Biological Basis for Psychopharmacology Study Notes

Learning Objectives and Core Concepts in Psychopharmacology

• Identify Major Brain Structures: Determine at least three major brain structures and eight major functions altered by mental illness and psychotropic medication.
• Evidence-Based Neuroimaging: Describe how neuroimaging (CT, MRI, fMRI, PET, SPECT) is used to understand abnormalities in brain function, structure, and receptor pharmacology.
• Process of Neurotransmission: Explain the basic process of neurotransmission and synaptic transmission.
• Neurotransmitter Systems and Drug Classes: Identify the specific systems affected by:
  • Antidepressants
  • Antianxiety agents
  • Sedative-hypnotics
  • Mood stabilizers
  • Antipsychotic agents
  • Anticholinesterase drugs
• Safety and Interactions: Explain the relevance of psychodynamic and psychokinetic drug interactions for safe nursing care.
• MAOIs Restrictions: Discuss safety concerns regarding dietary (tyramine) and drug restrictions with monoamine oxidase inhibitors (MAOIs).
• Typical vs. Atypical Antipsychotics: Compare and contrast these drugs regarding side-effect profiles and impact on quality of life.
• Psychoneuroimmunology: Discuss the relationship between the immune system and the nervous system in the context of mental health.
• Cultural and Genetic Factors: Describe how genes (pharmacogenetics) and culture affect response to psychotropic medications.

Intracranial Regulation and Major Brain Functions

• Intracranial Regulation (ICR): Normal and abnormal processes of intracranial function depend on a consistent supply of blood, oxygen, and nutrients. Carbohydrates are the primary fuel for the brain.
• Impact of Mental Illness and Medications: Mental disturbances are often associated with alterations in brain functions. Conversely, psychotropic drugs can relieve symptoms but also cause undesired effects such as sedation, motor disturbances, sexual dysfunction, and weight gain.
• Core Brain Functions:
  • Monitoring changes in the external world.
  • Monitoring the composition of body fluids.
  • Regulating the contraction of skeletal muscles and internal organs.
  • Mediating basic drives: hunger, thirst, sex, and aggressive stimulation.
  • Mediating conscious sensation.
  • Storing and retrieving memories.
  • Regulating mood (affect and emotion) and intellectual functions.
  • Regulating the sleep cycle.
  • Producing and interpreting language.
  • Processing visual and auditory data.

Neuroanatomy and Functional Localization

• Plasticity: The brain's architecture is genetically programmed but undergoes plasticity throughout life—the process of adapting and changing as gray matter shrinks or thickens and connections are pruned or forged.
• The Cerebrum (Cerebral Cortex):
  • Known as the "human brain" or "higher brain," responsible for cognition, self-awareness, and executive functions.
  • Frontal Lobe: Responsible for conscious movement (voluntary motor ability), problem-solving, speech production, goal formulation, and decision-making.
  • Prefrontal Cortex (PFC): Mediates social behaviors, personality, insight, and motivation.
  • Parietal Lobe: Involved in tactile sensation, spatial awareness (proprioception), concept formation, reading, and mathematics.
  • Occipital Lobe: Primary center for vision, visual processing, and visual memories.
  • Temporal Lobe: Responsible for hearing, language reception/comprehension, and storing sounds into memory.
• Brainstem:
  • Composed of the midbrain, pons, and medulla.
  • Regulates basic life functions: heart rate, breathing, and sleep.
  • Reticular Activating System (RAS): Projections from the brainstem that control levels of consciousness and sedation.
• Cerebellum:
  • Involved in motor control, balance, and coordination of skeletal muscles.
  • Plays a role in cognitive processing and eye movement.
  • Alterations are associated with positive symptoms (hallucinations/delusions) and negative symptoms (poor coordination/cognition) in schizophrenia.
• The Limbic System ("Emotional Brain"):
  • A group of structures linking the frontal cortex, basal ganglia, and upper brainstem.
  • Hippocampus: Involved in making new memories. Chronic stress can cause it to shrink.
  • Amygdala: Processes fear and anxiety. Hyperactivity is common in trauma and paranoia.
  • Basal Ganglia: Deep gray matter pockets involved in motor responses via the extrapyramidal motor system. Relies on dopamine for muscle tone and stability.
• Thalamus: Functions as a filter for sensory information before it reaches the cerebral cortex. Disruption in filtering is associated with schizophrenia.
• Hypothalamus: Maintains homeostasis (temperature, blood pressure, libido, hunger, thirst, circadian rhythms). Directs the secretion of hormones from the pituitary gland.

Cellular Composition and Synaptic Transmission

• Neurons: There are more than $100 \times 10^{9}$ (100 billion) interconnected nerve cells. They conduct electrical impulses (neurotransmission).
• Synaptic Transmission Process:
  1. An electrical impulse reaches the end of the presynaptic neuron.
  2. Neurotransmitters are released from the axon terminal into the synapse.
  3. Transmitters diffuse across the synapse and attach to receptors on the postsynaptic neuron.
  4. The interaction either inhibits or excites the postsynaptic cell.
• Neurotransmitter Destruction: Necessary to avoid continuous stimulation.
  • Enzymatic Destruction: Enzymes like acetylcholinesterase destroy acetylcholine ($ACh$) at the postsynaptic membrane. Monoamine oxidase ($MAO$) destroys norepinephrine ($NE$), dopamine, and serotonin inside the cell.
  • Reuptake: The transmitter is taken back into the presynaptic cell and either reused or destroyed.
• Neurotransmission Abnormalities:
  • Deficient Transmission: Caused by deficient neurotransmitter release or a reduction in receptors.
  • Excess Transmission: Caused by excess neurotransmitter release or increased receptor responsiveness.

Major Neurotransmitter Systems

• Dopamine: Involved in cognition, motivation, movement, and reward.
  • Increase: Psychosis, mania.
  • Decrease: Parkinson’s disease, depression.
• Norepinephrine (NE): Mediates mood, attention, arousal, and the "fight or flight" response.
  • Increase: Mania, anxiety, psychosis.
  • Decrease: Depression.
• Serotonin (5-HT): Regulates mood, sleep, hunger, pain perception, and aggression.
  • Increase: Anxiety states.
  • Decrease: Depression.
• Histamine: Involved in alertness and inflammatory response.
  • Decrease: Sedation and significant weight gain.
• $\gamma$-Aminobutyric Acid (GABA): Major inhibitory neurotransmitter; reduces anxiety and aggression.
  • Decrease: Mania, anxiety, psychosis.
• Glutamate: Major excitatory neurotransmitter; vital for learning and memory.
  • Unregulated Increase: Neurotoxicity (can kill neurons); associated with Alzheimer's disease.
• Acetylcholine (ACh): Affects memory, learning, and the parasympathetic nervous system.
  • Decrease: Alzheimer’s disease, Huntington’s chorea, Parkinson’s disease.

Neuroimaging Techniques

• Structural Imaging:
  • Computed Tomography (CT): Slices of X-ray images. Detects lesions, aneurysms, and ventricle abnormalities in schizophrenia.
  • Magnetic Resonance Imaging (MRI): Uses magnetic fields and radio waves. Provides higher resolution than CT; detects edema, ischemia, and infection.
• Functional Imaging:
  • Positron Emission Tomography (PET): Uses radioactive substances to visualize brain activity ($O_2$ utilization, glucose metabolism). Shows decreased frontal lobe metabolism in depression/schizophrenia.
  • Single-Photon Emission Computed Tomography (SPECT): Similar to PET but uses $\gamma$-radiation (photons); less costly with lower resolution.
  • Functional MRI (fMRI): Measures blood flow without radioactive isotopes; used to predict response to antipsychotics via the Striatal Connectivity Index (SCI).

Psychotropic Drug Classes: Antidepressants

• Monoamine Hypothesis: Suggests depression is caused by a deficiency in dopamine, NE, or serotonin.
• Monoamine Receptor Hypothesis: Suggests low neurotransmitter levels lead to receptor upregulation; antidepressants eventually cause downregulation, explaining the delayed therapeutic effect.
• Selective Serotonin Reuptake Inhibitors (SSRIs): (e.g., fluoxetine, sertraline, paroxetine).
  • Side effects: Anxiety, insomnia, sexual dysfunction, GI disturbances.
  • Serotonin Syndrome: Risk increases if combined with other serotonergic agents (St. John’s wort, MAOIs, etc.). Symptoms include restlessness, shivering, fever, and seizures.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): (e.g., venlafaxine, duloxetine). Blocks reuptake of both 5-HT and NE.
• Tricyclic Antidepressants (TCAs): (e.g., amitriptyline). "Dirty drugs" due to lack of selectivity. Blocked $H_1$ receptors cause sedation; blocked muscarinic receptors cause anticholinergic effects; blocked $\alpha_1$ receptors cause orthostatic hypotension.
• Monoamine Oxidase Inhibitors (MAOIs): (e.g., phenelzine, tranylcypromine).
  • Hypertensive Crisis: Occurs when combined with pseudoephedrine or tyramine (found in aged/fermented foods). Dietary restrictions must last 2 weeks after stopping the drug.
• Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs): (e.g., bupropion). Does not act on serotonin; used for smoking cessation because it inhibits nicotinic receptors.
• Serotonin Antagonists/Reuptake Inhibitors (SARIs): (e.g., trazodone). Low doses are used for insomnia; can cause priapism.

Antianxiety, Mood Stabilizers, and Hypnotics

• Benzodiazepines: (e.g., diazepam, alprazolam). Enhance GABA activity.
  • Risks: Tolerance, abuse, dementia link, life-threatening respiratory depression if combined with CNS depressants (alcohol/opioids).
  • Side Effects: Ataxia due to GABA receptors in the cerebellum.
• Buspirone: Non-addictive, non-sedating anxiolytic; acts as a serotonin partial agonist.
• Z-Hypnotics: (e.g., zolpidem, eszopiclone). Selective for $GABA_A$ $\alpha_1$-subunits; purely sedative.
• Lithium: Mood stabilizer with a low therapeutic index.
  • Monitoring: Requires blood levels; kidney and thyroid function checks. Sodium depletion causes lithium retention and toxicity.
• Anticonvulsants:
  • Valproate: Inhibits GABA catabolism. Black box warnings for hepatotoxicity, pancreatitis, and teratogenicity.
  • Lamotrigine: Inhibits glutamate. Risk of Stevens-Johnson syndrome (SJS).
  • Carbamazepine: Used for rapid cycling; requires periodic CBC due to risk of aplastic anemia and agranulocytosis.

Antipsychotic Medications

• First-Generation (FGAs/Typical): (e.g., haloperidol, chlorpromazine). Strong $D_2$ receptor antagonists.
  • Side Effects: Extrapyramidal symptoms (EPS) including dystonia, akathisia, and tardive dyskinesia ($TD$).
  • Neuroleptic Malignant Syndrome (NMS): Emergency characterized by muscle rigidity, high fever, and autonomic instability.
• Second-Generation (SGAs/Atypical): (e.g., clozapine, risperidone, olanzapine). Serotonin-dopamine antagonists.
  • Clozapine: Can cause agranulocytosis. Requires weekly blood draws for Absolute Neutrophil Count (ANC).
  • Risperidone: High risk for orthostatic hypotension and increased prolactin (gynecomastia/amenorrhea).
  • Olanzapine: Significant weight gain and metabolic side effects (measured by BMI, waist circumference, and glucose).
  • Ziprasidone: Must be taken with food (at least 350-500 calories); risk of QT interval prolongation.
  • Aripiprazole: Dopamine-serotonin stabilizer (partial agonist).

Questions & Discussion

• Q: What nursing diagnosis is priority for a patient with a cerebellum abscess?
• A: Risk for falls related to loss of balance and equilibrium.
• Q: Which intervention is crucial for a patient starting risperidone?
• A: Assessing sitting, standing, and lying blood pressure daily to monitor for orthostatic hypotension.
• Q: Why was trazodone prescribed for a non-depressed patient at 50 mg?
• A: In low doses, trazodone helps relieve insomnia; higher doses are required for antidepressant effects.
• Q: Which patient would have the most difficulty with problem-solving?
• A: A 52-year-old diagnosed with schizophrenia at age 21 on long-term haloperidol, due to possible sustained cognitive effects and the nature of the chronic illness.

Additional Biological Interactions

• Psychoneuroimmunology (PNI): Researches the link between the immune and nervous systems. Chronic inflammation can release cytokines that shrink the hippocampus and reduce neurogenesis, leading to learning delays and mood changes.
• Cross-Cultural Psychopharmacology: Explores ethnic variations in drug response due to genetic predisposition (e.g., $CYP450$ polymorphisms) and cultural beliefs regarding mental health treatment.