Lecture 21 - Non-Opioids and Opioids

‭Approaches to Managing Pain‬ ‭Non-Pharmacologic‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ ehabilitation‬ R ‭Exercise‬ ‭Heat/cold‬ ‭Transcutaneous electrical nerve stimulation (TENS)‬ ‭Acupuncture‬ ‭Massage‬ ‭Distraction‬ ‭Spiritual guidance/support‬ ‭Pharmacologic‬ ‭Non-Opioids‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ spirin‬ A ‭NSAIDs‬ ‭Acetaminophen‬ ‭Antidepressants‬ ‭Natural Opioids‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ orphine‬ M ‭Codeine‬ ‭Oxycodone‬ ‭Hydrocodone‬ ‭Synthetic Opioids‬ ‭‬ F ● ‭ entanyl‬ ‭●‬ ‭Tramadol‬ ‭●‬ ‭Methadone‬ ‭Non-Opioids: Cyclooxygenase Inhibitors‬ ‭COX Enzymes‬ ‭●‬ ‭Synthesizes prostaglandins and related compounds‬ ‭COX-1, “Good”‬ ‭‬ P ● ‭ rotects gastric mucosa‬ ‭●‬ ‭Supports renal function‬ ‭●‬ ‭Promotes platelet aggregation‬ ‭COX-2, “Bad”‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ ediates inflammation‬ M ‭Sensitizes receptors to painful stimuli‬ ‭Brain: Mediates fever and contributes to pain perception‬ ‭Kidneys: Supports renal function‬ ‭Blood vessels: Promotes vasodilation‬ ‭Colon: Contributes to colon cancer‬ ‭Aspirin‬ ‭Uses‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ ain relief‬ P ‭Suppression of inflammation‬ ‭Fever reduction‬ ‭Suppression of platelet aggregation‬ ‭Mechanism of Action‬ ‭●‬ ‭Irreversibly inhibits COX-1 and COX-2‬ ‭Adverse Effects‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ astric ulceration‬ G ‭Acute renal failure‬ ‭Bleeding‬ ‭Reye’s syndrome‬ ‭Drug Interactions‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ nticoagulants‬ A ‭Glucocorticoids‬ ‭Alcohol‬ ‭NSAIDs‬ ‭First Generation NSAIDs‬ ‭●‬ ‭Prototype: Ibuprofen‬ ‭Uses‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ ain relief‬ P ‭Suppression of inflammation‬ ‭Fever reduction‬ ‭Dysmenorrhea‬ ‭Rheumatoid arthritis‬ ‭Mechanism of Action‬ ‭●‬ ‭Reversibly inhibits COX-1 and COX-2‬ ‭Adverse Effects‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ astric ulceration‬ G ‭Acute renal failure‬ ‭Bleeding‬ ‭Increased risk from thrombotic events (MI and stroke)‬ ‭Drug Interactions‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ nticoagulants‬ A ‭Glucocorticoids‬ ‭Alcohol‬ ‭NSAIDs‬ ‭Lithium‬ ‭SSRIs‬ ‭Second Generation NSAIDs‬ ‭●‬ ‭Prototype: Celecoxib (Celebrex)‬ ‭Uses‬ ‭‬ D ● ‭ ysmenorrhea‬ ‭●‬ ‭Arthritis‬ ‭●‬ ‭Acute pain‬ ‭Mechanism of Action‬ ‭●‬ ‭Selective COX-2 inhibitor‬ ‭Adverse Effects‬ ‭‬ G ● ‭ astric ulceration‬ ‭●‬ ‭Acute renal failure‬ ‭●‬ ‭Increased risk from thrombotic events (MI and stroke)‬ ‭Drug Interactions‬ ‭‬ A ● ‭ nticoagulants‬ ‭●‬ ‭Lithium‬ ‭Acetaminophen‬ ‭Uses‬ ‭‬ P ● ‭ ain relief‬ ‭●‬ ‭Fever reduction‬ ‭Mechanism of Action‬ ‭●‬ ‭Inhibits COX-1 and COX-2 in the CNS but not periphery‬ ‭Adverse Effects‬ ‭‬ L ● ‭ iver injury (with overdose)‬ ‭●‬ ‭Hypersensitivity (rare)‬ ‭●‬ ‭Stevens-Johnson Syndrome‬ ‭Drug Interactions‬ ‭‬ A ● ‭ lcohol‬ ‭●‬ ‭Warfarin‬ ‭●‬ ‭Vaccines‬ ‭Terminology Review‬ ‭Pure Agonists‬ ‭●‬ ‭Have affinity for binding and efficacy‬ ‭Pure Antagonists‬ ‭●‬ ‭Have affinity for binding but no efficacy‬ ‭Agonist-Antagonist‬ ‭‬ P ● ‭ roduces an agonist effect when given as monotherapy‬ ‭●‬ ‭Acts as an antagonist in the presence of a full agonist‬ ‭●‬ ‭Has affinity for binding but low efficacy‬ ‭Opioid Analgesics‬ ‭Endogenous Opioid Peptides‬ ‭‬ P ● ‭ roduced by the body‬ ‭●‬ ‭Have opioid-like properties‬ ‭●‬ ‭Act as neurotransmitters, neurohormones, and neuromodulators‬ ‭Opioid-Like Peptides‬ ‭‬ E ● ‭ ndorphins‬ ‭●‬ ‭Enkephalins‬ ‭●‬ ‭Dynorphins‬ ‭Opioid Receptors‬ ‭‬ M ● ‭ u (μ1 and μ2), kappa, delta‬ ‭●‬ ‭Endogenous opioid peptides act on all three‬ ‭●‬ ‭Exogenous opioid analgesics only act on mu and kappa receptors‬ ‭Opioid Receptor Activation‬ ‭Response‬ ‭Mu‬ ‭Kappa‬ ‭Analgesia‬ ‭✓‬ ‭✓‬ ‭Respiratory Depression‬ ‭✓‬ ‭Sedation‬ ‭✓‬ ‭Euphoria‬ ‭✓‬ ‭Physical Dependence‬ ‭✓‬ ‭Decreased GI Motility‬ ‭✓‬ ‭✓‬ ‭✓‬ ‭Pure Opioid Agonists‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ ctivate both mu and kappa receptors‬ A ‭Produce: Analgesia, sedation, respiratory depression, physical dependence, constipation‬ ‭Strong:‬‭Morphine‬‭, fentanyl, hydromorphone‬ ‭Moderate-Strong:‬‭Codeine‬‭, hydrocodone, oxycodone‬ ‭Strong Opioids: Morphine‬ ‭Mechanism of Action‬ ‭●‬ ‭Mimic endogenous opioid peptides to activate opioid receptors in the CNS and periphery‬ ‭Therapeutic Uses‬ ‭●‬ ‭Relief of moderate-severe pain‬ ‭●‬ ‭Sedation‬ ‭●‬ ‭Anxiety‬ ‭●‬ ‭Dull pain vs. sharp‬ ‭Pharmacokinetics‬ ‭●‬ ‭Inactivated by hepatic metabolism‬ ‭●‬ ‭Can be given PO, IM, IV, or subQ‬ ‭○‬ ‭PO: High first-pass effect, peaks 30-90 minutes‬ ‭○‬ ‭IV/IM/subQ: Peaks 15-20 minutes‬ ‭●‬ ‭Must cross the BBB, caution in infants‬ ‭Adverse Effects‬ ‭●‬ ‭Respiratory depression‬ ‭●‬ ‭Sedation‬ ‭●‬ ‭GI effects‬ ‭●‬ ‭Orthostatic hypotension‬ ‭●‬ ‭Urinary retention‬ ‭●‬ ‭Cough suppression‬ ‭●‬ ‭Neurotoxicity‬ ‭●‬ ‭Miosis‬ ‭●‬ ‭Euphoria/dysphoria‬ ‭Drug-Drug Interactions‬ ‭●‬ ‭CNS depressants: Alcohol, benzodiazepines, barbiturates‬ ‭●‬ ‭Anticholinergic drugs: Antihistamines, TCAs, antidepressants‬ ‭●‬ ‭Antihypertensives‬ ‭●‬ ‭Agonist-antagonist opioids‬ ‭●‬ ‭GI meds (ex. Phenergan)‬ ‭Precautions/Contraindications‬ ‭●‬ ‭Decreased respiratory reserve‬ ‭●‬ ‭Pregnant or breastfeeding‬ ‭●‬ ‭Head injury‬ ‭●‬ ‭Very young or old‬ ‭●‬ ‭Liver dysfunction‬ ‭●‬ ‭Hypotensive‬ ‭Nursing Implications‬ ‭●‬ ‭Respiratory depression:‬ ‭○‬ ‭Monitor respiratory rate before and after‬ ‭○‬ ‭Naloxone can reverse‬ ‭●‬ ‭Constipation:‬ ‭○‬ ‭Increase physical activity‬ ‭○‬ ‭Increase fiber and fluids‬ ‭ ‬ ‭Laxatives can be used PRN‬ ○ ‭ ‬ ‭Orthostatic hypotension:‬ ● ‭○‬ ‭Teach symptoms‬ ‭○‬ ‭Move slowly when changing positions‬ ‭●‬ ‭Urinary retention:‬ ‭○‬ ‭Monitor I&Os‬ ‭○‬ ‭Palpate lower abdomen q4-6h‬ ‭Other Strong Opioids‬ ‭●‬ ‭Fentanyl (Duragesic), meperidine (Demerol), methadone, hydromorphone (Dilaudid)‬ ‭Fentanyl (Duragesic)‬ ‭●‬ ‭High potency, greater than morphine‬ ‭●‬ ‭Adverse effects: Similar to morphine‬ ‭●‬ ‭Used for patients with opioid tolerance‬ ‭Meperidine (Demerol)‬ ‭●‬ ‭Strong analgesic effect‬ ‭●‬ ‭Similar to morphine‬ ‭●‬ ‭Increased drug-drug interactions‬ ‭Moderate Opioids: Codeine‬ ‭‬ M ● ‭ oderate-strong agonist‬ ‭●‬ ‭Also hydrocodone, oxycodone‬ ‭●‬ ‭Often combined with NSAIDs or acetaminophen (Vicodin, Vicprofen)‬ ‭Therapeutic Use‬ ‭●‬ ‭Mild-moderate pain relief‬ ‭●‬ ‭Cough suppression‬ ‭Pharmacokinetics‬ ‭●‬ ‭Oral administration‬ ‭●‬ ‭Prodrug‬ ‭●‬ ‭10% converted to morphine by CYP2D6 in the liver‬ ‭○‬ ‭Poor metabolizers‬ ‭○‬ ‭Ultra-rapid metabolizers‬ ‭Adverse Effects‬ ‭●‬ ‭Similar to morphine but less analgesia and fewer adverse effects‬ ‭●‬ ‭Less risk for respiratory depression but increases with dosing‬ ‭●‬ ‭Lower potential for abuse‬ ‭Precautions/Contraindications‬ ‭●‬ ‭Breastfeeding mothers‬ ‭Agonist-Antagonists‬ ‭Characteristics‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ ct on mu and kappa receptors‬ A ‭Monotherapy = agonist activity (analgesia)‬ ‭Antagonizes analgesic effect when taken with a pure-opioid agonist‬ ‭Less analgesic efficacy‬ ‭Lower potential for abuse and respiratory depression‬ ‭Pentazocine‬ ‭Mechanism of Action‬ ‭●‬ ‭Act as an agonist at kappa, antagonist at mu‬ ‭●‬ ‭Kappa: Produces analgesia, sedation, respiratory depression‬ ‭Therapeutic Use‬ ‭●‬ ‭Mild-moderate pain‬ ‭Adverse Effects‬ ‭●‬ ‭Similar to morphine but increases cardiac effort‬ ‭●‬ ‭Precipitates withdrawal in someone physically dependent on agonist opioids‬ ‭Prolonged Use of Opioids‬ ‭Tolerance‬ ‭‬ C ● ‭ ellular adaptation for prolonged usage‬ ‭●‬ ‭Increased dosage needed for desired effect‬ ‭●‬ ‭Develops for some effects: Analgesia, euphoria, sedation‬ ‭○‬ ‭Not constipation and miosis‬ ‭●‬ ‭Cross-tolerance‬ ‭Physical Dependence‬ ‭●‬ ‭Related to adaptive cellular changes from prolonged usage‬ ‭Abstinence Syndrome‬ ‭‬ S ● ‭ everity depends on half-life of drug used‬ ‭●‬ ‭Degree of physical dependence‬ ‭●‬ ‭Initial reaction: Yawning, rhinorrhea, sweating‬ ‭○‬ ‭Anorexia, irritability, tremor, chills‬ ‭○‬ ‭Violent sneezing, weakness, GI symptoms, bone pain, muscle spasms‬ ‭Nursing Implications of Opioid Administration‬ ‭●‬ ‭Baseline assessment:‬ ‭○‬ ‭Pain assessment‬ ‭○‬ ‭LOC‬ ‭○‬ ‭Respiratory rate: If < 10, withhold dose and contact provider‬ ‭○‬ ‭O‬‭2‬ ‭saturation‬ ‭○‬ ‭Blood pressure‬ ‭○‬ ‭Pulse‬ ‭●‬ ‭Reassess‬ ‭●‬ ‭Importance of scheduled dosing‬ ‭●‬ ‭Avoiding withdrawal reaction‬ ‭Acute Opioid Toxicity‬ ‭‬ R ● ‭ esults from clinical overdose, accidental overdose, or suicide attempts‬ ‭●‬ ‭S/S: Triad (coma, pinpoint pupils, depressed respiration)‬ ‭●‬ ‭Treatment required‬ ‭Pure Opioid Antagonists‬ ‭‬ P ● ‭ rototype: Naloxone (Narcan)‬ ‭●‬ ‭Block mu and kappa receptors‬ ‭●‬ ‭Do not produce analgesia or opioid-like responses‬ ‭Primary Use‬ ‭●‬ ‭Reversal of overdose‬ ‭○‬ ‭CNS effects‬ ‭○‬ ‭Respiratory depression‬ ‭●‬ ‭Reversal of post-op opioid effects‬ ‭●‬ ‭Reversal of opioid-induced constipation‬ ‭●‬ ‭Reversal of neonatal respiratory depression‬ ‭Mechanism of Action‬ ‭●‬ ‭Competitive antagonist at the opioid receptors‬ ‭Pharmacokinetics‬ ‭●‬ ‭Parenteral administration (pushed over 2 minutes)‬ ‭ ‬ ‭Rapid first-pass effect‬ ○ ‭ ‬ ‭Immediate effects‬ ● ‭●‬ ‭Hepatic metabolism‬ ‭●‬ ‭Half-life: 30-80 minutes‬ ‭Adverse Effects‬ ‭ ‬ I‭ n the absence of opioids, no effect‬ ● ‭●‬ ‭Precipitates immediate withdrawal reactions‬