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 pain management Methadone detoxification and maintenance (agonist) treatment of opioid addiction pain management Codeine pain management 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 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 5 1 2 3 4 5 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + 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) 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? Review Topic QID: 101678 1 Neuronal hyperpolarization due to potassium efflux 44% (52/118) 2 Neuronal depolarization due to potassium influx 12% (14/118) 3 Neuronal hyperpolarization due to sodium influx 8% (10/118) 4 Neuronal depolarization due to sodium efflux 13% (15/118) 5 Neuronal hyperpolarization due to chloride influx 16% (19/118) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.NE.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? Review Topic QID: 101689 FIGURES: A 1 Low respiratory rate 18% (21/120) 2 Rhinorrhea 3% (4/120) 3 Sweating 7% (8/120) 4 Miosis 68% (81/120) 5 Diarrhea 3% (4/120) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4