Module E-1 Opiod/non-opioid

Question 1

Functions of GPCR after opioid binding

Answer 1

Outward K flow
Inhibits influx of calcium
Inhibits adenylyl cyclase (conversion of atp to cAMP)

Question 2

Location of opioid receptors in Brain

Answer 2

Periaqueductal gray
Limbic system
Area postrema (medulla)
Locus ceruleus (pons)
Thalamus
Cerebral cortex

Question 3

Location of opioid receptors in spinal cord

Answer 3

Dorsal horn (substantia gelatinosa)

Question 4

Mu actions/subtypes and endogenous agonists

Answer 4

B-Endorphin

Mu-1 supraspinal analgesia and euphoria

Mu-2 respiratory depression and miosis

Pruritis

Question 5

Kappa Endogenous agoinst and actions

Answer 5

Dynorphin A

Spinal analgesia, sedation, dysphoria, hallucinations, antishivering

Implicated in neurobiology of addiction

Question 6

Delta Endogenous agoinst and actions

Answer 6

Enkephalins

Supraspinal and spinal analgesia

Sedation, potentially antidepressant/anxiolytic
Respiration depression

Question 7

Clinically relevant effects of opioid agents on body systems

Answer 7

Cough suppression
Nausea and vomiting
Vasodilation
Bradycardia
Pruritus
Delayed gastric emptying
Ileus and constipation
Urinary retention
Increased biliary pressure
Muscle rigidity
Depressed cellular immunity

Question 8

Why can’t we use mu-agonists as sole agent for anesthesia?

Answer 8

Don’t produce amnesia

Question 9

Explain Dextromethorphan

Answer 9

Dextrorotatory isomer that does not have analgesic activity but still produces anti-tussive effect

Common additive in OTC cough syrup

Question 10

Explain dose dependent offset of opioids

Answer 10

Action of small doses are terminated due to redistribution

Large doses/infusions are dependent on metabolism

Question 11

Metabolism of opioids

Answer 11

Hepatic cytochrome enzymes

Remifentanil- tissue/plasma esterases

Renal excretion of metabolites- this is why we are careful with active metabolites in renal failure

Question 12

Which opioids have active metabolites?

Answer 12

Morphine-
Morphine-6-glucuronide

Meperidine-
Normeperidine is neurotoxic-accumulates in hepatic or renal insufficiency and can precipitate seizures

Question 13

Opioids-CNS Adverse effects

Answer 13

Increased ICP
Sedation
Euphoria
Dysphoria
Hallucinations
Tolerance/dependence

Question 14

Explain Respiratory response to opioids

Answer 14

Central response

Hypoventilation due to altered response to PaCO2 by the brain stem

-loss of hockey-stick shape in curve=apneic/severe hypoventilation at lower PaCO2

May see synergism with other CNS depressants

Question 15

Explain cardiovascular effects of opioids

Answer 15

Venodilation via depression of brain stem vasomotor nuclei

Sympatholytic effects cause:
Arteriolar vasodilation, decreased BP & HR

No direct effect on myocardial contractility

Fentanyl-associated with profound bradycardia due to parasympathomimetic (increased vagal tone)

Question 16

Gastric effects- opioids

Answer 16

Decreased peristalsis

Delayed gastric emptying

Question 17

Opioid Clinical implications during cholangiography

Answer 17

Gall bladder and sphincter of Oddi spasm

Question 18

PONV in opioids

Answer 18

Stimulation of chemoreceptor trigger zone in the medulla

Multi factorial- CNS/GI/vestibular system

Question 19

Musculoskeletal and opioids

Answer 19

Muscle rigidity
-impact on ventilation/chest wall rigidity

-administer muscle relaxants

Question 20

Pruritis and opioids

Answer 20

Transient, not drug allergy,
Antihistamines administration of antagonists or agonists-antagonists (nalbuphine)

Question 21

Outline prostaglandin formation

Answer 21

Tissue injury
Phospholipids
Arachidonic acid

Produces Cox1 and Cox2

Question 22

COX-1 effects

Answer 22

Cytoprotective prostaglandins

Protect gastric mucosa

Aid platelet aggregation

Question 23

What does COX stand for

Answer 23

cyclooxygenase enzyme

Question 24

COX-2 Effects

Answer 24

Inflammatory prostaglandins

Recruit inflammatory cells
Sensitize skin pain receptors
Regulate hypothalamic temp control

Question 25

Chronic Adverse effects of NSAIDs

Answer 25

Increase risk of stroke/MI-imbalance of clotting pathway Inhibit bone healing-controversial Gastric/colonic mucosal damage and GI bleeding Hemostatic-increased bleeding Renal toxicity- decrease function

Question 26

Phenanthrenes

Answer 26

Morphine backbone Chiral center-Levo enantiomer is active Hydromorphone Hydrocodone Oxycodone Codeine Nalbuphine Naloxone

Question 27

Phenylpiperidines

Answer 27

Meperidine-first synthetic Fentanyl series Sufentanil Remifentanil Alfentanil NO chiral form-not racemic

Question 28

Euphoria receptor

Answer 28

MU

Question 29

Dysphoria receptor

Answer 29

Kappa Q

Question 30

Miosis in opiate use mechanism

Answer 30

Opiate depression of inhibitory gamma-aminobutyric acid (GABA) interneurons leads to stimulation of the Edinger Westphal nucleus, which sends a parasympathetic signal via the ciliary ganglion to the oculomotor nerve to constrict the pupil

Question 31

Impact of opioids on CO2 curve

Answer 31

Right shift, loss of hockey stick

Question 32

Describe sensitizing soup

Answer 32

Tissue injury causes release of many different pain mediators from the damaged tissue H, K Serotonin Prostaglandins**, leukotrienes Bradykinin Histamine

Question 33

Afferent signal

Answer 33

Peripheral to central

Question 34

What GI symptom do we look for in chronic opioid consumption

Answer 34

Delayed gastric emptying/GERD

Question 35

What to give for ercp spasm with opioid admin

Answer 35

Glucagon Smooth muscle dilator

Question 36

Meperidine contraindications

Answer 36

Hx seizures MAOI Elderly-renal? Neuro cases (high risk seizures)

Question 37

Which class of opioids has a chiral center and describe its orientation

Answer 37

Phenantrenes Levo-enantionmer