Chapter 28: Narcotic Analgesics

Question 1

The endogenous opioid peptides are produced how?

Answer 1

1. Pro-opiomelanocortin produces B-endorphin as well as Andrenocorticotropic hormone (ACTH) and melanocyte stimulating hormone.
2. Pro-enkephalin produces met-enkephalin and leu-enkephalin (enkephalins).
3. Pro-dynorphin produces dynorphin.

Question 2

Explain the Pain Sensory system.

Answer 2

• In the** dorsal horn of the spinal cord**, primary pain sensory afferent fibers release excitatory neurotransmitters such as glutumate and Substance P.
• This stimulates neurons that project up to the thalmus and limbic system, and then to the somatosensory cortex.
• Descending pain-inhibitory systems originate in the perioaqueductal gray region of the midbrain and nucleus raphe magnus.
• The descending systems (NE, 5HT) project to the dorsal horn and inhibit activity of the ascending pain pathways.
• Directly: Through 5HT or NE
• Indirectly: By activating inhibitory interneurons (Enkephalin)

Question 3

What do EOPs modulate?

Answer 3

1. EOPS modulate pain sensory tansmission in the spinal cord, limbic strucures, hypothalamus, and medial thalamus.
2. EOPs also modulate GI function - opioid receptors on intestine increase random contraction or circular muscles.
   - This disrupts sequential segmental conractions and blocks propulsive transport. (Results in Constipation)

Question 4

What are the 3 classes of Endogenous Opioid Peptide Receptors?

Answer 4

Question 5

Explain how the G-coupled protein receptors mechanism leads to reduced pain transmission.

Answer 5

• Opioids are coupled negatively to Adenyl cyclase by G-Proteins.
• Activation of Opioid Receptor –> Decreases AD Activity –> Decreases caMP –> Increase Efflux of K+ –> Hyperpolarizes Cell
• Also decreases influx of Ca –> Lower Intracellular Ca –> Decreases release of Neurotransmitters.

Efflux K - > More imp in Postsynapctic Less Ca - More imp in Pre synaptic - decrease NT release

Question 6

What does Mu Receptor stimulation lead to?

Answer 6

• Produces analgesia in the spinal cord and brain
• In the limbic system and related brain areas produces euphoria (main reason for abuse) -> Through activation of Dopamine Reward System; Morphine does this.
• Suppresses pCO2 sensors in brain stem -> respiratory depression.
• Suppresses cough in brain stem
• In the GI tract they block propulsive motility -> Constipation.

Question 7

What does Kappa receptor stimulation lead to?

Answer 7

Produces analgesia in the spinal cord and brain with less euphoria.

Question 8

What does Delta Receptor stimulation lead to?

Answer 8

Produces analgesia in the spinal cord and brain.

Question 9

What Drug

• Is a Kappa Receptor Stimulator
• Affininity for opioid receptors in vitro of 1:4:25 (mu: delta: kappa)
• Produces Less Euphoria acting as a less addictive Analgesic.

Answer 9

Butorphanol

Better than morphine.

Question 10

What are the Natural Agonist Analgesics?

Answer 10

Morphine
Codeine

Question 11

What natural agonist analgesic is this?

Answer 11

Morphine

Question 12

What natural agonist analgesic is this?

Answer 12

Codeine

Drug that would we better taking home after the hospital.

Question 13

What are the synthetic agonist analgesics?

Answer 13

1. Meperidine
2. Methadone
3. Tramadol
4. Fentanyl

Question 14

What synthetic agonist analgesic is this?

Answer 14

Meperidine

Question 15

What synthetic agonist analgesic is this?

Answer 15

Methadone

Question 16

What synthetic agonist analgesic is this?

Can be Used as an Anti-Depressant 5HT and NE Reuptake Inhibitor: Causes more direct inhibtion.

Answer 16

Tramadol

Question 17

What are the chracteristics of Fentanyl?

Answer 17

• Very potent opioid (100-fold ptency of morphine)
• Highly lipophilic with rapid onset and short duration (15-30 min) - Quick onset high and highly addictive.
• Usually administered IV, epidurally, or intrathecally -> Used in surgery (Need ventilation because it can supress respiration)
• Oral transmucosal and transdermal patch also available.
• Good for chronic cancer pain and palliative care.

Question 18

What are the Opiod Antagonists and what are their characteristics?

Answer 18

Naloxone

• Blocks all EOP Receptors
• Poor Oral Absorption, IV Administered
• T1/2 - 1 Hr
• Used in opioid overdose, may need several injections.
• Can stop overdose right away.

Naltrexone

• Blocks all EOP receptors
• Good oral absorption
• T1/2 - 3-4 Hrs But active Metabolite with T1/2 - 12 Hours.
• Used in addiction treatment for narcotics
• Reduces craving for alcohol by alcoholics.

Question 19

What are the different comparisons of analgesic activity?

Answer 19

Question 20

How long can metabolites of Opiods be detected in urine and what does that show?

Answer 20

Detected up to one week after consumption. Urine Toxicology Screen

Shows Abuse/Toxicity

Question 21

How are opioids metabolized and excreted?

Answer 21

• Opioids are metabolized by hepatic glucuronidation.
• The highly polar glucuronides are then excreted readily by the kidneys.
• Beware of toxicity in renal failure.

Question 22

What are the pharmacological/physiological effects of Opioid analgesics?

Answer 22

• Dose Dependent
• Mood changes: Usually mellow, pleasant, euphoria, occasionally dysphoria.
• The negative emotional overtone of the pain is fone (altered pain perception)
• The pain sensation is reduced or blocked (altered pain sensory transmission)

Question 23

What does Morphine and Meperidine do to the pupil and what does that signify?

Answer 23

Morphine: Enchances parasympathetic stimulation ot the eye -> Pinpoint Pupils

Meperidine: Inhibits parasympathetic stimulation to the eye -> **Dilates Pupils
**
Both signs of Opiod Overdose.

Question 24

What are all the adverse effects of Opioid analgesics?

Answer 24