Neurological and Pain Medications - Week 8 Past Paper

# Neurological and Pain medications - Week 8 - [Woo 5th ed Ch. 37 (HA) & 44 (Pain), 6th ed 38 (HA) & 46 (Pain)] ## Pain Assessment 1. **Relate the importance of pain assessment to effective pharmacotherapy.** - Catherine > *Pain assessment is crucial for selecting the proper treatment for p...

# Neurological and Pain medications - Week 8 - [Woo 5th ed Ch. 37 (HA) & 44 (Pain), 6th ed 38 (HA) & 46 (Pain)] ## Pain Assessment 1. **Relate the importance of pain assessment to effective pharmacotherapy.** - Catherine > *Pain assessment is crucial for selecting the proper treatment for pain, considering both the type of pain and its severity. Pain assessment allows doctors to tailor their pharmacotherapy to the individual patient's needs, improving treatment effectiveness and minimizing adverse effects. It also helps to monitor the patient's response to treatment, adjusting medication or dosage appropriately.* ## Neural Mechanisms in Pain 2. **Explain the neural mechanisms at the level of the spinal cord responsible for pain.** - Kristen C Pps1241- > Pain transmission involves three pathways: - **Afferent Pathway:** - Nociceptive receptors in tissues detect injury and release arachidonic acid. - COX enzymes convert arachidonic acid into prostaglandins. - Afferent nerve fibers transmit pain signals to the dorsal horn of the spinal cord. - **Central Nervous System (CNS):** - Pain signals enter the posterior nerve root of the spinal cord. - They travel through the lateral spinothalamic tract, where they can be modulated (intensified or blocked) within the substantia gelatinosa. - Neurotransmitters bind to secondary neurons in the substantia gelatinosa to relay pain signals to the brain. - **NMDA receptors are involved in pain memory and sensitization, which are particularly significant in chronic pain.** - **Efferent Pathway:** - Efferent pathways from the brain modulate pain sensation through the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in areas like the periaqueductal gray (PAG) and dorsal horns of the spinal cord. - Neurons projecting from the rostral pons to the raphe magnus secrete norepinephrine, which has an analgesic effect. - Serotonin is also released from the PAG and contributes to analgesia. ## Controlling Pain 3. **Explain how pain can be controlled by inhibiting the release of spinal neurotransmitters.** - Princess > *Pain can be controlled by inhibiting the release of spinal neurotransmitters through several mechanisms:* - **Modulation in the Spinal Cord:** Inhibition of neurotransmitter release within the substantia gelatinosa, a key region in the spinal cord containing multiple synapses, can help control pain.&#x20; - **Specific Neurotransmitter Release:** Several neurotransmitters are involved in pain transmission within the spinal cord, including substance P, GABA, cholecystokinin, somatostatin, calcitonin gene-related peptide, and excitatory amino acids such as glutamate. Inhibiting the release of these neurotransmitters, especially the excitatory ones, can reduce pain signaling.&#x20; - **NMDA Receptor Involvement:** Glutamate binding to NMDA receptors in the spinal cord contributes to pain memory. Inhibiting glutamate release or blocking NMDA receptors could potentially reduce chronic pain syndromes.&#x20; - **Efferent Modulation:** Efferent pathways from the brain contribute to the modulation of pain sensation through the release of endogenous opioids in areas like the PAG and dorsal horns of the spinal cord. Increasing the release of these endogenous opioids or mimicking their effects can inhibit the release of pain-transmitting neurotransmitters in the spinal cord.&#x20; - **Serotonin and Norepinephrine:** Neurons projecting from the rostral pons to the raphe magnus secrete norepinephrine, which has an analgesic effect. Additionally, serotonin release from the PAG sends analgesic signals to the raphe magnus. Enhancing the release or activity of these neurotransmitters can help inhibit pain signaling in the spinal cord.&#x20; - **Opioid Receptors:** Opioid receptors (mu, kappa, and delta) are present in the brain, spinal cord, and peripheral tissues. Activating these receptors, particularly the mu and kappa receptors which have primary analgesic activity, can lead to the inhibition of pain-transmitting neurotransmitters in the spinal cord. ## Complementary and Alternative Therapies 4. **Describe the role of complementary and alternative therapies in pain management.** - Lauren H > *Complementary and alternative therapies can play a significant role in pain management by addressing various aspects of pain beyond the purely physiological:* - **Cognitive Behavioral Interventions:** These therapies focus on changing thoughts and behaviors that contribute to pain perception and experience. Examples include acupuncture, transcutaneous electrical nerve stimulation (TENS), yoga, and massage. - **Nonpharmacological Measures:** These interventions aim to provide pain relief through physical means, such as heat, ice, massage, touch, and distraction. - **Exercise, rest, and heat therapy** have all been shown to improve pain management. ## Opioid Receptor Types 5. **Compare and contrast the types of opioid receptors and their importance in effective management of pain.** - Angela (pg 261;1244) > There are three major types of opioid receptors: mu, kappa, and delta. - **Mu Receptors:** - Primarily responsible for analgesia, respiratory depression, and physical dependence. - Activation of mu receptors is the primary mechanism of action for most opioid analgesics. - **Kappa Receptors:** - Contribute to analgesia, sedation, and dysphoria. - Less potent than mu receptors and have a lower risk of dependence. - **Delta Receptors:** - Their role in pain management is less understood, but they may contribute to analgesia and modulation of pain. > Understanding the different opioid receptor types and their respective roles is crucial for effective pain management. It allows prescribers to select medications with the appropriate receptor profile for the specific type of pain, minimizing side effects and optimizing patient outcomes. ## Opioid Antagonists 6. **Explain the role of opioid antagonists in the diagnosis and treatment of acute opioid toxicity.** - Princess E > **Naloxone** is a first-line rescue medication used to treat opioid overdose. It is a pure opioid antagonist that prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. It works by competitively binding to opioid receptors and blocking the effects of opioids.&#x20; > Naloxone is administered in the absence of opioids, it does not exhibit any pharmacological activity. Providers should consider prescribing naloxone for patients at risk for opioid overdose. Naloxone became available over the counter in 2023. > **Serotonin Syndrome** is a potentially life-threatening condition that can occur with the use of opioid antagonists, especially when patients are already taking serotonergic antidepressants. Symptoms include a high body temperature, agitation, hyperreflexia, tremors, sweating, dilated pupils, diarrhea, and seizures. Management involves stopping either the opioid or the SSRI or both and providing supportive care until the patient is stable. ## Long-term Opioid Dependence 7. **Describe the long-term treatment of opioid dependence.** - Kristin M > *Long-term opioid dependence is a complex medical condition requiring a multidisciplinary approach that addresses both the physical and psychological aspects of dependence. Treatment aims to reduce opioid cravings, alleviate withdrawal symptoms, and provide support for recovery. Key aspects of treatment include:* - **Detoxification:**&#x20; - A gradual reduction in opioid dosage under medical supervision to manage withdrawal symptoms. - Medications like methadone or buprenorphine may be used to help manage withdrawal symptoms and cravings. - Detoxification can be challenging, and careful monitoring is crucial to prevent relapse. - **Maintenance Therapy:** - Use of long-acting medications like methadone or buprenorphine to help maintain stability and reduce cravings. - Medications are typically administered in a controlled setting to prevent misuse or diversion. - **Behavioral Therapies:** - Cognitive-behavioral therapy (CBT) focuses on identifying triggers and modifying behaviors associated with opioid use. - Contingency management involves rewarding positive behavior changes. - Support groups provide a safe space for individuals to share experiences and provide mutual support. - **Recovery Support:** - Post-treatment support is vital to prevent relapse. - Individuals may need to participate in ongoing therapy, counseling, and community support groups. - Access to medications and resources to manage cravings and prevent relapse is crucial. ## Comparing Migraine Treatments 8. **Compare the pharmacotherapeutic approaches of preventing migraines with those of aborting migraines.** - Lauren B > *Migraine treatments can be categorized into abortive therapies, which focus on stopping an ongoing migraine, and preventive therapies, which aim to reduce the frequency and severity of migraine attacks.* ### Abortive Therapy - **Over-the-counter (OTC) analgesics** such as NSAIDs (ibuprofen or naproxen) and migraine formulas (Excedrin Migraine or Advil Migraine) are most effective early in migraine. - **Triptans (serotonin receptor agonists):** - Examples include sumatriptan (Imitrex) and other triptans. - Taken at the onset of migraine. - Contraindicated in patients with coronary artery disease, hypertension, and pregnancy. - Drug interactions include ergotamines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors. ### Preventive Therapy - **Beta Blockers:** - Commonly used in patients experiencing more than two migraines per month.&#x20; - Examples include propranolol, timolol, telmisartan, and candesartan.&#x20; - Aim for a 50% reduction in migraines. - **Propranolol:** - Start at 60 to 80 mg/day and increase to 240 mg/day. - Children: 0.5 mg/kg/day, increase to 2 to 4 mg/kg/day. - Perform a 3-month trial and reassess every 6 months. - Taper off slowly. - **Adverse effects include fatigue, lethargy, and depression.** - **Antidepressants:**&#x20; - Amitriptyline and venlafaxine are often used. - **Antiepileptic Drugs:** - Examples include divalproex sodium, sodium valproate, and topiramate.&#x20; > **Nonpharmacological Treatments for Migraines:** - **Identifying Triggers:** Keeping a headache diary helps identify specific triggers, such as food, stress, or environmental factors. - **Alternative Therapies:** - Consider acupuncture, aromatherapy, hypnosis, reflexology, massage, yoga, ice, biofeedback, and other alternative treatments.&#x20; ## Drug Classes and Their Clinical Applications 9. **For each of the following drug classes, and representative drug examples, describe the mechanism of action, primary actions and therapeutic uses, special considerations, and important adverse effects (may be beneficial to categorize drugs used in the treatment of pain based on their classification and mechanism of action).** - EVERYONE | Name/Type | MOA | Indications | SE | Considerations | | :---------------------- | :-------------------------------------------------------------------------------------------------------------------------------------- | :-------------------------------------- | :-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | :--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | **Non-Opioid:** | | | | | | Acetaminophen | Antipyretic and analgesic properties, but no anti-inflammatory. Thought to inhibit COX-3 in the CNS, reducing prostaglandins and increasing the pain threshold for analgesic effect. | Fever, pain | 4 grams daily max. N-acetylcysteine - Antidote Safe in pregnancy and lactation. Not recommended for first-line therapy except in pregnant patients. Risk for MOH with daily use. Use with caution if altered LFTs, hepatitis, excessive alcohol consumption. Renal dosing parameters. IV formulation approved for 2 years and older IV- if CrCL <30, adjust dosing Overdose leads to production of NAPQI (phase 2 metabolism) which can cause oxidative damage to hepatocytes. Antidote for overdose is n-acetylcysteine (mucomyst; acetadote). | Safe in pregnancy. Safe in infants. Safe in most older adults. | | **NSAIDs:** | | | | | | Aspirin (not an NSAID) | **potent inhibitor of both prostaglandin synthesis and platelet aggregation than its other salicylic derivatives due to the acetyl group on the aspirin molecule, which irreversibly inactivates cyclooxygenase via acetylation. This prevents the conversion of arachidonic acid to thromboxane A(2). Platelet aggregation is inhibited for their lifespan of 7 to 10 days. The inhibition of the synthesis of thromboxane A(2) is irreversible as the thrombocytes without nucleus are unable to synthesize new cyclooxygenase after the existing one has been acetylated by acetylsalicylic acid**. COX-1 - **irreversible inhibition** | Mild to moderatepain, Rheumatoid arthritis, Osteoarthritis, Acute rheumatic fever, Myocardial infarction prophylaxis, Fever, Pain, Upper GI | GI upset, GI bleed, ulcers, Reye's syndrome if administered to children with flu-like illness | Not an NSAID. Take with plenty of water, and remain upright for 15 to 30 minutes. Do not crush or chew enteric-coated tablets. Tablets with a vinegar-like odor should be discarded. Do not use in pregnancy or children. Contraindicated in pregnancy (Category D)† Avoid use within 7 days of surgery (antiplatelet activity). Risk for MOH with daily use. Renal dosing parameters. Caution in patients with kidney disease, ulcer disease, gastritis. | | Celecoxib | Inhibit prostaglandin synthesis, primarily via inhibition of cyclooxgenase-2 (COX-2). Its mode of action may be due to a decrease of peripheral tissue prostaglandins, which sensitize afferent nerves, potentiate the action of bradykinin in inducing pain, and mediate inflammation COX-2. | All headache types, OA, Juvenile Idiopathic Arthritis | Pregnancy: avoid use at 30 wk gestation. | | | Diclofenac | Potent anti-inflammatory, analgesic, and antipyretic properties. Like other NSAIDs, although the mechanism is not completely understood, it may involve inhibition of prostaglandin synthetase and COX-1 and COX-2 pathways. COX-2 | All headache types, OA analgesia, RA, Ankylosing spondylitis, Dysmenorrhea, Ophthalmic- cataracts surgery, corneal refractive surgery, Available in topical form | Dose >150mg worsen renal function. | Contraindicated in third trimester of pregnancy; probably safe at low doses during lactation. Use with caution in kidney disease, ulcer disease, gastritis. Renally dosed. Risk for MOH with daily use. | | Indomethacin | Has anti-inflammatory, antipyretic, and analgesic properties. Inhibition of cyclooxgenase (COX-1 and COX-2), which leads to decreased prostaglandin synthesis, thought to be the primary mecanism of action. COX-1 | PDA closure, Gout, OA, Bursitis | | | | Ibuprofen | Nonsteroidal antiinflammatory drug (NSAID) that exhibits analgesic and antipyretic activities by inhibiting prostaglandin synthesis. Ibuprofen has an inhibitory effect on platelet aggregation stimulated by ADP (adenosine phosphate) or collagen COX-1 | All headache types, Pain, Fever, RA, OA | Hypotension, Hypernatremia, Hypoalbumemia, Dizzy, GI upset, heartburn | Contraindicated in third trimester of pregnancy; probably safe at low doses during lactation. Use with caution in kidney disease, ulcer disease, gastritis. Renally dosed. Risk for MOH with daily use. | | Ketoprofen | Nonsteroidal anti-inflammatory | RA | | Probenecid increases | | Ketorolac (Toradol) | Nonsteroidal antiinflammatory drug (NSAID) with both analgesic and antipyretic activities. The exact mechanism of action is unknown but its anti-inflammatory effect is thought to be related to its ability to inhibit prostaglandin and leukotriene synthesis, to its antibradykinin activity, as well as its lysosomal membrane-stabilizing action. COX-2 | OA, Gout, Mild to mod pain, Dysmenorrhea, | | | | Edema, HTN, Eye burning, Nasal irritation, Nasal pain | Limit duration to 5 day Dosage therapeutic threshold Contraindicated in pregnancy, lactation, kidney disease, ulcer disease, gastritis. Do not exceed 5 consecutive days of use. Renal dosing. Risk for MOH possible with daily use. Caution in patients with changing renal function, bleeding risk, on anticoagulants or anti platelet drugs, and with risk of CVD or GI bleeding. | | Naproxen | Propionic acid derivative NSAID with analgesic, anti-inflammatory, and antipyretic activities. The mechanism of action is unknown but involves inhibition of cyclooxygenase (COX-1 and COX-2), which leads to reduced prostaglandin synthesis. COX-1 | Headaches- good BBB penetration, All headache types, Menstrual migraine prophylaxis | Edema, Ecchymosis, Itching, GI upset, Dizzy, Tinnitus | Contraindicated in third trimester of pregnancy; probably safe at low doses during lactation. Absorbed more slowly than naproxen sodium. Use with caution in kidney disease, ulcer disease, gastritis. Renally dosed. Risk for MOH with daily use. | | **Opioid** | | | | | | Analgesics: | **Interact with Mu (agonises), Kappa, Delta, or Sigma receptors reducing cAMP which closes Ca++ channels stopping pain neurotransmitters (glutamate and substance p) from being released Binds primarily to supraspinal and spinal Mu receptors -reduction in ascending pathways for pain stimuli** | | N/V, Hallucinations, Constipation: can be made worse if using a TCA, Euphoria, Lethargy, Itching due to release of histamine NOT type 1 hypersensitivity mediated by IGE, Opioid poisoning: coma, apnea, pinpoint pupils, Sphincter of oddi spasm (reduces secretions of bile and pancreatic fluids leads to worsening of acute pancreatitis), Smooth muscle spasm of ureters and bronchioles, Opioid induced myoclonus or neurotoxicity, Depression of cough reflex, Miosis (pupillary constriction) | >50 mg morphine eq. /day increases risk of OD 2x Converting: recommended to decrease the dose of the new opioid by 25% to 50% to avoid overdose due to incomplete cross-tolerance and individual variability in opioid pharmacokinetics -10-15% of total daily MME (Morphine milligram equivalents) reserved for PRN dosing -do not use in right sided MI | | Tramadol | **Active and M1 metabolite bind to Mu opioid receptor as well as inhibits reuptake of serotonin and NE -Mu opioid receptor agonist** | Moderate to severe chronic pain | Bradypnea, seizures | Concerns with SSRIs (paroxetine, fluoxetine)) for risk of Serotonin syndrome No approved for children Avoid XR products in those with CrCL<30 or with severe hepatic impairment Drug interactions with cyclobenzaprine and amitriptyline | | Tramadol + Acetaminophen (ultracet) | | | | | | **Partial opioid agonist/antagonist** | | | | | | Buprenorphine (c-III) | Kappa agonist Mu antagonist | Mod to severe pain, Opioid dependence | Has a ceiling effect, not for chronic pain control. | | | Buprenorphine + Naloxone | | | | | | Butorphanol (c-IV) | Kappa agonist Mu partial agonist/antagonist | Pain, Pre-anesthesia sedation | | | | Nalbuphine (No class) | Mu agonist Kappa antagonist | Mod to severe pain, Pre-op sedation | (gtt to counteract opioid pruritus /itching w/ more histaminergic opioids) Don't give IV in line w. Nafcillin or ketorolac Effect lost if crushed | | | Pentazocine (c-IV)