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Pharm- 17 Flashcards

1
Q

What is the role of the limbic system in pain?

A

Responsible for emotion, social behavior, autonomic control, perception of pain, and memory

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2
Q

What happens in the descending pain modulation?

A

An ↑ or ↓ of the sensation of pain, possibly due to a 2º neural pathway

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3
Q

What is the fxn of N-type Ca channels?

A

Plays a strong role in controlling the release of neurotransmitters
AP’s generated in primary afferents induce neurotransmitter release at the dorsal horn of the spinal cord

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4
Q

What happens if u block N-tpye voltage gated Ca channels?

A

analgesia

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5
Q

Which receptors are between the C-fiber and secondary projection nuerons?

A

glutamate R’s (NMDA and AMPA)

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6
Q

What is the roles of cannabinoid receptors?

A

These have regulatory roles in the spinal cord and both are G protein-coupled

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7
Q

What is the fxn of CB1 receptors?

A

expressed in brain, spinal cord, and sensory neurons; mediator of analgesia following a stressor

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8
Q

What is the fxn of CB2 receptors?

A

largely expressed in nonneural tissue; especially immune cells including microglia. Up-regulated in spinal cord microglia after peripheral nerve injury

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9
Q

Where is substance P at?

A

dorsal horns

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10
Q

What is the fxn of substance P?

A

to aid in the signaling response to stimuli of particularly high intensity because they require higher frequency and longer-lasting action potential trains than release of glutamate-containing vesicles.

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11
Q

What is the fxn of B-endorphin, enkapalins, and dynorphins (mu, k, and d receptors) in the CNS?

A

inhibit synaptic transmission to the brain (reducing pain sensed; analgesia) and are released at several CNS sites in response to pain stimuli

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12
Q

What are the effects of opioid receptor stimulation?

A

reduced presynaptic calcium conductance (↓ Presynaptic Nt release), enhanced postsynaptic potassium conductance (↓ post-synaptic excitability), and reduced adenylyl cyclase activity. Gi crap.

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13
Q

True or False: Norepinephrine, serotonin (5-HT), glycine, and GABA are major inhibitory neurotransmitters in the dorsal horn of the spinal cord

A

True

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14
Q

What is the fxn of the NE/5-HT system for pain?

A

These systems can limit transfer of incoming sensory to the brain and descending information from the brainstem to the dorsal horn

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15
Q

What is the role of the NE receptors in the spinal cord?

A

it works on a2 receptors –> Gi mediated inhibition of pain excitation

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16
Q

What is the role of 5-HT3 ligand-gated channels in the spinal cord?

A

excitatory actions of serotonin in the spinal cord

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17
Q

What is the role of 5-HT G protein-coupled receptors in the spinal cord?

A

mediate the inhibitory actions of 5-HT

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18
Q

How does the GABA R work?

A

by hyperpolarizing the membrane by opening K+ or Cl- channels and causing an influx of Cl- or an efflux of K+ .

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19
Q

What are the 2 types of different pain perceptions can result from peripheral sensitization?

A

alldynia (noninjurous pain) and hyperalgesia

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20
Q

What causes the peripheral sensitization?

A

peripheral stimuli which induce primary afferents to lower their activation THRESHOLDS thereby making them more sensitive/responsive

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21
Q

What are the mediators to peripheral sensitization?

A

bradykinin, protons, histamine, prostaglandin E2 (EP receptors), and nerve growth factor (NGF; TrkA receptors)

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22
Q

What types of receptors do the mediators to peripheral senstization act on?

A

G-protein coupled or receptor tyrosine kinase on nociceptors

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23
Q

What is the first-line drug for peripheral sensitization?

A

NSAIDs

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24
Q

What is the mechanism of action of NSAIDs?

A

inhibits COX → ↓ prostaglandins → ↓ local inflammatory response and peripheral sensitization

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25
celecoxib, rofecoxib, and valdecoxib block which COX?
COX2
26
celecoxib, rofecoxib, and valdecoxib have an increased risk of what?
MI
27
What happnens in central sensitization?
Hyperalgesia and allodynia can extend beyond the primary area of inflammation and tissue damage resulting in secondary hyperalgesia/allodynia; this depends on changes in sensory processing in the dorsal horn of the spinal cord.
28
Why does central sensitization occur?
occurs with repetitive high-intensity stimuli; synaptic transmission activates intracellular signal transduction cascades in the dorsal horn neurons that enhance the response to subsequent stimuli.
29
What are the receptors invovled with central senstiization?
AMPA, NMDA, glutamate, substance P receptor NK1 and the neutrophin receptor TrkB
30
How can drugs like Ketamine and Dextromethorphan treat central sensitization if it doesn't self resolve?
they are NMDA receptor blockers used to oppose the activation of sensitized NMDA receptors
31
Which channels are upregulated in neuropathic pain?
Na-channels (1.3) in primary sensory neurons
32
What are the 2 Na-channel blockers to treat neuropathic pain?
carbazepine and carbamazepine
33
What is the progression of events to cause the cortical spreading depression for migranes?
a region of neuronal inactivation spreads across the Ca → release of mutliple peptides in the dural vasculature → trigeminal afferents from vasculature activated and sensitized → ↑activity in trigeminal afferent → secondary central sensitzation with hyperalgesia and tactile alldynia
34
What is an effetive Tx for migranes?
the triptan class of serotonin receptor agonist such as sumatriptan (selective for 5-HT1B & 5-HT1D receptors) and NSAIDs
35
What type of migranes are triptans good at treating?
acute Sx but not recurring attacks
36
How do ergot alkaloids treat migranes?
vasoconstriction
37
How do full agonists to opioid receptors work?
produce both analgesia and other effects by acting on μ-opioid receptors and resulting in inhibition of neurotransmission
38
What are some drugs that are full opioid agonists?
morphine, codeine, oxycodone, hydrocodone, tramadol
39
What are synthetic opioid agonists?
utilize the μ-opioid receptors; result in inhibition of neurotransmission
40
What are some example sof synthetic opioid agonists?
Phenlyheptylamines (methadone) and phenylpiperidines (fentanyl and meperidine)
41
What do partial and mixed opioid agonists do?
utilize both μ & κ agonist; partial μ-receptor agonist and a κ-agonist with partial μ-receptor antagonist activity
42
What are some partial/mixed opioid agonsts?
μ-agonist butorphanol and buprenorphine, as well as nalbuphine, a κ-agonist with μ-antagonist activity
43
What do pure opioid antagonists do?
antagonists of μ- opioid receptors, thereby blocking endogenous and exogenous opioid effects
44
What are some exampoles of pure opioid antagonists?
Naloxone & Naltrexone; Alvimopan & Methylnaltrexone
45
What types of receptors are opioid receptors?
G proteins
46
What are the intraceullular events that occur once an opioid receptor is activated?
Close voltage-gated Ca2+ channels on presynaptic nerve terminals and thereby reduce transmitter release Hyperpolarize and thus inhibit postsynaptic neurons by opening K+ channels
47
What are the physiological responses to μ receptor activation?
Supraspinal and spinal analgesia; sedation; inhibition of respiration; slowed GI transit; modulation of hormone and NT release
48
What are the physiological responses to δ receptor activation?
Supraspinal and spinal analgesia; modulation of hormone and NT release
49
Which drug classes act on μ and δ receptors?
endorphins > enkephalins > dynorphins
50
What are the physiological responses to κ receptor activation?
Supraspinal and spinal analgesia; psychotomimetic effects; slowed GI transit
51
Which drug classes act on κ receptors?
dynorphins > endorphins . enkephalins
52
Where are the opioid receptors to inhibit pain transmission?
Dorsal horn
53
What is tolerance?
repeated use of a constant dose of a drug results in a decreased therapeutic effect; development of tolerance requires either a change of analgesic drug or an increase in the dose or frequency of administration to maintain analgesia
54
What is physical dependence?
abrupt cessation of tx results in a characteristic withdrawal syndrome
55
What is addiction liability?
physical dependence is accompanied by drug abuse or drug-seeking behavior; need to balance the risk of addiction and under-tx of pain
56
What is cardio toxicity?
opioids can reduce sympathetic tone and lead to orthostatic hypotension; can also cause bradycardia
57
What is torsade de pointes?
opioids (esp methadone) can cause QT prolongation and Torsade de pointes
58
Acetaminophen- mech of action
non-specific COX inhibitor, acts only centrally, prevents PGE2-induced reduction in glycinergic inhibiton
59
Celecoxib- mech of action
COX-2 inhibitor
60
Aspirin- mech of action
acetylates both COX 1 & 2 active sites therefore it tx’s mild or moderate pain
61
Ibuprofen- use
used for analgesia and anti-inflammatory action, antipyretic, and it has lower incidence of adverse effects.
62
Tramadol- mech of action
centrally acting analgesic; its analgesic effect results from monoaminergic effect w/in the CNS.
63
What other classes of drugs help treat pain, especially in chronic pain conditions?
Anti-depressants
64
What are the 2 ways tricyclic antidepressants treat pain?
1. blocking Na channels | 2. increasing the activity of NE and 5HT projections.
65
What are some examples of tricyclics?
Amitriptyline, nortryptiline, imipramine
66
Desipramine and maprotiline are examples of what class of drug that can treat pain,but are not as strong as tricyclics?
selective NE reuptake inhibitors
67
Paracoxetine,fluoxetine and citalopram are examples of what types of drugs to treat pain,but are the least effective?
SSRI's
68
Define: these 2 drugs are dual NE and 5HT ruptake inhibitors, used to Tx neuropathic pain and fibromyalgia.
Venlafaxine and duloxetine
69
Generally, how can antiepileptic and antiarrhythmic drugs treat pain?
by reducing neuronal excitability
70
What class of meds does gabapentin belong to?
Antiepileptic
71
Gabapentin- mech of action
GABA agonist, binds to a2d subunit of Ca++ channels and reduces the trafficking of the channel to the membrane.
72
Pregabalin- mech of action
GABA analogue
73
Pregabalin- use
potent and predictable, analgesia with neuropathic pain and fibromyalgia
74
Lamotrigine- mech of action
Na channel blocker
75
Lamotrigine- use
reduces painful sensory Sx that can occur in neuopathy,stroke, MS and phantomlimb
76
Carbamezapine- mech of action
Na channel blocker
77
Carbamexapine- use
trigeminal neuralgia
78
Oxcarbazepine- mech of action
blocks Na channels
79
Oxcarbazepine- use
trigeminal neuralgia and doesnt have the risk of aplastic anemia which is associated with carbamazepine
80
Mexiletine- class
antiarrhythmatic
81
Lidocaine- mech of action
use-dependent Na channel blocker
82
Lidocaine- use
local anesthetic, may be administered IV for blunting ANS for high-intensity painful stimuli
83
How does NMDA antagonists treat tings like chronic paina nd post-op pains?
NMDA R's play a critical role in the induction and maintenance of central sensitization
84
Which adrenergic receptor can you target int he dorsal horn to provide anti-nociceptive effects?
alpha2

Clinical Neuroscience 2 (16 decks)

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