Updated: 4/14/2019


Review Topic
  • 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.
  • 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


  • Morphine, fentanyl, meperidine, codeine
    • pain management
  • Methadone
    • detoxification and maintenance (agonist) treatment of opioid addiction 
    • pain management

Mixed agonist-antagonist

  • Buprenorphine
    • maintenance treatment of opioid addiction
    • pain management
    • withdrawal symptoms 
  • 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
  • Dextromethorphan
  • Codeine
  • 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


  • Vasodilation
  • Hypotension
  • Respiratory depression
  • Constipation
    • tolerance does not develop to constipation
  • Increased tone/pressure in the biliary sphincter
  • Nausea and vomiting
  • Urinary retention
  • May prolong labor
  • Increases antidiuretic hormone (ADH) and prolactin secretion
  • Decrease luteinizing hormone (LH) secretion
  • Pruritus
  • Flushing
  • 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)
  • 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

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Questions (5)
Lab Values
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/L
Female: 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/mL
Female: 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/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative 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/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 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
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 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
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 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 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 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

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(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

Low respiratory rate




















Select Answer to see Preferred Response


(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

Neuronal hyperpolarization due to potassium efflux




Neuronal depolarization due to potassium influx




Neuronal hyperpolarization due to sodium influx




Neuronal depolarization due to sodium efflux




Neuronal hyperpolarization due to chloride influx




Select Answer to see Preferred Response

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