Opioid Pharmacology

Question 1

What are the two components of pain perception?

Answer 1

• Nociceptive component
• Affective component

Question 2

What are the terminals of primary afferent neurons fibers?

Answer 2

Adelta: fast conducting
C: slow conducting

Question 3

What is the Opioid Receptor Transducer Mechanism?

Answer 3

• Agonist binding
• Conformational changes in the GPCR
• Inhibition of adenylyl cyclase activity
• Stimulation of K+ current
• Inhibition of voltage-gated Ca2+ channels
• Decreased release of neurotransmitter (substance-P, neurokinin A, neurokinin B, glutamate)

Question 4

What are the phenanthrene derivatives?

Answer 4

• Morphine (10% in opium)
• Codeine (0.5% in opium)
• Thebaine (0.2% in opium)

Question 5

What are the classifications of opioids?

Answer 5

• Natural opioid alkaloids
• Semisynthetic opiates
• Synthetic opioids

Question 6

Natural opium alkaloids

Answer 6

• Morphine
• Codeine

Question 7

Semisynthetic opiates

Answer 7

• Diacetylmorphine (Heroin)
• Pholcodine

Question 8

Synthetic opioids

Answer 8

• Pethidine (Meperidine)
• Fentanyl, sufentanil, alfentanil, remifentanil
• Methadone
• Dextropropoxyphene
• Tramadol

Question 9

What happens when major opioid receptors are coupled to their effectors via G proteins?

Answer 9

• Affect ion channel gating
• Modulate intracellular Ca2+ disposition
• Alter protein phosphorylation

Question 10

What are the prescription forms of morphine?

Answer 10

• Injectable (0.5-25 mg/mL strength)
• Oral solution (2-20 mg/mL)
• Immediate and controlled release tablets and capsules (15-200 mg)
• Suppositories (5-30 mg)

Question 11

What is the PK of morphine?

Answer 11

• Orally absorbed very slowly
• Extensive first pass metabolism 20-40% of bioavailability
• Duration of action (3-6 hours)
• Distribution is wide, concentration in liver, spleen and kidney is greater than placenta
• Morphine freely cross placenta, 30% is plasma protein bound

Question 12

Acute morphine poisoning

Answer 12

• > 50 mg of morphine
• Lethal dose is 250 mg

Question 13

What is the treatment of acute morphine poisoning?

Answer 13

• Positive pressure respiration
• IV fluids
• Gastric lavage with potassium permanganate
• Naloxone

Question 14

Fentanyl

Answer 14

• A potent, synthetic opioid analgesic
• 80-100 times more potent than morphine
• Few cardiovascular effects
• Little propensity to release histamine
• B/c of high lipid solubility, it enters brain rapidly and produces peak analgesia in 3-5 min after 1. v. injection
• The duration of action is short: 30-60 min IV, 1-2 hours IM

Question 15

Methadone

Answer 15

• A synthetic delta opioid agonist
• Absorption and complete
• Drug levels can be measured 30 min after oral dosing, peak concentrations occur at 2.5 hours
• Less abuse potential
• Use- as substitute therapy for opioid dependence

Question 16

Naloxone

Answer 16

• Mu, delta, kappa antagonist
• Sedation is less completely reversed
• Naloxone can reverese opioid overdose
• If the first dose does NOT work, you administer a 2nd dose
• It takes approximately 2-5 min to take effect
• Narcan stays in the system for one hour
• Someone who overdosed should NOT use any type of depressant following the overdose