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