27993642
Description
Flashcards by Majd Fawaz, updated more than 1 year ago
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Created by Majd Fawaz
over 3 years ago
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| Question | Answer |
| What are the symptoms of Schizophrenia | Positive: Hallucination, Delusion, Thought disorder - Negative Symptoms: Lack of pleasure, Trouble with speech, Flattening, Withdrawal |
| 4 major pathways of dopamine | - The Nigro Striatil: Low dopamine = EPS - The Mesocortical: High dopamine = -ve symp - The Mesolimbic: High dopamine = +ve symp - Turbo Infundibular: Prolactine hormone deficiency |
| Classic Vs Atypical Drugs | Classic: D2 receptor block, EPS and hyperprolactinemia, Effective against positive symptoms Atypical: 5-HT2 affinity, Less side effects, Effective against positive and negative symptoms, Effective with patients refractory to classical drugs |
| Effects of blocking 1) Histamine 2) Serotonine 3) Dopamine 4) Muscarine 5) Adrenergic | 1) Sedation 2) Weight gain 3) EPS, Prolactine release, Thera use 4) Tachycardia, dry mouth, urine retension (makes EPS less) 5) Hypotension, Tachycardia |
| SAR of Phenothiazines | - EWG at C2 - Subs at C1 or C4 dec. activity - Propyl chain needed (ethyl or butyl dec. activity) - Ethyl chain inc. affinity to ACh and H1 (side effects) - 3-amine is best for activity (2-amine dec. activity + Side effects) - Branching on side chain with large groups dec. activity |
| Name the 7 Phenothiazines | - Clorpromazine (aliphatic) - Thioridazol (piperidine) - Mesoridazol (piperidine) - Perphenazine (piperazine) - Prochlorperazine (piperazine) - Fluphenzine (piperazine) - Trifluperazine (piperazine) |
| - Chlorpromazine | |
| - Thioridazine | |
| - Mezoridazine | |
| - Perphenazine - Formulated as a prodrug ester (Enanthate) - Given IM for slow release (DEPO) - Helps in bioavailability (no first pass) - Helps with compliance | |
| - Prochlorperazine | |
| - Fluphenazine - Formulated as a prodrug ester (Enanthate/Decanoate) - Given IM for slow release (DEPO) - Helps in bioavailability (no first pass) - Helps with compliance (long acting) | |
| - Trifluoperazine | |
| Metabolism of Chlorpromazine | - 1st N-dealkylation (active) - 2nd N-dealkylation (active) - N-Gly (inactive) - Deamination (inactive) - 7-OH (active) - Phenothiazene N-dealkylation (inactive) - Sulfer oxidation (inactive) - Sulfer dioxidation (inactive) |
| - Thiothixine - Class: Thioxanthene - Cis is more active - Equipotent to phenothiazenes - Similiar sedative and EPS effects as piperazine phenothiazines but more orthostatic hypotension | |
| - Flupenthixol Decanoate - Class: Thioxanthene - Cis is more active - Prodrug given IM for compliance - DOA: 1-2 weeks - Equipotent to phenothiazenes | |
| - Butyrophenone | - Discovered from mepiridine - Has chlorpromazine like antipsychotic activity (lower analgesia) - Altering in the butyl chain --> Dec. potency - X is usually F - Changing the Keto group --> Dec. potency - High affinity at D2 and a-1 - Moderate affinity at 5-HT and D1 |
| - Haloperidol - Higher Affinity to D2 --> More EPS - Sedative effect < Phenothiazenes - Mild hypotension - Less likely to produce weight gain (than chlorpromazine and atypical) - Cause more EPS for 2 reasons: * Higher affinity to D2 * HPP+ (damage DA neurons) | |
| Metabolism | |
| - Name the 4 butyrphenone analogues | - Haloperidol (Decanoate) - Spiperone - Trifluperidol - Droperidol |
| Name the 3 Diphenylbutylpiperidines | - Pimozide - Penfluridol - Fluspiriline |
| - Pimozide - Chemical class: Diphenylbutylpiperidines - They have longer DOA than butyrphenones - Used to treat acute exacerbation of Schizophernia and Tourette syndrome | |
| Atypical Neuroleptics | - Lower affinity for D2 and more selective to mesolimbic system --> Less EPS - Higher affinity to 5-HT2 receptors --> Inc. dopamine in the nigro striatil pathway --> Less EPS |
| - Metochlopramide - Antiemetic drug - Class: Benzamide - Not used as a antipsychotic - Binds to 5HT3/4 with low affinity making it useful to treat gastroesophageal reflux disease and good for gastric emptying | |
| - Sulpiride - Pyrolidine analogues of metochlopramide - Neuroleptic properties - Low EPS - Very hydrophilic --> poor bioavailability + low CNS crossing --> low potency | |
| Remoxipiride | - More potent that Haloperidol - Lower EPS and autonomic side effects - Aplastic anemia - Withdrawn from the market |
| Benzazepine | - Heterocycle is lipophilic with weak basicity - C-11 sub gives a water soluble N to help with oral dosing |
| - Clozapine - Benzodiazipine - Great affinity at D4 rather than D2 - Blocks muscarine + 5-HT2 - Orally active - Min EPS - Effective against -ve symptoms - Potential Fatal agranulocytosis (take blood tests daily) - Highest weight gain potential - DDI: Smoking and coffee | |
| Clozapine Induced Agranulocytosis | - The dehydrogenation of Clozapine leads to the formation of the nitronium ion which binds vs quickly to glutathione and depletes it. The neutrophile under stress undergoes apoptosis and eventually agranulocytocis |
| - Olanzapine - Thienobenzodiazepine - High affinity to D-2 and 5-HT 2 - Causes the highest weight gain - Well absorbed after oral - Gives inactive metabolites | |
| Metabolism | |
| - Quetiapene - Dibenzothiazepene - Moderate affinity to D2-3 and 5-HT2A - Effective for positive and negative symptoms - Orally bioavailable - Inactive metabolites | |
| Toxic Metabolism of | - Neutrophile toxicity |
| - Loxapine - Dibenzoxazepine - High affinity to D2 and 5-HT2 | |
| - Risperidone - Benzisoxazole - High affinity at D2 and 5-HT2 - Orally active - Effective against -ve symptoms - Has high EPS - Causes weight gain | |
| Paliperidone causes EPS | |
| - Zeprasidone - High affinity to D2 and 5-HT2 - Orally active - Has effect on cognition - Gives inactive metabolites | |
| - Aripiprazole - Arlypiperazine quinolinone derivative - Partial D2-3 agonits --> Low EPS - Full agonist on D2 autoreceptors --> Regulation of dopamine in the brain - Partial agonist 5-HT2A --> Less likely to cause weight gain - Good oral Bioavailability - Long DOA - Give active metabolite (long T1/2) | |
| Aripiprazole metabolism | |
| - Molindone - Tetrahydro indolone - Less affinity at D2 --> weaker than haloperidol (more EPS) - No 5-HT, adrenergic, muscarinic, H1 - Oral | |
| - Sertindol - High affinity to 5-HT2A/C, D2/3/4, adrenergic - Equipotent to Haloperidol at treating + symptoms, more potent at treating - symptoms - Long Half life - Has active metabolites |
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