D₂ Blocking Effects

Drugs that block D₂

GOOD: Mesocortical tracts - improve higher functioning & thought processing. Mesolimbic - improve mood, affect

BAD: Nigrostriatal: extrapyramidal dysfunction, hyperprolactinemia

1st gen: fluphenazine, haloperidol> Chlorpromazine

2nd gen: Risperidone>aripiprazole (partial agonist)

Classification of 1st gen by potency

D₂ effects - fluphenazine, haloperidol greater sensitivity than chlorpromazine

>potency = less likely for anticholinergic side effects, sedation, hypotension

Clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole - unknown

-antagonism for 5-HT_A

-Clozapine - D₄ affinity

Muscarinic - chlorpromazine, clozapine, olanzapine - less likely to cause extrapyramidal, but cause sedation, atropine-like actions

Alpha₁-causes sexual dysfunction - esp. ejaculation

H₁ - sedation, prevents nausea, vomiting - low-potency phenothiazine (chlorpromazine), clozapine-like drugs (clozapine, olanzapine, quetiapine)

oral, first-pass hepatic metabolism

All are lipid-soluble, use cytochrome P450

Half-life varies 10-24 hours

Available as long-acting esters that last 3-4 weeks

Schizophrenia - early and vigorous tx reduces later symptoms. 2nd gen - better tolerated,better for negative sx,can improve cognitive deficits.  Extrapyramidal symptoms made better with antimuscarinic drugs

-also bipolar, schizoaffective, drug-induced, Tourette's

-Also antiemetics - esp. promethazine

Sedation - esp. first generation, clozapine-like

Extrapyramidal - first gen, risperidone - treat w/benztropine, diphenhydramine

Tardive Dyskinesias - late-occurring, difficult to reverse - less w/atypicals - dose-related

Endocrine - hyperprolactinemia (1st gen)

Metabolic - atypical - weight gain, diabetes

Neuroleptic malignant syndrome - treated w/dantrolene

Seizures - clozapine, low potency antipsych

Cardiac tox - ziprasidone - prolong QT. Clozapine - myocarditis

Hematopoietic - clozapine - agranulocytosis