opioid analgesics
TRANSCRIPT
Opioid analgesics
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
Nonopioid analgesics
• NSAIDs Asp., PCM, Indo., Ibup., Diclofenac
• TCAs Amit., Nort., Imipramine
• Antiepileptics CBMZ, Pregabalin, Gabap., Lamot.
• NMDA antag. Ketamine
• Adrenergic agonists Clonidine
Diagnostic of opioid overdose
Tolerance does not develop
Treatment of pain
• Mild pain NSAIDs
• Moderate to severe pain Codeine/hydrocodone
± nonopioid
• Severe pain Strong opioid agonist
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
• 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
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)
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
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
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
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
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.
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.
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?
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?
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.
I) The most appropriate oral medication for his
increasing pain is
(A) Buprenorphine
(B) Codeine plus aspirin
(C) Levorphanol
(D) Pentazocine
(E) Propoxyphene
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
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
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.
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
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
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.
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”
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
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
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
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