Pharma 2: Treatment Of Pain

Question 1

Morphine

Derived from

Administration

Answer 1

Derived from opium (papaver somniferum)

Available orally, IV IM epidural

Question 2

Endogenous opioid peptides

Answer 2

B-endorphin

Leu-enkephalin

Met-enkephalin

Dynorphin

(natural)

Question 3

Opioid receptors

Answer 3

U
S
K

Question 4

Opioid receptor mechanism

Answer 4

G protein coupled; Go/Gi—> inhibit AC

There4 no cAMP no PKA

Question 5

U agonists

Answer 5

MAIN ANALGESIC OPIOID

Question 6

Where are opioid receptors located

Answer 6

Nociceptive Primary Afferent Fibers

SC

Supraspinal sites

Periphery

GIT

Question 7

U agonist

Answer 7

Morphine

Question 8

Opioid analgesics and u agonists

Answer 8

Morphine

Codeine

Pethidine

Fentanyl

Question 9

U agonist and SNRI

Answer 9

Tramadol

Question 10

U agonist NMDA RECEPTOR ANTAGONIST

Answer 10

Methadone (used to treat addicts)

Question 11

U antagonist with longer duration of action

Answer 11

Naloxone

Naltrexone

Question 12

Drug of abuse and u agonist

Answer 12

Heroin (diamorphine)

Question 13

Opioid receptor like (ORL1)

Properties

Answer 13

An orphan receptor ie has no affinity for opioid nor is it bind or gets blocked by NALOXENE

It has a similar amino acid sequence though

Question 14

Opioid receptor location

Answer 14

70% of m-OR found on central terminals of small-medium diameter PRIMARY AFFERENT FIBERS—> C and Ad fibers which transmit sensations of pain

Question 15

Ab fibers and opioid receptors

Answer 15

NONE since Ab is for touch sensation

Question 16

Opioid receptors location in spinal cord

Answer 16

Highest levels are found superficially in Lamina 1 and 2 where the c fibers end

Lower levels (quantities)—> deepest laminae

Question 17

Supraspinal OR

Answer 17

Reostral ventromedial

Periaqeuductal grey body

Question 18

Opioid receptors in the cns

Answer 18

Most are presynaptic ie not even in the lamina

Question 19

Mechanism of the top down- descending pain modulatory circuit

Answer 19

Opioid activates u agonist

Inhibit AC—> reduce cAMP—> reduce PKA—> no phosphorylation of enzymes, receptors, channels—> no further activation

Activate K conductance—> hyperpolarisation—> no ap generation

Inhibit Ca conductance presynaptically

—>—> reduce NT release

Question 20

Tramadol

MOA

Answer 20

Partial u agonist ans serotonin-norepi reuptake inhibitor ie SNRI

Question 21

Tramadol side effects

Answer 21

Serious: seizures, decreased alertness, drug addiction

Common: constipation, nausea itchiness

Possibly—> increased risk of serotonin syndrome if used with other serotogenic drugs

Question 22

Tramadol advantage over pure u agonists

Answer 22

Fewer resp depression and gi depression

Question 23

Tramadol contraindications

Answer 23

Pt with high suicide risk

Question 24

Tramadol interactions

Answer 24

Alcohol
Narcotics
Sedatives
Anxiol
Antidepressants

Question 25

Tramadol vs morphine

Answer 25

Affinity for u agonist is 6000X lower —> only partially blocked by naloxene

Question 26

Supraspinal opioid receptors in periaqueductal grey matter caudal projections

Answer 26

Parabrachial area Rvm—> acts to connect it to the soinal cord Few direct spinal projections

Question 27

RVM role

Answer 27

Connects PAG to spinal cord Controls sensory information (relay for PAG induced analgesia) Homeostatic functions

Question 28

The different cells that make up the RVM

Answer 28

On Off Neutral

Question 29

The effect of morphine administration in RVM

Answer 29

Suppress ON cell firing directly No effect on neutral cells OPIOIDS—>inhibit GABA (normally inhibit PAG which inhibits RVM)—> therefore PAG is freed from inhibitory effect of GABA—> inhibits RVM

Question 30

Morphine Pharmacological effects

Answer 30

Analgesia Euphoria Sedation Codeine—> with subanalgesic dose suppresses cough Loperamide—> doesnt penetrate CNS but acts on OR in gi—> treat diarrhea with no analgesic effect

Question 31

Morphine administration

Answer 31

IV, IM more effective than orally due to first pass metabolism

Question 32

Codeine given..

Answer 32

Orally, well absorbed

Question 33

Fentanyl advantage over morphine

Answer 33

Very lipophilic + faster onset—> transdermal, sublingual

Question 34

Morphine plasma half life

Answer 34

3-6 hrs

Question 35

Morphine inactivation

Answer 35

Hepatic metabolism—> conjugated by glucuronide—> morphine-6-glucuronide is more active as analgesic (kosy pharamaco effect)

Question 36

Morphine side effects

Answer 36

Resp depression—> death Constipation Pinpoint pupils N/V Histamine release—>bronchoconstriction, hypotension, pruritis Tolerance Bronchoconstriction Dependence

Question 37

Dependance on morphine (opioids) treated by

Answer 37

Methadone—> u opioid receptor agonist and NMDA ANTAgonist

Question 38

Care in asthmatics

Answer 38

Bronchoconstriction where pethidine taken

Question 39

Tolerance extends to

Answer 39

Most of pharmacological effects except pupil constriction and constipation

Question 40

Tolerance can be treated by

Answer 40

NMDA ANTAGONIST Dextromethorpan Ketamine

Question 41

Dependence physical symptoms

Answer 41

Yawning Pupillary dilation Fever Sweating Piloerection Nausea, diarrhea Restless..insomnia Last few days

Question 42

Psychological symptoms of dependence

Answer 42

Craving for months to years—> relapse

Question 43

Clinical use of strong opioids

Answer 43

Severe acute pian

Question 44

Weak opioids supplement

Answer 44

NSAIDS for arthtritic pain

Question 45

Opioid receptor antagonists

Answer 45

Naltrexone and naloxone

Question 46

Review note for neuropathic pain and note one

Answer 46

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