1st generation antipsychotics

- low potency

- high potency

Low potency:

- chlorpromazine

- thioridazine

High potency:

- haloperidol

- fluphenazine

2nd generation "atypical" antipsychotics

Clozapine

Quetiapine

Ziprasidone

Paliperidone

Iloperidone

Risperidone

Olanzapine

Aripiprazole

Asenapine

1st generation antipsychotic general properties

-receptor

-treats

-side effects

Receptor:

- high affinity D2 antagonists

Treats:

- positive symptoms 

- minimal effects on negative symptoms

Side effects:

- high incidence of extrapyramidal s/e's

- sedation

- elevated prolactin levels

Thioridazine

Chlorpromazine

- class

- side effects

Class:

- 1G "typical" low potency antipsych meds

Side effects:

- autonomic effects

- sedation

Haloperidol

Fluphenazine

- class

- side effects

Class:

- 1G "typical" high potency antipsych meds

Side effects:

- more extrapyramidal s/e's

- less sedation

General features of 2nd generation antipsychotics

First-line therapy

Lower incidence of EP s/e's

Used to treat levodopa-induced

Augmentation of Rx-resistant depression

Effective in patients not receiving benefit from 1G agents

Substituted for 1G agents when signs of tardative dyskinesia appear 

Weight gain + hyperglycemia (compliance issue)

QT prolongation

Sedation

Somnolence, dizziness, constipation, postural hypotension, dry mouth

Mortality risk in dementia-related psychosis

Suicidal risk if indicated for depression

Clozapine

-receptors

-side effects

Receptors:

- 5-HT₂ > D₂    (D₄ , D₃ > D₂) antagonist

- H1 antagonist

- α₁ antagonist

- M₁ antagonist

Side effects:

- most effective antipsychotic limited in used due to agranulocytosis

- sedative effects high

Risperidone

-receptors

Receptors:

- 5-HT₂ > D₂ antagonists

- H₁ antagonists

- α₁ antagonists

- M₁ antagonists

- selectivity for limbic system (targets D₃)

Ziprasidone

-receptors

-uses

Receptors:

- potent 5-HT_2A antagonist >> D₂

- high affinity for 5-HT_1A , 5-HT_1D, and 5-HT_2C

- less potent α₁ antagonists

- less affinity for M₁ & H₁ receptors

Uses:

- antipsych

- good anxiolysis and antidepressant

- low potential for impairing cognitive abilities = good in AD

Quetiapine

-receptors

-side effects

Receptors:

- 5-HT₂ > D₂ 

- H1

- α₁ & α₂ adrenergic antagonists

Side effects:

- possibility of cataracts

Olanzapine

-receptors

-contraindications

Receptors: (antagonists)

- D1, D2, D4

- 5-HT2, 5-HT3

- H1

- α1

- M1

Contraindicated:

- diabetics due to weight gain and hyperglycemic effects

Aripiprazole

-receptors

-uses

Receptors:

- D₂ and 5-HT_1A partial agonists

Uses:

- antipsych

- good for bipolar disorder

- improved blunted affect

**considered 3G antipsych

Asenapine

-receptors

5-HT_2A > D₂

D₃ and D₄ antagonists

5-HT₆ and 5-HT₇ antagonists

α₁ & α₂ adrenergic antagonists

Iloperidone

-receptors

5-HT₂ > D₂ 

low/no affinity for other receptors (H1, M1, α1)

Paliperidone

-receptors

Major active metabolite of risperidone

5-HT₂ > D₂ 

α₁ and α₂

H₁

D₂ receptor antagonists

-therapeutic effect

-side effect

Therapeutic effect:

- reduced positive signs of psychosis

Side effects:

- extrapyramidal sypmtoms

- elevated prolactin and its effects

Serotonin 5-HT_2A 

-therapeutic effect

-side effect

Therapeutic effect:

- Reduced negative signs of psychosis

- mitigation of EPS

- potentiation of antipsychotic effect on positive signs

Side effects:

- sexual disturbances

α₁ adrenergic antagonists

-therapeutic effect

-side effect

Therapeutic effect:

- unknown

Side effects:

- postural hypotension

- dizziness

- reflex tachycardia

- potential for drug interactions (esp anti-HTNs)

Muscarinic-cholinergic antagonist effects

-therapeutic

-side effects

Therapeutic effects:

- mitigation of EPS

Side effects:

- blurred vision

- urinary retention

- sinus tachycardia

- memory impairment

- narrow angle glaucoma

H₁ antagonist effects

-therapeutic

-side effects

Therapeutic:

- sedation

Side effect:

- sedation

- increased appetite

- weight gain

- hypotension