Biological Basis for Understanding Psychopharmacology Study Notes

Core Concepts and Objectives of Psychopharmacology

• The primary goal of psychiatric-mental health nursing is to comprehend the neurobiology of psychiatric disorders and the role of psychotropic medications in symptom management and relapse prevention.

• Intracranial Regulation (ICR): Includes all normal and abnormal processes of intracranial function. Nurses manage ICR issues in both community and inpatient settings. ICR depends on a consistent supply of blood, oxygen, and nutrients, specifically carbohydrates, which are the main fuel source for the brain.

• Neurotransmission and Medication Interaction: Mental disturbances are often linked to alterations in brain functions because all brain functions operate through the specialized interactions of neurons. Psychotropic drugs aim to relieve symptoms but can also interfere with other essential brain activities.

• Brain Plasticity: While the basic architecture of the brain is genetically programmed, plasticity (the process of adapting and changing) occurs throughout life. This involves gray matter shrinking or thickening and the forging or pruning of neuronal connections.

Functional Anatomy of the Cerebral Lobes

• Cerebrum (Cerebral Cortex): Often referred to as the "human brain" or "higher brain," it is responsible for higher cognitive skills, self-awareness, and executive functions. It consists of four main lobes:

  • Frontal Lobe: Responsible for thought processes, formulating and selecting goals, planning, initiating/terminating actions, decision-making, insight, motivation, social judgment, and voluntary motor ability.

  • Prefrontal Cortex (PFC): The most anterior portion of the frontal cortex; involved in moderating social behaviors, personality, and goal setting.

  • Parietal Lobe: Involved in sensory and motor functions, including receiving and identifying sensory info, concept formation, abstraction, proprioception (body awareness), reading, mathematics, and right/left orientation.

  • Temporal Lobe: Responsible for auditory functions, language comprehension, and storing sounds into memory. It connects with the limbic system to allow the expression of emotions (sexual, aggressive, fear).

  • Occipital Lobe: Primarily responsible for vision, interpreting visual images, visual association, visual memories, and language formation.

Brainstem, Cerebellum, and Limbic System

• Brainstem: Composed of the midbrain, pons, and medulla oblongata. It regulates basic life functions:

  • Midbrain: Controls pupillary reflex and eye movement.

  • Pons: A major processing station in auditory pathways.

  • Medulla Oblongata: Contains reflex centers for balance, heart rate, rate/depth of respirations, coughing, swallowing, sneezing, blood pressure maintenance, and vomiting.

  • Reticular Activating System (RAS): Projections from the brainstem that control levels of consciousness and sedation.

• Cerebellum: Regulates skeletal muscle coordination, contraction, and maintenance of equilibrium. It also handles cognitive processing and eye movement.

  • Clinical Link: Cerebellar dysfunction or decreased size is often noted in schizophrenia, potentially explaining coordination issues and poor cognitive performance (negative symptoms).

• Limbic System ("The Emotional Brain"): A group of structures including the hippocampus, amygdala, hypothalamus, and thalamus that mediate thought and feeling through complex bidirectional connections.

  • Hippocampus: Involved in making new memories; interacts with the PFC. Chronic stress can cause it to shrink, leading to depression and cognitive impairment.

  • Amygdala: Processes fear and anxiety. Hyperactivity is common in trauma and may underlie paranoia in schizophrenia; hypoactivity may predict a capacity to respond to antidepressants.

  • Basal Ganglia: Subcortical pockets of gray matter that play a major role in motor responses via the extrapyramidal motor system. They rely on dopamine for muscle tone and stability.

  • Thalamus: Filters sensory information before it reaches the cerebral cortex. Disrupted filtering is associated with schizophrenia.

Homeostasis and the Autonomic Nervous System (ANS)

• Hypothalamus: Maintains homeostasis by regulating temperature, blood pressure, perspiration, libido, hunger, thirst, and circadian rhythms (sleep/wake cycles).

  • Neurohormones: Releasing hormones (e.g., Corticotropin-Releasing Hormone or $CRH$) direct the anterior pituitary gland. The hypothalamus-pituitary-adrenal axis is often disrupted in depression, anxiety, and insomnia.

  • Thyroid Regulation: The hypothalamic-pituitary-thyroid axis regulates nearly every organ system. Thyroid hormones are used to treat depression, rapid-cycling bipolar $I$ disorder, or lithium-induced hypothyroidism.

  • Prolactin Regulation: Dopamine from the hypothalamus inhibits prolactin. Blocking dopamine (via typical antipsychotics) can cause hyperprolactinemia, leading to amenorrhea, galactorrhea, gynecomastia, or sexual dysfunction.

• Sympathetic Nervous System: Dominant in stress situations (fight-or-flight), causing pupil dilation, increased heart rate, and decreased intestinal motility. Highly activated by stimulants like amphetamines and cocaine.

• Parasympathetic Nervous System: Associated with a calm, relaxed state, causing pupil contraction, decreased heart rate, and increased stomach motility/insulin.

• ADHD Treatment: Sympathomimetics (stimulants) like methylphenidate ($Ritalin$, $Concerta$) and amphetamines ($Adderall$) increase synaptic levels of dopamine and norepinephrine ($NE$) to improve focus.

  • Note: Lisdexamfetamine ($Vyvanse$) is a "prodrug" requiring intestinal enzymes to activate, reducing abuse potential.

  • Side Effect Management: Decreased appetite can be managed by eating a high-calorie breakfast before medication and adding cheese, butter, or whole milk to meals.

Neuroimaging and Cellular Composition

• Structural Imaging: Shows gross anatomical details.

  • Computed Tomography (CT): Uses $x$-ray slices for a $3$-dimensional reconstruction; detects lesions/infarcts. In schizophrenia, it shows gray-matter reduction and ventricle abnormalities.

  • Magnetic Resonance Imaging (MRI): Uses magnetic fields for high-resolution cross-sectional images; used to exclude neurological disorders.

• Functional Imaging: Shows brain activity.

  • Positron Emission Tomography (PET): Radioactive substances visualize oxygen utilization, glucose metabolism, and neurotransmitter-receptor interaction. Shows decreased frontal lobe metabolism in schizophrenia/depression and increased metabolism in OCD.

  • Single-Photon Emission Computed Tomography (SPECT): Similar to PET but uses $\gamma$-radiation; less costly but lower resolution.

  • Functional MRI (fMRI): Measures communication between brain regions via blood flow. Striatal Functional Connectivity ($SCI$) may eventually predict drug response.

• Neurons and Synaptic Transmission: The brain has over $100$ billion neurons. Neurotransmission involves an electrical impulse converting into a chemical signal at the synapse.

  • Presynaptic Neuron: Releases neurotransmitters into the synapse.

  • Postsynaptic Neuron: Contains receptors that are either excited or inhibited by the transmitter.

  • Destruction of Neurotransmitters: Inactivated by enzymes (e.g., acetylcholinesterase destroys acetylcholine; monoamine oxidase destroys monoamines) or via cellular reuptake into the presynaptic cell.

Neurotransmitters and Their Clinical Relevance

• Dopamine ($DA$): Involved in fine muscle movement, integration of emotions/thoughts, decision-making, and reward/pleasure.

  • Increase: Psychosis, mania.

  • Decrease: Parkinson’s disease, depression.

• Norepinephrine ($NE$): Affects mood, attention, and arousal; stimulates the sympathetic nervous system.

  • Increase: Mania, anxiety, psychosis.

  • Decrease: Depression.

• Serotonin ($5-HT$): Regulates mood, sleep, hunger, pain perception, and aggression.

  • Decrease: Depression.

  • Increase: Anxiety states.

• Histamine ($H_1$, $H_2$): Involved in alertness and inflammatory response.

  • Decrease: Causes sedation and weight gain.

• $\gamma$-Aminobutyric Acid (GABA): Major inhibitory neurotransmitter; reduces anxiety and aggression; has anticonvulsant properties.

  • Decrease: Mania, anxiety, psychosis.

  • Increase: Reduction of anxiety.

• Glutamate: Major excitatory neurotransmitter; plays a role in learning and memory.

  • Prolonged increase in NMDA activity: Neurotoxicity, cell death (Alzheimer’s disease).

• Acetylcholine ($ACh$): Role in learning, memory, and parasympathetic stimulation.

  • Decrease: Alzheimer’s disease, Huntington’s chorea, Parkinson’s disease.

Antidepressant Drug Classes

• Monoamine Hypothesis: Suggests depression results from a lack of dopamine, $NE$, or serotonin.

• Selective Serotonin Reuptake Inhibitors (SSRIs): Block reuptake of serotonin (e.g., fluoxetine [$Prozac$], sertraline [$Zoloft$], paroxetine [$Paxil$]).

  • Vortioxetine ($Trintellix$): A multimodal SSRI with agonist and antagonist properties at varying serotonin receptors.

  • Serotonin Syndrome: Occurs if combined with other serotonergic drugs (e.g., $St. J_{ohn’s}$ wort, dextromethorphan); symptoms include restlessness, shivering, muscle rigidity, and seizures.

• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Block reuptake of both serotonin and $NE$ (e.g., venlafaxine [$Effexor$], duloxetine [$Cymbalta$]).

• Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs): Bupropion ($Wellbutrin$/$Zyban$) does not affect serotonin; used for depression and smoking cessation.

• Tricyclic Antidepressants (TCAs): Prevent $NE$/serotonin reuptake. Termed ‘dirty drugs’ due to side effects: anticholinergic effects, sedation ($H_1$ block), and hypotension ($\alpha_1$ block). Highly lipid-soluble; overdose can cause fatal cardiotoxicity.

• Monoamine Oxidase Inhibitors (MAOIs): (e.g., phenelzine [$Nardil$], tranylcypromine [$Parnate$]). Inhibit the $MAO$ enzyme to increase monoamines.

  • Safety Concern: Hypertensive crisis can occur if consumed with tyramine (aged cheese, fermented foods, wine). Restriction must continue for $2$ weeks after stopping the drug.

Antianxiety, Hypnotic, and Mood Stabilizing Drugs

• Benzodiazepines: Promote GABA activity (e.g., diazepam [$Valium$], alprazolam [$Xanax$]). Risk of tolerance, withdrawal, and respiratory depression if combined with alcohol or opioids. Ataxia is a common side effect due to GABA receptors in the cerebellum.

• Buspirone ($BuSpar$): Reduces anxiety without sedation or addiction; has a high affinity for $5-HT_{1A}$ receptors.

• Short-Acting Sedative-Hypnotics ("Z-hypnotics"): (e.g., zolpidem [$Ambien$], eszopiclone [$Lunesta$]). Selective for $GABA_A$ receptors with $\alpha_1$-subunits; used for sleep without antianxiety effects.

• Lithium: Mood stabilizer for bipolar disorder; low therapeutic index requires blood level monitoring dependent on kidney function.

  • Toxicity Risk: Sodium depletion causes kidneys to retain lithium, leading to toxicity.

• Anticonvulsant Mood Stabilizers:

  • Valproate ($Depakote$): Useful for non-responders to lithium. Side effects: hepatotoxicity, pancreatitis, teratogenicity (needs birth control).

  • Lamotrigine ($Lamictal$): Inhibits glutamate/aspartate. Risk of Stevens-Johnson Syndrome ($SJS$).

  • Carbamazepine ($Tegretol$): Used for rapid-cycling bipolar disorder. Requires periodic $CBC$ due to risk of agranulocytosis/aplastic anemia.

Antipsychotic Medications

• First-Generation Antipsychotics (FGAs/Typical): Strong dopamine receptor antagonists ($DRA$s) at $D_2$ receptors.

  • Therapeutic Effect: Decreases positive symptoms of schizophrenia.

  • Adverse Effects: Extrapyramidal symptoms ($EPS$) like dystonia, akathisia, and Tardive Dyskinesia ($TD$).

  • Neuroleptic Malignant Syndrome (NMS): Life-threatening; symptoms include severe muscle rigidity, high fever, and autonomic instability.

• Second-Generation Antipsychotics (SGAs/Atypical): Serotonin-dopamine antagonists ($SDA$s). Higher ratio of $5-HT_{2A}$ to $D_2$ blockade; fewer $EPS$.

  • Clozapine ($Clozaril$): Most effective for treatment-resistant patients but carries risk of agranulocytosis. Requires absolute neutrophil count ($ANC$) monitoring: weekly for $6$ months, every $2$ weeks for the next $6$ months, then monthly.

  • Olanzapine ($Zyprexa$): High weight gain risk ($H_1$ block). $Zyprexa Relprevv$ (injectable) requires $3$ hours of post-injection observation for delirium/sedation.

  • Risperidone ($Risperdal$): Can cause $EPS$ at doses > $4$ to $6\,mg/day$. Increases prolactin (gynecomastia). $Perseris$ is a once-monthly long-acting injectable ($LAI$).

  • Ziprasidone ($Geodon$): Must be taken with food (at least $350$ calories). Risk of QTc interval prolongation.

  • Aripiprazole ($Abilify$): Dopamine-serotonin stabilizer; partial $D_2$ agonist. $Abilify MyCite$ includes an ingestible sensor tracked by a smartphone app.

  • Lurasidone ($Latuda$): High affinity for $D_2$ and $5-HT_{2A}$. Must be taken with $350$ calories; avoid grapefruit juice (inhibits $CYP3A4$).

• Metabolic Monitoring: Necessary for SGAs (weight, $BMI$, waist circumference, fasting glucose/lipids). Metformin is sometimes used to manage weight gain.

Specialized Research and Cultural Considerations

• Psychoneuroimmunology (PNI): Investigates the link between the immune system (cytokines, inflammation), the nervous system, and behavior. Chronic inflammation can reduce neuroplasticity and neurogenesis in the hippocampus.

• Cross-Cultural Psychopharmacology: Studies ethnic variations in drug response due to genetic predispositions and cultural beliefs.

• Pharmacogenetics: Uses technology (e.g., $GeneSight$) to identify how individuals metabolize medications based on $CYP450$ genes.

Questions & Clinical Application

• Understanding Normal Function: Knowledge of normal brain function (circadian rhythms, hormones) helps nurses identify how psychotropic drugs or illnesses alter a patient’s baseline.

• Use of Neuroimaging for Families: Functional scans (like PET) can provide visual evidence of illness (e.g., reduced frontal metabolism in schizophrenia), which can help families understand mental illness as a biological reality rather than a character flaw.

• Educational Points for Altered Transmitters:

  • D2 Blockade: Educate on motor stiffness ($EPS$) and prolactin changes.

  • Muscarinic Blockade: Teach management of dry mouth, constipation, and blurred vision.

  • H1 Blockade: Warn about sedation and substantial weight gain.

  • MAO Inhibition: Stress the necessity of the tyramine-free diet to prevent hypertensive crisis.

  • GABA Potentiation: Warn against activities requiring high reflexes (driving) and the dangers of combining with alcohol.