Bipolar Disorder PDF

URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH...

URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS A. BIPOLAR DISORDER example, affects calcium channel function and has been associated with PATHOPHYSIOLOGY mood regulation and susceptibility to  Bipolar disorder is a mood disorder bipolar disorder. characterized by episodes of mania, 3. Structural Brain Abnormalities hypomania, and depression.  Prefrontal Cortex and Limbic System: Brain imaging studies indicate 1. Neurotransmitter Dysregulation abnormalities in the prefrontal cortex  Dopamine: Dopamine is important in and limbic structures like the amygdala mood regulation, reward processing, and hippocampus in individuals with and motivation. Elevated dopamine bipolar disorder. These areas are activity, especially in the mesolimbic responsible for regulating emotions, pathway, is associated with manic impulse control, and decision-making. symptoms, such as heightened energy A smaller or less active prefrontal and risk-taking behaviors. Conversely, cortex may impair emotional lower dopamine levels are thought to regulation, while an overactive contribute to depressive episodes, amygdala may intensify emotional which are marked by low motivation responses during mood episodes. and anhedonia.  White Matter Changes: Abnormalities  Serotonin: Serotonin is also involved in in white matter, particularly in tracts mood regulation. Dysregulation of connecting emotional and cognitive serotonin pathways, particularly brain areas, have been observed. decreased serotonin activity, is linked These changes could affect to depressive symptoms. This deficit communication between brain may contribute to low mood, regions, leading to the instability of irritability, and suicidal tendencies mood and behavior seen in bipolar seen in the depressive phases of disorder. bipolar disorder. 4. Circadian Rhythm Disruption  Norepinephrine: Increased  Circadian rhythms, or the body’s norepinephrine levels are linked to the natural cycles of sleep and hyperarousal and heightened energy wakefulness, play an important role in of manic episodes, while lower levels mood regulation. Individuals with are associated with the lethargy and bipolar disorder often experience fatigue typical of depressive states. disturbances in sleep patterns, which 2. Genetic Predisposition can act as both triggers and symptoms  Bipolar disorder is highly heritable, of mood episodes. Genetic variants with first-degree relatives of related to circadian rhythm regulation, individuals with bipolar disorder having such as those involving CLOCK and CRY a higher risk of developing the genes, are associated with an disorder. Multiple genes contribute to increased risk of bipolar disorder. this predisposition, especially genes Disrupted circadian rhythms can also involved in neurotransmitter signaling, affect neurotransmitter levels, circadian rhythms, and cellular exacerbating mood swings. resilience. The CACNA1C gene, for 5. Neuroinflammation and Immune PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS Dysregulation trauma, or significant life changes can  Emerging research suggests that trigger the onset or exacerbation of neuroinflammation and immune bipolar episodes in susceptible individuals. dysregulation may play a role in bipolar  Substance Abuse: Substance abuse, disorder. Elevated levels of pro- particularly stimulants or drugs that affect inflammatory cytokines and markers of mood and behavior, can induce manic or oxidative stress have been observed, depressive episodes and complicate the particularly during manic and management of bipolar disorder. depressive episodes. Inflammation can  Hormonal Changes: Hormonal impact neurotransmitter metabolism, fluctuations, such as those occurring disrupt neuroplasticity, and alter brain during pregnancy or menopause, can structure, potentially contributing to impact mood and potentially trigger the cyclic nature of mood episodes. bipolar episodes. 6. Neuroendocrine Factors  Sleep Disruption: Sleep disturbances or  The hypothalamic-pituitary-adrenal disruptions in circadian rhythms may (HPA) axis, which regulates the body’s trigger mood swings in individuals with response to stress, appears to be bipolar disorder. hyperactive in individuals with bipolar  Medications: Certain medications, disorder. This overactivity may lead to including antidepressants or elevated cortisol levels, particularly corticosteroids, can induce manic episodes during depressive episodes. Chronic in some individuals. stress and HPA axis dysregulation may  Seasonal Changes: Some people negatively impact brain structure and experience seasonal patterns of bipolar function, increasing susceptibility to disorder, with mood episodes more likely mood episodes. to occur during specific times of the year.  Medical Conditions: Certain medical POTENTIATING FACTORS conditions, such as thyroid disorders,  Genetic Factors: Family history of bipolar multiple sclerosis, and neurological disorder increases the risk, suggesting a diseases, can mimic bipolar symptoms or genetic component. Specific genes are exacerbate the disorder. associated with susceptibility, although  Family Environment: Adverse family the inheritance pattern is complex. dynamics or a dysfunctional family  Neurobiological Factors: Imbalances in environment can contribute to the onset neurotransmitters, including dopamine, or worsening of bipolar symptoms in serotonin, and norepinephrine, are susceptible individuals. implicated in the disorder's pathophysiology. These imbalances may CLINICAL PRESENATIONS influence mood regulation. Manic Episode: During a manic episode,  Neuroanatomical Changes: Structural individuals typically experience an elevated or brain abnormalities, such as alterations in irritable mood and an increase in energy the prefrontal cortex and limbic system, levels. are observed in individuals with bipolar  Increased Energy: A noticeable surge disorder. in energy, often leading to  Stressful Life Events: High levels of stress, hyperactivity. PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS  Elevated Mood: An abnormally  Feelings of Guilt or Worthlessness: elevated or euphoric mood. Negative self-evaluation and self-criticism.  Racing Thoughts: Rapid thinking,  Difficulty Concentrating: Trouble making frequent changes of topic, and decisions or focusing. difficulty concentrating.  Thoughts of Death or Suicide: Suicidal  Reduced Need for Sleep: Feeling thoughts, ideation, or suicide attempts. rested with very little sleep.  Talkativeness: Rapid and excessive Mixed Episode: Some individuals with bipolar speech. disorder may experience a combination of  Grandiosity: An inflated sense of self- manic and depressive symptoms esteem or importance. simultaneously or in quick succession. This can  Distractibility: Difficulty staying be a particularly challenging phase, as it focused on one task. involves both high and low mood states.  Impulsivity: Engaging in high-risk behaviors, such as reckless spending,  Cycling Patterns: Bipolar disorder often substance abuse, or risky sexual presents with cycling patterns, meaning that behaviors. individuals may experience repeated  Agitation: Increased restlessness and episodes of mania, hypomania, or irritability. depression over time. The frequency and intensity of these episodes can vary Hypomanic Episode: Hypomania is a less between individuals. severe form of mania and shares some DIAGNOSTIC AND LABORATORY TESTS features with manic episodes but with milder  Psychiatric Evaluation: A thorough intensity. Individuals in a hypomanic state evaluation by a mental health professional, may experience increased creativity and including a detailed psychiatric history and a productivity. However, these episodes are not discussion of mood symptoms, behavior, as disruptive as full-blown manic episodes. and family history, is the cornerstone of diagnosing bipolar disorder. Depressive Episode: In a depressive episode,  Mood Symptom Assessment: Mental health individuals experience symptoms of professionals use standardized assessment depression, including: tools and questionnaires to gather  Persistent Sadness: An overwhelming information about mood episodes, their feeling of sadness, hopelessness, and duration, and severity. The most commonly despair. used tool for assessing mood disorders is the  Loss of Interest: A decreased interest or Mood Disorder Questionnaire (MDQ). pleasure in activities that were once  Medical History and Physical Examination: enjoyed. A comprehensive medical history and  Fatigue: A significant decrease in energy physical examination are essential to rule levels, often leading to physical and mental out any underlying medical conditions or fatigue. medications that may be causing mood  Changes in Appetite: Appetite changes, symptoms. leading to weight loss or gain.  Neuroimaging: Brain imaging techniques,  Sleep Disturbances: Insomnia or excessive such as magnetic resonance imaging (MRI) sleeping. or computed tomography (CT) scans, are not PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS used for diagnosing bipolar disorder but may management techniques, and maintaining a be performed to rule out other brain healthy lifestyle through exercise and a conditions that could be causing symptoms. balanced diet can aid in managing  Psychological Assessments: Psychological symptoms. testing, including cognitive and personality  Support Systems: Building a strong support assessments, may be conducted to gather network, which may include family, friends, additional information about an individual's support groups, and mental health mental health and cognitive functioning. professionals, can help individuals manage the challenges of bipolar disorder. The diagnosis is typically made based on  Regular Monitoring and Maintenance: criteria outlined in the Diagnostic and Consistent monitoring by healthcare Statistical Manual of Mental Disorders (DSM- professionals, regular medication 5), a widely accepted classification and management, and adherence to treatment diagnostic tool used by mental health plans can aid in maintaining stability and professionals. preventing relapses. THERAPEUTIC OUTCOMES  Stabilizing Mood Swings: The primary aim is to stabilize mood fluctuations and reduce B. SCHIZOPHRENIA the frequency and intensity of manic, PATHOPHYSIOLOGY hypomanic, and depressive episodes. Since the late 19th century there have been  Medication Management: Mood frequent attempts to deine the illness we now stabilizers, such as lithium, anticonvulsants, call schizophrenia. Kraepelin, in the late 1890s, and atypical antipsychotics, are commonly coined the term ‘dementia praecox’ (early prescribed to manage mood swings. madness) to describe an illness where there Additionally, antidepressants or other was a deterioration of the personality at a medications may be used to address specific young age. Kraepelin also coined the terms symptoms, but they're often cautiously ‘catatonic’ (where motor symptoms are prescribed due to their potential to induce prevalent and changes in activity vary), manic episodes. ‘hebephrenic’ (silly, childish behaviour, affective  Psychotherapy: Psychotherapy, including symptoms and thought disorder prominence) cognitive-behavioral therapy (CBT), family- and ‘paranoid’ (clinical picture dominated by focused therapy, and interpersonal and paranoid delusions). A few years later Bleuler, a social rhythm therapy, can help manage Swiss psychiatrist, introduced the term symptoms and teach coping strategies for ‘schizophrenia’, derived from the Greek words dealing with stressors. skhizo (‘to split’) and phren (‘mind’), meaning  Education and Self-Management: the split between the emotions and the intellect Educating individuals and their families 1. Neurotransmitter Imbalance about bipolar disorder, recognizing warning  Dopamine Dysregulation: signs of mood episodes, and learning Schizophrenia has long been associated effective self-management techniques are with abnormalities in dopamine crucial for long-term stability. signaling, leading to the “dopamine  Lifestyle Adjustments: Establishing a hypothesis.” The theory suggests that regular sleep schedule, practicing stress PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS hyperactivity of dopamine transmission, interact with genetic predispositions to especially in the mesolimbic pathway, increase the likelihood of developing underlies positive symptoms like schizophrenia. hallucinations and delusions, while 3. Structural Brain Abnormalities hypoactivity in the mesocortical  Gray Matter Reduction: Brain imaging pathway is linked to negative symptoms studies show that individuals with and cognitive deficits. schizophrenia often have reductions in  Glutamate Hypofunction: The gray matter volume, especially in the glutamate hypothesis, focusing on prefrontal cortex, temporal lobes, NMDA (The N-methyl-D-aspartate hippocampus, and thalamus. These receptor is a glutamate receptor, the regions are involved in cognition, human brain's primary excitatory memory, and sensory processing, neurotransmitter) receptor aligning with the cognitive and hypofunction, complements the perceptual symptoms of schizophrenia. dopamine hypothesis. Reduced NMDA  Enlarged Ventricles: People with receptor activity disrupts glutamate schizophrenia frequently show enlarged signaling, particularly in areas lateral and third ventricles, indicating a connected to dopamine pathways. This loss of brain tissue and connectivity leads to overactivity in some brain within key areas. regions and underactivity in others, 4. Neurodevelopmental Hypothesis potentially contributing to the full  Prenatal and Perinatal Influences: spectrum of schizophrenia symptoms. Environmental stressors during prenatal  Serotonin Dysfunction: Serotonin development, such as maternal dysregulation, particularly through the infections or malnutrition, can disrupt 5-HT2A receptor, is also implicated. brain development, increasing Atypical antipsychotic drugs target both vulnerability to schizophrenia later in dopamine and serotonin receptors, life. suggesting a role for serotonin in  Abnormal Synaptic Pruning: managing symptoms and modulating Adolescence is a period of significant dopamine pathways. brain development, including synaptic 2. Genetic Factors pruning, where unnecessary synaptic  Polygenic Inheritance: Schizophrenia is connections are eliminated. In highly heritable, with multiple genes schizophrenia, excessive or abnormal involved. Variants in genes related to pruning may occur, especially in the dopamine (e.g., DRD2), glutamate (e.g., prefrontal cortex, which affects GRIN2A), and immune function (e.g., cognitive functions and could complement component 4, or C4) have contribute to symptom onset during been associated with increased risk. late adolescence or early adulthood.  Epigenetic Modifications: 5. Immune System and Inflammatory Environmental factors, such as prenatal Processes stress or infection, can lead to  Immune Dysregulation: Evidence epigenetic changes, which alter gene suggests that immune dysfunction, expression without changing the DNA including inflammation and sequence. These modifications can autoimmunity, might play a role in PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS schizophrenia. For example, elevated  Social and Psychological Stress: High levels of pro-inflammatory cytokines levels of chronic stress, social isolation, have been found in individuals with and adverse life events are associated schizophrenia, and certain immune- with increased risk and symptom related genetic variants (such as C4 exacerbation in schizophrenia. overexpression) are linked to the disorder. CLINICAL MANIFESTATIONS  Microglial Activation: Microglia, the Schizophrenia symptoms are typically brain’s immune cells, show increased categorized into positive, negative, and activity in schizophrenia, which can lead cognitive symptoms: to synaptic dysfunction and contribute  Positive Symptoms: These include to structural brain changes. hallucinations (most commonly auditory), delusions (fixed false beliefs, POTENTIATING FACTORS such as paranoia or grandiosity),  Genetic Predisposition: Schizophrenia disorganized thinking, and abnormal has a strong hereditary component, motor behaviors. These symptoms are with first-degree relatives of individuals often the most noticeable and lead to with schizophrenia having a significantly initial diagnosis. higher risk. Specific gene variations,  Negative Symptoms: These involve such as those affecting dopamine and deficits in normal emotional responses glutamate signaling, are linked to and behaviors. Common negative increased susceptibility. symptoms include flattened affect  Environmental Triggers: Environmental (reduced emotional expression), stressors during critical development anhedonia (lack of pleasure in stages can trigger schizophrenia in activities), avolition (lack of motivation), genetically predisposed individuals. Key social withdrawal, and alogia (reduced factors include prenatal infections, speech output). maternal malnutrition, complications  Cognitive Symptoms: Individuals may during birth, and childhood trauma. experience impairments in attention,  Neurodevelopmental Abnormalities: memory, and executive function. This Abnormal brain development, can lead to difficulties with decision- especially during adolescence, is making, problem-solving, and adapting thought to be a risk factor. Excessive or to new information, impacting daily atypical synaptic pruning and structural functioning and social interactions. changes in the brain during this period  Mood Symptoms: Some individuals can contribute to onset. may experience mood disturbances,  Substance Abuse: Psychoactive such as depression or anxiety, though substances like cannabis, these are not core symptoms of methamphetamine, and hallucinogens schizophrenia. can exacerbate or trigger psychotic symptoms in at-risk individuals, LABORATORY AND DIAGNOSTIC TESTS potentially leading to earlier onset or worsening of schizophrenia symptoms. While no definitive laboratory test exists for schizophrenia, a combination of clinical PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS assessments and imaging studies is used to positive symptoms. Common support diagnosis: medications include:  Psychiatric Evaluation: Diagnosis o Typical Antipsychotics (e.g., primarily relies on a comprehensive haloperidol) are effective but psychiatric evaluation, including a associated with higher rates of thorough history of symptoms, family extrapyramidal side effects. history, substance use, and overall o Atypical Antipsychotics (e.g., mental health. Psychiatrists often use risperidone, olanzapine, standardized diagnostic criteria, such as clozapine) have a broader the DSM-5 or ICD-10. mechanism of action, impacting  Cognitive and Psychological Testing: dopamine and serotonin Cognitive assessments help evaluate pathways, and are often deficits in memory, attention, and preferred due to a lower risk of executive function, which are common motor side effects. in schizophrenia. Psychological testing  Psychosocial Interventions: can rule out mood disorders or other Psychotherapy, cognitive behavioral psychotic disorders. therapy (CBT), and family therapy are  Imaging Studies: Neuroimaging (e.g., essential in supporting individuals with MRI, CT scans) is used to identify brain schizophrenia, especially in managing structural abnormalities. Findings may negative and cognitive symptoms. Skills include ventricular enlargement, training and supported employment reduced gray matter volume, or programs can improve social irregularities in the prefrontal cortex functioning and quality of life. and hippocampus, though these  Cognitive Remediation Therapy: This changes are not diagnostic. therapy targets cognitive symptoms by  Laboratory Tests: Blood tests, including providing training exercises designed to drug screening, are performed to improve memory, attention, and exclude substance-induced psychosis or problem-solving skills. medical conditions that may mimic  Long-term Outcomes: With early schizophrenia, such as thyroid intervention and consistent treatment, disorders, autoimmune encephalitis, or many individuals can manage vitamin deficiencies. symptoms effectively, though full  Electroencephalogram (EEG): In cases remission is rare. Some individuals where seizure disorders or other experience periods of stability with low neurological conditions are suspected, symptom intensity, while others may an EEG may be used to rule out these have recurrent relapses and ongoing factors. disability. Treatment adherence, social support, and early access to mental THERAPEUTIC OUTCOMES health care are key to improving  Medication Management: outcomes. Antipsychotic medications, primarily those affecting dopamine receptors, are the mainstay treatment for managing PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS C. SLEEP DISORDERS from sleep to re-establish normal breathing. This repeated arousal PATHOPHYSIOLOGY fragments sleep, reducing sleep quality It generally involves disruptions in the brain’s and leading to excessive daytime regulation of sleep-wake cycles, abnormalities sleepiness. in neurotransmitter systems, and alterations in  Sympathetic Nervous System the functioning of specific brain regions. Activation: Frequent apneic episodes 1. Insomnia stimulate the sympathetic nervous  Hyperarousal State: Insomnia is system, causing increased blood characterized by a state of hyperarousal pressure and heart rate. Chronic that persists during the day and night. activation of this system is associated This arousal can be physiological, with cardiovascular complications often cognitive, or emotional. Hyperactivity of seen in patients with OSA. the hypothalamic-pituitary-adrenal 3. Narcolepsy (HPA) axis is often seen, leading to  Orexin (Hypocretin) Deficiency: elevated levels of cortisol and increased Narcolepsy, especially narcolepsy type 1 metabolic rate, even during sleep. (with cataplexy), is strongly linked to a  Neurotransmitter Imbalance: deficiency of orexin-producing neurons Imbalances in neurotransmitters that in the hypothalamus. Orexin is a promote wakefulness (e.g., orexin, neuropeptide that stabilizes dopamine, norepinephrine) and sleep wakefulness and prevents REM sleep (e.g., GABA, serotonin) can disturb the from occurring at inappropriate times. ability to fall or stay asleep. Increased  REM (Rapid Eye Movement) Sleep orexin and noradrenergic activity are Dysregulation: Individuals with commonly observed in people with narcolepsy experience disruptions in insomnia, promoting wakefulness. REM sleep regulation, leading to  Psychological Factors: Anxiety, stress, features like sleep paralysis, and other psychological factors hypnagogic/hypnopompic contribute to increased cognitive hallucinations, and sudden transitions arousal, further disrupting sleep onset into REM sleep (cataplexy). This and maintenance. dysregulation contributes to the 2. Obstructive Sleep Apnea (OSA) excessive daytime sleepiness and “sleep  Airway Obstruction: OSA is caused by attacks” characteristic of narcolepsy. the repetitive collapse of the upper  Autoimmune Component: The loss of airway during sleep, leading to orexin neurons is thought to have an breathing interruptions. This collapse autoimmune basis, potentially triggered often occurs due to anatomical factors, by genetic susceptibility and such as a narrow airway, enlarged environmental factors such as tonsils, or excess weight around the infections. neck. 4. Circadian Rhythm Sleep-Wake Disorders  Oxygen Desaturation and Arousal:  Misalignment of Internal Clock: These Each episode of airway obstruction disorders result from a misalignment causes oxygen levels to drop between the body’s internal circadian (hypoxemia) and carbon dioxide levels clock and the external environment. to rise, triggering an arousal response PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS The circadian clock, located in the  Partial Arousal from Deep Sleep: suprachiasmatic nucleus (SCN) of the Parasomnias typically occur during non- hypothalamus, regulates sleep-wake REM sleep, particularly stages 3 and 4 cycles through signals like light and (deep sleep). These episodes involve darkness. partial arousal, where parts of the brain  Melatonin Dysregulation: The pineal are awake enough to cause movement gland’s secretion of melatonin, a but not fully conscious. hormone that promotes sleep, is  Impaired Sleep-Wake Transition: regulated by the SCN. Disruptions in During these events, there is melatonin production or sensitivity to incomplete transition between sleep light exposure, as seen in shift work and wake states, resulting in complex disorder and delayed sleep-wake phase behaviors like walking or talking disorder, alter sleep timing and quality. without awareness. Parasomnias are  Genetic Factors: Mutations in circadian more common in children and may genes (e.g., PER, CRY) can predispose decrease with age as brain individuals to disorders like advanced development and sleep architecture sleep-wake phase disorder and delayed change. sleep-wake phase disorder, causing them to have natural sleep-wake cycles POTENTIATING FACTORS that differ from the standard 24-hour  Genetics: Many sleep disorders, such as day. narcolepsy, restless legs syndrome 5. Restless Legs Syndrome (RLS) (RLS), and some circadian rhythm  Dopamine Dysfunction: RLS is disorders, have genetic components. associated with dysfunction in Mutations in specific genes, such as dopamine pathways in the brain, those regulating dopamine or circadian particularly in the basal ganglia, which rhythms, can predispose individuals to plays a role in movement control. these conditions. Dopaminergic dysfunction may lead to  Age and Developmental Factors: abnormal sensations and the urge to Certain sleep disorders are more move the legs, especially during rest or common at specific ages. For example, nighttime. parasomnias (like sleepwalking) are  Iron Deficiency: Iron is a cofactor in more common in children, while dopamine synthesis, and low levels of insomnia and obstructive sleep apnea iron in the brain have been observed in (OSA) increase with age. individuals with RLS. Iron deficiency  Lifestyle and Environmental Factors: may impair dopamine production and Poor sleep hygiene, high stress, signaling, further contributing to irregular sleep schedules, and exposure symptoms. to artificial light at night can exacerbate  Genetic Predisposition: Genetic factors or trigger sleep disorders. For example, also play a role in RLS, with several shift work disrupts circadian rhythms, genetic loci associated with increased and excessive caffeine or alcohol intake risk. can worsen insomnia. 6. Parasomnias (e.g., Sleepwalking, Night  Medical and Psychological Conditions: Terrors) Chronic health issues, such as obesity (a PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS risk factor for OSA), depression, anxiety, disorder (difficulty falling asleep until and chronic pain, contribute to the late at night) and shift work disorder. development or worsening of sleep  Parasomnias: Episodes of abnormal disorders. movements, behaviors, or perceptions  Substance Use: Drugs like alcohol, during sleep, such as sleepwalking, caffeine, and certain medications (e.g., sleep talking, night terrors, or REM stimulants, antidepressants) can disrupt sleep behavior disorder (acting out sleep architecture, increase arousal, dreams). and precipitate disorders like insomnia or sleep-disordered breathing. LABORATORY AND DIAGNOSTIC TESTS  Sleep History and Questionnaires: A CLINICAL MANIFESTATIONS thorough sleep history, including sleep The symptoms of sleep disorders vary patterns, duration, and symptoms, is depending on the type: essential. Questionnaires like the  Insomnia: Difficulty falling asleep, Epworth Sleepiness Scale, Insomnia staying asleep, or waking up too early. Severity Index, and Pittsburgh Sleep Daytime symptoms include fatigue, Quality Index help assess sleep quality irritability, cognitive impairment, and and daytime functioning. mood disturbances.  Polysomnography (PSG): An overnight  Obstructive Sleep Apnea (OSA): sleep study is the gold standard for Recurrent breathing interruptions diagnosing sleep disorders like OSA, during sleep, typically noticed as parasomnias, and REM sleep behavior snoring, gasping, or choking sounds. disorder. PSG records brain waves, OSA leads to fragmented sleep, causing oxygen levels, heart rate, breathing excessive daytime sleepiness, morning patterns, and body movements during headaches, and decreased sleep. concentration.  Multiple Sleep Latency Test (MSLT):  Narcolepsy: Characterized by excessive Used mainly for diagnosing narcolepsy, daytime sleepiness, sudden “sleep the MSLT measures how quickly an attacks,” cataplexy (sudden muscle individual falls asleep during several weakness triggered by strong scheduled daytime naps. The test also emotions), sleep paralysis, and vivid assesses whether REM sleep occurs hallucinations upon falling asleep or abnormally soon after sleep onset. waking.  Actigraphy: A wrist-worn device that  Restless Legs Syndrome (RLS): tracks movement and helps measure Uncomfortable sensations in the legs, sleep-wake patterns over several days often described as tingling, crawling, or or weeks. Actigraphy is useful for itching, that create an irresistible urge assessing circadian rhythm disorders to move the legs, particularly at rest or and sleep patterns outside of the lab at night. setting.  Circadian Rhythm Disorders: Disruption  Home Sleep Apnea Testing (HSAT): This in the timing of sleep, leading to portable test measures breathing, insomnia or excessive sleepiness at oxygen levels, and heart rate at home inappropriate times. Common types include delayed sleep-wake phase PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS and is often used to diagnose OSA in  Restless Legs Syndrome (RLS): patients who may not need full PSG. Dopaminergic agents (e.g.,  Blood Tests: In some cases, blood tests pramipexole, ropinirole) and iron are conducted to rule out other supplements (if iron-deficient) are underlying conditions that may impact effective in reducing symptoms. sleep, such as thyroid function tests, Consistent symptom control enhances iron levels (for RLS), and inflammation sleep quality and reduces daytime markers. impairment.  Circadian Rhythm Disorders: Light THERAPEUTIC OUTCOMES therapy, melatonin, and lifestyle Treatment outcomes for sleep disorders adjustments help reset the circadian depend on accurate diagnosis, individualized clock and improve sleep timing. treatment, and adherence to therapies. Treatment can effectively improve  Insomnia: Cognitive-behavioral therapy sleep regularity and quality, though for insomnia (CBT-I) is highly effective, long-term adherence to lifestyle aiming to reduce arousal, improve sleep changes is often required. habits, and recondition sleep behavior.  Parasomnias: Treatment depends on Medications (like benzodiazepine the specific parasomnia. Managing receptor agonists, melatonin agonists) sleep hygiene and addressing triggers, may be used short-term. CBT-I shows like stress or sleep deprivation, are lasting benefits, while medication often beneficial. Medications like provides symptom relief during use. benzodiazepines or antidepressants are  Obstructive Sleep Apnea (OSA): used for severe cases. Outcomes vary; Continuous Positive Airway Pressure parasomnias are often self-limiting in (CPAP) therapy is the standard children but may persist or require treatment for OSA, maintaining open management in adults. airways during sleep and reducing daytime sleepiness and cardiovascular D. SUBSTANCE USE DISORDER risks. Alternatives include oral appliances and, in severe cases, surgical PATHOPHYSIOLOGY options. CPAP adherence is key to Substance Use Disorder (SUD) involves complex positive outcomes, as untreated OSA is changes in the brain’s structure and function linked to cardiovascular and metabolic that contribute to addictive behaviors. issues. 1. Brain Reward Pathways and Dopaminergic  Narcolepsy: Stimulant medications System Dysfunction (e.g., modafinil, methylphenidate)  Mesolimbic Dopamine System: SUD improve daytime alertness, while primarily affects the brain’s reward antidepressants and sodium oxybate system, particularly the mesolimbic may manage cataplexy and REM- dopamine pathway, which includes related symptoms. Symptom structures like the ventral tegmental management can significantly improve area (VTA) and nucleus accumbens quality of life, but lifelong treatment is (NAc). This pathway is responsible for usually necessary. the rewarding effects of substances. Substances of abuse, including opioids, PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS alcohol, cocaine, and nicotine, increase glutamate signaling, particularly in dopamine release in the NAc, producing pathways between the prefrontal feelings of pleasure or euphoria. cortex and the NAc. This dysregulation  Dopaminergic Dysregulation: Chronic increases sensitivity to substance- exposure to substances can disrupt related cues and leads to intensified normal dopamine function, leading to craving and compulsive behavior. tolerance (requiring larger amounts for  Stress Pathways and CRF: Chronic the same effect) and dependence substance use activates stress response (needing the substance to feel systems, including the hypothalamic- “normal”). Over time, the brain’s pituitary-adrenal (HPA) axis and dopamine system becomes less corticotropin-releasing factor (CRF). CRF responsive, reducing pleasure from dysregulation contributes to withdrawal both the substance and natural rewards symptoms and relapse, as individuals (a process known as anhedonia), which experience heightened stress sensitivity reinforces substance-seeking behavior and may use substances to self- to achieve desired effects. medicate or relieve stress. 2. Neuroplastic Changes and Synaptic 4. Genetic and Epigenetic Factors Remodeling  Genetic Predisposition: Genes related  Structural Changes in the Brain: Long- to dopamine and glutamate receptors, term substance use induces stress-response pathways, and other neuroplastic changes in brain regions neurotransmitter systems can increase associated with reward, memory, and susceptibility to SUD. For example, executive control, such as the variations in the DRD2 gene (encoding prefrontal cortex, amygdala, and dopamine D2 receptors) and genes hippocampus. These changes impair associated with serotonin transporters decision-making, impulse control, and are linked to higher addiction risk. stress regulation.  Epigenetic Modifications: Substance  Synaptic Plasticity: Substances of abuse exposure can cause epigenetic changes can alter synaptic strength through (e.g., DNA methylation, histone processes like long-term potentiation modification) that alter gene expression (LTP) and long-term depression (LTD), without changing DNA sequence. These particularly in the NAc and prefrontal changes can affect the brain’s reward cortex. These changes reinforce and stress pathways, perpetuating memories of the rewarding effects of addictive behaviors and increasing the substance, making it harder to resist vulnerability to relapse. cravings and contributing to the 5. Craving and the Role of Cues in Relapse persistent nature of addiction.  Conditioned Learning: Repeated 3. Role of Glutamate and Corticotropin- substance use often creates strong Releasing Factor (CRF) associations between the substance  Glutamatergic Dysregulation: and environmental cues (e.g., places, Glutamate, the primary excitatory people, or paraphernalia). These cues neurotransmitter, is heavily involved in can trigger intense cravings even after learning, memory, and motivation. In long periods of abstinence, a SUD, chronic substance use alters PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS phenomenon known as conditioned executive functions such as decision- learning. making, self-control, and assessing risks  Cue-Induced Craving: Cue-induced and rewards. This dysfunction makes it craving is mediated by brain areas challenging for individuals to resist involved in memory and emotion, such urges, regulate behavior, and make as the amygdala and hippocampus. decisions that align with long-term well- Exposure to substance-related cues being. activates these areas and the  Impaired Inhibitory Control: Reduced dopaminergic reward pathway, activity in prefrontal circuits decreases contributing to high relapse rates in inhibitory control, making it difficult for SUD. individuals with SUD to stop using 6. Negative Reinforcement and Withdrawal substances even when they are aware Symptoms of the harmful consequences. This lack  Physical and Psychological of control is a hallmark of the Dependence: Prolonged substance use compulsive nature of addiction. can lead to both physical dependence (e.g., withdrawal symptoms when the POTENTIATING FACTORS substance is discontinued) and  Genetic Predisposition: Genetics play a psychological dependence (e.g., strong role in SUD risk, with certain gene urges or cravings). Withdrawal variants influencing dopamine symptoms, which vary depending on receptors, opioid receptors, and other the substance, contribute to negative neurotransmitter systems, increasing reinforcement—individuals continue vulnerability. For instance, variations in using to avoid unpleasant withdrawal the DRD2 gene, related to dopamine effects. receptors, have been linked to higher  Changes in Brain Stress Systems: addiction susceptibility. Chronic use of substances like alcohol  Environmental and Social Factors: and opioids shifts the brain from a Exposure to substances at a young age, reward-focused state to a stress- peer pressure, family history of SUD, dominant state, characterized by trauma, and high-stress environments increased activity in stress-related increase the likelihood of developing neurotransmitters like CRF and SUD. Social isolation and lack of support norepinephrine. This shift perpetuates a systems also contribute to substance cycle where individuals use substances misuse. not only for pleasure but also to reduce  Psychological Factors: Co-occurring stress and avoid discomfort. mental health conditions, such as depression, anxiety, PTSD, or ADHD, can increase the risk of SUD as individuals may use substances to cope with 7. Impairment of Executive Control and symptoms. Personality traits like Decision-Making impulsivity and sensation-seeking are  Prefrontal Cortex Dysfunction: Chronic also associated with a higher risk of substance use impairs the prefrontal substance misuse. cortex, the brain region responsible for PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS  Biological and Neurobiological Factors: and Drug Abuse Screening Test (DAST), Repeated exposure to substances help assess the severity and impact of changes brain pathways, especially the substance use. dopamine and reward systems, leading  Biological Markers and Toxicology to tolerance and dependence. Testing: Blood, urine, saliva, and hair Neuroadaptations increase the brain's tests can detect recent and chronic "need" for the substance to feel substance use. Commonly screened pleasure or relief, making individuals substances include alcohol, opioids, more susceptible to addiction. stimulants, benzodiazepines, and cannabis. Blood alcohol concentration CLINICAL MANIFESTATIONS (BAC) and urine drug screens are SUD symptoms vary by substance but generally frequently used for immediate include the following: assessment.  Behavioral Symptoms: Compulsive  Liver Function Tests: Chronic alcohol or drug-seeking behavior, inability to drug use can impact liver health. Liver control or reduce substance use, enzymes like AST and ALT, along with neglect of personal responsibilities, bilirubin levels, can indicate liver social withdrawal, and a preoccupation damage, which is especially common in with obtaining and using the substance. alcohol use disorder.  Physical Dependence and Withdrawal:  Imaging and Neuroimaging: Structural Symptoms like tolerance (requiring and functional MRI or PET scans can larger doses) and withdrawal symptoms detect brain changes in severe SUD (headache, nausea, tremors, or cases, such as reduced gray matter in seizures) when substance use is areas involved in impulse control and reduced or stopped. decision-making (e.g., prefrontal  Psychological Symptoms: Intense cortex). Neuroimaging is not routine cravings, mood swings, irritability, but may be used in research or specific anxiety, depression, and cognitive clinical evaluations. impairment, often leading to risky  Psychiatric Evaluation: Given the high behaviors or poor decision-making. comorbidity with mental health  Social and Functional Impairment: disorders, a comprehensive psychiatric Substance use may impair personal, evaluation is crucial to identify and social, and occupational functioning, address co-occurring mental health leading to relationship problems, job conditions that may influence SUD loss, legal issues, and financial progression or treatment. instability. THERAPEUTIC OUTCOMES Effective treatment for SUD typically combines behavioral therapies, medications (when appropriate), and support systems, aiming to LABORATORY AND DIAGNOSTIC TESTS reduce or eliminate substance use, improve  Screening Tools: Clinical interviews and functioning, and enhance quality of life. questionnaires, such as the Alcohol Use  Behavioral Therapies: Disorders Identification Test (AUDIT) PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS oCognitive Behavioral Therapy manage symptoms in specific (CBT): Helps patients identify cases. and modify thought patterns  Support Groups and Psychosocial and behaviors that contribute Support: to substance use. CBT is o 12-Step Programs: Groups like effective in reducing relapse Alcoholics Anonymous (AA) and and managing triggers. Narcotics Anonymous (NA) o Contingency Management offer community support, (CM): Provides incentives for shared experiences, and abstaining from substance use, structured steps to aid in long- reinforcing positive behaviors. term recovery. CM has shown success in o Family and Community improving treatment retention Support: Engagement with and adherence. family therapy, peer support o Motivational Interviewing groups, and community (MI): Assists individuals in resources can significantly recognizing and increasing improve treatment adherence motivation to change and help individuals rebuild substance-related behaviors, social connections. focusing on enhancing personal  Long-Term Outcomes: reasons for quitting. o Recovery from SUD is an  Medications: ongoing process, with success o Opioid Use Disorder: typically defined as sustained Medications like methadone, abstinence, improved mental buprenorphine, and naltrexone and physical health, and are used to reduce cravings and restored social and withdrawal symptoms, lowering occupational functioning. relapse rates. Relapse is common, but with o Alcohol Use Disorder: comprehensive care and Medications like disulfiram, support, individuals can achieve acamprosate, and naltrexone significant recovery milestones help reduce cravings and deter and maintain long-term drinking. remission. o Nicotine Dependence: Nicotine replacement therapy (NRT), bupropion, and varenicline reduce cravings and help manage withdrawal. o Stimulant Use Disorder: Although no FDA-approved medications exist for stimulant E. EATING DISORDERS use disorder, certain a. ANOREXIA NERVOSA antidepressants or Anorexia nervosa is a complex eating antipsychotics may be used to disorder characterized by severe PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS restriction of food intake, intense fear various hormonal systems. Low of gaining weight, and a distorted body body weight and malnutrition result image, often leading to significant in decreased secretion of sex weight loss and nutritional deficiencies. hormones (estrogen and testosterone), which can cause PATHOPHYSIOLOGY menstrual irregularities in females and decreased libido in males. 1. Neurobiological Factors Cortisol levels may also be elevated  Dopaminergic and Serotonergic due to stress responses associated Systems: Anorexia nervosa is with starvation, impacting associated with dysregulation in metabolism and increasing neurotransmitter systems, catabolic activity. particularly the dopaminergic and  Thyroid Dysfunction: Individuals serotonergic pathways. These with anorexia nervosa may neurotransmitters are involved in experience hypothyroidism due to regulating mood, appetite, and reduced thyroid hormone reward mechanisms. Individuals production, contributing to a slower with anorexia often exhibit metabolism and feelings of alterations in serotonin levels, coldness. This can further reinforce which may contribute to anxiety, the cycle of starvation and weight depression, and the restriction of loss. food intake. Dopamine is also linked  Leptin and Ghrelin: Leptin, which is to the pleasure associated with secreted by adipose tissue and food; thus, dysregulation may regulates appetite and energy diminish the reward response to expenditure, tends to be low in eating. individuals with anorexia nervosa  Hypothalamic Function: The due to reduced body fat. Ghrelin, a hypothalamus plays a crucial role in hunger hormone, may be elevated, regulating hunger, satiety, and promoting appetite but often failing energy balance. In anorexia to result in increased food intake nervosa, the hypothalamus may due to the psychological factors become less responsive to hunger associated with the disorder. signals, leading to decreased appetite and energy intake. 3. Cognitive and Psychological Factors Changes in neuropeptides (such as  Distorted Body Image: A core neuropeptide Y and agouti-related feature of anorexia nervosa is the peptide) that signal hunger and distorted perception of body size satiety are often observed, and weight. Individuals often view contributing to the pathological themselves as overweight despite restriction of food intake. being underweight. This cognitive distortion is believed to arise from 2. Endocrine and Metabolic Changes complex interactions among  Hormonal Imbalances: Anorexia genetic predispositions, nervosa leads to disruptions in environmental influences (such as PROPERTY OF: TGBM,RPH  URDANETA CITY College of Pharmacy UNIVERSITY Owned and operated by the City Government of Urdaneta CLINICAL PHARMACY WITH PHARMACOTHERAPEUTICS societal standards of beauty), and  Cardiovascular Changes: Individuals personal experiences (such as with anorexia nervosa may trauma or perfectionism). experience bradycardia (slow heart  Perfectionism and Control: Many rate), hypotension (low blood individuals with anorexia nervosa pressure), and arrhythmias due to exhibit traits of perfectionism and a electrolyte imbalances and heart strong desire for control. Restricting muscle atrophy. These food intake and achieving weight cardiovascular changes can increase loss can be seen as a means of the risk of sudden cardiac arrest. gaining control over their lives or  Bone Health: Malnutrition and environments, often in response to hormonal changes (particularly low feelings of inadequacy or anxiety. estrogen levels) lead to decreased bone mineral density, increasing 4. Genetic Factors the risk of osteoporosis and  Heritability: Anorexia nervosa has a fractures. This is particularly significant genetic component, with concerning in adolescents, whose heritability estimates ranging from bones are still developing. 50% to 80%. Specific genes related  Gastrointestinal Issues: to neurotransmitter systems, Malnutrition can cause appetite regulation, and personality gastrointestinal dysfunction, traits (such as those involved in including delayed gastric emptying, impulsivity and anxiety) may constipation, and bloating. This can contribute to the risk of developing further deter food intake, creating a the disorder. vicious cycle.  Gene-Environment Interactions: POTENTIATING FACTORS Environmental factors, including familial patterns of eating behavior, Genetic Factors: cultural influences on body image,  Heritability: Anorexia nervosa has a and life stressors, interact with genetic component, with studies genetic predispositions to increase suggesting a heritability estimate of vulnerability to anorexia nervosa. 50% to 80%. Family studies indicate that first-degree relatives of individuals 5. Physiological Consequences of with anorexia are at increased risk. Malnutrition  Genetic Variants: Certain genes related  Energy Deficit: Prolonged caloric to neurotransmitter systems restriction leads to an energy (dopamine, serotonin) and appetite deficit, resulting in severe