Antipsychotics

Question 1

chlorpromazine

Answer 1

Phenothiazines, neuroleptic
- TYPICAL ANTIPSYCHOTIC/ CONVENTIONAL ANTIPSYCHOTIC

Chemical type 1
- Aliphatic side chain

Primarily used to treat schizophrenia

• block response to increased/abnormal neurotransmitter levels
• Does not cure/elimiate fundamental and chronic though disorder
• Decrease the intensity of hallucinations and delusions

Selective for DA receptor
- Low Potency = not selective for D2 (desired) or D1

Metabolism:

• CYP2D6 and CYP3A4
• Significant delay of onset 4-8 weeks

Side Effect:

• Blockade of Cholinergic Muscarinic Receptor
  
  • Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, and confusion
• Blockade of alpha Adrenergic Receptor
  
  • Vasodilation, orthostatic hypotension, light headedness, reflex tachycardia and sexual dysfunction
• Pituitary D2 Receptor Block
• Increased prolactin release
• Infertility and impotence

H1 histamine receptor Block
- Sedation and Weight Gain

Question 2

fluphenazine

Answer 2

Phenothiazine

Chemical Type I:
- Piperazine side chain

Primarily used to treat schizophrenia

• block response to increased/abnormal neurotransmitter levels
• Does not cure/elimiate fundamental and chronic though disorder
• Decrease the intensity of hallucinations and delusions

Selective for DA receptor
- High Potency= more selective for D2 (desired) or D1

Metabolism:

• CYP2D6 and CYP3A4
• Significant delay of onset 4-8 weeks

Fluphenazine Decanoate is a slow release formula (2-4 weeks)

• Deep gluteal intramuscular injection
• Used for patients non-compliant with oral meds

Mechanism:
- Inhibits ATP to cAMP formation

Side Effect:

• Blockade of Cholinergic Muscarinic Receptor
  
  • Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, and confusion
• Blocks Dopamine D2R
• Pituitary D2 Receptor Block
• Increased prolactin release
• Infertility and impotence

H1 histamine receptor Block
- Sedation and Weight Gain

Side Effect:
- Neuroleptic Malignant Syndrome (NMS)
- Instability and collapse of ANS
- Excessive sweating/salivary excretion
- Unstable BP and CV instabitility
- Fever, muscle stiffness, delirium, stupr
- Incidence: 0.2 to 3.2% of patients
Fatal in 10% of these
- Less likely if had been stable before
- Manifested in patients with Parkinson's disease who stop/reduce dose of Dopaminergics

Question 3

thiothixene

Answer 3

Thioxanthene

Antipsychotic Chemical Type 1

Typical Antipsychotic (conventional antipsychotic)

Medium Efficacy: moderate more selectivity for D2 receptors

Metabolism:

• CYP2D6 and CYP3A4
• Significant delay of onset 4-8 weeks

Mechanism:
- Inhibits ATP to cAMP formation

Side Effect:

• Blockade of Cholinergic Muscarinic Receptor
  
  • Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, and confusion
• Blocks Dopamine D2R
• Pituitary D2 Receptor Block
• Increased prolactin release
• Infertility and impotence

H1 histamine receptor Block
- Sedation and Weight Gain

Side Effect:
- Neuroleptic Malignant Syndrome (NMS)
- Instability and collapse of ANS
- Excessive sweating/salivary excretion
- Unstable BP and CV instabitility
- Fever, muscle stiffness, delirium, stupr
- Incidence: 0.2 to 3.2% of patients
Fatal in 10% of these
- Less likely if had been stable before
- Manifested in patients with Parkinson's disease who stop/reduce dose of Dopaminergics

Question 4

haloperidol

Answer 4

Antipsychotic
Chemical Type 1

Butyrophenones

Typical Antipsychotic (conventional antipsychotic)

High Efficacy: More selectivity for D2 receptors

Metabolism:

• CYP2D6 and CYP3A4
• Significant delay of onset 4-8 weeks

Haloperidol Decanoate is a slow release formula (2-4 weeks)

• Deep gluteal intramuscular injection
• Used for patients non-compliant with oral meds

Mechanism:
- Inhibits ATP to cAMP formation

Side Effect:

• Blockade of Cholinergic Muscarinic Receptor
  
  • Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, and confusion
• Blocks Dopamine D2R
• MOST PROMINENT Pituitary D2 Receptor Block
• prolactin release
• Infertility and impotence

H1 histamine receptor Block
- Sedation and Weight Gain

Side Effect:
- Neuroleptic Malignant Syndrome (NMS)
- Instability and collapse of ANS
- Excessive sweating/salivary excretion
- Unstable BP and CV instabitility
- Fever, muscle stiffness, delirium, stupr
- Incidence: 0.2 to 3.2% of patients
Fatal in 10% of these
- Less likely if had been stable before
- Manifested in patients with Parkinson's disease who stop/reduce dose of Dopaminergics

Question 5

aripiprazole

Answer 5

Antipsychotic Chemical Type II

2nd generation antipsychotic

Dopamine Partial Agonist

3rd generation

Competitive partial agonist for dopamine receptors (selectivity for D2 receptors) antagonizes serotonin receptors

Discontinuation must be done gradually to avoid marked withdrawal or relapse

Side Effects:

• Blocks other receptors
• Alpha Adrenergic
  
  • Vasodilation, orthostatic hypotension, light headedness, reflex tachycardia, sexual dysfunction
• Dopamine receptor
• Serotonin receptor
  
  • Sedation and weight gain

Question 6

clozapine

Answer 6

Atypical Antipsychotic
Chemical type II

Synthetic BZ derivative

Selective antagonist for serotonin and dopamine receptors

Drug induced agranulocytosis, leukopenia

Blocks Activation of postsynaptic 5-HT2A receptor

Blocks activation of postsynaptic D2 Receptors

Blocks

• Cholinergic Receptor
• alpha-adrenergic
• Dopamine receptor
• Serotonin receptor
• H histamine receptor

Metabolism: Induction of CYP1A2

Inhibits CYP2D6 and CYP3A4 to decrease drug elimination

Acute adverse events only with overdose
- Hypotension, hyper/hypothermia, seizures and coma, Ventricular tachycardia

Question 7

olanzapine

Answer 7

Atypical Antipsychotic
Chemical type II

Synthetic BZ derivative

Selective antagonist for serotonin and dopamine receptors

Blocks Activation of postsynaptic 5-HT2A receptor

Blocks activation of postsynaptic D2 Receptors

Blocks

• Cholinergic Receptor
• alpha-adrenergic
• Dopamine receptor
• Serotonin receptor
• H histamine receptor

Metabolism: Induction of CYP1A2

Inhibits CYP2D6 and CYP3A4 to decrease drug elimination

Acute adverse events only with overdose
- Hypotension, hyper/hypothermia, seizures and coma, Ventricular tachycardia

Outperformed Other Typical Antipsychotics

• NIMH sponsored CATIE study
• Superior Efficacy

Severe metabolic side effects

• Major weight gain
• Increase in glucose, cholesterol, and TGs

Question 8

paliperidone

Answer 8

Antipsychotic Chemical Type II

2nd generation antipsychotic

Selective antagonist for serotonin and dopamine receptors

Metabolized by p450

A Major Active Metabolite of Risperidone
- CYP2D6 for elimination

Side Effects:

• Blocks other receptors
• Dopamine receptor
• Serotonin receptor
  
  • Sedation and weight gain

Inhibition of Cyp2D6 and CYP3A4 decreases drug elimination lesser extent

Question 9

quetiapine

Answer 9

Atypical Antipsychotic
Chemical type II

Synthetic BZ derivative

Selective antagonist for serotonin and dopamine receptors

Blocks Activation of postsynaptic 5-HT2A receptor

Blocks activation of postsynaptic D2 Receptors

Blocks

• Cholinergic Receptor
• alpha-adrenergic
• Dopamine receptor
• Serotonin receptor
• H histamine receptor

Metabolism: Induction of CYP1A2

Inhibits CYP2D6 and CYP3A4 to decrease drug elimination

Acute adverse events only with overdose
- Hypotension, hyper/hypothermia, seizures and coma, Ventricular tachycardia

Outperformed Other Typical Antipsychotics

• NIMH sponsored CATIE study
• Superior Efficacy

Severe metabolic side effects

• Major weight gain
• Increase in glucose, cholesterol, and TGs

Question 10

risperidone

Answer 10

2nd generation antipsychotic

Selective antagonist for serotonin and dopamine receptors

Metabolized by p450

Produces Major Active Metabolite Paliperidone
- CYP2D6 for elimination

Risperiodone microspheres

• Slow release formula (2-4 weeks
• Deep gluteal intramuscular injection
• Used for patients non compliant with oral med

Side Effects:

• Blocks other receptors
• Dopamine receptor
• Serotonin receptor
  
  • Sedation and weight gain

Inhibition of Cyp2D6 and CYP3A4 decreases drug elimination lesser extent

Question 11

prochlorperazine

Answer 11

Atypical antipsychotic

D2 receptor blockade goes to antipsychotic effects

H1 histamine receptor blockade– antiemetic effects

Question 12

promethazine

Answer 12

Atypical antipsychotic

D2 receptor blockade goes to antipsychotic effects

H1 histamine receptor blockade– antiemetic effects