Narcotic Analgesics

Question 1

Describe the basic mechanisms of Pain Transduction:

Answer 1

Pain sensory fibres sense noxious stimuli, which leads to the opening Ca2+ channels on the pre synaptic membrane and the release of pain mediators (Ex. Substance P & Glutamate)
-These mediators stimulate the post synaptic membrane which stimulate neurons in different areas of the brain and spinal cord.

Question 2

Mediators which inhibit Pain Transduction?

Answer 2

5HT and NE

(descending tracts of the locus coerulus and raphe nucleus.

Question 3

Name the 3 kinds of endogenous opioids, as well as their receptors:

Answer 3

Beta Endorphins, Enkephalins and Dynorphins.

-Mu, Kappa and Delta receptors

Question 4

What is the most common receptor opioids bind?

Answer 4

Mu

Question 5

What are the key effects of Mu agonists?

Answer 5

• Analgesia, Sedation & Euphoria, Inhibit Respiration in overdose & Reduced GI Peristalsis.
• Mu agonists inhibit transmission of SubP and Glutamate, and alter the response to pain.

Question 6

What opioids are primarily used for Analgesia?

Answer 6

Kappa and Delta

Question 7

What is the main mechanism of action of opioids?

Answer 7

Opioids bind to Mu G protein coupled receptors, which inhibit Ca2+ channel opening, therefore inhibiting the release of pain mediators.

Question 8

Morphine

Answer 8

Full Agonist

• High abuse potential
• Euphoric effects

Question 9

Buprenorphine

Answer 9

• Partial agonist at Mu receptors.
• Antagonist at kappa receptors
• Used alongside Naloxone to manage addiction, as well as for chronic pain.
• Very lipophilic (can easily cross cell membranes)
• Oral administration is standard, but can be administered by buccal, sublingual, rectal, transdermal, inhaled and parental routes (SC and IM)

Question 10

Tramadol:

Answer 10

-Weak Mu receptor agonist and NE/ 5HT Re-uptake Inhibitor

Advantages: Less respiratory depression, constipation and abuse potential.

Question 11

Naltrexone

Answer 11

Antagonist
-Naltrexone blocks the effects of opioid medication, including pain relief or feelings of well-being that can lead to opioid abuse.

Question 12

Analgesic Potency

Answer 12

Codeine< Morphine< Fentanyl

Question 13

Common uses for Opioids:

Answer 13

• Pain- various types of pain (Acute and Chronic)
• To treat Diarrhea
• to treat a Cough (codeine)

Question 14

Opioid Side Effects:

Answer 14

• Nausea
• Constipation
• Sedation
• Euphoria (Addictive Potential)
• Miosis ‘Pinpoint Pupils’
• Respiratory Depression in the case of opioid OD

Question 15

Naloxone:

Answer 15

Opioid Antagonist

• Used to treat Opioid Overdose
• Injected

Question 16

What is one of the major problems with opioids?

Answer 16

Tolerance*
-Constant opioid use leads to reductions in the number of Mu receptors, and an increase in the number of pain mediating receptors (gradual use leads to more opioid to cause the same effect)

Question 17

What are the withdrawal effects of opioids?

Answer 17

Anxiety/ Insomnia, Enhanced GI Motility, Hyperalgesia & Mydriasis

Question 18

Heroin:

Answer 18

• Opioid most associated with addiction (increasing shift to Fentanyl)
• Injected Intravenous
• Highly Lipophilic (short half- life, enhanced withdrawal symptoms)

Question 19

Methadone:

Answer 19

Used to treat opioid withdrawal
-T1/2= 35 hours
(Administered orally)
-Less euphoric effects

Question 20

Less Common Adverse Effects of Opioids:

Answer 20

• Vasodilation (hypotension & dizziness)
• Histamine release (can cause itchiness)
• Dysphoria (unease/ dissatisfaction)