Pharm: 28 - Opioids

Front 1

What is analgesia?

Back 1

A state in which no pain is felt despite the presence of normally painful stimuli

Front 2

What are analgesics?

Back 2

Drugs that alleviate pain without impairing other sensory modalities

Front 3

What are the receptors for pain called? What fibers does the message travel on? How does the message get to the brain?

Back 3

- Nociceptors
- Aδ and C fibers terminate in dorsal horn of spinal cord (via glutamate and substance P)
- Spinal Thalamic pathway projects from dorsal horn to thalamus, then to limbic nuclei and somatosensory and association cortex

Front 4

What is the descending pathway that modulates pain sensation?

Back 4

- Originates in periaqueductal gray of midbrain and nuclei of rostro-ventral medulla
- Projects to dorsal horn via dorsolateral funiculus
- Releases NE, serotonin, and enkephalin
- Inhibits activity of ascending pain pathway (analgesic)

Front 5

Which ascending pain fibers mediate sharp localized pain to the dorsal horn of the spinal cord? Where specifically do they terminate? Which NT?

Back 5

- Aδ fibers
- Terminate in lamina I
- Uses glutamate as NT (somatic pain)

Front 6

Which ascending pain fibers mediate dull, diffuse, aching or burning pain? Where specifically do they terminate? Which NT?

Back 6

- C fibers
- Terminate in lamina II
- Uses glutamate and substance P (visceral or neuropathic pain)

Front 7

Secondary neurons bringing pain input travel on the spinothalamic tracts to what destinations?

Back 7

- Thalamic nuclei -->
- Limbic system
- Sensory and association cortex

Front 8

What are the endogenous opioid peptides? Precursors?

Back 8

- β-endorphins - from POMC (proopiomelanocortin)
- Enkephalin - from proenkephalin
- Dynorphins - from prodynorphin

Front 9

What are the three major classes of opioid receptors?

Back 9

- Mu (µ) receptor
- Kappa (κ) receptor
- Delta (δ) receptor

Front 10

What kind of proteins are the opioid receptors? Actions?

Back 10

- G-protein coupled receptors (65% homology) - Gi
- Inhibit adenylyl cyclase
- Decreases cAMP
- Increases efflux of K+, hyperpolarization
- Decreases influx of Ca2+
- Lowers intracellular conc. of free Ca2+
- Decreased release of NT

Front 11

What are the endogenous ligands for the mu (µ) receptor?

Back 11

- Enkephalins
- β-endorphins

Front 12

What are the drug ligands for the mu (µ) receptor?

Back 12

- Morphine
- Fentanyl
- Methadone
- Meperidine
- Heroin
- Codeine
- Oxycodone
- Buprenorphine
- Hydromorphone

Front 13

What are the drug antagonists for the mu (µ) receptor?

Back 13

- Naloxone
- Naltrexone

Front 14

What are the endogenous ligands for the kappa (κ) receptor?

Back 14

Dynorphins

Front 15

What are the drug ligands for the kappa (κ) receptor?

Back 15

Nalbuphine

Front 16

What are the endogenous ligands for the delta (δ) receptor?

Back 16

Enkephalins, β-endorphin

Front 17

Where are the opioid receptors localized?

Back 17

- Found in periaqueductal gray, dorsal horns of spinal cord, medulla, and hypothalamus
- Also in peripheral organs such as GI system
- Mu (µ) and delta (δ) receptors are also in limbic areas (involved in drug dependence)
- Kappa (κ) receptors are also in limbic areas (involved in dysphoric actions)

Front 18

What is a narcotic?

Back 18

Morphine like drug and some other abused substances; produce stuperous sleep-like state and may or may not be analgesic

Front 19

What are opiates?

Back 19

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

Front 20

What are opioids?

Back 20

All opiates, agonist-antagonists, and endogenous peptides

Front 21

How are opioid drugs administered?

Back 21

- Oral absorption and bioavailability varies by compound (typically well absorbed)
- Also can be administered parenterally

Front 22

Which drugs have extensive first-pass metabolism / can't be administered orally?

Back 22

- Morphine
- Naloxone

Front 23

What determines the onset of action of opioids?

Back 23

Lipophilicity

Front 24

What determines the duration of action of opioid drugs?

Back 24

- Lipophilicity
- Elimination rate

Front 25

Which drugs are metabolized to active drugs by metabolism?

Back 25

- Heroin
- Codeine

Front 26

How are opioids metabolized?

Back 26

By liver to more polar and less active metabolites via N-dealkylation, hydrolysis, and conjugation

Front 27

What are the effects of opioids?

Back 27

- Analgesia
- Cough suppression
- Antidiarrheal effect
- Euphoria
- Sedation
- Respiratory depression
- Nausea
- Decreased LH, Increased ADH
- Pupillary constriction - miosis

Front 28

How do opioids affect pain?

Back 28

- Decrease perception of pain
- Decrease appreciation of pain

Front 29

Which drugs are most / least effective for analgesia?

Back 29

- Most full agonists are equally effective
- Except: codeine (less effective)

Front 30

Which drugs mediate cough suppression?

Back 30

Codeine and Dextromethorphan (may not be mediated by opioid receptors)

Front 31

How do opioids affect bowel movements?

Back 31

- Antidiarrheal and constipation
- Delays gastric emptying, spasmodic increases in intestinal tone and decrease propulsive movements
- CNS and PNS effects - Mu (µ) receptors on GI nerves

Front 32

What is the most serious side effect of opioids?

Back 32

Respiratory depression - due to decreased sensitivity of brainstem chemoreceptors to CO2 (additive w/ other CNS depressing drugs)

Front 33

How do opioids affect nausea?

Back 33

Stimulation of chemoreceptor trigger zone (CTZ) in postrema area (more when standing)

Front 34

What are the endocrine effects of opioids?

Back 34

- Decrease LH release - µ effect
- Increase ADH secretion - stimulated by µ receptors and decreased by κ receptors

Front 35

How do opioids affect the pupils?

Back 35

- Constriction (miosis)
- Stimulation of Edinger-Westphal nucleus of oculomotor nerve
- No tolerance for this effect (abusers will have very small pupils)

Front 36

What are the opioid antagonists?

Back 36

- Naloxone
- Naltrexone

Front 37

What symptoms are affected by tolerance?

Back 37

- Develops to most of the effects, rate differs:
- Rapid - emetic action
- Moderate - analgesic, respiratory, euphoria, and endocrine effects
- Little or no tolerance - constipation and miosis

Front 38

How are opioids affected by physical dependence?

Back 38

- Continuous exposure to opioid analgesics results in the development of physical dependence
- When drug administration is stopped or an antagonist, such as naloxone is given, body functions abnormally

Front 39

What are the signs and symptoms of opioid withdrawal at 6-12 hours?

Back 39

- Drug-seeking behavior
- Restlessness
- Lacrimation
- Rhinorrhea
- Sweating
- Yawning

Front 40

What are the signs and symptoms of opioid withdrawal at 12-24 hours?

Back 40

- Restless sleep for several hours
- Irritability
- Tremor
- Dilated pupils
- Anorexia
- Goosebumps

Front 41

What are the signs and symptoms of opioid withdrawal at 24-72 hours?

Back 41

- Increased intensity of early symptoms
- Weakness
- Depression
- Nausea
- Vomiting
- Intestinal cramps
- Diarrhea
- Alternating chills and flushes
- Aches and pains
- Increase HR and BP
- Involuntary movements of arms and legs
- Dehydration and possible electrolyte imbalance

Front 42

What are the signs and symptoms of opioid withdrawal after 72 hours?

Back 42

- Earlier symptoms of autonomic hyperactivity alternate with brief periods of restless sleep w/ gradual decrease in intensity until addict recovers in 7-10 days
- Strong cravings for drug
- Mild signs and symptoms are detectable for up to 6 months
- Delayed growth and development in infants born to addicted mothers for up to 1 year

Front 43

What are the symptoms of opioid abuse?

Back 43

- Euphoria
- Craving
- Drug-seeking behavior
- Withdrawal

Front 44

How do you treat opioid abuse?

Back 44

- Methadone
- Buprenorphine / Naloxone - sublingual
- Naltrexone
- Behavioral therapy