Opioids - Slattery

Question 1

Describe the ways in which drugs can relieve pain

Answer 1

Eliminate cause (NSAIDS, chemo, antiulcers)

Prevent transmission (Local anesthetic)

Change perception (general anesthetic, opioid)

Change patient reaction (anxiolytics, opioids)

Question 2

Describe and distinguish among the subtypes of opioid receptors

Mu, Kappa and Delta:

Answer 2

Mu (μ)

• Analgesia
• Respiratory depression
• Decreased gastrointestinal motility
• Physical Dependence

Kappa (κ)

• Analgesia
• Sedation
• Decreased gastrointestinal motility

Delta (δ)
-Modulates μ activity

Question 3

Give an example of an agonist, antagonist, mixed agonist/antagonist, and a partial agonist, in terms of opioids

Answer 3

Agonist: morphine or methadone
Antagonist: naloxene or naltrexone
Partial agonist: Buprenorphine
Mixed Ag/Ant: Pentazocine (Ag at Kappa, Ant at Mu)

Question 4

List the advantages and disadvantages of the various routes by which opioids are administered

Answer 4

Oral
Convenient, but high first pass metabolism
Slower onset, delayed peak effect, longer duration
Better for chronic treatment

Intravenous
Precise and accurate, Rapid onset
increased risk of adverse effects

Spinal
Longer duration at lower doses
Can avoid some brain-mediated adverse effects
- LIKE Respiratory depression

Rectal suppository
Administration may be easily discontinued

Buccal/Sublingual
Faster onset than oral, Avoids first pass metabolism, Convenient (no injection)
Example: Fentanyl “lollipop”

Transdermal
Convenient, avoids first pass metabolism
Examples: Fentanyl, Buprenorphine

Question 5

Give examples of opioids with active and toxic metabolites and the significance of this information in the treatment of pain

Answer 5

Active metabolite Mophine-6-gluconoride is excreated in urine, so you have to think about pt’s renal function

Meperedine makes TOXIC metabolite normperidine

• causes tremor, convulsions
• inly use meperedine acutely

Question 6

List the clinical uses of opioids and how they relate to their sites of action centrally and peripherally

Answer 6

Cortex - pain preception and rection, euphoria, sedation

Medulla - resp. depression, nausea, thermoregulation

Spinal cord - depress pain reflexes, stinualtes non-pain reflexes

Eye - pinpoint pupils (little tolerance, so good sign)

Vagus nerve - Bradycardia, increased GI tone

GI - Constipation, cramping

Bronchiolar constriction

Uterus - prolongs labor

Ureters - difficulty in urination

Histamine release - itchy skin

Question 7

What are the two ways that opioids can effect ascending pain transmission:

Answer 7

Presynaptic inhibition of afferent neurons

• Receptor activation blocks v-gated Ca2+ channels on presynpase
• This stops release of glutamate and substance P onto the post-synapse

Postsynaptic inhibition

• Receptor activation opens K+ channels
• Hyperpolaraization inhibits excitation of postsynaptic neuron

Question 8

How can opioid signal transduction affect the descending inhibitory pathway?

Answer 8

The opioid receptor inhibits GABA release from the presynapse and stops the postsynaotic cell from being inhibited.

The postsynaptic cell is then freely able to inhibit nocicpetive processing in dorsal horn of spinal cord.

Question 9

How can loperamide (imodium) be used so safely as an anti-dirrhea med?

Answer 9

It doesn’t cross the BBB, so it affects the GI without the crazy brain effects

Question 10

What medications are used for opioid overdose or opioid addiction?

Answer 10

overdose - Naloxone

Addiction recovery - Naltroxene (blocks heroine effects)
Methadone - extends similar effects of opioids to wean the addict off