Pharmacology Of Opioid/narcotic Analgesics

Front 1

What are the three opioid receptors and what are their ligands?

Back 1

Mu - endorphins
Kappa - dynorphins
Delta - enkephalins, endorphins

Front 2

T or F: Opioid receptors are found in the brain, spinal cord, gut, uterus, and other places.

Back 2

True

Front 3

T or F: The majority of clinically useful opioids have agonistic activity at the delta receptor.

Back 3

False!
Mu receptor is most clinically useful

Front 4

What are the 4 steps of opioid mediated signaling?

Back 4

1. Blunts afferent pain signal
2. Blunts Calcium influx
3. Blunts glutamate discharge
4. Increases potassium efflux

Front 5

What are the clinical effects of activating the mu receptor?

Back 5

Analgesia
Euphoria
CNS and respiratory depression
Drug dependence
Miosis
Constipation

Front 6

What are the clinical effects of activating the kappa receptor?

Back 6

Analgesia
Sedation
Miosis
Constipation

Front 7

When you build a tolerance to mu agonists, what effects are the exception (no tolerance develops)?

Back 7

Miosis
Constipation

Front 8

Why do people die from mu agonist overdoses?

Back 8

In limbic system, they cause euphoria
In brainstem, they cause respiratory depression which can be lethal

Front 9

What drugs belong to group 1 mu agonists (full agonists, parenteral and oral)?

Back 9

Morphine
Methadone
Meperidine
Hydromorphone
Oxymorphone
Levorphanol

Front 10

What drugs belong to group 2 mu agonists (full agonists, short acting)?

Back 10

Fentanyl
Sufentanil
Remifentanyl

Front 11

What drugs belong to group 3 mu agonists (codeine-related)?

Back 11

Hydrocodone
Oxycodone

Front 12

What are the clinical indications for morphine,the prototype mu agonist?

Back 12

Post-op pain
Cancer pain
Other pain

Front 13

T or F: Morphine analgesia can be separated from the adverse effects like sedation, miosis, emesis, pruritis, constipation, euphoria, respiratory depression.

Back 13

False
The analgesia is inseparable from adverse effects

Front 14

Since morphine causes respiratory depression, what are the contraindications?

Back 14

Brain injury, emphysema, heart failure

Front 15

What are the active metabolites of morphine? Inactive metabolites?

Back 15

Active - M-3-glucuronide and M-6-glucuronide via UGT 1A1 and UGT 2B7
Hydromorphone via dehydrogenase

Inactive - normorphine via CYP3A4

Front 16

T or F: Oral morphine has high bioavailability.

Back 16

False, first pass metabolism leads to a low bioavailability for oral morphine.
Parenteral opioids have HIGH bioavailability

Front 17

What is methadone useful for and why is it useful?

Back 17

Used for withdrawal/maintenance and detox
Useful because it has a longer half life and better oral availability than morphine

Front 18

What can methadone cause in acute overdose or during long-term treatment?

Back 18

QT interval prolongation

Front 19

T or F: The group 2 mu agonists are about 100x more potent than morphine.

Back 19

True

Front 20

Which of the group 2 mu agonists is the shortest acting?

Back 20

Remifentanil

Front 21

Which of the group 2 mu agonists works at all 3 opioid receptors (mu, delta, and kappa)?

Back 21

Sufentanil

Front 22

What is fentanyl used for and why?

Back 22

Anesthesia
Rapid onset and distribution (lipophilic)
Short duration of action (procedures)

Front 23

What are two common delivery methods of fentanyl?

Back 23

Transmucosal (lollipop) - for breakthru pain
Transdermal patch - slower onset
***Abuse potential via heating the patches***

Front 24

How is meperidine distinguished from other mu agonists?

Back 24

Less effects on smooth muscle, so useful in labor - fast onset and short acting
Causes mydriasis
*Normeperidine, toxic metabolite, accumulates and can cause seizures

Front 25

What is codeine useful for and why?

Back 25

Used for moderate pain relief (may contain acetaminophen)
Anti-tussive - cough relief is mu independent
Reliable oral absorption and less potential for abuse since it is only a partial agonist

Front 26

T or F: Codeine is metabolized into morphine

Back 26

True

Front 27

What gene is responsible for dictating the speed at which people metabolize codeine?

Back 27

CYP2D6
Ultrafast - gene duplication and ultrafast allele
Intermediate - heterozygous
Poor - gene deletion and slow allele

Front 28

What is the blackbox warning on codeine for children?

Back 28

Contraindicated on use after tonsillectomy and/or adenoidectomy

Front 29

What two opioids are used as anti-diarrheals?

Back 29

Loperamide
Diphenoxylate
*limited risk of abuse, poor penetration of BBB, interact with mu receptors in gut

Front 30

What is tramadol, its active metabolite, uses, MOA, and contraindications?

Back 30

Moderate mu agonist
N-desmethyl active metabolite
Used for moderate pain
MOA - Inhibits catecholamine reuptake
Caution in patients on tricyclic or SRI antidepressants
Associated with seizures

Front 31

Describe pentazocine.

Back 31

Kappa agonist plus mu/delta antagonist
Supraspinal analgesia
Can precipitate withdrawal in abusers

Front 32

Describe buprenorphine.

Back 32

Mu partial agonist plus kappa/delta antagonist
Used in office-based detox/maintenance

Front 33

What is a safer alternative to using opioids as antitussives?

Back 33

Dextromethophan relieves cough independently of all opioid receptors

Front 34

What is heroin?

Back 34

Di-acetylmorphine
Penetrates BBB rapidly, causes exaggerated euphoria, highly addictive

Front 35

What are the mu receptor antagonists?

Back 35

Naloxone - iv
Naltrexone - po - long duration of action ~48 hours for single dose
Competitively inhibit other opioids from mu receptors
Antidote for opioid overdose***

Front 36

T or F: Naloxone can reverse coma and respiratory depression ~ 1 minute after iv bolus.

Back 36

True
But depends on what opioid and what dose!!

Front 37

T or F: Antidotes for opioid overdose can precipitate withdrawal.

Back 37

True