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FOCUS POINTS
Acetaminophen has no known pharmacologically active metabolites.
Oxidized acetaminophen leads to N-acetyl-p-benzoquinone imine (NAPQI), the compound responsible for hepatic toxicity in the event of an overdose.
The mechanism of action for nonsteroidal anti-inflammatory drugs (NSAIDs), which explains their anti-inflammatory and analgesic properties, is the ability to block the production of prostaglandin via inhibition of the COX-1 and COX-2 enzymes.
Short-term use of ketorolac has been extremely useful in the perioperative management of pediatric patients with minimal risks.
Codeine is metabolized in the liver to its active metabolite, morphine.
As a morphine metabolite, morphine-3-glucoronide is devoid of analgesic activity but morphine-6-glucuronide (M6G) is an opioid agonist more potent than the parent compound.
Remifentanil possesses unique characteristics among opioids with pharmacokinetics exhibiting independence of age and organ function. It is rapidly metabolized by non-specific blood and tissue esterases.
Meperidine is metabolized to normeperidine, an active metabolite with a long half-life and central excitatory and neurotoxic effects that can lead to seizures.
Methadone is extensively used in children and serves as first-line treatment for neonatal abstinence syndrome.
Ketamine is an N-methyl-d-aspartate (NMDA) receptor noncompetitive antagonist with bronchodilator properties.
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One of the primary roles of the anesthesiologist as perioperative physician is to provide adequate analgesia both during and after a painful procedure. It is therefore imperative to have a good working knowledge of the various analgesics that can be used to accomplish this goal. The purpose of this chapter is to provide that working knowledge.
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Pharmacology can be divided into two broad areas, pharmacokinetics and pharmacodynamics. Pharmacokinetics (PK) can be thought of as “what a body does to a drug” and includes such topics as drug absorption, distribution, metabolism, and elimination. Pharmacodynamics (PD) can be thought of as “what the drug does to the body” in terms of interacting with a target and eliciting a clinical response, and its potential side effects and toxicities.1,2 Much more is known about pharmacokinetics in pediatric patients than is known about pharmacodynamics.3
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The chapter begins with the basic pharmacokinetic differences of the pediatric patient compared to the adult before discussing the pharmacology of acetaminophen and other NSAIDs, multiple opioids used both intraoperatively and postoperatively, and an assortment of other drugs that are used in the perioperative setting for pain modulation and treatment. The pharmacology of local anesthetics is covered in a separate chapter.
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MATURATIONAL PHARMACOKINETICS
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Pediatric patients, especially neonates and infants, are not simply small adults. There are many rapidly maturing biological systems which can have an influence on the absorption, distribution, metabolism, and elimination of drugs. As a result, drug dosing and dosing schedules, accumulation of active, inactive, and toxic metabolites, and pathways of biotransformation and elimination can differ significantly from older patients. In this rapidly changing environment, it is essential for the pediatric anesthesiologist to understand the basic pharmacokinetic differences ...