Collier Antipsychotics General

What neurotransmitters plat a role in schizophrenia

1. Serotonin

2. Gluatamte

3. Ach

4. Dopamine

What are the 4 major dopaminergic tracts and what does each one do?

Nigrostriatal: Motor control

Mesolimbic: Reward

Mesocortical: Cognition

Tuberoinfundibular: regualtes prolactin

What are the Dopminergic families

D1 fam: 1 &5

D2 fam: 2,3,4

D2 Blockade effects

Movement disorders, Tardive dyskinesia, hyperprolactinemia, neuroleptic malignant syptom, antiemtic, secondary negative symptoms

D2 Bloackade Movement Disorders

1) Acute dystonias

2)Parkinsonism like effects

3)Perioral tremor (rabbit syndrome)

Akathisia: the feeling of motor restlessness

D2 Blockade Tardive Dyskinesia

Receptor upregulation in the nigrostriatal tract leads to involuntary hyperkinetic movements

→Late occurring

Options: Botox, Valbenazine, Deutetrabenazine

* work by blocking the VMAT2 packaging of dopamine into presynaptic vesicles

D2 Blockade Hyperprolactinemia

Infertility in women

Loss of libido in men, abnormal growth of breast

→ Most SGAs have a low risk of hyperprolactinemia

D2 bloackde Neuroleptic malignant symptom

Fever, rigidity, mental status changes, autonomic instability

*Cause not completely clear

D2 blockade effect on central reward pathway

May lead to secondary negative symptoms

5HT2A antagonism

•Therapeutic efficacy→ May facilitate Dopamine release in cortex

•May help limit EPS → May also facilitate dopamine release in the striatum

H1 Antagonism

•Neurotransmitter in CNS

•H1 antagonists lead to sedation

•Possible tolerance leading to rebound insomnia

What receptors cause weight gain

H1 and 5HTsc antagonism increases appetite

Adverse effects: antimuscarinic effects

M1 blockade

Dry mouth, difficulty peeing,

M4 Agonism by clozapine → contributes to sialorrhea (drooling)

Adverse effects: alpha blockade

→ Orthostatic hypotension

→Often accompanied by orthostatic tachycardia

→Elderly patients sensitive

→Most common when starting therapy or after dose increase

→Tolerance can develop

Clozapine’s alpha 2 antagonism may contribute to its drool risk

adverse effects: metabolic

Dyslipidemia

Impaired glycemic control

adverse effects: Electroencephalographic Effects

Lower seizure threshold

adverse effects: cardiac

QT prolongation: Block Ikr channel

Myocarditis

DRESS

Drug Reaction with Eosinophilia and Systemic Symptoms

Adverse effects: leukopenias

a condition where the body doesn't have enough disease-fighting leukocytes in the blood

→Clozapine with agranulocytosis

a condition in which the absolute neutrophil count (ANC) is less than 100 neutrophils per microlitre of blood

Antipsychotic indications

Schizophrenia

Bipolar

Adjunct for unipolar depression

Tourette’s

Irritability in autism

Clinical respone time for Psychosis

hours to weeks

Clinical respone time for mania

within a week

Overdose risk

Chlorpromazine, thioridazine- risk of torsade

Pediatrics on antipsychotics

•Sensitive to EPS and weight gain

•Hyperprolactinemia

Geriatrics on antipyshotics

•Sensitive to EPS, TD, orthostasis, sedation, anticholinergic effects

•Cerebrovascular event risk

•Dementia risk

Pregnancy and antipyschotics

•Category B or C

•infants metabolize drugs more slwoly

•Cross placenta

Breast feeding and antipsychotics

•Small amount secreted in breast milk