Opioids

Question 1

Natural opiates

Answer 1

Morphine and Codine

Question 2

How do opioids work?

Answer 2

They act on GABA neurotransmission by disinhibiting presynaptic release of GABA.

Question 3

Types of opioid receptors

Answer 3

Mu (endorphins, morphine)
Delta (enkephalins)
Kappa (Dynorphins)

Question 4

Distribution of opioids

Answer 4

Distribute to highly perfused tissues (lungs, brain, kidneys, spleen, liver)

Question 5

Is there a first pass effect?

Answer 5

yes, big one.

Question 6

Metabolism/excretion

Answer 6

Converted to polar metabolites and excreted through the kidney.

Question 7

Morphine

Answer 7

Mu receptor agonist, causes analgesia, euphoria, vasodilation, decreased GI motility, decreased urination

Question 8

How to opioids effect pupils?

Answer 8

Cause pupillary constriction because parasympathetic inputs are indirectly stimulated.

Question 9

Metabolism of Morphine

Answer 9

90% to morphine-3-glucuronide, 10% to morphine-6-glucuronide (which is an active analgesic). Happens in liver

Question 10

Excretion of morphine

Answer 10

90% excreted as M3G in the urine

Question 11

Codeine

Answer 11

Another opiate, binds to mu receptor as an opiate receptor agonist, gets converted to morphine. Used as a cough suppressant, and a weaker analgesic than morphine

Question 12

Side effects of codeine

Answer 12

Increased nausea/vomiting, worstening pruritis

Question 13

Diacetylmorphine

Answer 13

Heroin, converted to morphine and 6-acetylmorphine (also active) in blood.

Activity at all opioid receptors.

Question 14

Half-life of diacetylmorphine

Answer 14

3 minutes before conversion to constituent drugs.

Question 15

Oxycodone

Answer 15

Semi-synthetic opioid, acts similarly to morphine. Used for analgesia (moderate to severe), not great in liver/kidney.

Question 16

Hydrocodone

Answer 16

Semisynthetic, chemically related to codeine. Used for analgesia (mild-moderate) and as a potent anti-tussive. With acetaminophen as vicodin.

Question 17

Hydromorphone

Answer 17

The powerful. Morphine derivative that is 7-8x times more potent. Used for moderate to severe pain, safer in patients with liver/kidney disease. Better for kidney disease.

Question 18

Meperidine

Answer 18

First synthetic opioid. Mu and kappa receptor agonist. Some anticholinergic properties (like atropine). High first pass metabolism.

Question 19

Fentanyl

Answer 19

Strong, safe, portable.

Mu receptor agonist. Doesn’t cause histamine release. For severe pain and dyspnea. Great transdermal bioavailablilty.

Question 20

Methadone

Answer 20

Opioid with extra powers. Mu receptor agonist, but also NMDA receptor ANTAGONIST. Analgesia and neuropathic pain (as NMDA receptor). Safe in liver/kidney patients. Can have cardiac side effects.

Question 21

Loperamide

Answer 21

Doesn’t cross BBB, slows intestinal contractions and stops diarrhea.

Question 22

Dextromethorphan

Answer 22

The psychedelic cough suppressant. Mu receptor agonist (little analgesia) NMDA receptor antagonist.

Question 23

Tramadol

Answer 23

The opioid thats not an opioid. Serotonin releasing agent, NMDA receptor antagonist, NE reuptake inhibitor. Used for moderate analgesia. Lowers seizure threshold. Side effects are not like other opioids.

Question 24

Naloxone

Answer 24

Mu, kappa delta competitive ANTAGONIST. Used for opioid intoxication.

Question 25

Naltrexone

Answer 25

Twice as potent as naloxone, lasts twice as long. Use with opioid overtose, alcohol intoxication, or opioid abuse.

Question 26

Methylnaltrexone

Answer 26

Peripherally acting antagonist. Relieves constipation related to opioids.

Question 27

Hypothesis for development of tolerance

Answer 27

Hypothesized to be due to upregulation of cAMP, failure of receptor recycling, receptor and G-protein uncoupling.

Question 28

Tolerance for sedation/respiratory depression vs tolerance for nausea/vomiting/constipation

Answer 28

Tolerance for sedation develops first (days), nvd takes weeks.

Question 29

Three step ladder for pain relief prescribing

Answer 29

Step one: NSAIDs/acetominophen Step two: Hydrocodone, codeine, oxycodone, oral morphine, tramadol. Step three: morphine IV, hydromorphone, fentanyl, methadone

Question 30

Rotating from one opioid to another requires 2 steps:

Answer 30

1) calculate equianalgesic dose 2)reduce for incomplete cross tolerance -- reduce by half. Don't need to do this if switching from PO to IV though.

Question 31

Dependence

Answer 31

The development of a withdrawal syndrome following dose reduction or administration of an antagonist

Question 32

Tolerance

Answer 32

Change in dose-response relationship induced by exposure

Question 33

OUD

Answer 33

Opioid use disorder: a problematic pattern of use leading to impairment or distress

Question 34

Addiction

Answer 34

Compulsive use despite harm

Question 35

Pseudo-addiction

Answer 35

Behaviors that are reminiscent of addiction, but are driven by pain

Question 36

How do opioids lead to addiction?

Answer 36

Inhibition of GABAergic neurons in VTA, leading to disinhibition of DA neurons

Question 37

Buprenorphine

Answer 37

Partial mu agonist, good for treating opioid dependence. Antagonist of delta and kappa. High affinity for mu so can replace morphine etc.

Question 38

Suboxone

Answer 38

Buprenorphine/Naloxone. Used so that injection doesnt work.