This presentation deals with the various opioid analgesics used in our day-to-day practice.

1. Opioid analgesics

3. Classification of analgesics
• Opioid
• Strong opioid agonists  Morphine, Fentanyl (its
derivatives), Meperidine, Methadone
• Moderate opioid agonists  Codeine, Hydrocodone
• Other Opioid Agonists  Dextromethorphan (NMDA),
Diphenoxylate, Loperamide, Tramadol, Tapentadol
• Mixed Opioid Agonist-Antagonists  Buprenorphine
Butorphanol, Nalbuphine, Pentazocine

5. Nonopioid analgesics
• NSAIDs  Asp., PCM, Indo., Ibup., Diclofenac
• TCAs  Amit., Nort., Imipramine
• Antiepileptics  CBMZ, Pregabalin, Gabap., Lamot.
• NMDA antag.  Ketamine
• Adrenergic agonists  Clonidine

8.  Diagnostic of opioid overdose
 Tolerance does not develop

9. Treatment of pain
• Mild pain  NSAIDs
• Moderate to severe pain  Codeine/hydrocodone
± nonopioid
• Severe pain  Strong opioid agonist

10. Important points
• Endogenous opiate peptides  Endorphins,
enkephalins & dynorphins
• Three receptor families: µ, K, and δ
• Naloxone  Reversal for respiratory depression
• Naltrexone  ↓ craving for alcohol and used in
opiate addiction
• Classical triad of acute opioid toxicity  Pinpoint
pupils, respiratory depression & coma

11. • Tolerance  Occurs to all effects, except miosis &
constipation
• Opioid withdrawal signs  Yawning, Lacrimation,
rhinorrhea, salivation, anxiety, sweating, goose
bumps, Muscle cramps, spasms, CNS-origin. Pain
• Management of withdrawal  Supportive,
Methadone, Clonidine
• Loperamide  Diarrhea; dmethorphan  Cough

12. Review questions
1. Most clinically used opioid analgesics are selective
for which type of opioid receptor?
(A) κ (kappa)
(B) α (alpha)
(C) β (beta)
(D) µ (mu)
(E) δ (delta)

13. 2. Codeine has a greater oral bioavailability
compared with morphine because of which reason?
(A) codeine undergoes less first-pass metabolism
(B) morphine is conjugated more quickly
(C) morphine directly passes into systemic circulation
(D) codeine is available only in liquid formulation
(E) codeine is metabolized more by hepatic enzymes

14. 3. Which of the following statements best explains the
observation that morphine is more likely to cause nausea
and vomiting in ambulatory patients?
(A) morphine inhibits CTZ neurons
(B) morphine sensitizes medulla cough center neurons
(C) opioids cause sedation, which makes walking more
difficult
(D) patients on opioids eat more
(E) opioids increase vestibular sensitivity

15. 4. Which of the following opioids is so lipophilic that
it is marketed in a skin patch used to treat chronic
pain?
(A) morphine
(B) naltrexone
(C) scopolamine
(D) methadone
(E) fentanyl

16. 5. In a case of an opioid overdose, naloxone can be
given in repeated doses because of which property
of naloxone?
(A) may have a shorter half-life than the opioid
agonist
(B) is effective only at high cumulative doses
(C) is needed to stimulate the respiratory center
(D) is safe only in extremely small doses
(E) is only a partial opioid agonist

17. 6. A 19-year-old college student is brought to the
emergency department by his roommate, who found
him sitting outside their room breathing shallowly.
The patient is difficult to understand because he is
intoxicated, has slurred speech, and is drowsy.
Physical examination reveals pinpoint pupils. The
roommate admits they were both drinking at a party
earlier in the evening, but he lost track of the patient
and is not sure what else he could have ingested.

18. 7. A newborn baby boy who was delivered at home is brought to
the emergency department by his grandmother 30 minutes after
birth. The grandmother says the baby “isn’t acting right.” He
weighs 2700 g (approximately 6 lb) and was born at 35 weeks’
gestation. He is limp and unresponsive and breathing infrequently,
with bluish skin and pupils 2 mm in diameter. The infant is
immediately resuscitated and stabilized for transfer to the
neonatal intensive care unit. On day 3 of life, his nurse says he is
vomiting, has diarrhea, and cries excessively. Physical examination
reveals tachycardia, tachypnea, dilated pupils, diaphoresis,
tremors, increased muscle tone, and piloerection.

19. a) What is the most likely diagnosis?
b) What pharmacologic agent should this patient
receive in the emergency department?
c) What is the most likely diagnosis on day 3 of life?
d) What is the appropriate long-term treatment for
this patient?

20. 8. A 60-year-old man with a history of moderate
COPD presents in the emergency dept. with a broken
hip suffered in an automobile accident. He complains
of severe pain. What is the most appropriate
immediate treatment for his pain? Are any special
precautions needed?

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

22. I) The most appropriate oral medication for his
increasing pain is
(A) Buprenorphine
(B) Codeine plus aspirin
(C) Levorphanol
(D) Pentazocine
(E) Propoxyphene

23. II) 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) Constipation
(C) Nausea and vomiting
(D) Sedation
(E) Urinary retention

24. 10. You are on your way to take an examination and
you suddenly get an attack of diarrhoea. 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) Tramadol

25. 11. An emergency department patient with severe
pain thought to be of gastrointestinal origin received
80 mg of meperidine. He subsequently developed a
severe reaction characterized by tachycardia,
hypertension, hyperpyrexia, and seizures.

26. 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) Isocarboxazid
(D) Lithium
(E) Mirtazapine

27. 12. Genetic polymorphisms in certain hepatic enzymes
involved in drug metabolism are established to be
responsible for variations in analgesic response to
(A) Codeine
(B) Fentanyl
(C) Meperidine
(D) Methadone
(E) Tramadol

28. 13. A young male patient 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. 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.

29. I) What is the most likely cause of these signs and
symptoms?
(A) The patient had injected methamphetamine
(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”

30. II) Which drug will be most effective in alleviating the
symptoms experienced by this patient?
(A) Acetaminophen
(B) Codeine
(C) Diazepam
(D) Methadone
(E) Naltrexone

31. 14. Which statement about butorphanol is 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

32. 15. 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) Amphetamine
(B) Buprenorphine
(C) Naloxone
(D) Naltrexone
(E) Propoxyphene

33. 16. Which statement about dextromethorphan is
accurate?
(A) Activates κ receptors
(B) Analgesia equivalent to pentazocine
(C) Highly effective antiemetic
(D) Less constipation than codeine
(E) No abuse potential