Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 12e

Chapter 31: Opioid Analgesics & Antagonists

A 63-year-old man is undergoing radiation treatment as an outpatient for metastatic bone cancer. His pain has been treated with a fixed combination of oxycodone plus acetaminophen taken orally. Despite increasing doses of the analgesic combination, the pain is getting worse.

The most appropriate oral medication for his increasing pain is

(A) Buprenorphine

(B) Codeine plus aspirin

(C) Hydromorphone

(D) Pentazocine

(E) Tramadol

In most situations, pain associated with metastatic carcinoma ultimately necessitates the use of an opioid analgesic that is equivalent in strength to morphine, so hydromorphone, oxymorphone, or levorphanol would be indicated. Pentazocine or the combination of codeine plus salicylate would not be as effective as the original drug combination. Propoxyphene is even less active than codeine alone. Buprenorphine, a mixed agonist-antagonist, is not usually recommended for cancer-associated pain because it has a limited maximum analgesic effect (“ceiling”) and because of possible dysphoric and psychotomimetic effects. The answer is C.

It is possible that this patient will have to increase the dose of the analgesic as his condition progresses as a result of developing tolerance. However, tolerance will not develop to a significant extent with respect to

(A) Biliary smooth muscle

(B) Emesis

(C) Pupillary constriction

(D) Sedation

(E) Urinary retention

Chronic use of strong opioid analgesics leads to the development of tolerance to their analgesic, euphoric, and sedative actions. Tolerance also develops to their emetic effects and to effects on some smooth muscle, including the biliary and the urethral sphincter muscles. However, tolerance does not develop significantly to the constipating effects or the miotic actions of the opioid analgesics. The answer is C.

You are on your way to take an examination and you suddenly get an attack of diarrhea. If you stop at a nearby drugstore for an over-the-counter opioid with antidiarrheal action, you will be asking for

(A) Codeine

(B) Dextromethorphan

(C) Diphenoxylate

(D) Loperamide

(E) Nalbuphine

Codeine and nalbuphine could decrease gastrointestinal peristalsis, but not without marked side effects (and a prescription). Dextromethorphan is a cough suppressant. The other 2 drugs listed are opioids with antidiarrheal actions. Diphenoxylate is not available over the counter because it is a constituent of a proprietary combination that includes atropine sulfate (Lomotil). The answer is D.

An emergency department patient with severe pain thought to be of gastrointestinal origin received 80 mg of meperidine. She subsequently developed a severe reaction characterized by tachycardia, hypertension, hyperpyrexia, and seizures. Questioning revealed that the patient had been taking a drug for a psychiatric condition. Which drug is most likely to be responsible for this untoward interaction with meperidine?

(A) Alprazolam

(B) Bupropion

(C) Lithium

(D) Phenelzine

(E) Mirtazapine

Concomitant administration of meperidine and monoamine oxidase inhibitors such as isocarboxazid or phenelzine has resulted in life-threatening hyperpyrexic reactions that may culminate in seizures or coma. Such reactions have occurred even when the MAO inhibitor was administered more than a week after a patient had been treated with meperidine. Note that concomitant use of selective serotonin reuptake inhibitors and meperidine has resulted in the serotonin syndrome, another life-threatening drug interaction (see Chapter 16). The answer is D.

Genetic polymorphisms in certain hepatic enzymes involved in drug metabolism are established to be responsible for variations in analgesic response to

(A) Buprenorphine

(B) Codeine

(C) Fentanyl

(D) Methadone

(E) Tramadol

Codeine, hydrocodone, and oxycodone are metabolized by the cytochrome P450 isoform CYP2D6, and variations in analgesic response to these drugs have been attributed to genotypic polymorphisms in this isozyme. In the case of codeine, this may be especially important since the drug is demethylated by CYP2D6 to form the active metabolite, morphine (see Chapter 5). An ultra-rapid metabolizer of codeine given a normal dose may suffer symptoms of severe opioid overdose. The answer is B.

A young man is brought to the emergency department in an anxious and agitated state. He informs the attending physician that he uses “street drugs” and that he gave himself an intravenous “fix” approximately 12 h ago. After an initial period of contentment and relaxation, he now has chills and muscle aches and has also been vomiting. His symptoms include hyperventilation and hyperthermia. The attending physician notes that his pupil size is larger than normal.

What is the most likely cause of these signs and symptoms?

(A) The patient had injected dextroamphetamine

(B) The patient has hepatitis B

(C) The patient has overdosed with an opioid

(D) The signs and symptoms are those of the opioid abstinence syndrome

(E) These are early signs of toxicity due to contaminants in “street heroin”

The signs and symptoms are those of withdrawal in a patient physically dependent on an opioid agonist, especially morphine or heroin. They usually start within 6–10 h after the last dose; their intensity depends on the degree of physical dependence, and peak effects usually occur at 36–48 h. Mydriasis is a prominent feature of the abstinence syndrome; other symptoms include rhinorrhea, lacrimation, piloerection, muscle jerks, and yawning. An overdose of dextroamphetamine would not produce an initial feeling of contentment and relaxation. The answer is D.

Which drug will be most effective in alleviating the symptoms experienced by this patient?

(A) Buprenorphine

(B) Codeine

(C) Methadone

(D) Naltrexone

(E) Tramadol

Prevention of signs and symptoms of withdrawal after chronic use of a strong opiate like heroin requires replacement with another strong opioid analgesic drug. Methadone is most commonly used, but other strong µ-receptor agonists would also be effective. Acetaminophen and codeine will not be effective. Beneficial effects of diazepam are restricted to relief of anxiety and agitation. The antagonist drug naltrexone may exacerbate withdrawal symptoms. The answer is C.

Which statement about nalbuphine is most accurate?

(A) Activates µ receptors

(B) Does not cause respiratory depression

(C) Is a nonsedating opioid

(D) Pain-relieving action is not superior to that of codeine

(E) Response to naloxone in overdose may be unreliable

Nalbuphine and butorphanol are κ agonists, with weak µ-receptor antagonist activity. They have analgesic efficacy superior to that of codeine, but not equivalent to that of strong µ-receptor agonists. Although these mixed agonist-antagonist drugs are less likely to cause respiratory depression than strong µ activators, if depression does occur, reversal with opioid antagonists such as naloxone is unpredictable. Sedation is common. The answer is E.

Which drug does not activate opioid receptors, has been proposed as a maintenance drug in treatment programs for opioid addicts, and with a single oral dose, will block the effects of injected heroin for up to 48 h?

(A) Fentanyl

(B) Nalbuphine

(C) Naloxone

(D) Naltrexone

(E) Propoxyphene

The opioid antagonist naltrexone has a much longer half-life than naloxone, and its effects may last 2 d. A high degree of client compliance would be required for naltrexone to be of value in opioid dependence treatment programs. The same reservation is applicable to the use of naltrexone in alcoholism. The answer is D.

Which drug is a full agonist at opioid receptors with analgesic activity equivalent to morphine, a longer duration of action, and fewer withdrawal signs on abrupt discontinuance than morphine?

(A) Fentanyl

(B) Hydromorphone

(C) Methadone

(D) Nalbuphine

(E) Oxycodone

Fentanyl, hydromorphone, and methadone are full agonists with analgesic efficacy similar to that of morphine. When given intravenously, fentanyl has a duration of action of just 60–90 min. Hydromorphone has poor oral bioavailability. Methadone has the greatest bioavailability of the drugs used orally, and its effects are more prolonged. Tolerance and physical dependence develop, and dissipate, more slowly with methadone than with morphine. These properties underlie the use of methadone for detoxification and maintenance programs. The answer is C.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.

Chapter 31: Opioid Analgesics & Antagonists

Send Email

Citation

Jump to a Section

Chapter 31: Opioid Analgesics & Antagonists

Pop-up div Successfully Displayed