Introduction to Analgesic Drugs - Opioids

Question 1

What is the difference between an opiate and an opioid?

Answer 1

Opiate - drug with a morphine-like structure, derived from the opium poppy (naturally-ocurring alkaloid).
Opioid - drug with a morphine-like action

Question 2

Give 3 examples of opiate drugs (morphine analogues).

Answer 2

• Codeine
• Diamorphine (heroin)
• Naloxone (antagonist; others are agonists on opioids)

Question 3

Give 4 examples of synthetic opioids (not derived from morphine structure).

Answer 3

• Pethidine
• Fentanyl
• Methadone
• Pentazocine

Question 4

What are the different types of opioid receptors/what class of receptors do they belong to?

Answer 4

• μ (mu, Mu Opioid Peptide - MOP)
• κ (kappa, KOP)
• δ (delta, DOP)

They are G-protein coupled receptors at the cell surface, localised on presynaptic membranes.

Question 5

What type of G-coupled receptors do the opioid receptors belong to, and describe how they affect the body.

Answer 5

Gi proteins:

• Inhibit adenylyl cyclase/reduce cAMP levels
• Open K+ channels (hyperpolarisation)
• Close Ca2+ channels (less glutamate release)

Question 6

Where are the μ, κ and δ receptors mainly expressed?

Answer 6

μ - periphery, spinal cord and brain (main nig)
δ - mainly periphery (increased expression in inflammation)
κ - mainly spinal.

Question 7

List the effects opioids have on the CNS.

Answer 7

• Analgesia
• Euphoria
• Respiratory depression
• Cough suppression (antitussive)
• Nausea + vomiting
• Pupillary contrstriction

Question 8

Expand on the analgesic component of opioids.

Answer 8

Effective in most acute and chronic pain, but less so neuropathic. Antinociceptive (inhibiting nociception) and reduces affective/conscious component of pain.

Question 9

Expand on the euphoric component of opioids and which opioid receptors are mediate it?

Answer 9

• Patient experiences feelings of well being and reduced anxiety, particularly w/I.V.
• Mainly μ-mediated; possibly offset by κ-mediated dysphoria (state of unease/dissatisfaction)

Question 10

Expand on how opioids initiate respiratory depression?

Answer 10

• Decreased sensitivity of respiratory centre (medulla) to pCO2.
• All analgesic doses reduce respiration (potentially fatal), but no CVS depression.

Question 11

How much codeine is required for its antitussive effect?

Answer 11

• Codeine works at sub-analgesic doses.

Question 12

How common is nausea + vomiting w/opioids?

Answer 12

Up to 40% patients suffer (common reason to stop); opioids influence the area postrema (medullary structure in the brain - often transient (short periods of time).

Question 13

How does pupillary constriction help diagnose opioid abusers?

Answer 13

It’s a telltale sign, centrally mediated.

Question 14

What effects do opioids have peripherally, and how are they managed?

Answer 14

• Inhibition of GI tone and motility; causing constipation (laxatives co-prescribed), slowing drug absorption (potential for interactions).
• Histamine release from mast cells (independent from opioid receptors); causes itching and urticaria, with potential bronchoconstriction (caution: asthmatics) and hypotension

Question 15

List the endogenous opioid peptides.

Answer 15

• Endorphins
• Enkephalins
• Dynorphins
• Endomorphins

Question 16

Where are endorphins distributed/on which receptor sub-type?

Answer 16

• In the brain

- μ receptor agonists

Question 17

Where are enkephalins distributed/on which receptor sub-type?

Answer 17

• In the CNS and in immune cells

- μ and δ receptor agonists

Question 18

Where are dynorphins distributed/on which receptor sub-type?

Answer 18

• In the CNS

- κ receptor agonists

Question 19

On which receptor sub-type do endomorphins act, and what sets it apart from the other OPs?

Answer 19

• μ receptor agonists

- Most potent; w/highest known affinity and selectivity for the μ-opioid receptor.