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What neurotransmitters plat a role in schizophrenia
Serotonin
Gluatamte
Ach
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