Opioid Anagelsics

Question 1

Opioid vs narcotic

Answer 1

Opioid is anything that binds to the Mu receptor and inhibits pain
Narcotics are anything that produce sedation/drowsiness

Question 2

Classification 1: weak vs strong

Answer 2

Codeine is weak
Everything else is considered strong
Antitussives and antidiarrheals are excluded

Question 3

Mu receptor agonists

Antagonists

Answer 3

Morphine, merperidine, hydromorphone, etc.

Mu antagonists, bind to this receptor and elicit no response (also but less at kappa and delta)- naloxone and naltrexone

Question 4

Agonist/antagonists

Partial agonist

Answer 4

Kappa agonist/Mu antagonist: nalbuphine

Partial Mu agonist but HIGH affinity: buprenorphine (used for opioid maintenance in addiction)

Question 5

High vs low lipophilicity

Answer 5

High- fast onset (1min IV), short duration (20 min): fentanyl, merperidine
Low- slow onset (10 min IV), long duration (hour): morphine, hydromorphone

Question 6

Opioid receptors

Answer 6

Mu, kappa, delta: one gene codes for each one. Subtypes come from splice variants. All involved in spinal and supraspinal sites

Question 7

Mu receptor produces:

Site:

Answer 7

Analgesia, euphoria, dependence, respiratory depression, miosis
Mu1 is more supraspinal, Mu2 is more spinal

Question 8

Kappa receptors produce:

Answer 8

Mild analgesia, less respiratory depression, psychomimetic effects (unlike euphoria)

Question 9

Locations of opioid receptors and what they elicit

Answer 9

Thalamus/amygdala:suffering of pain, emotional perception of it
Brainstem ventilation nuclei: can knock out and stop breathing
PAG: gateway in MB when switched on to send endorphins down spinal cord to blunt pain transmission and reduce suffering
Area postrema: nausea
Spinal trigeminal nucleus: itchy AEs
Substantial gelatinosa: pain relief
*GI tract (enteric NS layer): constipation

Question 10

Opioid mechanism

Answer 10

Work via G receptor proteins which then inhibit cellular adenylyl cyclase. Increase K+ and decrease Ca++ currents, causes hyperpolarization, and decreased nociceptive transmission.
Doesn’t affect touch and motor fibers like with alcohol and local anesthetics dampening touch receptors

In SG, the opioid receptors are primary pre-synaptic on C fibers.

Opioids also activate the PAG- trigger descending inhibitory paths to release endorphins by inhibiting GABA releasing inhibitory neurons in the PAG (freeing them of inhibition)

Question 11

What drug is notable for having a half life of 24 hours?

Answer 11

Methadone. Can range from 12-104 hours. Which is why you never start treatment with methadone*

Question 12

What is special about the miosis effect of opioids?

Answer 12

There is no tolerance built to this effect

Same with constipation, if this SE is present.

Question 13

What is a good opioid to use/switch to deal with opioid side effects?

Answer 13

Antagonist
Agonist/antagonist
Amphetamines

Question 14

Abstinence syndrome

Answer 14

Withdrawal occurs after cessation of use

Unique to someone who has been exposed to the opioid before

Question 15

Symptoms of opioid withdrawal

Answer 15

Sweating, HTN/tachycardia, hyperventilation, mydriasis- essentially opposing sympathetics of each opioid parasympathetic effect, except diarrhea/abdominal cramping occurs via direct withdrawal from gut receptors.
NON LETHAL WITHDRAWAL

Question 16

Opioid agonists

Answer 16

Morphine, codeine, oxycodone, hydrocodone (Vicodin), heroin, meperidine, hydromorphone (Dilaudid), fentanyl, methadone, tramadol

Question 17

Antagonists

Answer 17

Naloxone- near an. IV form

Naltrexone- oral form

Question 18

Agonist/antagonist

Answer 18

Nalbuphine

Buprenorphine (technically a partial agonist)

Question 19

Diarrhea opioids

Answer 19

Loperamide

Dephenoxylate

Question 20

Antitussive

Answer 20

Dextromethorphan

Question 21

Morphine metabolites

Answer 21

Morphine 3-Glucoronide and 6-Glucoronide in liver. If there is kidney dysfunction, build up of 6-G in blood will harm, get into spinal fluid and be 50-100x more potent than morphine, cannot cross BBB unless you have a lot of it by mass effect

Question 22

Oxycontin

Answer 22

Extended release oxycodone. Matrix releases during GI transit. Abuse by crushing- but no ER should be crushed. Started new formulations that prevented this.

Question 23

What is special about methadone?

Answer 23

Takes 3-5 half lives to see full effect: takes this long to see the steady state, so need to watch for accumulation, keep on same dose for a full week to watch for sedation.
NMDA receptor blocker- blunts central sensitization, but analgesic mechanisms are unknown

Question 24

Meperidine caution

Answer 24

Metabolite: normeperidine- half life is 10 hours, cleared by kidneys, can cause seizures, DO NOT use in kidney failure patients

Question 25

Fentanyl uses

Answer 25

Transdermal- chronic or cancer pain. NOT FOR ACUTE PAIN or for the opioid naive, do not apply heat, sub-Q depot before absorbed in blood so watch for overdose, depot continues in blood even after patch is removed Lollipop is for cancer pain breakthrough- not for sustained effect

Question 26

Tramadol- works by two mechanisms

Answer 26

Mu receptor agonism and blocks reuptake of 5-HT and NE | Technically a pro-drug and the M1 metabolite is Mu agonist

Question 27

Agonist/antagonist: Nalbuphine

Answer 27

Analgesia is kappa mediated, weak Mu antagonism (avoids Mu side effects), ceiling effects, less GI side effects and less respiratory suppression DO NOT USE IN OPIOID TOLERANT PERSON- will cause withdrawal Problem- kappa agonism causes psychomimetic effects Low doses used to reverse opioid side effects while maintaining analgesia

Question 28

Partial agonist- buprenorphine

Answer 28

Only partial Mu agonist HIGH affinity, makes naloxone reversal difficult in OD Has ceiling on agonism* Currently use for opioid maintenance: less intense than heroin withdrawal and briefer than methadone withdrawal suboxone= buprenorphine +naltrexone

Question 29

What is special about naloxone?

Answer 29

It can reverse the effects of a placebo and acupuncture | Reversal is SHORT LIVED

Question 30

Opioids for diarrhea

Answer 30

Poorly absorbed orally, do not enter CNS very well, constipation side effect (naloxone type formulations exist designed to stay in gut and block this side effect) Loperamide (Imodium) Dephenoxylate- with atropine: Lomotil

Question 31

Dextromethorphan antitussive

Answer 31

No analgesic or habituation get properties Acts centrally, but not via opioid receptors NMDA antagonist Similar potency to codeine