Snapshot A 22-year-old male is brought into the emergency department by the police due to depressed mental status. He was found in the park with an empty syringe by his side. Vital signs are notable for a respiratory rate of 7 breaths/min. Physical exam is significant for bilateral track marks, and miotic pupils. Introduction Opioids act on mu (most important), kappa, and delta transmembrane receptors in the central and peripheral nervous system mu, kappa, and delta receptors are Gi protein coupled inhibition of adenylyl cyclase → decrease cAMP concentration → increased K+ conductance + decreased Ca2+ conductance inhibits presynaptic neurotransmitter release prevents release of acetylcholine, norepinephrine, serotonin, glutamate, substance P inhibits postsynaptic depolarization Endorphines, enkephalins, dynorphins are examples of endogenous opioid peptides Pharmacokinetics morphine, hydromorphone, oxymorphone undergo first pass metabolism morphine gets metabolized to morphine-6-glucoronide, which is highly active (the active analgesic) opioids are generally metabolized by liver into inactive glucuronide conjugates after metabolism they get excreted by the kidneys codeine, oxycodone, hydrocodone are metabolized by hepatic cytochrome enzymes cytochrome has genetic variability → variable analgesic response meperidine can get metabolized to normeperidine N-demethylation normeperidine can lead to anxiety, tremors, seizures heroin gets metabolized into 6-monoacetylmorphine, which can be detected on urine screening Clinical Uses Physicans should assess patient's pain medication history prior to prescribing opioids Drug Classification Subclass Medication Agonists Morphine, fentanyl, meperidine, codeine pain management Methadone detoxification and maintenance (agonist) treatment of opioid addiction pain management has relatively slow onset of action (30 minutes) and long half life (1 day) Mixed agonist-antagonist Buprenorphine maintenance treatment of opioid addiction pain management withdrawal symptoms Antagonists Naltrexone treatment of alcohol dependence prevention of opioid relapse blocks the effects of opioid if used Methylnaltrexone opioid-induced constipation Naloxone opioid overdose for reversal of opioid depression Antitussives Dextromethorphan Codeine Others Tramadol pain management Butorphanol pain management Loperamide/dyphenoxylate manages diarrhea Side Effects by System Opiate Pharmacologic Effects by System System Side Effect Central nervous Analgesia Euphoria/dysphoria Miosis tolerance does not develop in miosis Sedation Cough reflex inhibition Cardiovascular Vasodilation Hypotension Pulmonary Respiratory depression Gastrointestinal Constipation tolerance does not develop to constipation Increased tone/pressure in the biliary sphincter Nausea and vomiting Genitourinary Urinary retention May prolong labor Endocrine Increases antidiuretic hormone (ADH) and prolactin secretion Decrease luteinizing hormone (LH) secretion Dermatological Pruritus Flushing Toxicity Acute overdose triad miosis, respiratory depression, coma respiratory depression due to ↓ response to ↑ pCO2 Tolerance a decrease in pharmacologic effect after prolonged drug usage secondary to down-regulation of opioid receptors miosis and constipation are not affected by tolerance NMDA receptor antagonists (eg, ketamine) and delta-receptor antagonists have been reported to prevent opioid tolerance Withdrawal side effects pain originating from the CNS flu-like symptoms lacrimation, sweating, rhinorrhea, salivation muscle cramps and spasms yawning diarrhea Drug specific side-effects meperidine (seizures and serotonin syndrome with MAOIs/SSRIs) only opioid to cause mydriasis vs miosis (pinpoint pupils) nalbuphine (hallucinations) Contraindications Head trauma ↑ pCO2 can cause vasodilation and ↑ intracranial pressure Pulmonary dysfunction patient may not be able to compensate for respiratory depression Liver/kidney dysfunction poor excretion mechanisms may result in accumulation Adrenal/thyroid deficiencies opiates may show greater effects Pregnancy fetus may show dependency exception is meperidine
QUESTIONS 1 of 8 1 2 3 4 5 6 7 8 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.NE.14.25) You are seeing a patient in clinic with chronic low back pain. Despite frequent physical therapy, and multiple attempts to control the pain with non-steroidal anti-inflammatory drugs (NSAIDs), the patient requires morphine to control his pain. He has been using morphine for several months now and the dose required to control his pain has doubled in that time. He has been complaining of persistent abdominal pain, and in the course of evaluating his abdominal pain you obtain an abdominal radiograph (see Figure A).Which additional opioid side effect would you expect to see in this patient? Tested Concept QID: 101689 FIGURES: A Type & Select Correct Answer 1 Low respiratory rate 22% (35/156) 2 Rhinorrhea 3% (5/156) 3 Sweating 6% (9/156) 4 Miosis 63% (99/156) 5 Diarrhea 4% (6/156) M 4 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review tested concept (M1.NE.14.14) A 17-year-old male presents with altered mental status. He was recently admitted to the hospital due to a tibial fracture suffered while playing soccer. His nurse states that he is difficult to arouse. His temperature is 98.6 deg F (37 deg C), blood pressure is 130/80 mm Hg, pulse is 60/min, and respirations are 6/min. Exam is notable for pinpoint pupils and significant lethargy. Which of the following describes the mechanism of action of the drug likely causing this patient's altered mental status? Tested Concept QID: 101678 Type & Select Correct Answer 1 Neuronal hyperpolarization due to potassium efflux 41% (76/185) 2 Neuronal depolarization due to potassium influx 12% (22/185) 3 Neuronal hyperpolarization due to sodium influx 12% (22/185) 4 Neuronal depolarization due to sodium efflux 11% (20/185) 5 Neuronal hyperpolarization due to chloride influx 19% (35/185) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK