Pharm - Neuro - Pain Management

Front 1

"Is pain all in your head?"

Back 1

yes

Front 2

How do morphine and acetaminophen work?

Back 2

Still not completely sure.

Front 3

Nociception

Back 3

This is not pain!

It is the activity produced in the nervous system by potentially tissue-damaging stimuli

Front 4

Types of nociceptors

Back 4

Thermo, chemical and mechano.

Front 5

Benefits of pt controlled analgesia

Back 5

Pt has more control and feels less stressed.

Pt uses less drug.

Decreases number of days in hospital.

Maintains even plasma level of drug.

Front 6

Transition from acute to chronic pain

Back 6

Still unclear.

Front 7

Nociceptors deal more with acute or chronic pain?

Back 7

Acute

Front 8

Neuropathic pain

Back 8

Due to damage of periph or CNS

Mediated at glutamate sites.

Burning, tingling.

Opioid resistant unless at high doses.
(so that is why you would use neuroleptics in this case)

Front 9

Sites of pain transmission

Back 9

Peripheral - Nociceptors (free nerve endings)

Spinal cord - Gating of pain control (dorsal horn)

Supraspinal - Brain - This is key for perception, previous experience and stress.

Front 10

Can descending pathways transmit pain?

Back 10

yes

Front 11

Things released at periphery to cause pain

Back 11

prostaglandings, serotonin, bradykinin, CGRP, substance P

Front 12

NSAIDS - mech of action

Back 12

Inhibit COX 1,2 and thus PGs.

Note they also stop formation of prostacyclin (COX 2) and thromboxane A2 (COX 1)

Front 13

Is aspirin an NSAID?

Back 13

Yes, but it is the only one that IRREV blocks COX for the life of the platelet.

Front 14

NSAIDs - SE

Back 14

GI, tinnitus, metabolic acidosis, central hyperventilation.

Front 15

NSAID and aspirin combination

Back 15

Dangerous because it negates the antiplatelet activity of aspirin.

Front 16

Specific COX-2 inhibitors

Back 16

Celecoxib, Vioxx

Originally there to have less SE than traditional NSAIDs

***(Celebrate! We weren't pulled like Vioxx was!***)

Front 17

COX2 controversy

Back 17

COX2 produces prostacyclin which is cardioprotective in some ways. So inhibition resulted in failure to inhibit thrombotic CV events.

Basically, thromboxane A2 (a vasoconstrictor) was still being made (from COX1) and the protective prostacyclin was not.

Front 18

acetaminophen

Back 18

Active metabolite of phenacetin.

Liver toxicity, especially with alcohol.

Mech of action is unclear - maybe supp PGE2 release in the CNS and may also be a COX2 inhibitor.

Front 19

Ways to block pain at periphery

Back 19

NSAIDs, regional analgesia, neural ablative procedures.

Front 20

Spinal cord contains which pain relevant receptors?

Back 20

Opioid, substance P, CGRP, VR1 (TRPV receptors), glutamate

Front 21

SNRIs in pain modulation

Back 21

Enhancing NE in the synapse at the dorsal horn may be helpful to enhance descending inhibitory modulation.

Front 22

Endogenous opioid peptides

Back 22

Endorphins, enkephalins, dynorphins, endomorphins.

Front 23

Mu receptor

Back 23

Bio ligand: Endorphin
Drug - Morphine

Front 24

Kappa receptor

Back 24

Bio ligand - Dynorphins
Drug - Butorphanol

Front 25

Delta receptor

Back 25

Bio ligand - Enkephalins
Drug - None

Front 26

Ways to activate inhibitory processes that gate pain at the spinal cord and brain

Back 26

Opioids, alpha 2 adrenergic agonists (she said clonidine--it has a cholinergic effect), tricyclic antidepressants, SNRIs, transcutaneous electrical nerve stimulation, acupuncture, spinal cord stimulators.

Front 27

Periaqueductal grey

Back 27

Contains many opioid receptors.

Part of that supraspinal modulation.

Front 28

Emotional pain

Back 28

A hot topic now.

These emotions take place in the medial prefrontal cortex.

Chronic back pain activates these neurons and may explain why the longer you have pain, the harder it is to decrease it.

(Psych factors don't cause pain, but they can definitely make it worse)

Front 29

Ways to interfere with perception of pain

Back 29

Complementary medicine, CBT, hypnosis, relaxation, biofeedback, opioids, coping mechanisms ("I have pain, but I'll get through it." - this works)

Front 30

Targets which 3 systems is the best approach to pain management

Back 30

Periphery, spinal cord/brain, perception of pain (supraspinal)

Front 31

Opioid proposed mech of action

Back 31

Directly inhibits ascending transmission of nociceptive input from the dorsal horn of spinal cord and it activates pain control circuits that descend from midbrain via the rostral ventral medulla.

Decreases release of substance P. But this has been found to be true only after spinal admin of a drug.

Also acts peripherally to release endogenous opioids.

Interacts with lymphocytes at periph

(So it works at many levels)

Front 32

CNS SE of morphine

Back 32

Analgesia, neuroendocrine effects (e.g. testosterone), miosis, RESPIRATION DEPRESSION, n/v, constipation.

Front 33

Morphine - other facts

Back 33

Hypotension and itching (due to histamine release - this can be relieved with Naloxone)

Delays labor (anti-oxytocic)

Large first pass metab (poor bioavail)

Front 34

Morphine - how is it inactivated?

Back 34

Glucoridation
Genetic variability of CYP isozymes may have clinical consequences.

Front 35

Uses of morphine

Back 35

Pain, cough, dyspnea, constipating.

Front 36

Codeine

Back 36

Opioid - it is converted to morphine by CYP2D6

Well absorbed orally

Has less effectiveness at analgesia (has a ceiling unlike morphine)

Low abuse potential, antitussive.

Synergy with NSAIDs and aspirin.

Front 37

Codeine - important polymorphism

Back 37

Conversion to morphine by CYP2D6. Dangerous in new mothers because too much morphine in breast milk can make baby stop breathing.

Front 38

Hydromorphone (Dilaudid)

Back 38

5-10X mroe potent than morphine.

Front 39

Oxycodone

Back 39

This is not a morphine drug. It can be dosed the same.

The oral sustained release is called OxyContin

Very good bioavail

Front 40

Percodan

Back 40

Oxycodone with aspirin

Very good bioavail

Front 41

Percocet

Back 41

Oxycodone with acetaminophen.
Very good bioavail
Abuse potential.

Front 42

Diacetylmorphine (Heroin)

Back 42

Not rx in US (schedule I)

quickly crosses BBB

Front 43

Tramadol (Ultram)

Back 43

Synthetic codeine analog (so it is not that potent...), weak mu opioid agonist with NE and serotonin reuptake inhibition.

Used to tx mild to mod pain.

Front 44

Phenylpiperidines - main drug in this class?

Back 44

Meperidine (Demerol)

1/10 potent as morphine, can produce sz, antimuscarinic, euphoric effects.

**M for michael jackson

Front 45

Phenylpiperidines - others

Back 45

Diphenoxylate and loperamide - constipating and low solubility

Fentanyl, sufentanil, alfentanil, remifentanil - all 100X more potent than morphine, quick acting due to being very lipophilic.

***fentanyl, DIFENoxylate. and those two make the interlopers (loperamide)

Front 46

Methadone

Back 46

Mu agonist. also an NMDA antagonist.

Orally effective and qualitatively similar to morphine with milder withdrawal.

Front 47

Propoxyphene (Darvon, Darvacet)

Back 47

Not widely used today.
Very weak analgesic.
In it's own class.

Front 48

Opioids with mixed actions - Mu antagonist and kappa agonist

Back 48

Pentazocine (Talwin) and nalbuphine

Front 49

Opioids with mixed actions - kappa agonist

Back 49

Butorphanol (Stadol)

Front 50

Opioids with mixed actions - Partial mu receptor agonist

Back 50

Buprenorphine

***BU PRETENDS TO BE MORPHINE***

Front 51

What to be careful of when rxing opioids with mixed actions (including agonist-antagonists and partial agonists)

Back 51

Be careful not to produce withdrawal effects to pts previously on other opioids.

Front 52

Opioid antagonists

Back 52

Naloxone and Naltrexone (longer acting)

Front 53

Dextromethorphan

Back 53

Central antitussive, not an opioid.
OTC abuse potential in teens.

Front 54

What to try after NSAIDS and before long-term opioids?

Back 54

Physical therapy/muscle relaxants, nerve blocks, behavioral programs, corrective surgery