Chapter 109

### INTRODUCTION

Postoperative pain control begins in the preoperative period through careful assessment of the patient’s medical history and anticipated procedure. A multimodal approach to pharmacological therapies should be considered, combining different medication to decrease overall pain scores.

### OPIOIDS

Opioids act by G-protein coupled receptors. They work on nociceptive systems by mimicking endogenous ligands. Opioid receptor binding increases K+ conductance, causing hyperpolarization and Ca2+ channel inactivation. This decreases neurotransmitter release. Opioids also inhibit gamma-aminobutyric acid (GABA) transmission, thus inhibiting descending pain pathways. Commonly used opioid medications are discussed below:

#### Morphine

Morphine is a hydrophilic, opioid receptor agonist with typical onset from 15 to 30 minutes and duration of action around 3-4 hours. Morphine undergoes hepatic glucuronidation, producing the active metabolite, morphine-6-glucuronide, which causes analgesia and respiratory depression. Morphine-3- glucuronide, another metabolite, is pharmacologically inactive but may cause agitation, myoclonus, delirium, and hyperalgesia. Morphine is metabolized by the liver and excreted renally. It can be associated with prolonged sedation and respiratory depression in renal failure patients.

#### Fentanyl

Intravenous (IV) fentanyl administration provides immediate onset with analgesia that lasts 30 minutes to 1 hour. Fentanyl is a lipid soluble selective mu receptor agonist. It is 80 times more potent than IV morphine. Fentanyl is metabolized by the liver into inactive metabolites and excreted in urine and bile. It is a good choice of analgesic in renal failure patients.

#### Sufentanil

Sufentanil has an immediate onset when delivered IV. Sufentanil can last 30 minutes to 1 hour. Sufentanil is 1000 times more potent than IV morphine. It is known for a smaller volume of distribution than fentanyl. Compared to fentanyl, sufentanil administration may be associated with higher rates of respiratory depression and bradycardia. It undergoes liver and small intestine metabolism.

#### Meperidine

Meperidine’s typical onset is 5-7 minutes with duration of 2-4 hours. Meperidine is one-tenth as potent as morphine. It acts via mu, kappa, and delta receptor activation. It is typically used for short-term management of acute pain or for the treatment of postoperative shivering. It undergoes liver metabolism. Repetitive doses may cause buildup of the active metabolite normeperidine, which can cause seizures, myoclonus, and tremulousness. Meperidine should not be used with MAOIs, as it may cause serotonin syndrome. Also, meperidine is not used in renal or central nervous system (CNS) disease. Finally, meperidine administration may be associated with mild anticholinergic effects, such as increased heart rate and mydriasis.

#### Hydromorphone

Hydromorphone is 4-6 times more potent than morphine. It has a quick onset (15 minutes) and a long duration (4-5 hours). Hydromorphone is metabolized by the liver into active metabolites and excreted in urine. It is known to produce fewer opioid-related side effects than morphine.

#### Codeine

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