Neurotransmission and CNS Mechanisms

Neurotransmission

• Neurotransmitters (NTs) are released at synapses, binding to receptors on postsynaptic neurons.
• This binding either stimulates or inhibits an action potential.
• Some NTs are excitatory, some inhibitory, and some have mixed activity (e.g., acetylcholine).
• NTs are removed from the synaptic cleft by enzymatic degradation (e.g., COMT, MAO, acetylcholinesterase) or recycling (transport and repackaging).

Agonism and Antagonism

• Agonists or enzyme inhibitors increase central nervous system (CNS) neurotransmitters.
• Antagonists decrease CNS neurotransmitter action.
• Some CNS NTs also exist in the peripheral nervous system (PNS), so changes affect the entire body (e.g., norepinephrine, acetylcholine, serotonin).
• The GI tract produces substantial amounts of serotonin.
• NTs with high affinity for specific receptors cause specific side effects.

Cellular Depolarization

• Cellular depolarization involves calcium and sodium influx, potassium efflux.

Cholinergic System

• Cholinergic agents mimic or enhance acetylcholine activity, stimulating neurons.
• Associated with rest and digest functions in the PNS.
• Examples include increased salivation, reduced heart rate and blood pressure, increased GI activity (diarrhea).
• Anticholinergic agents suppress acetylcholine activity.

Adrenergic/Catecholamine/Inotrope System

• These agents stimulate the sympathetic nervous system (SNS).
• Associated side effects include anxiety, rapid heart rate, sweating.
• Examples include epinephrine, norepinephrine, dopamine, dobutamine.

Adrenergic Antagonists

• Adrenergic antagonists block sympathetic nervous system stimulation.
• Beta-blockers are an example.
• Sympathomimetic agents mimic the sympathetic nervous system by acting mainly on norepinephrine, epinephrine, and acetylcholine.

Headaches

• Headaches are symptomatic of various causes, including imbalances in neurotransmitters, hormones, electrolytes, or cranial nerve irritation.
• Acute headaches relate to a trigger.
• Chronic headaches occur regularly.
• Treatment depends on the cause, often involving analgesics.
• SNOOP criteria aid in headache analysis (Systemic symptoms, Neurologic symptoms, Onset sudden, Older age, Progressive, Positional change, precipitators, Papilledema)

Migraine

• Migraines affect 12% of adults.
• Common cause in adult women linked to estrogen fluctuations and genetics as well as higher incidence in adult women.
• Theories suggest trigeminal nerve irritation leading to meningeal vasculature inflammation.
• Auras (unusual sensations) can precede a migraine.
• Symptoms range from fatigue and hypersensitivity to sensory disturbances to systemic symptoms.
• Treatment involves analgesics, serotonin agonists (triptans), and botulinum toxin injections.

Sleep

• Sleep is a period of unconsciousness, inactivity, and restoration.
• Structures regulating sleep include the RAS, thalamus, SCN, pineal gland, and sensory pathways.
• The SCN and melatonin secretion regulate sleep onset.
• Sleep cycles involve decreased RAS activity and increased melatonin levels.
• REM sleep is associated with dreaming, muscle paralysis, and elevated vital signs.
• Melatonin is a hormone crucial for inducing drowsiness

Insomnia

• Insomnia is characterized by difficulty initiating or maintaining sleep.
• Factors impacting insomnia include age, menopause, medical conditions, stimulant and drug usage, and medication side effects.
• Diagnosis often involves self-assessment and polysomnography (sleep study).
• Treatment may include melatonin, GABA agonists (benzodiazepines or non-benzodiazepines), or sedatives.

ADHD

• ADHD (attention-deficit hyperactivity disorder) involves symptoms like fidgeting, impulsivity, difficulty concentrating, and organizational issues.
• Treatment typically involves stimulants, and the most common medications are amphetamines and their related compounds.

Dementia

• Dementia is an umbrella term for neurocognitive disorders that affect memory and daily functioning.
• Neurotransmitter deficits are implicated.

Alzheimer's Disease

• Alzheimer's Disease is a progressive neurodegenerative disorder leading to memory loss and cognitive decline.
• Pathology involves amyloid plaques and neurofibrillary tangles, leading to neuronal loss.
• Treatment focuses on increasing acetylcholine levels.

Parkinson's Disease

• Parkinson's Disease is a movement disorder linked to dopamine neuron loss.
• Pathology features Lewy bodies.
• Defining symptoms appear at stage 4/5.
• Treatment aims at increasing dopamine levels using dopamine agonists.

Psychiatric Disorders

• Psychiatric disorders affect thoughts, mood, or behaviors.
• Diagnosis is based on the DSM-5 classification criteria.
• Examples include anxiety disorders, depression, schizophrenia, and bipolar disorder.

Hallucinations

• Hallucinations are sensory perceptions without external stimuli.
• Causes include sensory deprivation, pathway dysfunction, and neuronal hyperactivity.

Delusions

• Delusions are false beliefs about facts or personal status.
• Common causes include existential factors and environment.

Psychosis

• Psychosis involves a loss of touch with reality.
• Its causes include mental illnesses, drug side effects, electrolyte imbalances, and other conditions.

Anxiety

• Anxiety involves intense fear impacting the sympathetic nervous system.
• Symptoms include elevated vital signs and sweating.
• Treatment includes GABA agonists (benzodiazepines) or serotonin enhancers.

Depression

• Depression is characterized by lack of interest, motivation, and pleasure.
• Possible causes include neurotransmitter imbalances, drug use, past trauma, and medical conditions.
• Treatment involves targeting neurotransmitters such as serotonin and norepinephrine.
• Treatment involves medication (SSRIs, SNRIs, or tricyclics) or MAOIs.

Serotonin Syndrome

• Serotonin syndrome results from excessive serotonin levels.
• Symptoms can include altered mental state, sweating, diarrhea, muscle rigidity, and others.

Ketamine for Depression

• Ketamine is a dissociative anesthetic with potential for treating depression.
• It acts on glutamate, opioid, and serotonin receptors.

Adjunct Treatments (Mood Stabilizers)

• Mood stabilizers like lithium are often used to help lessen suicide risk.
• Lithium management includes serum monitoring and awareness of potential drug interactions.

Psychedelic Treatment

• Psychedelic therapies target mood or other CNS disorders.
• The therapeutic effects include neuro-plastic changes.
• Examples include ketamine and psilocybin.

Schizophrenia

• Schizophrenia is a chronic mental illness characterized by disordered thoughts, speech, and behavior.
• Genetic and structural factors are potential causes.
• Positive symptoms (e.g., delusions, hallucinations), negative symptoms (e.g., apathy, withdrawal), and disorganized symptoms (e.g., disorganized speech) are common.
• Treatment includes antipsychotics targeting D2 receptors in the limbic system.
• Side effects may include extrapyramidal and anticholinergic effects.