Analgesic Agents

Question 1

What can cause prolonged narcosis and ventilatory depression in patients with kidney failure when taking morphine?

Answer 1

The accumulation of morphine metabolites, morphine 3-glucuronide and morphine 6-glucuronide, in patients with kidney failure can cause prolonged narcosis and ventilatory depression lasting several days.

Question 2

What is a dangerous effect of rapidly administering large doses of opioids like fentanyl, sufentanil, remifentanil, and alfentanil?

Answer 2

Rapid administration of large doses of opioids can induce chest wall rigidity severe enough to prevent adequate bag-and-mask ventilation.

Question 3

What is opioid-induced hyperalgesia?

Answer 3

Opioid-induced hyperalgesia is a condition in which patients become more sensitive to painful stimuli after prolonged opioid dosing.

Question 4

What is the effect of large doses of opioids on the neuroendocrine stress response during surgery?

Answer 4

Large doses of opioids block the release of specific hormones, such as catecholamines, antidiuretic hormone, and cortisol, more completely than volatile anesthetics.

Question 5

How does aspirin inhibit COX-1?

Answer 5

Aspirin irreversibly inhibits COX-1 by acetylating a serine residue in the enzyme, leading to prolonged effects even after the drug is discontinued.

Question 6

What is the goal of multimodal analgesia in postoperative care?

Answer 6

The goal of multimodal analgesia is to provide pain relief using a combination of medications, often emphasizing COX inhibitors and local anesthetic techniques while minimizing opioid use.

Question 7

What receptors do opioids bind to in the body?

Answer 7

Opioids bind to specific receptors throughout the central nervous system, including mu (µ), kappa (κ), delta (δ), and sigma (σ) receptors.

Question 8

What is the cellular mechanism by which opioids work?

Answer 8

Opioids inhibit the presynaptic release and postsynaptic response to excitatory neurotransmitters, including acetylcholine and substance P, from nociceptive neurons.

Question 9

What type of analgesia is provided by opioids when administered intrathecally or epidurally?

Answer 9

Opioids provide analgesia by selectively modifying the transmission of pain impulses at the level of the dorsal horn of the spinal cord.

Question 10

What is the difference between full opioid agonists and agonist–antagonists?

Answer 10

Full opioid agonists (e.g., fentanyl) have greater efficacy than agonist–antagonists (e.g., nalbuphine, nalorphine, butorphanol, and pentazocine), which may antagonize the actions of full agonists in some situations.

Question 11

What are the common effects of opioids when administered peripherally, such as in the gastrointestinal system?

Answer 11

Opioids can reduce gastrointestinal motility, which may result in constipation and biliary colic due to contraction of the sphincter of Oddi.

Question 12

What is the role of opioid receptor activation in pain management?

Answer 12

Opioid receptor activation inhibits the transmission of pain signals by blocking the release of excitatory neurotransmitters and modulating pain perception via descending inhibitory pathways.

Question 13

What structural characteristics do opioids generally share?

Answer 13

Opioids share common structural characteristics, and small changes in their chemical structure can convert an agonist into an antagonist.

Question 14

What is the pharmacokinetics of opioid absorption through intramuscular injection?

Answer 14

Opioids like hydromorphone, morphine, and meperidine are rapidly and completely absorbed via intramuscular injection, with peak plasma levels usually achieved in 20–60 minutes.

Question 15

How is fentanyl absorbed transdermally?

Answer 15

Fentanyl, a lipid-soluble opioid, can be absorbed through the skin using a transdermal patch, with peak serum levels occurring within 14–24 hours of application.

Question 16

How does the lipid solubility of fentanyl and sufentanil affect their onset and duration?

Answer 16

The increased lipid solubility of fentanyl and sufentanil leads to a faster onset and shorter duration of action when administered in small doses.

Question 17

What is the role of pulmonary uptake in opioid distribution?

Answer 17

Significant amounts of lipid-soluble opioids can be retained by the lungs (first-pass uptake) and released into the bloodstream as systemic concentrations fall.

Question 18

How do opioids undergo biotransformation?

Answer 18

Opioids are primarily metabolized in the liver by the cytochrome P450 system, with some metabolites being active, like morphine 6-glucuronide, while others are inactive.

Question 19

What is unique about remifentanil’s metabolism compared to other opioids?

Answer 19

Remifentanil has an ester structure and is hydrolyzed by nonspecific esterases in red blood cells and tissues, resulting in a very short elimination half-life of less than 10 minutes.

Question 20

What cardiovascular effects do opioids generally have?

Answer 20

Opioids typically cause a decrease in arterial blood pressure due to bradycardia, venodilation, and decreased sympathetic reflexes, often requiring vasopressor support.

Question 21

What is the effect of opioids on the respiratory system?

Answer 21

Opioids depress ventilation, particularly respiratory rate, and shift the CO2 response curve downward, leading to a higher apneic threshold and decreased hypoxic drive.

Question 22

How do opioids affect the cerebral circulation?

Answer 22

Opioids reduce cerebral oxygen consumption, cerebral blood flow, and intracranial pressure, but to a much lesser extent than barbiturates, propofol, or benzodiazepines.

Question 23

How do opioids interact with the gastrointestinal system?

Answer 23

Opioids reduce peristalsis in the gastrointestinal tract, causing constipation, and can induce biliary colic due to contraction of the sphincter of Oddi.

Question 24

What is the risk of using meperidine in patients with renal failure?

Answer 24

Meperidine’s active metabolite, normeperidine, can accumulate in patients with renal failure, leading to seizures that are not reversed by naloxone.

Question 25

What is opioid-induced tolerance?

Answer 25

Opioid-induced tolerance occurs when patients require larger and larger doses to achieve the same analgesic effect after repeated opioid use.

Question 26

How do opioids affect endocrine function during surgery?

Answer 26

Large doses of opioids block the release of stress hormones like catecholamines, antidiuretic hormone, and cortisol during surgery more effectively than volatile anesthetics.

Question 27

What is the key action of cyclooxygenase (COX) in prostaglandin synthesis?

Answer 27

COX catalyzes the production of prostaglandin H1 from arachidonic acid.

Question 28

What are the two forms of COX and where are they found?

Answer 28

COX-1 is widely distributed throughout the body, including the gut and platelets, while COX-2 is produced in response to inflammation.

Question 29

How do COX-1 and COX-2 enzymes differ?

Answer 29

COX-1 and COX-2 differ in the size of their binding sites; the COX-2 site accommodates larger molecules that are restricted from binding at the COX-1 site.

Question 30

What are the risks associated with selective COX-2 inhibition?

Answer 30

Selective COX-2 inhibition increases the risk of heart attack, thrombosis, and stroke.

Question 31

How does aspirin inhibit COX-1?

Answer 31

Aspirin irreversibly inhibits COX-1 by acetylating a serine residue in the enzyme, leading to a nearly 1-week duration of clinical effects.

Question 32

What is the unique characteristic of acetaminophen (paracetamol) in relation to COX-2?

Answer 32

Acetaminophen is a COX-2 selective agent that is effective for analgesia but produces almost no effects on inflammation compared to other COX-2 selective agents.

Question 33

What is multimodal analgesia and its role in postoperative care?

Answer 33

Multimodal analgesia includes the use of COX inhibitors, regional or local anesthesia techniques, and other approaches to reduce opioid use and hasten recovery after surgery.

Question 34

How are COX inhibitors classified based on their chemical structure?

Answer 34

COX inhibitors can be classified into salicylic acids (eg, aspirin), acetic acid derivatives (eg, ketorolac), propionic acid derivatives (eg, ibuprofen), heterocyclics (eg, celecoxib), and others.

Question 35

How are COX inhibitors absorbed after oral administration?

Answer 35

COX inhibitors are well absorbed after oral administration, typically achieving peak blood concentrations in less than 3 hours.

Question 36

How do COX inhibitors distribute in the body?

Answer 36

After absorption, COX inhibitors are highly bound by plasma proteins (mainly albumin) and can readily permeate the blood-brain barrier and joint spaces for central analgesia and anti-inflammatory effects.

Question 37

What is the biotransformation of acetaminophen at toxic doses?

Answer 37

At toxic doses, acetaminophen forms large concentrations of N-acetyl-p-benzoquinone imine, which can lead to hepatic failure.

Question 38

How are COX inhibitors excreted?

Answer 38

Nearly all COX inhibitors are excreted in urine after biotransformation.

Question 39

What cardiovascular effects are associated with COX inhibitors?

Answer 39

COX inhibitors do not act directly on the cardiovascular system but can affect coagulation. They are used to promote closure of a patent ductus arteriosus in neonates.

Question 40

What respiratory effects do COX inhibitors have?

Answer 40

At appropriate clinical doses, COX inhibitors do not affect respiration or lung function.

Question 41

What gastrointestinal complications are associated with COX-1 inhibition?

Answer 41

COX-1 inhibition can cause gastrointestinal upset, including upper gastrointestinal bleeding, due to effects on mucosal protection and platelet aggregation inhibition.

Question 42

What is a common cause of fulminant hepatic failure associated with acetaminophen?

Answer 42

Acetaminophen abuse or overdose is a common cause of fulminant hepatic failure, sometimes requiring liver transplantation.