Term
| Distinguish between "nociceptive pain" and "neuropathic pain." |
|
Definition
1) Nociceptive or "somatic" pain involves activation of peripheral receptors of an intact nervous system (tissue damage)
2) Neuropathic pain arises from aberrant somatic sensory processing in either the PNS or CNS. |
|
|
Term
| What is the neurobiological basis for acute pain? |
|
Definition
1) Activated A-delta and C-fibers synapse in dorsal horn entry zone and ascend contralaterally in sponthalamic tract.
2) Pain from face is processed by spinal trigeminal nucleus and trigeminothalamic tract. |
|
|
Term
What are the 3 families of endogenous opioids?
What is each family derived from and where/what does it act on? |
|
Definition
1) Enkephalins (derived from proenkephalin)
- Act on Delta opioid receptor in CNS and sympathetic NS
- Descending pathways from pons and medulla to SC
- Neurons from entorhinal cortex to molecular layer of dentate gyrus in hippocampus.
2) Endorphins (derived from proopiomelanocortin)
- agonists of Mu opioid receptor
- mediate pain in medial hypothalamus, diencephalons and pons
3) Dynorphins (derived from prodynorphin)
- agonists of kappa opioid receptor
- dentate gyrus to CA3 |
|
|
Term
| What is the molecular mechanism of most endogenous opioid agents? |
|
Definition
1) Bind to opioid receptors pre- and post-synaptically
2) Inhibit N-type calcium channel conduction pre-synaptically and Adenylate Cyclase
3) Enhance K conduction post-synaptically |
|
|
Term
| What 2 pain modulating pathways involving opioid-induced analgesia have been documented? |
|
Definition
1) Direct inhibition of afferent pain conduction in Substantia Gelatinosa within dorsal horn
2) Activate descending pain modulatory pathways from periventricular and periaqeuductal grey matter regions ,which project to medullary nuclei (Raphe nuclei).
- 5-HT neurons in raphe nuclei activate Enkephalon-producing neurons, which inhibit C-fibers and Nucleus Proprius neurons in spinal chord. |
|
|
Term
| What are the important clinical effects of opioids? |
|
Definition
1) Analgesia (selective)
2) Cough suppression (in medulla)
3) Respiratory depression (brain stem respiratory centers)
4) Constipation (treat diarrhea)
5) Sedation
6) Vasodilation (during MI) |
|
|
Term
| What are the basic pharmacological properties of opioid agonists available for clinical use? |
|
Definition
Morphine, Oxy, Fentanyl, Methadone, Meperidine, ect
1) Lipophillic
2) Wide distribution
** Worry about dependence, tolerance, pseudo-addiction and addiction** |
|
|
Term
| Which opioids are used to treat diarrhea? |
|
Definition
1) Diphenoxylate
2) Loperamide
- Synthetic opioids |
|
|
Term
| What is the most common anti-tussive opioid agonist? What is its synthetic equivalent. |
|
Definition
1) Codeine- cough medicine
2) Dextromethorphan is d-isomer of codeine analog |
|
|
Term
| What are the important Nonopioid Analgesics? |
|
Definition
1) Tramadol- Dual action: supraspinal opioid-like agonist activity and spinal monoamine-reuptake inhibition potential
2) Acetaminophen- Analgesic and Antipyretic (NOT anti-inflammatory)
- Blocks peripheral pain impulse initiation, CNS prostaglandin formation and COX-3
3) Acetylsalicylic acid- Analgesic, anti-inflammatory and anti-pyretic
- Anti-thrombotic
- Irreversibly blocks COX1 and 2 through covalent modification |
|
|
Term
A young patient who was treated with aspirin for a viral infection presents with microvascular steatosis and hepatic encephalopathy.
What is going on?? |
|
Definition
Reye's syndrome.
Don't give aspirin to kids! |
|
|
Term
| What medications are available for the treatment of acute migraines? |
|
Definition
** Bulbalbital and Isometreptene don't work
1) Nonsteroidals
- AA pathway (phospholipase, AA, prostaglandin, leukotriene)
- reversible COX inhibition through hydrophobic channel blockage
2) 5-HT agonists (triptans)
- intercept pain impulse from activated peripheral trigeminal neurons prior to synapse in trigeminal nucleus caudalis. On First-Order or Second-Order cells.
- Bind vascular 5-HT1 B receptor, reversing vasodilation
- Bind neuronal 5-HT1 D receptor, blocking release of substance P , CGRP and neurokinin A from trigeminal neurons
Remember, migraine pain comes from trigeminovascular circuity with vasodilation and inflammation |
|
|
Term
| Why is it important for Tryptans to be given quickly after onset of migraine symptoms? |
|
Definition
Give Sumatriptan quick, because after Trigeminal nucleus caudalis is sensitized, it won't do any good
- drugs "prevent" but DO NOT "reverse" sensitization
**mode of administration is more relevant than pharmacology** |
|
|
Term
What opioid receptor is associated with each of the following endogenous compounds?
1) Dynorphin
2) Enkephalin
3) Endorphin |
|
Definition
All have hepatic metabolism
1) Kappa
- dentate to CA3 cells
2) Delta
- Descending cortical pathway
- Entorhinal to Dentate granular cells
3) Mu
- Medial ponds, diencephalon (pituitary) and pons |
|
|
Term
| Why are opioid receptor agonists contraindicated in the treatment of migraines? |
|
Definition
| Vasodilation is bad when the issue is already dilation/inflammation from CGRP/Neurokinin A |
|
|
Term
| What is the "dual mechanisms of action" of Tamadol? |
|
Definition
Atypical analgesic
Supraspinal opioid-like agonist activity and spinal monoamine-reuptake inhibition potential |
|
|
Term
| Under what conditions would you avoid prescribing Tylenol, Aspirin or NSAIDs? |
|
Definition
1) Tylenol (Acetominephin)
- Liver failure (has hepatic toxicity due to NAPQI metabolite)
2) Aspirin (Acetylsalicylic acid)
- Gut and heme toxicity
- KIDS (REYE's syndrome)
3) NSAIDs
- Asthma
- Kidney failure (renal toxicity, as well as GI and platelet issues) |
|
|
Term
| Use of what drug would be contraindicated in a patient with a CYP2D6 mutation? |
|
Definition
Tylenol.
This Cytochrome 450 issue would cause slow/inefficient breakdown of NAPQI metabolite from Tylenol, potentially causing Liver Damage. |
|
|
Term
Which Non-opioid analgesics have
1) antipyretic activity?
2) anti-inflammatory?
3) Reversible COX action?
4) Irreversible COX action?
5) Hepatic toxicity
6) Renal toxicity |
|
Definition
1) Tylenol, Aspirin and NSAID
2) Aspirin, NSAID (at high doses)
3) NSAID
4) Aspirin (COX 1,2), Tylenol (COX 2,3- weak)
5) Tylenol (NAPQI through TRPA1 channel)
6) NSAIDs |
|
|
Term
| What is the relevance of the 5-HT1b and 5-HT1d receptors in the treatment of migraine headaches? |
|
Definition
Tryptan drugs act on these receptors
1) Bind vascular 5-HT1 B receptor on blood vessels, reversing vasodilation
2) Bind neuronal 5-HT1 D receptor on Dural neurons, blocking release of substance P , CGRP and neurokinin A
Remember, migraine pain comes from trigeminovascular circuity with vasodilation and inflammation |
|
|
