RCP 110 Chapter 20 - CNS Drugs & Neurotransmitters

Drugs Affecting the Central Nervous System (CNS)

• The drugs that affect the CNS are the most widely used drugs both therapeutically and recreationally.
• The cortex of the brain is responsible for thought, memory, self-awareness, personality, and speech.
• The midbrain serves as a relay station for the cortex and hypothalamus.
• The brainstem (medulla) controls areas for autonomic functions.
• The cerebellum is responsible for fine motor control, and coordinates movement.

Neurotransmitters

• Neurotransmitters cause electrical depolarization and passage of signal to the next neuron.
• Most neurotransmitters are returned to releasing nerve terminal and recycled.

Neuron-to-Neuron Communication

• Neurotransmitters are synthesized in the nerve, then transported and stored in the nerve terminal.
• Transport proteins (TP) present in the synapse are components of neurotransmission.
• Receptors (R) are present on both, the postjunctional and prejunctional membranes.
• Membrane-bound enzymes (ENZ) along with modifying neurons are components of neurotransmission.

Neurotransmitter Pathway

• After axonal depolarization, stored neurotransmitter (NT) is released into the synapse.
• NT binds to transport or carrier protein (TP) in the synapse, is transported to and binds with postjunctional receptors (2).
• NT is metabolized by membrane-bound enzymes (2), actively taken up by the releasing neuron (3), or is released and binds to prejunctional receptors.
• NT substance that is degraded to its component parts is taken up by the releasing neuron to be resynthesized and reused (4).

Factors Impacting Neurotransmitter Effect

• Amount of neurotransmitter released
• Type and quantity of transport proteins
• Previous neurotransmitter release
• Presence of modifiers
• Efficiency of reuptake process
• Activities of modulating interneurons

Psychiatric Medications - Antidepressants

• Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment for depression.
• Serotonin norepinephrine reuptake inhibitors are a newer option for treating depression.

Mood Stabilizers

• Mood stabilizers are primarily used for bipolar disorder, which involves alternating depression and mania (or hypomania).
• Examples of mood-stabilizing drugs are: lithium, valproic acid, carbamazepine, gabapentin, lamotrigine, and antipsychotics.
• Sedation is the main side effect of mood stabilizers, except for lithium.
• Lithium can cause tremors, cognitive slowing, hypothyroid, renal insufficiency, leukocytosis, polyuria, and polydipsia
• Lithium has a narrow therapeutic window and can cause coma.

Antipsychotics

• Antipsychotics work by increasing dopamine levels in the brain.
• They are used to treat psychotic disorders, including:
  • Impaired reality
  • Schizophrenia
  • Psychosis associated with depression or mania
• Older antipsychotic agents have numerous side effects.
  • Thorazine
  • Thioridazine
  • Haloperidol
• Newer antipsychotic agents are more tolerable.
  • Risperidone
  • Olanzapine
  • Quetiapine

Drugs for Alzheimer's Dementia

• Cholinesterase inhibitors increase acetylcholine levels in the brain
  • Donepezil
  • Tacrine
  • Galantamine
  • Rivastigmine
• Cholinesterase inhibitors may cause gastrointestinal (GI) side effects.

Anxiolytics

• Used to reduce anxiety
• Also used as amnestics
• May augment opioid respiratory depression
• Benzodiazepines
  • Hyperpolarize neurons
  • Good for anesthesia induction
  • Prevent "unpleasant recall"
  • Terminate seizures/increase threshold
  • Promote sleep
  • Specific antagonist: flumazenil

Barbiturates

• Have toxic potential and rapid tolerance
• Depress neuron activity
• High risk of addiction and abuse
• Used for:
  • Anesthesia induction: thiopental, thiamylal, methohexital
  • Hypnotics: pentobarbital, secobarbital
  • Seizures: phenobarbital

Barbiturates: Mode of Action

• Barbiturates and benzodiazepines (BDZ) depress CNS function.
• Stimulation of receptors on the chloride ion channel facilitates γ-aminobutyric acid (GABA)–induced inhibition of neuronal function.

Other Hypnotics

• Often used to induce sleep
• Hypnotics to induce sleep are generally recommended for 1–2 weeks
• Eszopiclone:
  • New drug
  • Approved for long-term use

Ethyl Alcohol

• A socially acceptable, nonprescription sedative-hypnotic.
• Also has a disinhibiting effect.
• In excess, it acts as a general anesthetic.
• At 400 to 600 mg/dl, it can cause respiratory arrest.
• Delirium tremens results in CNS hyperactivity on withdrawal.

Pain Treatment

• Pain is now considered the fifth vital sign.
• Visual or numerical analogy pain scales assess pain.
• Pain is subjective, unpleasant, and difficult to quantify objectively.
• Pain experience:
  • Pain: Input from CNS pain receptors Suffering: Emotional response to pain experience

Nonsteroidal Antiinflammatory Drugs (NSAIDs)

• Affect the hypothalamus and inhibit the production of inflammatory mediators at the pain site.
• May cause gastric irritation/ulceration.
• Salicylates are the oldest, aspirin.
• Increased incidence of Reye’s syndrome in children.
• Acetaminophen (Tylenol):
• Effective on mild/moderate pain
• No antiinflammatory effects
• May cause lethal hepatic necrosis
• No negative GI effects
• COX-2 inhibitors are being reevaluated.

Opioid Analgesics

• Derivatives of naturally occurring opium
• Used to treat moderate to severe pain
• Exert effect by binding to receptors for endogenous opioids (endorphins and enkephalins)
• High enough doses result in loss of consciousness, respiratory arrest
• Popular drugs of abuse
  • Euphoric effect
  • May cause LOC & respiratory arrest
  • Strong opioids are narcotics

Opioid Analgesics Side Effects

• Respiratory depression
• Constipation
• Nausea
• Vomiting
• Antitussive effects

Routes of Opioid Administration

• As needed (by nurse)
• Patient-controlled analgesia (PCA) pumps
  • Better to keep control of pain than regain control
• Opioid inhalation
• Decreases dyspnea in advanced respiratory failure
• Showed good clinical effect on cancer patients without lung disease
• No studies show improved effectiveness when inhaled

Local Anesthetics

• Interrupt nerve signals (pain) from damaged area
• Block Na+ channels along nerve cells
• Also useful as analgesia and for terminating cardiac conduction abnormalities
• Can suppress irritant tracheal cough response

Chemical Structures of Local Anesthetics

• Chemical structures of local anesthetics procaine and lidocaine, showing their respective ester and amide linkages, location of the lipophilic group, and ionizable amine group.

Epidural Analgesia

• Infusions of local anesthetics/opioids improve postoperative pain therapy and outcome.
• Provides better pain control versus systemic analgesics.

Combinations of Analgesic Classes

• Prescription combinations of NSAIDs & opioids are widely available
• Separate dosing may prove better with various side effects, toxicities, and half-lives
  • More troublesome for patients to take independently

Chronic Pain Syndromes

• Central sensitization can occur secondary to acute pain from surgery or trauma
  • Hyperesthesia, hyperpathia, and allodynia
• Treatment during acute phase may reduce likelihood of neuropathic problems later

Characteristics of Neuropathic Pain

• Evidence of primary injury
• Pain involving body area with sensory loss
• Pain characterized as burning, electric or shooting
• Dysesthesias in the area
• Sympathetic hyperactivity
• Hyperalgesia, hyperpathia, and allodynia

Anesthesia

• Drug-induced absence of perception
• Usually inhaled or IV
  • Gases and volatile liquids
• Depth determined by response to painful stimuli
  • Change in heart rate or blood pressure

Anesthesia (cont’d)

• Pharmacological modification of painful and frightening experiences during medical procedures
• Patient remains conscious
  • Able to communicate and protect airway
  • Ability may be lost during procedure

Conscious Sedation

• Goal is improved patient comfort and outcome
• Conscious sedation standards are required by The Joint Commission (TJC)

Providing Conscious Sedation

• Resuscitation equipment and trained personnel immediately available
• Conscious sedation requires more than one person
• Deep sedation/general anesthesia requires at least three people
  • Progression from conscious sedation to deep sedation to general anesthesia may be difficult to control
  • One person solely monitors vital signs

CNS and Respiratory Stimulants

• Analeptic drugs increase activity of the brain
• Used to treat narcolepsy, attention-deficit hyperactivity disorder (ADHD), obesity
• No clinical role in treating respiratory failure