Opioids

Question 1

What can opioids be used for?

Answer 1

Opioids are good drugs to help deal with severe pain such as in cancer patients

Question 2

What are 2 major locations of pain sensation?

Answer 2

2 major locations involved in the sensation of pain:
1. Peripheral nerves – non-steroidal anti-inflammatory drugs
2. Central nervous system (spinal cord)

Question 3

What plant do opioids come from?

Answer 3

The opium poppy

Question 4

What are opiates?

Answer 4

• Alkaloids found in the opium poppy (high concentration of morphine, used to treat severe diarrhea and pain)

Question 5

What is heroin?

Answer 5

Heroin is a derivative of morphine

Question 6

How is opium harvested?

Answer 6

Harvested – scratch seed pods with a knife, the juice comes out, scrape it off
The same pod can be scratched and scrapped many times

Question 7

What was morphine named for?

Answer 7

Morpheus – the Greek goddess of dreams, gives morphine its name because you get sleepy when you take morphine

Question 8

Which administration gives a faster effect?

Answer 8

Smoking gives a faster effect than eating it

Question 9

Morphine oral administration?

Answer 9

When it taken orally, it is metabolized in the liver, less gets to the blood fast, less likely to be addictive, no high effect

Question 10

When was opioids mechanism of action discovered?

Answer 10

1975 – discovery of endogenous opioids, mechanism of action, after they were widely used

Question 11

Types of opiates/opioids?

Answer 11

Morphine (heroine is a derivative)
Codeine (weaker than morphine, better absorbed orally)
- Opiates are drugs derived from opium
- There are many side effects
- Many different derivatives where synthesised to try to find a similar drug with less side effects
- Opioids are drugs with morphine-like action
Fentanyl, methadone

Question 12

Is heroin more potent than morphine?

Answer 12

Yes, more potent = more addictive

Question 13

What is Naloxone?

Answer 13

Naloxone – antagonist (used to save lives of people who overdose) acts on the mu receptor

Question 14

What is Buprenorphine?

Answer 14

It is a weak agonist of the mu receptor, morphine is an agonist

Question 15

Where are opioid receptors found?

Answer 15

• Presynaptic membranes: decrease transmitter release
• Postsynaptic membranes: hyperpolarize membrane, open K+ channels

Question 16

What are the 4 types of opioid receptors?

Answer 16

Delta
Kappa
Mu
Nociceptin

Question 17

How does the mu receptor activation cause pain inhibition?

Answer 17

Main one is the mu receptor (decrease the influx of Ca2+, increase the outflux of K+, hyperpolarize membrane)
Decreases the release of neurotransmitters
Presynaptic decrease in transmitter release
Postsynaptic hyperpolarization

Question 18

Receptor turnover is important why?

Answer 18

GPCR, endosome or lysosomes
Internalized, recycled or degraded
Mechanism promoting tolerance – recycling can be modified (increased or decreased) can be put back into the membrane

Question 19

Receptor plasticity and morphine?

Answer 19

Synthesize more receptors
Pain stimulation alters the number of receptors to the membrane
Chronic morphine use alters receptor trafficking

Question 20

Effects of opioids? (4)

Answer 20

• Analgesia
  o Relief in pain in absence of impairment in other sensory modalities
  o No change in sight, movement, hearing, touch
  o “Soldiers disease” used in war
• Gastrointestinal effects, inhibit motility
• Cough suppression
• Euphoria

Question 21

Which opioid receptor is involved with analgesia, decreased respiration, GI tract constipation?

Answer 21

The mu receptor, less selective responses at higher doses

Question 22

Morphine Administration?

Answer 22

Absorption: oral, rectal, injection, GI absorption is slow and incomplete
- The usual rout is intramuscular, subcutaneous, or Intravenous
- Inhalation is rapidly absorbed
- Liver inactivation, will get to spinal cord, brain – takes more time, not as addictive, good for pain relief
For chronic pain, pumps can be placed under the skin to release more of the drug

Question 23

Morphine/Heroin distribution?

Answer 23

Distribution: only 20% crosses the Blood Brain Barrier, heroin is more lipid soluble (can cross BBB more)

Question 24

Morphine metabolism, half life?

Answer 24

Metabolism: in liver, half life is 2-4hours, the metabolites are different depending on if the drug was administered orally of parenteral (injection)

Question 25

Morphine excretion?

Answer 25

Through the urine

Question 26

The rout of morphine administration affects the metabolism, oral vs parenteral?

Answer 26

The rout affects the metabolism
- Orally: Psychoactive neurotoxic metabolite formed when given orally
- Parenteral:
o 60% inactive (4-hour half life) morphine 3-glucomonide (M-3-g)
o 40% highly active (M-6-G) – renal failure stays around for a long time

Question 27

What is morphine’s effect on the GI tract?

Answer 27

the neurons in the myenteric plexus and the submucosal plexus are slowed down by opioids. Motility of the GI tract is decreased. Constipation, fluid absorption, can treat with stool softeners. opioids can help treat diarrheas

Question 28

Side effects of morphine?

Answer 28

Nausea and vomiting

Question 29

Morphine’s effect on respiration and the eyes?

Answer 29

morphine depresses the respiratory center (stop breathing)
Miosic – pinpoint pupils
Urine decreases – increased water reabsorption

Question 30

Differential tolerance of opioids?

Answer 30

There is also a tolerance to analgesia so need to take more to relieve pain
There is minimal tolerance to miosis and constipation

Question 31

Codeine?

Answer 31

Given orally
Moderately effective analgesic
Codeine + aspirin = good for relieving pain and is a safer combination
Codeine is converted to morphine by CYP 2D6 in the body
Absorbed well, morphine causes the relief of pain

Question 32

What is Buprenorphine?

Answer 32

A partial agonist

Question 33

What is Naloxone?

Answer 33

Naloxone: antagonist (if give before morphine, morphine has no effect), half life is minutes, must inject
Naltrexone has oral absorption

Question 34

What is hydromorphone?

Answer 34

A mu agonist

Question 35

What is Meperidine?

Answer 35

Meperidine: good analgesic, side effects differ from morphine, metabolized to active metabolites

Question 36

What is Fentanyl?

Answer 36

Fentanyl: lipid soluble (can apply via patch) short half life, quick onset and leaves fast
- Given orally (lollypop) can get into the brain with no liver first pass

Question 37

What is loperamide?

Answer 37

Loperamide: (Imodium) minimal penetration of the BBB; treats diarrhea, no bad side effects in the brain

Question 38

What is methadone?

Answer 38

Methadone – oral absorption, long half life, block withdrawal in addicts, stabilize/maintain therapy

Question 39

Clinical uses of opioids?

Answer 39

• Analgesia: relieve pain, other systems intact, give pain relief to stay in therapeutic range
• Cough suppression
• Treat severe diarrhea

Question 40

Addiction opioids acute effects?

Answer 40

• Euphoria “high”
• Tranquility and sleepiness “nod”
• Last about 3-5 hours

Question 41

The first opioid epidemic due to?

Answer 41

Heroin (prototype)
- 10x more potent than morphine
- Crosses BBB fats
- Activates the dopaminergic reward pathway, blocks GABA receptors in the brain

Question 42

Current opioid crisis?

Answer 42

Oxycodone – being over prescribed for people who don’t need it (like a headache or back pain)
Heroin overdose is easy
Lethal dose of fentanyl is very small

Question 43

Fentanyl infused with tranquilizers?

Answer 43

xylazine – presynaptic decrease in adrenergic system, sedation, extends duration of opioids, NO antidote, this is for veterinarians not approved for humans

Question 44

Treatment of opioid overdose?

Answer 44

Naloxone pushes off morphine from receptors
Methadone lasts about a day, don’t get a peak/high
Nasal spray, rapid absorption, prevents overdose, naloxone