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CNS > Pharma 2: Treatment Of Pain > Flashcards

Pharma 2: Treatment Of Pain Flashcards

1
Q

Morphine

Derived from

Administration

A

Derived from opium (papaver somniferum)

Available orally, IV IM epidural

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2
Q

Endogenous opioid peptides

A

B-endorphin

Leu-enkephalin

Met-enkephalin

Dynorphin

(natural)

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3
Q

Opioid receptors

A

U
S
K

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4
Q

Opioid receptor mechanism

A

G protein coupled; Go/Gi—> inhibit AC

There4 no cAMP no PKA

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5
Q

U agonists

A

MAIN ANALGESIC OPIOID

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6
Q

Where are opioid receptors located

A

Nociceptive Primary Afferent Fibers

SC

Supraspinal sites

Periphery

GIT

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7
Q

U agonist

A

Morphine

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8
Q

Opioid analgesics and u agonists

A

Morphine

Codeine

Pethidine

Fentanyl

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9
Q

U agonist and SNRI

A

Tramadol

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10
Q

U agonist NMDA RECEPTOR ANTAGONIST

A

Methadone (used to treat addicts)

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11
Q

U antagonist with longer duration of action

A

Naloxone

Naltrexone

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12
Q

Drug of abuse and u agonist

A

Heroin (diamorphine)

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13
Q

Opioid receptor like (ORL1)

Properties

A

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

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14
Q

Opioid receptor location

A

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

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15
Q

Ab fibers and opioid receptors

A

NONE since Ab is for touch sensation

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16
Q

Opioid receptors location in spinal cord

A

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

Lower levels (quantities)—> deepest laminae

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17
Q

Supraspinal OR

A

Reostral ventromedial

Periaqeuductal grey body

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18
Q

Opioid receptors in the cns

A

Most are presynaptic ie not even in the lamina

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19
Q

Mechanism of the top down- descending pain modulatory circuit

A

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

20
Q

Tramadol

MOA

A

Partial u agonist ans serotonin-norepi reuptake inhibitor ie SNRI

21
Q

Tramadol side effects

A

Serious: seizures, decreased alertness, drug addiction

Common: constipation, nausea itchiness

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

22
Q

Tramadol advantage over pure u agonists

A

Fewer resp depression and gi depression

23
Q

Tramadol contraindications

A

Pt with high suicide risk

24
Q

Tramadol interactions

A 
Alcohol
Narcotics
Sedatives
Anxiol
Antidepressants
25
Q

Tramadol vs morphine

A

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

26
Q

Supraspinal opioid receptors in periaqueductal grey matter caudal projections

A

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

27
Q

RVM role

A

Connects PAG to spinal cord

Controls sensory information (relay for PAG induced analgesia)

Homeostatic functions

28
Q

The different cells that make up the RVM

A

On
Off
Neutral

29
Q

The effect of morphine administration in RVM

A

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

30
Q

Morphine

Pharmacological effects

A

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

31
Q

Morphine administration

A

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

32
Q

Codeine given..

A

Orally, well absorbed

33
Q

Fentanyl advantage over morphine

A

Very lipophilic + faster onset—> transdermal, sublingual

34
Q

Morphine plasma half life

35
Q

Morphine inactivation

A

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

36
Q

Morphine side effects

A

Resp depression—> death

Constipation

Pinpoint pupils

N/V

Histamine release—>bronchoconstriction, hypotension, pruritis

Tolerance

Bronchoconstriction
Dependence

37
Q

Dependance on morphine (opioids) treated by

A

Methadone—> u opioid receptor agonist and NMDA ANTAgonist

38
Q

Care in asthmatics

A

Bronchoconstriction where pethidine taken

39
Q

Tolerance extends to

A

Most of pharmacological effects except pupil constriction and constipation

40
Q

Tolerance can be treated by

A

NMDA ANTAGONIST

Dextromethorpan
Ketamine

41
Q

Dependence physical symptoms

A

Yawning

Pupillary dilation

Fever

Sweating

Piloerection

Nausea, diarrhea

Restless..insomnia

Last few days

42
Q

Psychological symptoms of dependence

A

Craving for months to years—> relapse

43
Q

Clinical use of strong opioids

A

Severe acute pian

44
Q

Weak opioids supplement

A

NSAIDS for arthtritic pain

45
Q

Opioid receptor antagonists

A

Naltrexone and naloxone

46
Q

Review note for neuropathic pain and note one

CNS (28 decks)

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