Karteikarten
Antipsychotic Drugs
Karten in diesem Stapel (44)
- 1What are the symptoms of SchizophreniaPositive: Hallucination, Delusion, Thought disorder
- Negative Symptoms: Lack of pleasure, Trouble with speech, Flattening, Withdrawal - 24 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 - 3Classic Vs Atypical DrugsClassic: 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 - 4Effects of blocking 1) Histamine 2) Serotonine 3) Dopamine 4) Muscarine 5) Adrenergic1) Sedation
2) Weight gain
3) EPS, Prolactine release, Thera use
4) Tachycardia, dry mouth, urine retension (makes EPS less)
5) Hypotension, Tachycardia - 5SAR 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
- 6—
- 7Name the 7 Phenothiazines- Clorpromazine (aliphatic)
- Thioridazol (piperidine)
- Mesoridazol (piperidine)
- Perphenazine (piperazine)
- Prochlorperazine (piperazine)
- Fluphenzine (piperazine)
- Trifluperazine (piperazine) - 8—- Chlorpromazine
- 9—- Thioridazine
- 10—- Mezoridazine
- 11—- Perphenazine
- Formulated as a prodrug ester (Enanthate)
- Given IM for slow release (DEPO)
- Helps in bioavailability (no first pass)
- Helps with compliance
- 12—- Prochlorperazine
- 13—- 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)
- 14—- Trifluoperazine
- 15Metabolism 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) - 16—- Thiothixine
- Class: Thioxanthene
- Cis is more active
- Equipotent to phenothiazenes
- Similiar sedative and EPS effects as piperazine phenothiazines but more orthostatic hypotension
- 17—- Flupenthixol Decanoate
- Class: Thioxanthene
- Cis is more active
- Prodrug given IM for compliance
- DOA: 1-2 weeks
- Equipotent to phenothiazenes
- 18- 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
- 19—- 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)
- 20Metabolism
- 21- Name the 4 butyrphenone analogues- Haloperidol (Decanoate)
- Spiperone
- Trifluperidol
- Droperidol - 22Name the 3 Diphenylbutylpiperidines- Pimozide
- Penfluridol
- Fluspiriline - 23—- Pimozide
- Chemical class: Diphenylbutylpiperidines
- They have longer DOA than butyrphenones
- Used to treat acute exacerbation of Schizophernia and Tourette syndrome
- 24Atypical 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 - 25—- 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
- 26—- Sulpiride
- Pyrolidine analogues of metochlopramide
- Neuroleptic properties
- Low EPS
- Very hydrophilic --> poor bioavailability + low CNS crossing --> low potency
- 27Remoxipiride- More potent that Haloperidol
- Lower EPS and autonomic side effects
- Aplastic anemia
- Withdrawn from the market - 28Benzazepine- Heterocycle is lipophilic with weak basicity
- C-11 sub gives a water soluble N to help with oral dosing - 29—- 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
- 30—
- 31Clozapine 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
- 32—- Olanzapine
- Thienobenzodiazepine
- High affinity to D-2 and 5-HT 2
- Causes the highest weight gain
- Well absorbed after oral
- Gives inactive metabolites
- 33Metabolism
- 34—- Quetiapene
- Dibenzothiazepene
- Moderate affinity to D2-3 and 5-HT2A
- Effective for positive and negative symptoms
- Orally bioavailable
- Inactive metabolites
- 35Toxic Metabolism of- Neutrophile toxicity
- 36—- Loxapine
- Dibenzoxazepine
- High affinity to D2 and 5-HT2
- 37—
- 38—- Risperidone
- Benzisoxazole
- High affinity at D2 and 5-HT2
- Orally active
- Effective against -ve symptoms
- Has high EPS
- Causes weight gain
- 39—Paliperidone causes EPS
- 40—- Zeprasidone
- High affinity to D2 and 5-HT2
- Orally active
- Has effect on cognition
- Gives inactive metabolites
- 41—- 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)
- 42Aripiprazole metabolism
- 43—- Molindone
- Tetrahydro indolone
- Less affinity at D2 --> weaker than haloperidol (more EPS)
- No 5-HT, adrenergic, muscarinic, H1
- Oral
- 44—- 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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- Beschreibung
- All Medicinal Chemistry 1 Karteikarten am Antipsychotic Drugs, erstellt von Majd Fawaz am 13/12/2020.
- Erstellt von
- Majd Fawaz
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