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IOS 8 Exam 3

Anti epileptic drugs, bipolar, schizophrenia

Normal Patients given Antipsychotics Sedation, restlessness, ANS effets (no euphoria)
Schizopherinc patients given antipsychotics Decreased motor activity, akathesia, Dystonia (muscle cramp), Cataleptic immobility,Bradykinesia
Signs/Symptoms of Schizophrenia Auditory hallucinations, Hyperviligant, Paranoid
NT involved in Schizophrenia DA (volume) Ach, GABA (filters), Glutamate (inappropiate memory)
Hyperviligance-cause Loss of sensory gating-theory nicotinic receptor-paired clicks
First generation antipsychotics Chlorpromazine, Perphenazine, Trifluoperazine, Thiothixene, Haloperidal
Atypical antipsychotics Clozapine, Risperidone, Olanzapine, Quetipine, Ziprasidone, Ariprazole
Chlorpromazine receptors alpha1=5HT>D2>D1
Haloperidol receptor D2>D1=D4>alpha 1>5HT
Clozapine receptors D4=alpha 1>5HT>D2>D1
ADME of antipsychotics Low ABs, High protein binding, high Vd, various metabolism
Area of antipsychotic effect mesolimbic area
First Generation effects on D1 and D2 DI increase cAMP, D2 decrease cAMP D3 decrease cAMP
Neuroleptic compounds work on what receptor D2
MOA of atypicals alpha 1, alpha2, M1, H1, 5HTD3, D4
Dopamine Hypothesis 1. Most drugs block D2 2. Drugs that induce D2- psychosis 3. More receptors (DA)
Dopamine Hypothesis shortcomings 1. NMDA-glutamate receptor can cause more pronounced psychosis 2. Atypicals less DA2 effect
Mesolimbic Substantia niagra to limbic-cortex and antipsychotic effets noted
Nigrostriatal Substantia nigria to putman, caudate, (Basal ganglia) to cause EPS
Hypothalamic tubular vendubar tract-increase prolactin
Medullary blockade Increase eating behavior
D1 like (D1 &D5) Phenothiazine, Thioanthenes, Butrophenones
D2 like (D2, D3, D4) Sulphiride, Phenothiazines, Butrophenones, Clozapine
Chlorpromazine receptors alpha=5HT>D2>D1
haloperidol receptor D2>D1=D4>alpha1>5HT
Clozapine receptor D4=alpha1>5HT>D2>D1
alpha 1 SE orthostatic hypoTH
D4 SE agranulocytosis
Neurolepetic syndeome There is suppression of sponantenous behavior but NOT unconditioned avoidance behavior nor spinal reflexes
Lithium ADE Well absorbed, low Vd, Excreted in Urine
Lithium Interactions Slow BBB absorption, Can substitute for Na and cause Action Potentials (cardiotoxic)
Lithium MOA unknown but inhibits second messenger inositol phosphates to (Ca) decrease cell activity
Lithium SE Tremor (propranolol) choreoathetosis, EPS, asthesia, dysarthia, polyuria, polydipsia, edema, vomiting
Cerebral Cortex interaction Decrease seizure threshold (clozapine, chlorpromazine)
Mesolimibic system Area of antipsychotic effects
DM risk Increased with second generation after 5 years
Cholesterol levels increase 10% Olanzapine
Cardio problems Chlorpromazine, Zipraisadone
D2 Key SE Sedation, orthostatic hypotension, EPS, akathesia, seizures, TD, weight gain, increase prolactin
Agranulocytosis Clozapine
Deposits in anterior lens Chlorpromazine
Ocular deposits in the retina Thioridizine
Neuroleptic malignant syndrome Sensitive EPS -life threatening treat with DA agonist-Bromocriptine
Antipsycotic DI's BZD, Barbiturates, anticholinergics
Psycharic indications for antipsychotics Schiz, Bipolar, tourettes, anti-emetics
Schizo characterized as 3 Symptoms-Positive, negative, and cognitive
Positive Symptoms Hallucinations, delusions, Loosing of associations
Negative Symptoms Anhedonia, Avolution, Povery of speech, Flat affect
Cognition symptoms Loss of short term memory,
Schizo heterogenous presentation prodromial (negative, cognitive), then later positive
Hallmarks of acute psychosis Response in 2 weeks and decreases severity and frequency of symptoms
Chlorpromazine SE Pronlong QT interval, block D2, alpha 1, M1, H1, 5HT
Haloperidol use ER and surgery
haloperidol SE Dystonia (1 day), Akathesia (1 wk), Pseudoparkinson (6 wk) TD( 6 months), tubular vendubular tract innervation (prolactin)
Cloazapine SE agranulocytosis, seizures, mycordial inflammation, weight gain, hypersalivation
Clozapine EPS and TD Does not cause EPS or TD
Clozapine monitoring WBC, Weight, lipids(5 y), DM
Chlorpromazine Stop will see TD symptoms initially (were masked)
Atypical antipsychotics treat Positive, and negative symptoms
Risperidone 2 problems EPS and Most potent prolactin release (Orthostasis, wt gain, sedation)
Olanzapine (Zyprexia) SE GLucose met, weight gain, Akathesia
Quetipine (Seroquel) Se Orthostastis, weight gain, sedation (good for parkinson pt & elderly)
Ziprasidone (Geoden) SE QT elongation, arrhythmias >>80mg
Ariprazole (abilify) SE Akathesia, insomnia, nausea
FDA Mania (antipsychotics Ariprazole, Olanzapine
Ariprazole Receptor Partial DA2
Ziprassidone Not good for Bipolar
Quetipine receptor DA2 /5HT antagonist
Ziprasidone Extra effects NE and 5HT receptor uptake do not used in Bipolar-causes Mania
Dystonia Uncoordinated involuntary contraction-non-compliance or dose esculation-anticholinergic
Akathesia Restlessness-after 1week, decrease dose or BZD or propranolol,
Pseudoparkinson Onset 1-2 week, decrease dose last choice add anticholinergic
Tardive Dyskinesia After 6 months choreorthetoid motions
AIMS or DISCUS Monitor all antipsychotics every 6 months and 3 months if symptoms
Low EPS or TD clozapine, Quetipine
No weight gain Ziprasidone, or Aripiprazole
Increase Lipids and glucose clozapine, olanzapine
EKG symptoms avoid Ziprasidone
Seizures avoid Clozapine
EPS/sedation then avoid Risperidone
Antipsychotic effects on day 1-7 Decrease hostility, agitation and increase sleep
antipsychotic effects in 2 -12 days Decrease hallucinations, paranoia, delusions, better judgement, increased participation
Antipsychotic effects in months to years Increase insight, decrease delusions, decrease Negative symptoms
Antipsychotic monitoring Weight, DM (base, 12, annual) Lipid( base, 12 week)
Bipolar I DSM IV 1 MDE and mania
Bipolar II DSMIV I MDE and hypomania
Cyclithalmic disorder Less severe depression and mania
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
Bipolar I prevelance Men=WOmen 10-15% of MDE develop bipolar Onst 20 y, LARGE FHX
Bipolar II prevelance Women> men and 5-15% become Bipolar I
Bipolar general 25-50% attempt sucide, substance abuse high, with increase in age, increase in frequency of episodes
Recurrrence Precipitated by sleep/wake cycle, and antidepressants
Hypomanic Decreased depression and mania, No psychotic symptoms
Rapid cycling >4 episidoes in 12 months women > men
Mixed Bipolar Combined state of depression and mania
Lithium Dose 300mg TID
Lithium serum level acute 0.8-1.4mEq/L
Lithium serum level maintenance 0.6-1.2mEq/L
Lithium Onset 7-14 days
Lithium monitoring CBC- leukocytosis and UA- specific gravity, neprogenic diabetes insipidous, Pregnancy D
Lithium SE Tremor, Diarrhea( take w/food) , weight gain,Competes with Na, acute renal failure( renal excretion), electrolyte abnormalities, leucocytocytosis, hyperthyroidism,
Sign of Lithium toxcity < 1.8 mEq/L Lethergy, sedation, nausea, anorexia, increased tremor
Lithium toxcity <2.3 Slurred speech, blurred vision
Lithium toxicity< 2.3 Coma
Lithium DI NSAIDS, Diiuretics, Acei, Chinese food, caffeine, excerise
Valproic Acid Monitoring LFT, CBC-leukocytosis, B-HCG Pregnancy
Valprotic Acid- Black box warning Hepatotoxcity (children), hemorrhagic pancreatitis, Thrombocytopenia, Rash (SJS), ALopecia
Valproic Acid Dose 250TID, increase by 250mg Q 2 days until at serum level
Valproic acid serum level 50-125 mcg/mL
Valproic acid first line Mixed mania
Valprotic acid SE GI-(take w/food), Sedation, Tremor, WEight Gain, Hyperammonemia (not significant)
Valprotic Acid DI Lamotrigine (SJS rash), Warfarin
Carbamazepine use DI limits use-inducer and autoinducer
Carbamazepine Monitoring Aplastic anemia, hyponatremia, hepatotoxcity, Pregnancy C-low birth
Carbamaxepine SE Sedation, Dizziness, SJS rash
Carbamazepine DI inducer and autoinducer (2 weeks) warfarin, Birth control, Theophylline
Oxacarbamazepine SE-Bipolar less hyponatremia, but does not have efficacy data
Lamotrigine Bipolar indication First line if in bipolar depression
Lamatrigine Biopolar dose Start low 25mg then increase weekly by 25mg (SJS rash avoid fast titration)
Lamatrigine SE HA, N/V, Rash (SJS)
Benzodiazipines acute mania Lorazepam 1-2mg BID (watch addiction)
Non-pharm Bipolar Stay away from illicit drugs, and alcohol, sleep cycles, stress, ECT, family/friend support
Acute mania drug choices mood stabilizer +/- BZD and or antipsychotic
Maintainenance Bipolar Mood stabalizer may consider antipsychotic
Mixed Mania first line Valprotic Acid consider Carbamezapine or oxcarbamazepine
Depressive Bipolar Mood stabalizer and antidepressant
Seizure length Usually seconds to minutes
Biochemical changes of seizures Can last days and patient do not remember occurances
Pseudoseizures Conversion disorder related to stress
3 Categories of seizures 1. Primary generalized (bilateral) 2. Focal partial onset seizure( mono), Epilepsy syndrome
Primary generalized seizures-types Tonic-clonic, tonic, clonic, atonic, absence, myoclonic
Tonic-clonic Called Gran Mal-Increased tone and rhythum
Atonic Without tone, the helemet people
Absence Children who stare and have 50-100 per day
Simple partial seizue Have the aura (feeling, smell, ) awareness is NOT impaired -can jump corpus collisum and cause Complex partial seizure
Complex partial Seizure Awareness impaired- blank look, speech arrest, communication is garbled, walk around
Juvienile Myoclonic Epilepsy onset near puberty- seizure associated with sleep Give Valprotic Acid)
Lennox Gastaut Syndrome Difficult to treat- Have gamut of seizures, generalized tonic clonic, atonic, partial=developmentaly disabled people
Receptors used to treat epilepsy GABA receptor, Ion channels (NA, CA) amino acid receptors (NMDA, AMPA)
GABAergic drugs Pregabalin, gabapentin, Tiagabine, Barbs, BZDs, Topimate, Felbamate, Valproate
Na Channel blockers Phenytoin, Carb, Valproate, Lamatrogine, Primadone, Topiramate, Oxcarbazepine, Zonisamide
Drugs that block Ca channels "Absence Seizures" Ethosuximide, valproate, topiramatem pregabalin, gabapentin
Glutamate block Felamate, Topitamate, Lamotrigine, Pregabalin
Broad Spectrum Valproate, Zonisimise, pregabalin, Levetiracetam, Topiramate, Felbamate, Lamotrigine
Blocks Synaptic vesicle 2 receptor Levetiracetam
Inducers Phenytoin, Phenobarbital, primidone, Carbamazepine (autoinducer)
Enzyme inhibitor Valprotic acid
Phase II metabolism Lamotrigine, Tigabine
Pregnancy-metabolism Clearance increase in last trimeter- do not forget to decrease dose after birth
Protein Binding-clinical significance Valprotic acid and phenytoin
Conditions that alter protein binding Pregnancy, malnutrition, alcholism (bad liver), age extremes, Hypo-albumin
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)
Drunk Feeling when toxic Carbamazepine, lamotrigine
Vaprotic acid-lab changes CBC-thrombocytopenia, WBC, down, PTL down, AED- trough
Phenobarbital SE Aggression, hepatotoxic, osterperosis, sexual dysfunction
DI birth control pills All inducers
No effect on Birth Control Valproate, Lamotrigine, gabapentin, zonisamide
Inducers and inhibitors Oxacarbamazeptine, Felbamate, Topiramate
Injectable drugs Phospenytoin, Phenobarbital, phenytoin, depason, levetriacetan (coming)
Phenytoin MOA Na channel blocker
Phenytoin administration proplyene glycol (solubility) causes crystalizations Rate<50mg/min monitor cardiac arrythmias
Phenytoin SE osteropeosis, gingival hyperplasia, hirtism, sexual dysfunction
Phosphenytoin-prodrug IV phenytoin must give >150mg/mL
Phosphenytoin SE groin itch(lower rate)
Ethosuximide treats absence seizures
Carbamazepine MOA Sodium channel blocker
Carbamazepine does not treat what type of seizure absence
Carbamazepine Dose 400-600mg QD (TID)
Carbamazepine Contra Sucidial patients
Carbatrol 3 beads of various release carbamazepine
Valproate MOA Increase GABA, Block Na channel
Valproate Dose-AED 500TID
Valproate serum concentration AED 50-150mcg/mL
Valproate SE High hepatotoxicity, tremor, hair changes, weight gain, osteroperosis, polysystic ovarian syndrome
Osteroporosis need Ca Inducers-Phenytoin, Carbamazepine, Phenobarbital, Primadone, Felbamate (osetoblast inhibited-valproate)
Felbamate SE aplasic anemia, hepatic failure (6-12 months!)
Felbamate monitor CBC (aplastic anemia), & LFT 2-4 times first 6-12 months
Lamotrigine DI Birth control decrease concentration of drug
Gabapentin MOA L-Type Ca channel in the gut has absorption limit 1200mg TID
Topiramate-carbonic anhydrase SE kidney stones, fast dose escalation (confusion), weight loss, glaucoma
Avoid if sulfa allergy Topiramate, Zonismide
Tiagabine SE if withdraw fast cause status epilepitus
Levetriacetam Dose 500BID immediately at theraputic level
Oxacarbamazepine-prodrug Monitor Monohydroxy derrivative and sodium levels
Zonisamide benefit Therapeutic in week!
Zonisamide SE parathesia, kidney stones
Pregabalin excretion renal
Staus Epilepticus-first line Lorazepam 0.1mg/kg (cool CNS) repeat in 15 min if does not work
Status Epilepticus-second line Phenytoin load 18-20mg, the NTE-50mg/min repeat half load if not effective
Status epilepticus 3rd line paraldehyde, propofol, lidocaine,depacon, depakote rectal
Created by: liza001



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