Opioids

Question 1

What is Pain?

Answer 1

Pain is a subjective symptom or an unpleasant sensory and/or emotional experience that is typically associated with actual or potential tissue damage from mechanical or thermal causes or disease

Question 2

Which ascending tract sends information about pain and temperature

Answer 2

Spinothalamic tract

Question 3

Where does the descending pain-inhibitory pathway originate

Answer 3

The midbrain

Question 4

A-delta and C fibers terminate in the ______ ____ of the spinal cord and transmit _______ and ______ pain

Answer 4

Dorsal horn; somatic; visceral

Question 5

Describe the descending pathways

Answer 5

• Originate in the periaqueductal gray region of the midbrain and nuclei of the rostro-ventral medulla
• Project to dorsal horn and release norepinephrine, serotonin and enkephalin
• Inhibit the activity of ascending pain pathways

Question 6

What are the endogenous opioid peptides

Answer 6

Endorphins
Enkephalin
Dynorphins

Question 7

Three major classes of opioid receptors (g-protein coupled receptors)

Answer 7

Mu receptor
Kappa receptor
Delta receptor

Question 8

Mu receptor
Endogenous ligands:
Drugs:

Answer 8

Endogenous ligands: Enkephalins, β-endorphin

Drugs: Morphine, fentanyl, methadone, meperidine, oxycodone, buprenorphine,

Question 9

Kappa receptor
Endogenous ligands:
Drugs:

Answer 9

Endogenous ligands: Dynorphins

Drugs: Nalbuphine, butorphanol and pentazocine

Question 10

Delta receptor
Endogenous ligands:
Drugs:

Answer 10

Endogenous ligands: Enkephalins

Drugs: none

Question 11

Localization of opioid receptors

Answer 11

Found in the periaqueductal gray, dorsal horns of spinal cord, medulla and hypothalamus - also peripheral organs such as GI system and heart

Question 12

Mu and delta receptors in limbic areas may be involved in ______ _______

Answer 12

Drug dependence

Question 13

Kappa receptors in limbic structures may be involved in ______ actions of kappa agents

Answer 13

dysphoric

Question 14

Narcotic

Answer 14

A term used to refer to morphine like drugs and some other abused substances - drugs that produce a stuporous sleeplike state and may or may not be analgesic

Question 15

Opiates

Answer 15

Drugs that are derived from opium or have a morphine like pharmacological profile

Question 16

Opioid

Answer 16

Refers to all opiates, agonist-antagonists and endogenous peptides

Question 17

Which drugs undergo extensive first pass metabolism

Answer 17

Morphine and naloxone

Question 18

Which opioid drugs are activated by metabolism

Answer 18

Codeine and heroin

Question 19

Duration of action is related to both _______ and _______ _____

Answer 19

Lipohilicity; elimination rate

Question 20

Effects of Opioid agonists

Answer 20

1) Analgesia (alleviating pain)
2) Cough suppression
3) Antidiarrheal effect and constipation (mu receptors on GI nerves)
4) Euphoria
5) Sedation
6) Respiratory depression (side effect) - decrease in the sensitivity of chemoreceptors in brainstem to CO2
7) Nausea
8) Endocrine Effects
9) Miosis (Edinger Westphal nucleus)

Question 21

Which drugs are less efficacious in alleviating pain

Answer 21

Codeine and propoxyphene

Question 22

Which opioids are used for cough suppression

Answer 22

Codeine, hydrocodone and dextromethorphan

Question 23

What are the endocrine effects of opioids

Answer 23

• Decreased release of LH - mu receptor

- ADH secretion is increased by mu stimulation and decreased by Kappa stimulation

Question 24

Opioid agonists (8)

Answer 24

1) Oxycodone
2) Codeine
3) Morphine
4) Heroin
5) Hydrocodone
6) Methadone
7) Fentanyl
8) Meperidine

Question 25

``` Morphine Receptor: Oral to Parenteral ratio: Administration: Duration of analgesia: ```

Answer 25

Receptor: mu agonist Oral to Parenteral ratio: 3 or 4 to 1 Administration: Available in injectable, oral, oral sustained release and suppository forms - sustaine release preparation Duration of analgesia: 4-5 hours

Question 26

Heroin More _____ than Morphine Converted to ______ and ______ Abuse potential:

Answer 26

More lipophilic than Morphine Converted to 6-mono-acetyl morphine and morphine Abuse potential: High

Question 27

Codeine, Hydrocodone and Oxycodone Which of these does not reach morphine like efficacy? These drugs are often used in combination with what? Which of these drugs are available as sustained release preparations?

Answer 27

Codeine; NSAIDS or acetaminophen; Oxycodone and Hydrocodone

Question 28

``` Methadone Receptor: Duration of action: Administration (most common): Use: ```

Answer 28

Receptor: mu agonist Duration of action: longer than morphine Administration (most common): has good oral availability Use: treatment of opioid abuse and chronic pain

Question 29

Meperidine - a phenylpiperidine Duration of action: What does this drug form: Interactions:

Answer 29

Duration of action: shorter duration of analgesia than morphine What does this drug form: forms toxic metabolite, normeperidine, that can accumulate with frequent use Interactions: with MAO inhibitors

Question 30

``` Fentanyl - structurally related to meperidine Receptor: Duration of action: Potency in comparison to morphine: Availability: ```

Answer 30

Receptor: mu agonist Duration of action: short acting - 1-1.5 hours Potency in comparison to morphine: 100 x as potent Availability: injectable form and as transdermal patches

Question 31

How potent is Hydromorphone compared to morphine

Answer 31

2-3 X as potent

Question 32

Mixed-Action Agonist/Antagonist (2)

Answer 32

1) Nalbuphine | 2) Buprenorphine

Question 33

``` Nalbuphine Receptors: Efficacy: Abuse potential: Availability: ```

Answer 33

Receptors: mu antagonist and kappa agonist Efficacy: similar to morphine Abuse potential: low Availability: only in injectable form

Question 34

Buprenorphine Receptors: Use: Administration:

Answer 34

Receptors: Partial mu agonist Use: Treatment of moderate to severe pain Administration: Oral or patch

Question 35

Opioid Antagonists (2)

Answer 35

1) Naloxone | 2) Naltrexone

Question 36

``` Naloxone Receptors: Administration: Duration of action: Use: ```

Answer 36

Receptors: High affinity for mu receptors, less for kappa and delta Administration: greater activity parenterally than orally Duration of action: 1 to 2 hours (short) Use: Treat opioid overdoses - decrease parenteral abuse liability

Question 37

Naltrexone Administration: Use:

Answer 37

Administration: Orally active with long half life Use: Treatment of alcoholism and opiate addiction

Question 38

Dextromethorphan

Answer 38

dextro isomer of levorphanol. Antitussive, but not analgesic. Also is an NMDA antagonist

Question 39

Tramadol

Answer 39

Weak mu agonist - also blocks NE and 5-HT uptake - Used for mild to moderate pain - Available for oral use including a sustained release preparation

Question 40

Tolerance of Opioids

Answer 40

Tolerance develops to most of the effects of the opioids - Rapid = emetic action - Moderate Rate = analgesic, respiratory, euphoria and endocrine effects - Little or no tolerance - constipation and miosis Cross tolerance

Question 41

Physical dependence on opioids

Answer 41

Continuous exposure to opioids results in development of physical dependence. When drug administration is stopped, the body functions abnormally

Question 42

``` Symptoms of withdrawal based on time 6-12 hours: 12-24 hours: 24-27 hours: Later: ```

Answer 42

6-12 hours: Drugs seeking behavior; restlessness, lacrimation, rhinorrhea 12-24 hours: Restless sleep for several hours; irritability, tremor, dilated pupils, anorexia 24-27 hours: Increased intensity of above, plus weakness, depression, nausea - possible electrolyte imbalance Later: Above symptoms alternate with restless sleep with gradual decrease in activity -- Delayed growth and development in infants born to addicted mothers may be detected for up to 1 year

Question 43

Signs of Opioid abuse

Answer 43

1) Euphoria 2) Craving 3) Drug-seeking behavior 4) Withdrawal

Question 44

Treatment of opioid abuse:

Answer 44

1) Methadone 2) Suboxone 3) Naltrexone