Anti epileptic drugs, bipolar, schizophrenia
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| Normal Patients given Antipsychotics | Sedation, restlessness, ANS effets (no euphoria)
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| Schizopherinc patients given antipsychotics | Decreased motor activity, akathesia, Dystonia (muscle cramp), Cataleptic immobility,Bradykinesia
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| Signs/Symptoms of Schizophrenia | Auditory hallucinations, Hyperviligant, Paranoid
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| NT involved in Schizophrenia | DA (volume) Ach, GABA (filters), Glutamate (inappropiate memory)
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| Hyperviligance-cause | Loss of sensory gating-theory nicotinic receptor-paired clicks
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| First generation antipsychotics | Chlorpromazine, Perphenazine, Trifluoperazine, Thiothixene, Haloperidal
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| Atypical antipsychotics | Clozapine, Risperidone, Olanzapine, Quetipine, Ziprasidone, Ariprazole
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| Chlorpromazine receptors | alpha1=5HT>D2>D1
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| Haloperidol receptor | D2>D1=D4>alpha 1>5HT
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| Clozapine receptors | D4=alpha 1>5HT>D2>D1
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| ADME of antipsychotics | Low ABs, High protein binding, high Vd, various metabolism
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| Area of antipsychotic effect | mesolimbic area
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| First Generation effects on D1 and D2 | DI increase cAMP, D2 decrease cAMP D3 decrease cAMP
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| Neuroleptic compounds work on what receptor | D2
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| MOA of atypicals | alpha 1, alpha2, M1, H1, 5HTD3, D4
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| Dopamine Hypothesis | 1. Most drugs block D2 2. Drugs that induce D2- psychosis 3. More receptors (DA)
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| Dopamine Hypothesis shortcomings | 1. NMDA-glutamate receptor can cause more pronounced psychosis 2. Atypicals less DA2 effect
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| Mesolimbic | Substantia niagra to limbic-cortex and antipsychotic effets noted
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| Nigrostriatal | Substantia nigria to putman, caudate, (Basal ganglia) to cause EPS
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| Hypothalamic | tubular vendubar tract-increase prolactin
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| Medullary blockade | Increase eating behavior
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| D1 like (D1 &D5) | Phenothiazine, Thioanthenes, Butrophenones
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| D2 like (D2, D3, D4) | Sulphiride, Phenothiazines, Butrophenones, Clozapine
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| Chlorpromazine receptors | alpha=5HT>D2>D1
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| haloperidol receptor | D2>D1=D4>alpha1>5HT
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| Clozapine receptor | D4=alpha1>5HT>D2>D1
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| alpha 1 SE | orthostatic hypoTH
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| D2 SE | EPS
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| D4 SE | agranulocytosis
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| Neurolepetic syndeome | There is suppression of sponantenous behavior but NOT unconditioned avoidance behavior nor spinal reflexes
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| Lithium ADE | Well absorbed, low Vd, Excreted in Urine
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| Lithium Interactions | Slow BBB absorption, Can substitute for Na and cause Action Potentials (cardiotoxic)
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| Lithium MOA | unknown but inhibits second messenger inositol phosphates to (Ca) decrease cell activity
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| Lithium SE | Tremor (propranolol) choreoathetosis, EPS, asthesia, dysarthia, polyuria, polydipsia, edema, vomiting
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| Cerebral Cortex interaction | Decrease seizure threshold (clozapine, chlorpromazine)
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| Mesolimibic system | Area of antipsychotic effects
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| DM risk | Increased with second generation after 5 years
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| Cholesterol levels increase 10% | Olanzapine
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| Cardio problems | Chlorpromazine, Zipraisadone
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| D2 Key SE | Sedation, orthostatic hypotension, EPS, akathesia, seizures, TD, weight gain, increase prolactin
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| Agranulocytosis | Clozapine
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| Deposits in anterior lens | Chlorpromazine
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| Ocular deposits in the retina | Thioridizine
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| Neuroleptic malignant syndrome | Sensitive EPS -life threatening treat with DA agonist-Bromocriptine
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| Antipsycotic DI's | BZD, Barbiturates, anticholinergics
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| Psycharic indications for antipsychotics | Schiz, Bipolar, tourettes, anti-emetics
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| Schizo characterized as | 3 Symptoms-Positive, negative, and cognitive
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| Positive Symptoms | Hallucinations, delusions, Loosing of associations
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| Negative Symptoms | Anhedonia, Avolution, Povery of speech, Flat affect
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| Cognition symptoms | Loss of short term memory,
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| Schizo heterogenous presentation | prodromial (negative, cognitive), then later positive
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| Hallmarks of acute psychosis | Response in 2 weeks and decreases severity and frequency of symptoms
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| Chlorpromazine SE | Pronlong QT interval, block D2, alpha 1, M1, H1, 5HT
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| Haloperidol use | ER and surgery
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| haloperidol SE | Dystonia (1 day), Akathesia (1 wk), Pseudoparkinson (6 wk) TD( 6 months), tubular vendubular tract innervation (prolactin)
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| Cloazapine SE | agranulocytosis, seizures, mycordial inflammation, weight gain, hypersalivation
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| Clozapine EPS and TD | Does not cause EPS or TD
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| Clozapine monitoring | WBC, Weight, lipids(5 y), DM
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| Chlorpromazine Stop will see | TD symptoms initially (were masked)
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| Atypical antipsychotics treat | Positive, and negative symptoms
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| Risperidone 2 problems | EPS and Most potent prolactin release (Orthostasis, wt gain, sedation)
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| Olanzapine (Zyprexia) SE | GLucose met, weight gain, Akathesia
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| Quetipine (Seroquel) Se | Orthostastis, weight gain, sedation (good for parkinson pt & elderly)
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| Ziprasidone (Geoden) SE | QT elongation, arrhythmias >>80mg
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| Ariprazole (abilify) SE | Akathesia, insomnia, nausea
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| FDA Mania (antipsychotics | Ariprazole, Olanzapine
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| Ariprazole Receptor | Partial DA2
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| Ziprassidone Not good for | Bipolar
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| Quetipine receptor | DA2 /5HT antagonist
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| Ziprasidone Extra effects | NE and 5HT receptor uptake do not used in Bipolar-causes Mania
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| Dystonia | Uncoordinated involuntary contraction-non-compliance or dose esculation-anticholinergic
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| Akathesia | Restlessness-after 1week, decrease dose or BZD or propranolol,
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| Pseudoparkinson | Onset 1-2 week, decrease dose last choice add anticholinergic
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| Tardive Dyskinesia | After 6 months choreorthetoid motions
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| AIMS or DISCUS | Monitor all antipsychotics every 6 months and 3 months if symptoms
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| Low EPS or TD | clozapine, Quetipine
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| No weight gain | Ziprasidone, or Aripiprazole
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| Increase Lipids and glucose | clozapine, olanzapine
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| EKG symptoms avoid | Ziprasidone
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| Seizures avoid | Clozapine
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| EPS/sedation then avoid | Risperidone
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| Antipsychotic effects on day 1-7 | Decrease hostility, agitation and increase sleep
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| antipsychotic effects in 2 -12 days | Decrease hallucinations, paranoia, delusions, better judgement, increased participation
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| Antipsychotic effects in months to years | Increase insight, decrease delusions, decrease Negative symptoms
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| Antipsychotic monitoring | Weight, DM (base, 12, annual) Lipid( base, 12 week)
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| Bipolar I DSM IV | 1 MDE and mania
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| Bipolar II DSMIV | I MDE and hypomania
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| Cyclithalmic disorder | Less severe depression and mania
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| Manic Episode | elevated or irritable mood lasting 1 week, and > 3 symptoms (4 if irritable): decreased sleep, more talkative, Flight of ideas, Distract, increased directed activity
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| Bipolar I prevelance | Men=WOmen 10-15% of MDE develop bipolar Onst 20 y, LARGE FHX
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| Bipolar II prevelance | Women> men and 5-15% become Bipolar I
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| Bipolar general | 25-50% attempt sucide, substance abuse high, with increase in age, increase in frequency of episodes
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| Recurrrence | Precipitated by sleep/wake cycle, and antidepressants
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| Hypomanic | Decreased depression and mania, No psychotic symptoms
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| Rapid cycling | >4 episidoes in 12 months women > men
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| Mixed Bipolar | Combined state of depression and mania
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| Lithium Dose | 300mg TID
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| Lithium serum level acute | 0.8-1.4mEq/L
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| Lithium serum level maintenance | 0.6-1.2mEq/L
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| Lithium Onset | 7-14 days
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| Lithium monitoring | CBC- leukocytosis and UA- specific gravity, neprogenic diabetes insipidous, Pregnancy D
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| Lithium SE | Tremor, Diarrhea( take w/food) , weight gain,Competes with Na, acute renal failure( renal excretion), electrolyte abnormalities, leucocytocytosis, hyperthyroidism,
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| Sign of Lithium toxcity < 1.8 mEq/L | Lethergy, sedation, nausea, anorexia, increased tremor
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| Lithium toxcity <2.3 | Slurred speech, blurred vision
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| Lithium toxicity< 2.3 | Coma
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| Lithium DI | NSAIDS, Diiuretics, Acei, Chinese food, caffeine, excerise
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| Valproic Acid Monitoring | LFT, CBC-leukocytosis, B-HCG Pregnancy
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| Valprotic Acid- Black box warning | Hepatotoxcity (children), hemorrhagic pancreatitis, Thrombocytopenia, Rash (SJS), ALopecia
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| Valproic Acid Dose | 250TID, increase by 250mg Q 2 days until at serum level
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| Valproic acid serum level | 50-125 mcg/mL
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| Valproic acid first line | Mixed mania
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| Valprotic acid SE | GI-(take w/food), Sedation, Tremor, WEight Gain, Hyperammonemia (not significant)
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| Valprotic Acid DI | Lamotrigine (SJS rash), Warfarin
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| Carbamazepine use | DI limits use-inducer and autoinducer
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| Carbamazepine Monitoring | Aplastic anemia, hyponatremia, hepatotoxcity, Pregnancy C-low birth
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| Carbamaxepine SE | Sedation, Dizziness, SJS rash
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| Carbamazepine DI | inducer and autoinducer (2 weeks) warfarin, Birth control, Theophylline
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| Oxacarbamazepine SE-Bipolar | less hyponatremia, but does not have efficacy data
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| Lamotrigine Bipolar indication | First line if in bipolar depression
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| Lamatrigine Biopolar dose | Start low 25mg then increase weekly by 25mg (SJS rash avoid fast titration)
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| Lamatrigine SE | HA, N/V, Rash (SJS)
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| Benzodiazipines acute mania | Lorazepam 1-2mg BID (watch addiction)
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| Non-pharm Bipolar | Stay away from illicit drugs, and alcohol, sleep cycles, stress, ECT, family/friend support
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| Acute mania drug choices | mood stabilizer +/- BZD and or antipsychotic
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| Maintainenance Bipolar | Mood stabalizer may consider antipsychotic
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| Mixed Mania first line | Valprotic Acid consider Carbamezapine or oxcarbamazepine
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| Depressive Bipolar | Mood stabalizer and antidepressant
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| Seizure length | Usually seconds to minutes
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| Biochemical changes of seizures | Can last days and patient do not remember occurances
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| Pseudoseizures | Conversion disorder related to stress
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| 3 Categories of seizures | 1. Primary generalized (bilateral) 2. Focal partial onset seizure( mono), Epilepsy syndrome
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| Primary generalized seizures-types | Tonic-clonic, tonic, clonic, atonic, absence, myoclonic
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| Tonic-clonic | Called Gran Mal-Increased tone and rhythum
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| Atonic | Without tone, the helemet people
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| Absence | Children who stare and have 50-100 per day
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| Simple partial seizue | Have the aura (feeling, smell, ) awareness is NOT impaired -can jump corpus collisum and cause Complex partial seizure
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| Complex partial Seizure | Awareness impaired- blank look, speech arrest, communication is garbled, walk around
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| Juvienile Myoclonic Epilepsy | onset near puberty- seizure associated with sleep Give Valprotic Acid)
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| Lennox Gastaut Syndrome | Difficult to treat- Have gamut of seizures, generalized tonic clonic, atonic, partial=developmentaly disabled people
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| Receptors used to treat epilepsy | GABA receptor, Ion channels (NA, CA) amino acid receptors (NMDA, AMPA)
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| GABAergic drugs | Pregabalin, gabapentin, Tiagabine, Barbs, BZDs, Topimate, Felbamate, Valproate
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| Na Channel blockers | Phenytoin, Carb, Valproate, Lamatrogine, Primadone, Topiramate, Oxcarbazepine, Zonisamide
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| Drugs that block Ca channels "Absence Seizures" | Ethosuximide, valproate, topiramatem pregabalin, gabapentin
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| Glutamate block | Felamate, Topitamate, Lamotrigine, Pregabalin
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| Broad Spectrum | Valproate, Zonisimise, pregabalin, Levetiracetam, Topiramate, Felbamate, Lamotrigine
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| Blocks Synaptic vesicle 2 receptor | Levetiracetam
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| Inducers | Phenytoin, Phenobarbital, primidone, Carbamazepine (autoinducer)
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| Enzyme inhibitor | Valprotic acid
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| Phase II metabolism | Lamotrigine, Tigabine
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| Pregnancy-metabolism | Clearance increase in last trimeter- do not forget to decrease dose after birth
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| Protein Binding-clinical significance | Valprotic acid and phenytoin
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| Conditions that alter protein binding | Pregnancy, malnutrition, alcholism (bad liver), age extremes, Hypo-albumin
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| Hypersensitivity syndrome- | Can happen 1 year after starting, Rash, and systemic because aromatics arene oxides lack epoxide hydroxylase to metabolize- Never give other AED with aromatic ring (NO antibiotics with aromatic ring)
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| Drunk Feeling when toxic | Carbamazepine, lamotrigine
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| Vaprotic acid-lab changes | CBC-thrombocytopenia, WBC, down, PTL down, AED- trough
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| Phenobarbital SE | Aggression, hepatotoxic, osterperosis, sexual dysfunction
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| DI birth control pills | All inducers
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| No effect on Birth Control | Valproate, Lamotrigine, gabapentin, zonisamide
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| Inducers and inhibitors | Oxacarbamazeptine, Felbamate, Topiramate
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| Injectable drugs | Phospenytoin, Phenobarbital, phenytoin, depason, levetriacetan (coming)
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| Phenytoin MOA | Na channel blocker
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| Phenytoin administration | proplyene glycol (solubility) causes crystalizations Rate<50mg/min monitor cardiac arrythmias
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| Phenytoin SE | osteropeosis, gingival hyperplasia, hirtism, sexual dysfunction
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| Phosphenytoin-prodrug | IV phenytoin must give >150mg/mL
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| Phosphenytoin SE | groin itch(lower rate)
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| Ethosuximide | treats absence seizures
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| Carbamazepine MOA | Sodium channel blocker
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| Carbamazepine does not treat what type of seizure | absence
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| Carbamazepine Dose | 400-600mg QD (TID)
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| Carbamazepine Contra | Sucidial patients
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| Carbatrol | 3 beads of various release carbamazepine
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| Valproate MOA | Increase GABA, Block Na channel
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| Valproate Dose-AED | 500TID
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| Valproate serum concentration AED | 50-150mcg/mL
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| Valproate SE | High hepatotoxicity, tremor, hair changes, weight gain, osteroperosis, polysystic ovarian syndrome
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| Osteroporosis need Ca | Inducers-Phenytoin, Carbamazepine, Phenobarbital, Primadone, Felbamate (osetoblast inhibited-valproate)
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| Felbamate SE | aplasic anemia, hepatic failure (6-12 months!)
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| Felbamate monitor | CBC (aplastic anemia), & LFT 2-4 times first 6-12 months
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| Lamotrigine DI | Birth control decrease concentration of drug
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| Gabapentin MOA | L-Type Ca channel in the gut has absorption limit 1200mg TID
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| Topiramate-carbonic anhydrase SE | kidney stones, fast dose escalation (confusion), weight loss, glaucoma
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| Avoid if sulfa allergy | Topiramate, Zonismide
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| Tiagabine SE | if withdraw fast cause status epilepitus
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| Levetriacetam Dose | 500BID immediately at theraputic level
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| Oxacarbamazepine-prodrug | Monitor Monohydroxy derrivative and sodium levels
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| Zonisamide benefit | Therapeutic in week!
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| Zonisamide SE | parathesia, kidney stones
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| Pregabalin excretion | renal
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| Staus Epilepticus-first line | Lorazepam 0.1mg/kg (cool CNS) repeat in 15 min if does not work
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| Status Epilepticus-second line | Phenytoin load 18-20mg, the NTE-50mg/min repeat half load if not effective
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| Status epilepticus 3rd line | paraldehyde, propofol, lidocaine,depacon, depakote rectal
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