reasons for Tx failure (5)
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1)inappropriate drug selection
2)inappropriate dose 3)poor compliance 4)refractory patient 5)(-) lifestyle--alcohol and drug abuse |
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Factors promoting complete withdrawal of AED (6)
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1)2yr seizure free of absence seizures
2)4yr seizure free for SP, CP, absence associated w/ TC 3)complete seizure control within 1yr of onset 4)onset of seizure after age 2 BUT before age 35 5)normal EEG 6)inappropriate use of AED |
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Factors against complete withdrawal of AED (5)
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1)hx of high frequency of seizures
2)repeated episodes of status epilepticus 3)combination of seizures 4)abnormal neurological exam 5)structural brain abnormality by MRI |
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Best way to withdraw AED to reduce relapse (3)
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1)withdraw over 6months
2)within 6months 12% relapse 3)32% in 12months |
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Polypharmacy and seizure (3)
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1)avoid if possible
2)titrate initial drug choice to maximal therapeutic levels--monitor seizure freq and ADR's 3)if 2nd drug is added, titrate it as above and attempt withdrawal of 1st drug |
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SCARs (severe cutaneous adverse reactions) implicated drugs (5)
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1)phenytoin
2)carbamazepine 3)primidone 4)phenobarbital 5)lamotrigine |
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Recognitions of SCARs (2)
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1)don't confuse w/ concmitant meds; especially Abx
2)differentiate from infexous, inflammatory or neoplastic processes (mono, TSS, SLE, lymphoma) |
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a)Stevens Johnson syndrome
b)Toxic epidermal necrolysis c)SJS-TEN overlap syndrome d)Lesions appearance of these 3 (3) |
a)less than 10% epidermal detachment
b)over 30% epidermal detachment c)10-30% epidermal detachment d1)macules w/ darker purpuric centers d2)develop into target lesions d3)In TEN, have blisters that spread w/ pressure |
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Anticonvulsant Hypersensitivity Syndrome
a)incidence b)def c)onset |
a)1/1000 to 1/10,000 WITH CROSS SENSITIVITY
b)triad of fever, skin rash and sympto/asymto internal organ involvement c)2-8wks initially, more rapidly on challenge |
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AHS
a)time to eruptions b)typical lesion c)fever d)facial edema e)hepatitis f)mucosal involvement g)neutrophil count |
a)2-8wks
b)fine, red rash becomes confluent & large blisters develop c)+++ d)+++ e)+++ f)- g)NORMAL |
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SJS/TEN
a)time to eruptions b)typical lesion c)fever d)facial edema e)hepatitis f)mucosal involvement g)neutrophil count |
a)1-3wks
b)rashes of all types (mainly morbilliform) c)+++ d)--- e)++ f)+++ (mouth/esophagus) g)DECREASED |
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Mechanism of SCARs (4)
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1)immune mediated
2)excess ARENE OXIDE metabolites 3)pt lack epoxide hydroxylase or that enzyme is mutated (this will normally get rid of arene oxide metabolites) 3)phenytoin, CBZ, phenobarbital CROSS SENSITIVITY |
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Management of SCARs (8)
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1)dc causative agent PLUS give symptomatic and supportive therapy
2)High-dose corticosteroids 2)new maintenance antiepileptic drug a)wait till SCAR wanes b)avoid drugs known to cross react c)avoid drugs associated w/ hepatotoxicity (vpa) d)avoid drugs associated w/ rash e)avoid drugs w/ long induction times (topamax, lamictal, tiagabine) |
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Rash less associated w/...(3) and highly associated w/...
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1)gabapentin
2)topiramate 3)tiagabine 4)BUT HIGHLY ASSOCAITED WITH LAMOTRIGINE |
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High dose corticosteroids w/ immune modulation controversial?
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decr survival vs. decr severity of disease progression
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Desirable PK properties of an AED (10)
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1)rapid and linear F
2)parenteral formulation 3)linear elimination kinetics 4)half-life allowing qd or bid 5)volume of distribution w/ a single compartment 6)rapid penetration into the brain 7)low and non-saturable protein binding (less than 80%) 8)no autoinduction of enzymatic biotransformation (no induce own metabolism) 9)no active metabolites 10)slow absorption or sustained-release formulation |
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Also want ____ w/ new AED's
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correlation b/w [] and therapeutic or toxic effects
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Therapeutic drug monitoring for newer agents when? (5)
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1)pt has concomitant therapies
2)metabolic differences 3)age 4)renal/hepatic dysfxn 5)pregnancy |
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PET scan measures...
SPECT scan measures.... |
glucose utilization by the brain
blood flow to the brain |
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Tegretol
a)Dose related ADR's (3) b)Idiosyncratic (3) |
a1)drowsy on initiation and dosage increases (lasts 7-10d)
a2)hyponatremia a3)leukopenia b1)agranulocytosis b2)aplastic anemia b3)Morbilliform rash |
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Tegretol PK (5)
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1)active metabolite is carbamazepine 10,11 epoxide
2)NOT detected by carbamazepine assays 3)suspect if pt is clinically toxic and subtherapeutic carbamazepine []s 4)VPA interferes with CL of carbamazepine-10,11-epoxide 5)will see incr in serum [] over first 3-4d, then gradual decline due over next month due to autoinduction |
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Guidelines for hematologic monitoring of Tegretol (3)
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1)If pretreatment CBC with differential is normal, no follow-up testing is necessary just ask pt to report signs of possible hematologic abnormalities
2)if pretx WBC/neutrophil is low, monitor every 2wks for first 1-3months; dc/decr dosage if WBC falls below 3000 OR neutrolphils below 1000 3)others recommend CBC, WBC w/ differential, platelets monthly for first 2months and yearly thereafter |
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Phenytoin
a)[] dependent ADR's of phenytoin (3) |
a1)20-30mcg/mL- nystagmus
a2)30-40mcg/mL- ataxia a3)over 40mcg/mL- severe cerebellar signs, drowsy, coma, paridoxical incr in seizures |
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Phenytoin
a)chronic toxicities (5) b)idiosyncratic (3) |
a1)hepatotoxic
a2)osteomalacia a3)megaloblastic anemia (decr folate absorption) a4)gingival hyperplasia a5)coarse face/hirsutism b1)rash/SJS b2)blood dyscrasias b3)SLE |
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Dosage forms of phenytoin (4)
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1)capsules
2)suspension 3)chewable 4)injection |
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Fosphenytoin
a)what is it? b)use (2) c)other (2) |
a)progrud of phenytoin that takes 30min to convert to pheytoin
b1)IV infusion (150mg/min)--has less pain and phlebitis than phenytoin b2)can be given IM, but NOT in status epilepticus c1)expensive c2)paresthesia and transient pruritis |
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PK of phenytoin (4)
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1)MM elimination
2)highly protein bound 3)F reduced w/ enteral feeding 4)monitor no more freq than 5-7d unless following dose change |
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VPA dosage forms (6)
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1)capsules
2)injection 3)syrup 4)enteric coated 5)sprinkles 6)ER tablets |
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Select VPA ADR's (5)
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1)liver toxicity
2)wt gain 3)hair loss 4)tremor 5)thrombocytopenia |
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VPA PK (4)
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1)80-95% protein bound
2)if plasma levels exceed 100mg/mL free drug fraction may incr significantly 3)free FAs displace VPA from binding sites 4)INHIBITS HEPATIC METABOLISM |
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Phenobarbital dosage forms (3)
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1)tablets
2)elixir 3)injection |
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Phenobarbital
a)dose related effects (2) b)idiosyncratic (3) |
a1)CNS depression including coma and respiratory depression
a2)hyper/irratable kids b1)hepatoxic b2)hypersensitivity (SJS/TEN) b3)arthritic changes |
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Phenobarbital PK (3)
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1)65% metabolized, 35% excreted unchanged in urine
2)acid/base changes alter renal elimination 3)induces hepatic enzymes |
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Primidone (Mysoline)
a)PK a)anticonvulsant activity attributed to.... c)when to use? |
a)metabolized in liver to phenobarbital and PEMA
b)metabolization to phenobarbital c)refractory pts; try Pb first due to cost and dosing frequency considerations |
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Clonazepam
a)main indication b)major limiting factor |
a)MYOCLONIC SEIZURES
b)high rate of tolerance and recurrence of seizures |
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Felbamate (Felbatol)
a)main indication and why? b)mechanism involves... c)ADR's (3) |
a)REFRACTORY seizures (mostly Lennox-Gastaut syndrome) due to deaths from aplastic anemia and hepatic failure
b)NMDA c1)aplastic anemia c2)hepatic failure c3)n/v/anorexia |
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Felbamate
a)PK b)drug interactions |
a)glucuronidation/xoxidation to reactive metabolite detoxified by conjugation to glutathione
b)both an enzyme inducer and inhibitor |
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Gabapentin
a)Nonepileptic uses... (5) b)dosing |
a1)neuropathic pain
a2)psychiatric disorders a3)movement disorders a4)migraine prophylaxis a5)cocaine dependence b)DOSAGE REDUCTION IS NECESSARY IN RENAL INSUFFICIENCY |
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Gabapentin
a)PK (3) b)drug interactions |
a1)absorption via saturable L-AA transport system
a2)NOT protein-bound/metabolized a3)EXCLUSIVELY RENALLY EXCRETED b)free of interaction with other anticonvulsants |
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Lamotrigine
a)approved for b)ADR's (3) c)drug interactions (3) |
a)2 YEARS AND OLDER
b1)dizzy b2)nausea b3)rash in 10% within 4-6wks (slow titration prevents) c1)tegretol, phenytoin, Pb decr half-life of phenytoin c2)VPA increases half-life of lamotrigne c3)lamotrigine induces its own metabolism and that of VPA |
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Lamotrigine
a)PK (2) b)metabolism (3) |
a1)F=98%
a2)55% protein bound b1)hepatic glucuronidation to inactive metabolite b2)auto-induction causes a 25% decr from original half-life b3)metabolite is renally eliminated |
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Tiagabine (Gabitril)
a)mechanism b)dosing c)ADR's (3) d)measuring serum []s |
a)inhibits GABA reuptake
b)slow titration AND WITH FOOD c1)depressed mood c2)dizziness c3)HA d)IN MCG/ML |
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Tiagabine (Gabitril)
a)PK (5) b)drug interactions (3) |
a1)to avoid ADR's associated w/ high peak levels take it w/ food
a2)protein binding 96% a3)metabolized by CYP3A a4)half-life 5-8hr a5)elimination of inactive metabolites in feces/bile and urine b1)CBZ, PHY, Pb incr elimination rate of Tiagabine b2)NO significant displacement of other protein bound AED's due to lower serum [] b3)is displace by naproxen, salicylates and Na VPA |
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Topiramate
a)ADR's (4) b)PK (2) c)drug interactions (2) |
a1)neurotoxicity/psycho motor slowing (word finding and impaired concentration)
a2)glaucoma a3)renal stones a4)teratogenic b1)normally metabolized only 20%, gets up to 40-50% w/ enzyme inducers (difference is excreted unchanged) b2)half-life decr in presence of enzyme inducers c1)PHY, CBZ, Pb decr serum []s of topiramate c2)topiramate can decr serum []s of ethinyl estradiol |
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Levetiracetam
a)dosing b)dosage forms (3) c)ADR's (3) |
a)dose adjustment in renal impairment
b1)tablet b2)injexn b3)solution c1)sedation/dizzy c2)weakness c3)asthenia |
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Zonisamide
a)ADR's (2) b)approved for... c)interactions |
a1)kidney stones
a2)hypersensitivity (w/ sulfa allergy) b)in kids for PS and secondary GTCS c)enzyme inducing AEDs decrease half life by about 1/2 |
