Week 7: CNS Disorders & Advanced Neuro Drugs

Signs and Symptoms of Parkinson Disease: Motor Symptoms

• Tremor (resting tremor)

• Bradykinesia (slowness of movement)

• Rigidity (muscle stiffness)

• Postural instability (balance problems)

Signs and Symptoms of Parkinson Disease: Non-Motor Symptoms

• Cognitive impairment

• Mood disorders (depression, anxiety)

• Sleep disturbances

• Autonomic dysfunction (e.g., constipation, orthostatic hypotension)

Neurotransmitter Imbalance in Parkinson’s

Deficient Neurotransmitter:

• Dopamine

  • Role of Dopamine: a crucial neurotransmitter involved in regulating movement, motivation, and reward. It is primarily produced in the substantia nigra and affects the basal ganglia, which are critical for motor control

Excess Neurotransmitter:

• Acetylcholine

  • Role of Acetylcholine: Another important neurotransmitter involved in muscle activation, learning, and memory. It is released at neuromuscular junctions and in various brain regions

Parkinson’s - Deficiency in Dopamine - Motor Symptoms

A deficiency in dopamine, as seen in conditions like Parkinson’s disease, leads to motor symptoms, such as:

• bradykinesia (slowness of movement)

• rigidity

• tremors

• postural instability

This occurs because the basal ganglia cannot properly regulate movement without adequate dopamine

Parkinson’s - Deficiency in Dopamine - Non-Motor Symptoms

Dopamine deficiency can also cause non-motor symptoms, including:

• depression

• cognitive impairment

• autonomic dysfunction (e.g., constipation, orthostatic hypotension)

Parkinson’s - Excess Acetylcholine - Motor Symptoms

When dopamine levels are low, the relative excess of acetylcholine in the basal ganglia exacerbates motor symptoms. This imbalance can lead to increased:

• muscle rigidity

• tremors

…because acetylcholine promotes muscle contraction

Parkinson’s - Excess Acetylcholine - Non-Motor Symptoms

Excess acetylcholine can also affect cognitive functions, potentially leading to symptoms, such as:

• confusion

• memory problems

Imbalance Effects of Dopamine and Acetylcholine - Motor Symptoms

• The imbalance between deficient dopamine and excess acetylcholine disrupts the normal functioning of the basal ganglia, leading to the characteristic motor symptoms of Parkinson’s disease and similar disorders

• The lack of dopamine means that inhibitory signals are reduced, while the excess acetylcholine increases excitatory signals, resulting in impaired movement control

Imbalance Effects of Dopamine and Acetylcholine - Non-Motor Symptoms

• The imbalance can also contribute to non-motor symptoms by affecting other brain regions involved in mood, cognition, and autonomic functions

• Example: reduced dopaminergic activity can lead to depression and cognitive decline, while the cholinergic overactivity can cause autonomic disturbances

Action of Carbidopa-Levodopa

Levodopa:

• Precursor to dopamine that crosses the blood-brain barrier

• Converted to dopamine in the brain

Carbidopa:

• Inhibits peripheral conversion of levodopa to dopamine

• Increases availability of levodopa to the brain

Clinical Use:

• Most effective treatment for motor symptoms of Parkinson Disease

What is levodopa?

• Precursor to dopamine that crosses the blood-brain barrier

• Converted to dopamine in the brain

What is carbidopa?

• Inhibits peripheral conversion of levodopa to dopamine

• Increases availability of levodopa to the brain

What is the clinical use of carbidopa-levodopa?

Most effective treatment for motor symptoms of Parkinson Disease

Action of Dopamine Agonists

Mechanism of Action:

• Mimic dopamine by stimulating dopamine receptors in the brain

Examples:

• Pramipexole

• Ropinirole

• Rotigotine

Clinical Use:

• Used as monotherapy in early stages or in combination with levodopa in advanced stages

What is the clinical use of dopamine agonists?

Used as monotherapy in early stages or in combination with levodopa in advanced stages

Action of Entacapone and Opicapone

Mechanism of Action:

• Catechol-O-methyltransferase (COMT) inhibitors

• Prevent breakdown of levodopa in the periphery

Clinical Use:

• Prolong the effect of levodopa

• Reduce “off” periods in patients with fluctuating response to levodopa

What is the clinical use of entacapone and opicapone?

• Prolong the effect of levodopa

• Reduce “off” periods in patients with fluctuating response to levodopa

Action of Monoamine Oxidase Inhibitors (MAOIS)

Mechanism of Action:

• Inhibit monoamine oxidase-B (MAO-B) enzyme

• Prevent breakdown of dopamine in the brain

Examples:

• Selegiline

• Safinamide

• Rasagiline

Clinical Use:

• Used as monotherapy in early stages or as adjunct therapy in advanced stages

Anticholinergic Agents in Parkinson Disease

Mechanism of Action:

• Block acetylcholine receptors

• Reduce the relative excess of acetylcholine

Clinical Use:

• Improve tremor and rigidity

• Less effective for bradykinesia

Symptoms Improved by Anticholinergic Agents

Specific Symptoms:

• Reduction in tremor

• Decrease in muscle rigidity

  • “better QoL”

Patient Considerations:

• Use with caution in elderly patients due to risk of cognitive side effects

Agents Used in the Treatment of Alzheimer Disease

Cholinesterase Inhibitors

• Mechanism:

  • Inhibit breakdown of acetylcholine, enhancing cholinergic transmission

• Examples:

  • Donepezil

  • Rivastigmine

  • Galantamine

NMDA Receptor Antagonists

• Mechanism:

  • Modulates glutamate activity to prevent excitotoxicity

• Example:

  • Memantine

Action of Cholinesterase Inhibitors

Mechanism of Action:

• Inhibit acetylcholinesterase enzyme

• Increase levels of acetylcholine in the brain

Clinical Use:

• Improve cognitive function and slow progression of symptoms in mild to moderate Alzheimer disease

What is the clinical use of cholinesterase inhibitors?

Improve cognitive function and slow progression of symptoms in mild to moderate Alzheimer disease

Action of NMDA Receptor Antagonists

Mechanism of Action:

• Block NMDA receptors to reduce glutamate-mediated excitotoxicity

Clinical Use:

• Used in moderate to severe Alzheimer disease

• Can be used in combination with cholinesterase inhibitors

What is the clinical use of NMDA Receptor Antagonists?

• Used in moderate to severe Alzheimer disease

• Can be used in combination with cholinesterase inhibitors

Generalized Anxiety Disorder (GAD)

Definition:

• Excessive, uncontrollable worry about various aspects of life

Symptoms:

• Restlessness

• Fatigue

• Difficulty concentrating

• Irritability

• Muscle tension

• Sleep disturbances

Duration:

• Symptoms present for at least 6 months

Panic Disorder

Definition:

• Recurrent, unexpected panic attacks

Symptoms:

• Palpitations, sweating, trembling, SOB, chest pain, dizziness, fear of losing control or dying

Duration:

• Persistent concern about having more attacks or significant behavioral changes for at least 1 month

Phobias

Definition:

• Intense, irrational fear of specific objects or situations

Types:

• Specific phobias (e.g., fear of heights, animals)

• Social phobia (social anxiety disorder)

• Agoraphobia (fear of open or crowded spaces)

Symptoms:

• Avoidance behavior, intense anxiety when exposed to the phobic stimulus

Obsessive-Compulsive Disorder (OCD)

Definition:

• Presence of obsessions (intrusive, unwanted thoughts) and/or compulsions (repetitive behaviors or mental acts)

Symptoms:

• Obsessions (e.g., fear of contamination)

• Compulsions (e.g., excessive handwashing)

Impact:

• Significant distress and impairment in daily functioning

Comparison of Anxiety Disorders: GAD vs. Panic Disorder

• GAD: Chronic worry, no specific triggers

• Panic Disorder: Sudden, intense panic attacks

Comparison of Anxiety Disorders: Phobias vs. OCD

• Phobias: Fear of specific objects/situations

• OCD: Obsessions and compulsions

Baseline Assessment of Mental Status

• Appearance:

  • General appearance, grooming, hygiene

• Behavior:

  • LOC, eye contact, motor activity

• Mood and Affect:

  • Patient’s reported mood, observed affect

• Thought Processes:

  • Coherence, logic, relevance of thoughts

• Thought Content:

  • Presence of delusions, obsessions, phobias

• Cognition:

  • Orientation, memory, attention, concentration

• Insight and Judgment:

  • Awareness of condition, decision-making ability

Drug Therapy for Anxiety Disorders

• Benzodiazepines

• Selective Serotonin Reuptake Inhibitors (SSRIs)

• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Drug Therapy for Anxiety Disorders: Benzodiazepines

Mechanism:

• Enhance GABA activity

Use:

• Short-term relief of acute anxiety symptoms

Examples:

• Diazepam

• Lorazepam

• Alprazolam

Drug Therapy for Anxiety Disorders: Selective Serotonin Reuptake Inhibitors

Mechanism:

• Increase serotonin levels in the brain

Use:

• Long-term management of anxiety disorders

Examples:

• Setraline

• Fluoxetine

• Escitalopram

Drug Therapy for Anxiety Disorders: Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Mechanism:

• Increase serotonin and norepinephrine levels

  • “norepinephrine mediates fight or flight response”

Use:

• Long-term management of anxiety disorders

  • “also used for combo anxiety+depression management, but cause overwhelming fatigue”

Examples:

• Venlafaxine

• Duloxetine

Adverse Effects of Anxiety Medications: Benzodiazepines

• Sedation

• Dizziness

• Dependence

• Withdrawal Symptoms

Adverse Effects of Anxiety Medications: SSRIs

• Nausea

• Insomnia

• Sexual dysfunction

• Weight gain

Adverse Effects of Anxiety Medications: SNRIs

• Nausea

• Dry mouth

• Increased BP

• Sexual dysfunction

Psychological and Physiologic Drug Dependence

Psychological Dependence:

• Craving for the drug, compulsive use despite negative consequences

Physiologic Dependence:

• Tolerance (need for higher doses to achieve the same effect)

• Withdrawal symptoms upon discontinuation

Management:

• Gradual tapering of the drug

• Supportive therapy and counseling

What is the definition of baseline assessment?

• A comprehensive evaluation conducted before starting treatment to understand the patient’s current health status

What is the importance of baseline assessments?

• Crucial for treatment planning as they provide a reference point to measure progress and identify any pre-existing conditions that may affect treatment

Baseline Assessment Components: Medical History

Includes a detailed review of the patient’s past and present medical and psychiatric conditions, family history, and any previous treatments

Baseline Assessment Components: Physical Examination

Key checks include vital signs, body mass index (BMI), and a general physical health assessment to identify any underlying conditions

Baseline Assessment Components: Mental Status Examination

Evaluates cognitive functions, mood, thought processes, and behavior to understand the patient’s mental health status

Baseline Assessment Components: Laboratory Tests

Relevant tests may include thyroid function tests, complete blood count (CBC), liver function tests, and other specific tests based on the patient’s history

Baseline Assessment for Depression

Specific Assessments:

• Tools like the Patient Health Questionnaire-9 (PHQ-9) are used to quantify the severity of depression

Symptom Evaluation:

• Assess the severity, duration, and impact of depressive symptoms on daily life, including sleeping patterns, appetite, and energy levels

Baseline Assessment for Bipolar Disorder

Specific Assessments:

• Tools such as the Mood Disorder Questionnaire (MDQ) help identify symptoms of mania and hypomania

Symptom Evaluation:

• Evaluate the frequency, duration, and intensity of manic, hypomanic, and depressive episodes, and their impact in the patient’s functioning

What is the definition of Premedication Assessments?

• Evaluations conducted before starting a new medication to ensure it is safe and appropriate for the patient

What is the importance of Premedication Assessments?

• Help prevent adverse reactions and ensure the chosen medication will be effective

Premedication Assessments for MAOIs

Medical History:

• Review for contraindications such as hypertension and dietary restrictions due to potential interactions with certain foods

Physical Examination:

• Monitor BP to detect any pre-existing HTN

  • “↑dopamine = ↑BP, use cautiously”

Laboratory Tests:

• Conduct liver function tests to ensure the liver can metabolize the medication safely

Premedication Assessments for SSRIs and SNRIs

Medical History:

• Assess previous responses to SSRIs/SNRIs and review other medications to avoid interactions

Physical Examination:

• Check weight and BP as these medications can affect both

Laboratory Tests:

• Evaluate electrolytes and renal function to ensure safe medication use

Premedication Assessments for TCAs

Medical History:

• Review cardiac history, glaucoma, and urinary retention as TCAs can exacerbate these conditions

Physical Examination:

• Perform an ECG to assess cardiac health

Laboratory Tests:

• Check blood glucose and liver function to monitor for potential side effects

Premedication Assessments for Anti-Manic Agents

Medical History:

• Assess renal and thyroid function as these medications can affect both

  • “lithium and thyroid go hand in hand”

Physical Examination:

• Monitor weight and BP regularly

Laboratory Tests:

• Conduct serum electrolyte and renal function tests to ensure safe use

Common Adverse Effects of MAOIs

Hypertensive Crisis:

• Symptoms include severe headache, chest pain, and palpitations; management involves immediate medical attention

Dietary Restrictions:

• Avoid foods high in tyramine, such as aged cheeses and cured meats

Other Effects:

• Insomnia, dizziness, and weight gain are common side effects

Common Adverse Effects of SSRIs and SNRIs

Gastrointestinal Issues:

• Nausea and diarrhea are common, especially when starting treatment

Sexual Dysfunction:

• Includes decreased libido and difficulty achieving orgasm

Other Effects:

• Insomnia, headache, and weight changes can occur

Common Adverse Effects of TCAs

Cardiovascular Effects:

• Includes arrhythmias and hypotension, which requires monitoring

Anticholinergic Effects:

• Dry mouth, constipation, and urinary retention are common

Other Effects:

• Weight gain and sedation can also occur

Common Adverse Effects of Lithium

*NCLEX (Most common for Bipolar)

Renal Effects:

• Polyuria (increased urination) and polydipsia (increased thirst) are common

  • “look for electrolyte disturbances”

  • “lithium is metabolized in kidneys”

Thyroid Effects:

• Hypothyroidism can develop, requiring regular thyroid function tests

Other Effects:

• Tremor, weight gain, and GI issues like nausea

Introduction to Psychotic Behavior

Psychosis is a mental disorder characterized by a disconnection from reality, often involving hallucinations and delusions

Prevalence:

• Psychosis affects approximately 3% of the population at some point in their lives

Signs and Symptoms of Psychotic Behavior

Positive Symptoms:

• Hallucinations (seeing or hearing things that aren’t there)

• Delusions (false beliefs)

• Disorganized thinking

Negative Symptoms:

• Affective flattening (reduced emotional expression)

• Alogia (poverty of speech)

• Anhedonia (inability to feel pleasure)

Cognitive Symptoms:

• Impaired executive function, attention deficits, and memory problems

Major Indications for Anti-Psychotic Agents

Schizophrenia:

• Primary indication for both acute and maintenance treatment

Bipolar Disorder:

• Used to manage manic and mixed episodes

Other Indications:

• Severe depression with psychotic features

• Other psychotic disorders

• Agitation in various conditions

First-Generation Antipsychotics (FGAs)

Mechanism of Action:

• Primarily block dopamine D2 receptors

Indications:

• Effective for acute psychosis and chronic schizophrenia

Examples:

• Haloperidol

  • “Nursing consideration → will increase QT interval → rarely given IV Push (could cause cardiac arrest) → USE IM”

• Chlorpromazine

Second-Generation Antipsychotics (SGAs)

Mechanism of Action:

• Block both dopamine and serotonin receptors

Indications:

• Used for schizophrenia, bipolar disorder, and as adjuncts in depression

  • “more commonly used for long-term control”

Examples:

• risperidone

• olanzapine

• quetiapine (“good for delirium; Seroquel”)

Comparison of FGAs and SGAs

Efficacy:

• SGAs are generally preferred due to better side effect profiles and efficacy in treating both positive and negative symptoms

Side Effects:

• FGAs are more likely to cause extrapyramidal symptoms (EPS), while SGAs are associated with metabolic side effects like weight gain and diabetes

Common Adverse Effects of FGAs

Extrapyramidal Symptoms:

• Tardive dyskinesia (involuntary movements)

• Akathisia (restlessness)

• Dystonia (muscle contractions)

***NCLEX ↑ “reason SGAs created”

Other Effects:

• Sedation

• Anticholinergic effects (dry mouth, constipation)

• Orthostatic hypotension (drop in BP when standing)

Common Adverse Effects of SGAs

Metabolic Syndrome:

• Includes weight gain, diabetes, and dyslipidemia (abnormal lipid levels)

Other Effects:

• Sedation

• QT prolongation (heart rhythm changes)

• Agranulocytosis (severe drop in WBCs) with clozapine

Monitoring and Management of Adverse Effects of SGAs

Regular Monitoring:

• Includes weight, glucose levels, and lipid profiles to detect early signs of metabolic syndrome

Management Strategies:

• May involve dose adjustments, switching medications, or adding treatments to manage side effects

Special Considerations in Antipsychotic Use

Elderly Patients:

• Increased risk of cerebrovascular events and mortality, requiring careful monitoring

  • “higher risk of stroke”

Pregnancy and Lactation:

• Weighing risks vs. benefits, with some medications preferred due to lower risk profiles

  • “antipsychotics can affect fetus”

Introduction to Seizure Disorders

Definition:

• Also known as epilepsy

• A group of neurological disorders characterized by recurrent, unprovoked seizures

Prevalence:

• Approximately 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally

Types of Seizure Disorders: Generalized Seizures

• Affect both sides of the brain and can cause loss of consciousness

• Types:

  • Tonic-clonic

  • Absence

  • Myoclonic

  • Atonic

Types of Seizure Disorders: Focal Seizures

• Originate in one area of the brain and can be classified based on the level of awareness during the seizure

• Types:

  • Focal aware

  • Focal impaired awareness

Types of Seizure Disorders: Unknown Onset Seizures

• Are those where the beginning of the seizure is not witnessed or is unclear

Nursing Interventions During Seizure Activity

Immediate Actions: Ensuring safety, timing the seizure

• Ensure the patient’s safety by clearing the area of any potential hazards and timing the duration of the seizure

Post-Seizure Care: Monitoring, documentation, patient reassurance

• Monitor the patient’s vital signs

• Document the seizure activity

• Provide reassurance and support to the patient

Seizure Precautions: Padded side rails, bed in lowest position

• Implement seizure precautions such as padded side rails and keeping the bed in the lowest position to prevent injury

Desired Therapeutic Outcomes from Anti-Epileptic Agents

Seizure Control: Reduction in frequency and severity

• Primary goal is to achieve optimal seizure control with minimal side effects

Quality of Life: Improved daily functioning and independence

• Improving the patient’s quality of life by enhancing daily functioning and promoting independence

  • “pts with uncontrolled seizures cannot drive”

Minimizing Adverse Effects: Balancing efficacy with tolerability

• Balancing the efficacy of anti-epileptic agents with their tolerability to minimize adverse effects

Drug Classes Used to Treat Seizure Disorders - Overview

• Hydantoins

• Barbiturates

• Benzodiazepines

• Succinimides

• Others: Valproic acid (Depakene), lamotrigine (Lamictal)

Drug Classes Used to Treat Seizure Disorders: Hydantoins

• Used to control generalized tonic-clinic seizures

• Example: Phenytoin (Dilantin)

Drug Classes Used to Treat Seizure Disorders: Barbiturates

• Enhance GABA activity and are used for generalized and partial seizures

• Example: Phenobarbital

Drug Classes Used to Treat Seizure Disorders: Benzodiazepines

• Increase GABAergic inhibition and are used for acute seizure management and status epilepticus

• Examples: diazepam (Valium), lorazepam (Ativan)

Drug Classes Used to Treat Seizure Disorders: Succinimides

• Reduce T-type calcium currents and are used for absence seizures

• Example: ethosuximide (Zarontin)

Drug Classes Used to Treat Seizure Disorders: Valproic acid (Depakene) & lamotrigine (Lamictal)

Used for various types of seizures and have different mechanisms of action

For Seizures: Hydantoins

Mechanism of Action:

• Work by stabilizing neuronal membranes and decreasing excitability

Common Uses:

• Commonly used for managing generalized tonic-clonic seizures

Adverse Effects:

• Gingival hyperplasia (overgrowth of gum tissues)

• Nystagmus (involuntary eye movement)

For Seizures: Barbiturates

Mechanism of Action:

• Enhance the activity of GABA, an inhibitory neurotransmitter, which helps to calm neuronal activity

  • “inhibit brain waves; not used as commonly”

Common Uses:

• Used for both generalized and partial seizures

Adverse Effects:

• Sedation and cognitive impairment, which can affect daily functioning

For Seizures: Benzodiazepines

Mechanism of Action:

• Increase GABAergic inhibition, which helps to reduce neuronal excitability

Common Uses:

• Used for acute seizure management and in the treatment of status epilepticus

Adverse Effects:

• Drowsiness

• Development of tolerance with long-term use

For Seizures: Succinimides

Mechanism of Action:

• Work by reducing T-type calcium currents in the brain

  • “reduce excitability”

Common Uses:

• Are primarily used to treat absence seizures

Adverse Effects:

• GI distress

• Fatigue

Neurologic Assessment for Anti-Epileptic Agents

Baseline Assessment:

• Conduct a baseline assessment of the patient’s cognitive function and mood before starting treatment

Ongoing Monitoring:

• Perform regular neuropsychological evaluations to monitor the patient’s response to treatment

Adverse Effects:

• Monitor for any cognitive and behavioral changes that may indicate adverse effects of the medication

“many contraindicated in pregnancy”

Pain Assessment for Patients Receiving Opiate Agonists

Initial Assessment:

• Conduct an initial assessment of the patient’s pain history, including intensity (using scales like VAS or NRS), location, quality, and duration

Ongoing Monitoring:

• Regularly reassess the patient’s pain, monitor for side effects, and evaluate the functional impact of the pain and treatment

• “look for respiratory depression, ↓BP/HR

Properties of Opiate Full Agonists

Full Agonists:

• Bind fully to opioid receptors (e.g., morphine, fentanyl), providing strong analgesic effects

Mechanism of Action:

• Activate mu receptors, leading to analgesia, euphoria, and potential respiratory depression

Properties of Opiate Partial Agonists

Partial Agonists:

• Bind partially to opioid receptors (e.g., buprenorphine), providing analgesia with a ceiling effect on respiratory depression

  • “kills pain, but it has a built-in safety limit on how much it can slow your breathing”

Mechanism of Action:

• Partial activation

• Provide pain relief with a lower risk of respiratory depression compared to full agonists

Properties of Opiate Antagonists

Antagonists:

• Block opioid receptors (e.g., naloxone aka Narcan), preventing activation by agonists

Mechanism of Action:

• Used to reverse the effects of opioid overdose by blocking the receptors

Common Adverse Effects of Opiate Agonists

Gastrointestinal:

• Nausea, vomiting, and constipation

Central Nervous System:

• Sedation

• Dizziness

• Respiratory depression

Other Effects:

• Include the development of physical dependence and tolerance with long-term use

Opiate Antagonists and Therapeutic Outcomes

Naloxone:

• Used to reverse opioid overdose by blocking opioid receptors

Monitoring:

• Monitor the patient’s RR, consciousness level, and withdrawal symptoms after administration

Introduction to Salicylates

Definition:

• Are derivatives of salicylic acid with analgesic, antipyretic, and anti-inflammatory properties

  • “antipyretic = reduce fever”

Common Examples:

• aspirin

• salsalate

Pharmacologic Effects of Salicylates

Analgesic Effect:

• Provide pain relief by inhibiting the synthesis of prostaglandins

Antipyretic Effect:

• Reduction of fever by acting on the hypothalamus

Anti-Inflammatory Effect:

• Decrease in inflammation by inhibiting cyclooxygenase (COX) enzymes

Common Adverse Effects of Salicylates

Gastrointestinal:

• Common GI side effects include gastric irritation, ulcers, and bleeding

  • “HUGE for long-term use → MONITOR”

Renal:

• Long-term use can impair kidney function

Other Effects:

• Include tinnitus and the risk of Reye’s syndrome in children

  • “not given for children under 18”

  • “Reye’s syndrome = a rare but serious, rapidly progressing condition causing brain swelling and liver damage in children (often aged 4–12), typically occurring 3–7 days after a viral infection like influenza or chickenpox”

Serious Adverse Effects and Drug Interactions of Salicylates

Serious Effects:

• Gastrointestinal bleeding

• Renal impairment

Drug Interactions:

• Can increase the risk of bleeding when taken with anticoagulants and reduce the efficacy of antihypertensives