Opioid Analgesics And Antagonists

Question 0

A delta neurons

Answer 0

Fast primary neurons

Sense intense sharp stinging pain . Functions to localize pain and in the withdrawal reflex

Question 1

Pain pathways : where are nociceptors located

Answer 1

Primary afferent neurons

Question 2

C neurons

Answer 2

Slow primary neurons

Sense dull, burning, aching pain. Functions to mediate autonomic reflexes, pain memory ,pain discomfort

Question 3

Descending inhibitory pathways are from where and inhibit what and active what?

Answer 3

Periaqueducal grey/ raphe and locus ceruleus inhibit ascending spinal thalamic tract neurons. They also activate inter neurons in spinal cord that release met-enkephalins that inhibit the release of pain mediators

Question 4

Sensory A beta fibers arise from where and inhibit what how

Answer 4

Arise from peripheral tissues inhibit pain transmission via the stimulation of release of enkephalins from interneurons

Question 5

Endogenous opioid peptides

Answer 5

Enkephalins
Small peptides met and leu-enkephalins are released from neurons in periaqueductal grey,medulla and spinal cord. They modulate neurotransmission by having an inhibitory effect.

Endorphins and dynorphins are larger peptides

Question 6

What are the three opioid receptors

Answer 6

Mu, delta, kappa - most of the useful opioid analgesics active mu receptors. Some of the agonist/antagonist agents also work at kappa receptors

Question 7

Types of opioid drugs

Answer 7

Full agonists- 1.strong opioids - tolerated when given in large doses to relieve pain 2.Moderate opioid - significant side effects so give sub maximally with NSAIDS

Mixed opioid agonist -antagonist
Opioid antagonists - used to counteract adverse effects of overdose

Question 8

MOA of opioids

Answer 8

Act through G protein receptors couple to Gi. The alpha subunit inhibits adenylate cyclase leading to a decrease in cAMP. The beta/gamma subunits increase potassium conductance and decrease the influx of calcium. These actions inhibit both presynaptic and postsynaptic neurons.

Question 9

7 CNS pharmacological effects of opioids

Answer 9

1. Analgesia : via receptors into e spinal cord and the CNS
2. Sedation, euphoria, dysphoria: via action serotonergic, dopaminergic, noradrenergic midbrain nuclei.
3. Miosis: via stim of edinger Westphal nuc. -dx overdose
4. Nausea/ vomititing : stim chemo trigger zone
5. Respiratory depression: via suppression of the medulla
6. Inhibition of cough reflex : at site in medulla
7. Truncal rigidity: intensification of tone in large trunk muscles

Question 10

Cardiovascular effects of opioids

Answer 10

Orthostatic hypotension: due to Release of histamine from mast cells and vasodilation

Question 11

Opioids effects on GI / urinary systems

Answer 11

1. Constipation: due to increased smooth muscle tone and inhibition of peristalsis.
2. Increased tone of biliary sphincter
3. Increased tone of the bladder sphincter causing urinary retention
4. Deceased uterine tone leading to prologation of labor

Question 12

Morphine

Answer 12

Strong opioid agonists
- absorbed orally but goes through significant first pass metabolism to 3- glucuronide which is in active and to 6- glucuronide which is more active than morphine.

Standard to which other drugs are compared .

Used for severe pain of trauma, mi

Question 13

Fentanyl

Answer 13

Fentanyl and sufentanil synthetic opioids
MOST POTENT agonists

Skin patch
Used parenterally preoperatively and postoperatively and as an adjunct to general anesthesia -> can cause truncal rigidity

Question 14

Meperidine

Answer 14

Synthetic opioid agonist

• has anti muscarinic properties so itm at cause pupils to dilate
• effects on smooth muscle Are less pronounced than morphine so can be used in pregnant people
• short term for moderate to severe pain but not long term because of neurotoxic metabolite called normeperidine which can cause CNS excitation, convulsions and tremors

Question 15

Methadone

Answer 15

Synthetic opioid agonist

• used orally for opioid dependence or chronic pain
• long half life- once a day
• can prevent craving for heroin but doesn’t cause significant euphoria other reinforcing side effects

Question 16

Oxycodone

Answer 16

Semisynthetic opioid morpheme derivative

• used with NSAID to treat moderate to severe pain
• sustained release - oxycontin-> caused deaths

Question 17

Codeine

Answer 17

Moderate opioid agonist

• naturally occurring opioid
• contains a methyl group at the 3 position which is where morphine conjugated - spit undergoes less first pass metabolism
• converted to morphine via CYP2D6
• used in combo with an NSAID to treat mild to moderate pain and cough syrup as anti tussive

Question 18

Propoxyphene

Answer 18

Half the analgesic potency of codeine

- recently taken off the market bc it can cause fatal heart rhythm abnormalities

Question 19

Tramadol

Answer 19

Weak agonist at mu
Inhibits serotonin and NE reuptake -> may potentiates the actions of the descending inhibitory pathways

Moderate and chronic pain

Question 20

Dextromethorphan

Answer 20

Analogue of codeine used as an anti-tussive

Minimal analgesic and addictive properties

Question 21

Diphenoxylate

Answer 21

Used for diarrhea in combo with atropine.

Atropine at too low of a dose to have therapeutic effects but reduces the likelihood of abuse

Question 22

Loperamide

Answer 22

Activates mu receptors in the periphery not the CNS

Abuse is low

Question 23

Buprenorphine

Answer 23

Partial agonist at mu receptors
Antagonist at kappa and delta receptors

• slow dissociation from mu receptors so it has a longer duration of action than most parenterally administered opioids
• less respiratory depression but effects can’t be readily reversed by naloxone
• oral and sublingual with naloxone to prevent IV abuse
• outpatient treatment for opioid abuse
• moderate to severe pain and postop

Question 24

Butorphanol

Answer 24

Mu antagonist /Partial agonist
Kappa agonist

• sedation , nausea, sweating
• acute pain relief
• IV and intranasally

Question 25

Pentazocine

Answer 25

Mu antagonist/ partial agonist
Kappa agonist

Can cause anxiety, nightmares, psychotomimetic effects as a result of stimulation of sigma receptors. Nausea and sweating
Moderate to severe pain

Oral contain naloxone used for moderate to severe pain . IV as a preanesthetic or as supplement to surgical anesthesia