Farris Study Guide

Acute suddenonst wounds myth 3ÉEÉy sogy Magat sherpintersefastfiberpain sedation Tuesday, August 20, 2024 9:53 PM Regional Radiating Pain and Analgesics 1. Discuss the four criteria used to classify pain a. Duration Localization 32 concelerthritis Globalspeific deepaching slowfiberpain I chronic pains Y8cation Farris Study Guide – Cindy Vo • Acute: Sudden onset • Wound • Present less than 3 months • A specific low back pain • Recurrent: occurs periodically • Chronic: Continuous over a long period (more than 3 months) • Cancer or arthritis recantperiodically continousoarlongperion month Duration widespread Source y 3 i 2. Differentiate between nociceptive pain and neuropathic pain i ending pathway tissue nerve sens't't needont issue res agent Sensation • Local: in specific area • Somatic: restricted to muscles, • Cut in finger joints, or skin • Regional: region of body • Strain or cramp • Abdominal pain • Visceral: originates from organs or • Radiating: starts in one area and tissues moves outward • Appendicitis • Pain to lower extremities • Referred: visceral pain perceived as from lumbar disk rupture somatic pain in embryologically • Widespread: extended part of related part of body body • Pain in left arm during heart • fibromyalgia attack ptg g not damaging orcesedby initiated neuropathicpain Yim • Fast fiber pain: sharp, intense, and well localized • Slow fiber pain: deep, aching, and poorly localized 33 Piggylesionordysfunction innervate a. s cercapsalipleurg nodin transduction active painarea no Transmissionisignalfromnoci 3. Characterize each of the four basic processes that define the classical “Pain Pathway” a. Transduction: activation of nociceptors in painful area b. Transmission: signal (action potential) carried from nociceptors to spinal cord and then to brain by afferent neurons c. Modulation: in CNS, signal is changed to reflect pain type and conditions charged signed d. Perception: signal is perceived as pain in higher brain centers 4. Define nociceptor and identify where they are found paintupeontiondition a. Nociceptor: free nerve endings in tissues that are sensitive to tissue damage i. Found in: preception 1. Superficial skin layers 2. Deeper tissues: periosteum, joints, arterial wall, liver capsule, pleura 3. Other deeper tissues: sparse pain nerve endings, but wide spread tissue damage results in pain 5. Differentiate between the two types of Afferent Pain Neurons owe to modulation galoot reflect signalisperbed aspaininhigler braincenth WE AΔ Neurons a. • • • • Sharp pain (fast fiber pain) Myelinated (Schwann cells) 1-5 micrometers in diameter Rapid conductance of actional potential – 15 m/sec C Neurons • • • • Dull pain (slow fiber pain) Unmyelinated 0.3 micrometers in diameter Relatively slow conductance of action potential – 1 m/sec nod 6. Identify the three levels at which the pharmacological treatment of pain can be targeted prosogeninhibit a. Nociceptors (e.g., prostaglandin synthesis inhibitors) inhibitnenesigned b. Inhibition of nerve signal (e.g., local anesthetics, TEN) c. Central Modulation (e.g., opioids) modulation 7. Define “Algia”, “Hyperalgesia”, and “Analgesia” a. Algia: suffix indicating pain (e.g., neuralgia, myalgia) b. Hyperalgesia: increased sensitivity to pain c. Analgesia: absence or reduction of pain induced by medications that diminish or block pain sensation 8. Explain how hyperalgesia can arise i. Arises from presence of inflammatory chemicals at damage site ii. Makes new transduction of new impulse more likely by lowering depolarization threshold iii. Increases sensitivity of the nociceptors 9. Explain the process by which prostaglandins are synthesized from arachidonic acid i. Prostaglandins are synthesized from arachidonic acid in a key inflammatory process: i. Arachidonic Acid Release: phospholipase releases AA from membrane phospholipids (stored) ii. Cyclooxygenase (COX) Pathway: COX enzymes convert arachidonic acid into prostaglandins and thromboxane (Prostanoids) iii. Prostaglandin Formation: PGH2 is then transformed into various specific prostaglandins that mediate inflammation, pain, and other physiological responses. 10. Differentiate between COX 1 and COX2 enzymes 3 gas central is Coxinhibit Selective non inhibitsoxtond2 feelsirreversible bindinayat Aspirin COX-1 i. • Found in all tissues and produced at stable rate – needed for baseline production • Constitutive • Inhibition undesirable • Homeostatic functions • Produces protection of GI, renal tract, platelet function, macrophage differentiation COX-2 • Induced in response to tissue injury and associated with inflammation • Induced • Inhibition desirable • Inflammation onticoagluentactivity NSAID 11. Explain the mechanism of action of the NSAIDs i. NSAIDs i. MOA: 1. Decrease prostaglandin synthesis and inflammatory hyperalgesia 2. Reduce recruitment of leukocytes and production of leukocyte-derived inflammatory mediators 3. NSAIDs that cross the BBB prevent production of prostaglandins that act as pain producing neuromodulators 12. Explain how Aspirin differs from the other NSAIDs i. Aspirin is a non-selective COX inhibitor – inhibits COX-1 and COX-2 ii. Acetylates the cyclooxygenase active site iii. Cox-1 inhibitors have antiplatelet activity and thus have anticoagulant activity (low dose aspirin therapy) iv. Unlike other NSAIDs, Aspirin is an irreversible inhibitor of the COX enzymes v. When Aspirin binds to a COX enzyme, the enzyme is inactivated permanently vi. All other NSAIDs are reversible COX inhibitors – they bind and dissociate vii. NSAIDs and COX-2 inhibitors act both peripherally and centrally 13. Explain how Acetaminophen differs from the NSAIDs Acetaminophen i. Acetaminophen has analgesic + anti-pyretic but no anti-inflammatory effect ii. One of the most widely used drugs i. No risk of Reye's Syndrome ii. Few GI disturbances iii. Major SEs: liver and renal damage w/ high doses or long term use iii. Unclear MOA i. No peripheral COX1 or COX2 inhibition ii. Believed to function in CNS but not sure exactly how iii. May inhibit COX enzymes in CNS 14. Explain the significance of “Periaqueductal Gray Matter” and “Rostroventral Medulla” i. Periaqueductal Gray Matter (PAG) and Rostroventral Medulla (RVM) i. Key brainstem regions involved in pain modulation. ii. PAG 1. located in the midbrain 2. can inhibit pain by releasing endogenous opioids and sending signals to suppress pain iii. RVM, 1. located in the medulla oblongata 2. can either facilitate or inhibit pain signals at the spinal cord level ii. Together, they form a crucial circuit for managing pain perception in the body. 15. Identify where enkephalins act to modulate the pain transmission signal i. Spinal cord 16. Differentiate between the three classes of endogenous opioids 81120 ondinthypan presslen tLeukocyte tBBB proactproste infusenatoy anti 0 reraldage liver Forest inhibitcox May someEIbler Midbrain MY RAG inhibitpainbyrelageirgendopoidto stoppain medullaoblongata crucial nor f point Roy facilitatorinhibitpain i. Dy Β-endorphins Inhibit transmission of pain in brain stem Enkephalins Inhibit transmission of pain in spinal cord Dynorphins Functions in learning, memory, emotional control, stress response, and pain in hippocampus, amygdala, hypothalamus, striatum, and spinal cord 17. Differentiate between the three opioid receptors a enplane bet respiratory as penpinyons Responsible for most analgesic effects and sedation µ (Mu) or MOR • • Responsible for strongest and most dangerous side effects: • Respiratory depression • Euphoria • Dependence Δ (Delta) or DOR • More in periphery > CNS i. signalinspicord B inhibitbrain as G spiralord spiral depression k only psychosis K (Kappa) or KOR • Lower levels of analgesia than MOR but less than respiratory depression and dependence • SE: sedation and psychological effects (e.g., anxiety, depression, psychosis) 18. Identify the structural components of Morphine that are essential for its analgesic activity i. Ind I 31,44N Ro ii. Aromatic Ring (Phenyl Group) olds i. Essential for binding to opioid receptor ii. Forms hydrophobic interactions w/ receptor's binding pocket → stabilizing morphine-receptor complex iii. Amine Group i. Essential for receptor activation ii. Nitrogen in tertiary amine group is positively charged at physiological pH → allows to form ionic bonds w/ anionic site of opioid receptor iv. Phenolic Hydroxyl Group (-OH) at Position 3 i. Essential for hydrogen bonding w/ opioid receptor ii. Enhances molecule's binding affinity + necessary for strong analgesic effects v. Modification of Phenolic Group (3) i. vi. Modification of Alcohol Group (6) i. vii. Removal of Double Bond (7 – 8) i. Hydromorphone (Dilaudid) 1. viii. The N-Methyl Group i. ix. The Aromatic Ring i. Essential for activity 1. Disruption or modification = lack activity x. The Ether Bridge Between Positions 4 – 5 i. Levorphanol (Levo-Dromoran) 1. Agonists w/ 6-8x potency of morphine at µ-opioid receptor 2. Also agonist at other receptor but lower potency 19. Differentiate between the terms “Opiate” and “Opioid” a wk Opiate • Drugs derived specifically from opium • Morphine, codeine, thebaine, and congeners Opioid • More inclusive • All agonist + antagonists w/ morphine-like activity • Naturally occurring and synthetic opioid peptides (endorphins) i. i 20. Name the alkaloid that is primarily responsible for the analgesic activity of Opium period a Morphine modentepoinicoghif methylene at activity littleanalgesic i. Morphine 21. Codeine has little or no analgesic activity. Explain why some analgesic effect is observed following codeine administration i. Codeine i. The methyl ether of Morphine ii. Used for moderate pain, coughs, and diarrhea iii. Has little if any analgesic activity iv. 10% converted to Morphine by CYP2D6 a poiconventtomophin by EG firestinteously 1 Convulsions and Epilepsy 1 neurons 70 Asondition zormoveungovokedseizure 1. Define the terms “seizure”, “hypersynchronous”, and “epilepsy” a. Seizure: a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system neurons b. Hypersynchronous: abnormal condition in which neurons in the brain fire simultaneously or in an excessively synchronized manner c. Epilepsy: condition in which a person has recurrent seizures due to a chronic, underlying process. i. Producing two or more unprovoked seizures 2. Distinguish between a seizure and epilepsy a. See #1 3. Explain why it is important to determine the type of seizure that a person experiences a. Accurate diagnosis b. Tailored treatment plans depending on type of seizure c. Prognosis and management d. Safety considerations e. Identify underlying cause 4. List the two major categories of seizures (current categorization) and explain the difference between them unitals Iponto Traditional Categorization a. 5. 6. 7. • Partial (Focal) Seizures • Part of brain • Generalized Seizures • Whole brain Gem bilateral Current Categorization pagonappg pontBrain • Partial (Focal) Seizures • Unilateral movement • Generalized Seizures • Bilateral movement primanyageneticabofinchenal sendensadoreannenuirrentdueto toxicexposure a. Primary Etiologies i. Genetic abnormalities of ion channels b. Secondary Etiologies i. Change in neuronal environment due to toxic exposure List the three criteria used for classification of seizures a. Where seizure beings in the brain b. Level of awareness during a seizure c. Other features When discussing “where a seizure begins in the brain” explain the meanings of “focal seizures”. “generalized seizures”, “unknown onset seizures”, and “secondary generalized seizures” a. Focal Seizures: one side of brain besininonesidetspreadtoggth b. Generalized Seizures: both sides of brain c. Unkown Onset Seizures: location of onset is unknown d. Secondary Generalized Seizures: begin on one side of brain + spread to both sides Explain why level of awareness is not categorized in generalized seizures a. Generalized Seizures: i. All are assumed to affect awareness to some degree Define “focal motor seizure”, “focal non-motor seizure”, and “auras” a. Focal Motor Seizure: some type of movement occurs (twitching, jerking, stiffening, and automatisms) b. Focal Non-Motor Seizure: non-motor changes including – thinking, sensations, emotions, etc. c. Auras: changes that occur at the beginning of seizures (not used in new terminology but will see in literature) Define “non-motor or absence seizures (petit mal)’, “myoclonic seizures”, and “motor or tonic-clonic seizures (grand mal)” a. Non-Motor or Absence Seizures (petit mal): brief changes in awareness, staring, in some cases automatic repeated movements b. Myoclonic Seizures: brief (1 second or less) muscle contractions, may be in isolated muscles or widespread c. Motor or Tonic-Clonic Seizures (grand mal): involve stiffening (tonic) and jerking (clonic) movements Define the terms “ictal” and “interictal” a. Ictal: period which a seizure is actively occurring i. Encompasses the entire duration of seizure, from onset of symptoms until seizure ends b. Interictal: period between seizures when brain is not experiencing seizure activity i. Phase occurs after one seizure ends and before the next one begins Define interictal spike and explain its significance a. Interictal Spike i. Surround inhibition often localizes discharges within the Focal region, preventing symptomatic pathology ii. Sharp spikes on EEG iii. May be useful in diagnosing epilepsy and in locating the seizure focus in patients not actively experiencing a seizure Explain the concept of “surround inhibition” in neurons a. Surround inhibition i. Neurons enhance signal precision and prevent excessive neuronal activity 1. Inhibiting surrounding neurons when one neuron is excited ii. Crucial for refining sensory inputs, focusing neural responses, and preventing pathological conditions like epilepsy Define the terms “Jacksonian March” a. Focal seizure that manifests as an ipsilateral spread of motor disturbances from distal to proximal i. (e.g. shaking hand progressing into arm and upper arm) b. Observed clinical symptoms result from progressive spread of synchronous activity across brain regions (in case of Jacksonian March – across the motor cortex) Explain the significance of “U fibers”, “Corpus Callosum”, and “Thalamocortical projections” as they relate to Secondary Generalized Seizures a. In secondary generalized seizures: i. U Fibers: Local connections within one hemisphere that help spread seizure activity to nearby areas. ii. Corpus Callosum: Connects the two brain hemispheres, allowing seizure activity to spread from one side to the other. psideBrain Bothside 8. 9. 10. 11. 12. 13. BI EH 14. 15. where µ im Describe the difference between primary and secondary etiologies in the pathophysiological development of seizures a glow É iii. Thalamocortical Projections: Links the thalamus and cortex, helping to amplify and spread the seizure activity across the brain. b. These structures contribute to the transition from a focal seizure to a widespread, generalized seizure. 16. List the primary mechanism of action for the drugs; carbamazepine, lamotrigine, lacosamide, valproic acid, phenytoin, ethosuximide, gabapentin, pregabalin, benzodiazepines, barbiturates, vigabatrin, felbamate, and rufinamide O Drug MOA • • • • • Phenytoin Carbamazepine Lamotrigine Lacosamide Valproic acid • bind to the voltage-gated Na+ channels in the neuronal membrane to slow the rate of channel recovery and decrease the rate of neuronal firing • show strong specificity for the treatment of focal and secondary generalized seizures • • • • Ethosuximide (T-type) Gabapentin (HVA) Valproic Acid (T-type) Pregabalin (HVA) • Inhibiting neuronal calcium channels, fall into one of two main classes: 1. Those that inhibit the T-type calcium channel T-type calcium channels are activated by low threshold membrane depolarization and are thought to be critical in onset of absence seizures 2. Those that inhibit the high-voltage activated (HVA) calcium channels HVA channels play an important role in controlling the entry of calcium into presynaptic terminals and inhibiting the release of neurotransmitters into the synapse thereby blocking propagation of the action potential a. • Used to treat absence seizures Benzodiazepines • AC (anticholinergic) activity act by enhancing the affinity of GABA for the GABAA channel, and increase Cl- influx through the channel • Tx for focal and tonic-clonic seizures • Barbiturates • Vigabatrin • Enhance GABA-Mediated Inhibition • bind to the GABA receptor (probably GABAA) to enhance the activity of or decrease the metabolism of GABA • Activation of the GABAA receptor facilitates the flow of chloride ion into the neuron ○ hyperpolarization of the membrane ○ Increasing the firing threshold of the membrane and decreasing the firing rate • Felbamate • Rufinamide • Inhibition of the NMDA and AMPA subtypes of glutamatergic receptors no Eam r off xx A at