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UIC PCOL 425 - Med School Handout

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1 Anxiolytics 1. GABA- inhibitory neurotransmitter 2. GABA receptors • GABAA and GABAB • “A” major binding site for GABA in CNS 3. GABA receptor complex • GABA binding site • BZD binding site • CL ion channel • Picrotoxin binding site 4. GABA Receptor Modulation • Agonist • Antagonist • GABA potentiators 5. 5HT1A receptor • 5HT1A partial agonist- buspirone 6. BZD pharmacokinetic • Lipid solubility determines rate of onset • Dosage adjustments Antidepressants 1. Neurotransmitters Involved • NE • 5HT • DA 2. Major Mechanism of actions • Monoamine oxidase inhibition phenelzine • 5HT and NE reuptake inhibitors venlafaxine, tricyclics and heterocyclic antidepressants • Selective 5HT reuptake inhibitors (SSRIs) fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram • 5HT2 antagonist and 5HT reuptake inhibitor nefazodone • NE and DA reuptake inhibitor bupropion2 • Noradrenergic and specific serotonergic mirtazepine 3. Receptor Profile and Side effects • 5HT2 • 5HT3 • DA • NE 4. Antidepressant kinetics • Protein binding • Metabolism Antipsychotics 1. traditional- • DA blockade • high vs. low potency 2. Atypical • DA blockade- selectivity • 5HT2 blockade 3. What make an antipsychotic an atypical? 4. Receptor profile and side effects • DA • 5HT • Histamine • Alpha1 adrenergic 5. Side effects of Atypical • Clozapine- seizures, agranulocytosis, weight gain, orthostasis, sialorrhea, anticholinergic • Risperidone- dose related EPS, low weight gain, hyperprolactinemia, anticholinergic • Olanzapine- weight gain, akathisia, sedation, • Quetiapine- weight gain, sedation, cataracts? • Ziprasidone- QTc prolongation, no weight gain, activating3 6. Antipsychotic Pharmacokinetics • Metabolized by CYP 450 • Dose adjustments Mood Stabilizers 1. Lithium- MOA unknown 2. Valproate- MOA- GABA facilitation 3. Carbamazepine- neurotransmitter turnover, second messenger systems 4. Various others 5. Pharmacokinetics • Serum levels correlated with efficacy • Metabolism 1. Lithium, not metabolize, excreted in urine 2. Carbamazepine- hepatic, induces hepatic isoenzymes, autoinduction 3. Valproate- inhibits some hepatic isoenzymes and glucoronidation 6. Lithium • Factor affecting clearance Stimulants 1. Mechanism of Action • Inhibition of reuptake of DA, NE • Presynaptic release of DA, NE, 5HT • Inhibition of Monoamine oxidase 2. Pharmacokinetics Drug interactions 1. Pharmacodynamic • Additive effects • Neurotoxicity • Serotonin syndrome 2. Cytochrome P450 isoenzymes • Inhibitors • Inducers 3. Pharmacokinetic interactions • Protein binding saturation • Protein binding displacement 4. Indication for Serum concentration


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UIC PCOL 425 - Med School Handout

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