PHRM 845: Therapeutics III > Pain: Barker > Flashcards

Pain: Barker Flashcards

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1
Q

What are the classifications of pain?

A
  • Acute and Chronic
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2
Q

What is Acute pain?

A
  • Refers to an injury or post-operative faire
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3
Q

What is Chronic pain?

A
  • Pain that last more than 3 months
  • Nociceptive [Somatic; Inflammatory], Neuropathic, Visceral [Inflammatory], Mixed
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4
Q

what is the basic function of pain?

A
  • Bodies warning system [1st warning]
  • Aid in repair [Hypersensitivity]
  • Can be maladaptive [further damage]
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5
Q

How does pain act as an alarm system?

A
  • Tissue Damage: releases cytokines and chemical mediators that increase vascularization and sensitizes somatosensory
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6
Q

What is Allodynia?

A
  • Spontnaeuos or breakthroug pain
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7
Q

What are some way that we can characterize pain?

A
  • Temporal [WHEN?], Intensity, Location [WHERE?], Quality [HOW DOES IT FEEL?]
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8
Q

What is Referred Pain?

A
  • Pain that is in one area that can lead to other areas of the body
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9
Q

What are some of the ways the chronic pain may appear?

A
  • Inflammatory Pain [Arthritis], Neuropathic Pain [Diabetes], Verceral Pain [Cancer], Breakthrough Pain, Fibromyalgia [Allodynia], Migraine, Phantom [Amputation]
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10
Q

What is the etiology of Chronic pain?

A
  • Tissue Injury leading to the release of Active factors [PG, BK, K]
  • Persistent activiation and sensitization of Ay/C
    -Activity in ascending pathway [Peripheral sensitization]
  • Output for the input
  • Ongoing pain [Central sensitization]
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11
Q

What are the peripheral receptors and channels that are involved in pain signaling?

A
  • Temperature, Acid, Chemical Irritant Sensitive
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12
Q

What are the Temperature Sensitive receptors for pain?

A
  • Transient receptor Potential Cation Channel
  • TRPV = Hot
  • TRPM = Cold
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13
Q

What are the Acid Sensitive receptors for pain?

A
  • Acid Sensing Ion channels [ASIC]
  • Activated by H+ and Conducts Na+
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14
Q

What are the Chemical irritant receptors for pain?

A
  • Histamine and Bradykinin
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15
Q

What are the three different pain fibers?

A
  • Ab - Fibers
  • Ay - Fibers
  • C - Fibers
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16
Q

What are the Ab - Fibers?

A
  • Bigger and More Myelinated [Fastest]
  • Non-noxious [Touch and Pressure]
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17
Q

What are the Ay - Fibers?

A
  • Less myelinated
  • Pain and Cold
  • “First Pain” [Sharp and Prickly]
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18
Q

What are the C - Fibers?

A
  • Unmyelinated
  • Pain, Temperature, Touch, Pressure
  • “Second Pain” [Dull, Aching]
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19
Q

How does Substance P play an important role in heightening pain responses?

A
  • Repeated Stimuli that reduces the firing treshold
  • Causes: vasodilation, Degranulation, Histamine Release, Inflammation
  • Increase expression of pain
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20
Q

How is a sunburn temporary peripheral pain?

A
  • UV radation damages the skin = Inflammation
  • Involves TRPV4 [Temperature Sensitive]
  • Allodynia occurs
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21
Q

What is the pathway for spinal pain?

A
  • The release of Substance p and glutamte from the primary neuron to the secondary neuron
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22
Q

What is found within the pain ciruitray of the brain?

A
  • High expression of opioid receptors along the descending pathway [Opioids, GABA, NA, & 5-HT]
  • Mu Receptors
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23
Q

What are the two type of alkaloids found witin opioids?

A
  • Phenanthrenes [Morphine] & Benzylisoquinolines
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24
Q

What are Opiates?

A
  • Opioids that are naturally occurring
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25
What are the structure relationships of Phenanthrenes in opioids?
- 3 Position: substitution decreases potency [Codeine] - 6 Position: Increases activity [Hydromorphone or Hydrocodone from Codeine] - 14 Position: OH increases potency [Oxycodone] - N-allyl: Antagonist [Narcan]
26
What are the Pharmacokinetics or Morphine [Phenanthrenes]?
- Metabolized in the Liver [Hepatic] - Bioavailability 25% - 2D6 and 3A4 - Glucuronidation at 3' and 6'
27
What are some of the Administration routes for Opioids?
- IV, Intra-axial, IM, Oral, Topical
28
Which opioids create active metabolites?
- Herion, Codeine, Tramadol = Prodrugs [Morphine, O-Hydroxy-oxymorphone, Morphine] - Fentanyl and Methadone DO NOT
29
What does CYP3A4 make within Opioids?
- Makes the "NOR"
30
What does CYP2D6 make within Opioids?
- Other active metabolites
31
What are the metabolizers for 2D6?
- PM, IM, EM, UM - UM: Higher blood concentration; higher SE - PM: NO therapeutic effect
32
What are the types fo opioid receptors?
- G Protein [Gi, GRIK], Mu [Morphine], Kappa [Ketocyclazocine], Delta [Defernes], Nociceptin, Sigma [NOT opioid]
33
What is the signal transduction within the opioids receptors?
- Presynpatic: Inhibition of Ca2+ channel [Gi] decreases the neurotransmitters release - Postsynaptic: Activation of GIRK channels [Gby] causing an efflux of K+ =>hyperpolarization
34
What are the endogenous opioids contained within the human genome?
- Pro-opiomelanocortin [POMC] - Preproenkephalin - Preprodynorphin - Nociceptin/Orphanin FQ
35
What is important to know for the MU opioids receptors?
- Linked to Beta-Endorphins - Uses: Analgesia [NOT Chronic], Sedation, Antitussive [Suppression of cough]
36
What are some of the opioid induced side effects?
- ON TARGET EFFECTS - Respiratory depression, Constipation, Itch [NOT allergic reaction], Addiction, Urinary retention, Nausea & Vomiting, Miosis
37
What is important to know about the KAPPA opioid receptors?
- Linked to Dynorphins - Activation is dysphoric [Negative feelings] - Treatment for addiction [Decreases dopamine]
38
What is important to know about the DELTA opioid receptor?
- Linked to Enkephalins - Reduces Anxiety, depression - Treats Alcoholism - SEIZURES
39
What is opioid induced hyperalgesia and how is it different than tolerance?
- Tolerance: INCREASE in dose to get the same effect - Hyperalgesia: INCREASED sensitivity toward pain; increasing the does makes that pain worsen
40
What are some of the clinically used opioids for?
- Cough/antitussive & Anti-Diarrheal
41
What are some of the Cough/Antitussive opioids used?
- Codeine [C-II] - Dextrometorphan [Limited Opioid activity; opens receptors in the brain stem]
42
What are some of the Anti-Diarrheal opioids that are used?
- Diphenoxylate with atropine [Lomotil] - Loperamide [Strong P-glycoprotein; pumps out of brain] - Eluxadoline [Mu/Kappa Agonist, Delta Antagonist
43
What opioids are used within the hospital setting?
- ALL ARE C-II - Agonist: Sufentanil, Remifentanil, Alfentanil [Breakdown by plasma esterases]; Fentanyl, [lollipop], Hydromorphone, Oxymorphone, Morphine, Hydrocodone, oxycodone
44
What are the Non-Phenanthrene opioids?
- Tramadol, Tapentadol [SNRI like; 5HT & NET inhibitor] - Meperidine [Toxic Metabolite: Normeperidine]
45
What opioids are able to block the NMDA receptors?
- Methadone [used for opioids dependence; QTc PROLONGATION, NMDA antagonist]
46
What are some of the opioids that are used in MOR and KOR?
- Pentazocine [k agoinst, mu antagonism] - Nalbuphine [Full k agonist, mu antagonist] - Buprenorphine [Partial mu agonist, weak k agonist & y antagonist]
47
What are the types of NASIDS?
- Salicylates [Aspirin] - Arylpropionic Acids [Ibuprofen, Naproxen] - Arylacetic Acids [Indomethain, Diclfenac...] - Enlic Acids [Piroxicam, Meloxicam]
48
What is the therapeutic applications for NSAIDs?
- Analgesic [Chronic Pain, Inflammatory Pain] - Anti-Inflammatory [Arthritis] - Antipyretic [Fever] - Reduce Myocardial Infarction
49
What contributes to the Inflammatory pain?
- Eicosanoids
50
What are the Eicosanoids that are recruited in Inflammatory cells?
- Arachidonic Acid Metabolites - Prostaglandins [Redness, Heat, Pain] - Thromboxanes - Leukotrienes [Swelling] - Cytokines [Pain]
51
What are the two pathways for Arachidonic Acid?
- COX-1 & COX-2
52
What happens COX-1 pathway?
- Induces platelet activity - TXA2 - Protects the Stomach lining
53
What happens COX-2 pathway?
- Induces the anti-platelet activity - PGI2
54
What is important to know about Aspirin in regards to COX?
- IRREVERSIBLY COX-1/2 Inhibitor - Low Dose = COX-1 & High Dose = COX-2
55
What is important to know about Other NSAIDs in regards to COX?
- REVERSIBLE COX-1/2 Inhibitors - anti-flammatory too
56
What is Aspirin's main use?
- Prophylactic for Anti-coagulation - NO tolerance development to analgesic effects - DO NOT use in children - Reye's Syndrome
57
What are the Pharmacokinetic Properties of Aspirin [Salicylates]?
- Absorption: Rapidly Absorbed - Distribution: Most tissues and Fluids - Metabolism & Excretion: Half-life 6-20 hour; increased excretion with increased urinary pH
58
What are some of the side effects that relate to Aspirin [Salicyism] Posioning?
- Vertigo, Tinnitus, Respiratory Alakalosis [hyperventilating], Metabolic Acidosis [lowering blood pH]
59
What is the treatment for Aspirin [Salicyism] Poisoning?
- REDUCE salicylate load - Will cause an increase in urinary excretion
60
What is important to know about the Enolic Acids NSAIDs?
- Used to treat ARTHRITIS - Meloxicam at low doses is COX-2
61
What are some of the adverse effects for NSAIDs?
- Renal function: Decrease PGE2 = Edema - Inhibition of Platelets = Increase bleeding - Inhibition of Uterine Motility
62
What is the therapeutic use of Acetaminophen?
- Highly effective analgesic and antipryretic - NO GI TOXICITY - Could lead to Hepatic Necrosis
63
What are the side effects of Acetaminophen?
- Renal Toxicity > aspirin - Hepatic Necrosis [High risk with alcohol] because of an increase in toxic acetaminophen metabolites [NAPQI]
64
What are some of the contraindications for NSAIDs?
- AVOID: chronic kidney disease, poptic uler disease, history of GI Bleeds - Cardiovascular risks [with CAD] - Interfere with Bone Healing [high doses] - Cause Asthma Exacerbations [COX-2 less likely]
65
What is another way that we are able to get analgesic effects?
- Blocking sodium channels - NaV1.7`
66
What are some Psychiatric drugs that are also NaV1.7 Blockers?
- Lamotrigine, Cabamazepine, Amitriptyline
67
What are some SNRIs that are also NaV1.7 Blockers?
- Increase Norepi [acting on a2A-Adrenergic] - Duloxtine, Venlafaxine, Milnacipran [lacking]
68
What are the controlled substance drug classifications?
- C-I: NO MEDICAL USE [Marjiuana, THC, LSD...] - C-II: High Abuse [Cocaine, PCP...] - C-III: Moderate Abuse [Marinol; THC oil] - C-IV: Low Abuse [Benzos] - C-V: Cough Suppressant with small amout of codeine or Lomotil
69
What are some substances of abuse that act INDIRECTLY on GCPRs?
- Cocaine, Amphetamine [block DAT] - MDMA/Ecstasy [block DAT & SERT] - Alcohol
70
What are some substance of abuse that act on Ion channels?
- Nicotine [Acetylcholine: Agonist] - PCP, Ketamine [NMDA; Antagonist] - Benzo [GABAa; allosteric modulators]
71
What are some of the important ares of the brain that drugs can affect causings abuse?
- Frontal Cortex: Decision Making - Striatum: Reward - NUCLEUS ACCUMBENS: Pleasure - VTA: Dopamine Source - Hippocampus: Memory Learning
PHRM 845: Therapeutics III
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