NERVOUS SYSTEM 3

Psychopharmacology Drugs for mental illness, Depression, anxiety, insomnia

CNS Neurotransmitters Physiology Review: • Central nervous system (CNS) neurotransmitters (NTs) are synthesized in axon terminals • After nerve stimulation, NTs are released • NTs diffuse and combine with central receptors resulting in an “effect” • NTs are “turned off” by reuptake and/or enzymatic inactivation • Major CNS NTs important to psychopharmacology include NE, 5-HT, Ach, DA, GABA, among others

CNS Neurotransmitters - continued Select Examples Comments Acetylcholine (Ach)2 • Role in ensuring smooth, initiated movement • Assists with cognitive function and memory • Kept in balance with dopamine Dopamine (DA)1 • Role in thought processes • Assists with movement • Kept in balance with acetylcholine Gamma-amino butyric acid (GABA) • Inhibitory NT • Causes relaxation Norepinephrine (NE)1 • Role in mood and well-being Serotonin (5-HT)1 • Role in mood and well-being • Facilitates motor activity

Psychosis Psychosis: • Symptom or feature of mental illness characterized by radical changes in personality, impaired functioning and a distorted sense of objective reality • Delusions: false beliefs or ideas strongly held in spite of invalidating evidence • Hallucinations: hearing, seeing or feeling things that are not actually there • Illusions: erroneous, false perception of reality • Paranoia: unfounded or exaggerated distrust of others

 Psychosis: Schizophrenia • Type of psychosis • The most common psychotic disorder • Characterized by severely impaired thinking, emotions and behaviors • Patients are typically unable to filter sensory stimuli • May have enhanced perceptions of sounds, colors and other features of the environment • Eventually become withdrawn and unable to take care of ADLs  high suicide risk

Schizophrenia – continued Pathophysiology Review: • Genetics? Family history often positive • Overproduction or over-activity of dopaminergic pathways in the basal nuclei (area of the brain responsible for motor activity) • Symptoms associated with dopamine type 2 (D2) receptors • All antipsychotic drugs act by entering dopaminergic synapses and competing with dopamine • By blocking most D2 receptors, antipsychotic drugs decrease schizophrenia symptoms

Schizophrenia – continued
Pharmacologic Management:
• Treatment reduces symptoms but does not provide a cure
• Little difference in terms of efficacy of all antipsychotic drugs but
patients may tolerate one drug better than another
• Treatment recommendations from schizophrenia Patient Outcomes
Research Team (PORT) were published in 2009
• Antipsychotic Drug Categories:
1. Conventional (Typical) Antipsychotics
• Phenothiazines (“Neuroleptics”; though all antipsychotic drugs
may be referred to by this term)
2. Atypical Antipsychotics

Phenothiazines: Conventional (Typical)
Antipsychotic Drugs
Agents: Chlorpromazine, (Thorazine), fluphenazine (Prolixin),
mesoridazine (Serentil), perphenazine (Trilafon),
thioridazine (Mellaril), trifluoperazine (Stelazine)
MOA: Blockade of dopamine receptors >> serotonin receptors
Adverse
Effects:
Sedation, drowsiness, dizziness, extra-pyramidal
symptoms, QTc prolongation, photosensitivity, orthostatic
hypotension, urinary retention, tardive dyskinesia,
neuroleptic malignant syndrome
Comments: All block the excitement associated with “positive”
schizophrenia symptoms
Not all phenothiazines are created equal
Many drug-drug interactions