SM_244a: Pharmacology, Opioids, and Pain Concepts III Flashcards

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1
Q

NSAIDs are related only because ____ and ____

A

NSAIDs are related only because they inhibit enzyme making prostaglandins and inhibit cyclooxygenase

(different structures)

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2
Q

Describe prostaglandins

A

Prostaglandins

  • Arachidonic acid is major precursor
  • Cannot be stored and are released right after synthesis
  • Involved in pyretic response
  • Acetaminophen (not NSAID) blocks brain prostaglandins (antipyretic)
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3
Q

NSAIDs block ____, preventing formation of ____ from ____

A

NSAIDs block COX, preventing formation of prostaglandin H2 from arachidonic acid

(note arachidonic acid also converted into leukotrienes via lipooxygenase)

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4
Q

Describe the types of COX

A

COX

  • Both make prostaglandins from arachidonic acid
  • Each has its own gene
  • COX1: present in most tissues all the time, constitutive, GI tract / platelets / kidneys

COX2: inflammatory, appears when inflammation/injury, responsible for pain, inducible, normally found in CNS / kidneys / uterus

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5
Q

COX __ is inflammatory

A

COX 2 is inflammatory

(COX-2 specific inhibits such as celexocib)

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6
Q

Describe the systems prostaglandins affect

A

Prostaglandins affect

  • PNS and CNS (pain)
  • GI
  • Renal and CV
  • Platelets (hemostasis)
  • Other: bone, reproductive systems
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7
Q

Describe role of prostaglandins in pain

A

Prostaglandins in pain

  • Cause allodynia (touch causes pain) and hyperalgesia (pain amplified)
  • Sensitize pain nerve endings: triggered by touch (allodynia)
  • Enhance pain in CNS (hyperalgesia)
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8
Q

Describe peripheral mechanisms of pain mediated through COX-2

A

Peripheral mechanisms of pain mediated through COX-2

  1. Tissue injury
  2. COX-2 expressed
  3. Increased Na influx into nerve
  4. Threshold becomes less negative
  5. Nociceptor ready to fire
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9
Q

Prostaglandins ____ the inhibitory pathway and ____ the ascending pathway

A

Prostaglandins inhibit the inhibitory pathway and upregulate the ascending pathway

(opioids decrease transmission of pain, NSAIDs decrease excitation of pain)

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10
Q

Prostaglandins enhance pain in the CNS via ____, ____, and ____

A

Prostaglandins enhance pain in the CNS via increased Substance P and glutamate release, increased sensitivity of 2nd order neurons, and decreased release of inhibitory transmitters

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11
Q

NSAIDs ____ but do NOT ____

A

NSAIDs blunt PNS/CNS sensitization but do NOT block pain transmission

(able to prevent self injury)

(analgesia is peripheral and central)

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12
Q

NSAIDs cause GI toxicity via ____ and ____

A

NSAIDs cause GI toxicity via direct gastric irritation and decreased cytoprotection in the stomach

  • Often silent ulceration
  • All but 1 NSAIDs are weak acids
  • NSAIDs reduce bicarbonate secretion, blood flow, epithelial cell turnover, and mucosal immunocyte function
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13
Q

GI ulcers after NSAIDs are often ____

A

GI ulcers after NSAIDs are often asymptomatic

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14
Q

NSAID GI toxicity can be prevented through ____, ____, and ____

A

NSAID GI toxicity can be prevented through enteric coating, PPIs, and misoprostol

  • Enteric coating: moves lesions into duodenum only
  • PPIs prevent NSAID upper GI ulcer but not intestinal ulcers
  • Misoprostol: synthetic PGE1 that increases mucus formation
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15
Q

Enteric coating protects against NSAID GI toxicity by ____

A

Enteric coating protects against NSAID GI toxicity by moving lesions into duodenum only

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16
Q

PPIs protect against NSAID GI toxicity by preventing ____ but not ____

A

PPIs protect against NSAID GI toxicity by preventing upper GI ulcers but not intestinal ulcers

17
Q

Misoprostol is a ____ that protects against NSAID GI toxicity by ____

A

Misoprostol is a synthetic PGE1 that protects against NSAID GI toxicity by increasing mucus formation

(causes diarrhea, sold as combo drug)

18
Q

Discuss prostaglandins in the kidney

A

Prostaglandins in the kidney

  • Renal prostaglandins from COX-1 and COX-2 so COX-2 selectivity is no help
  • Affect Na and H20 balance: affect BP
  • In decreased perfusion states, PGs dilate afferent blood vessels - needed to prevent ischemia when low volume / BP/ CO
19
Q

NSAIDs ____ BP in treated hypertensives but not normotensives

A

NSAIDs increase BP in treated hypertensives but not normotensives

(increases risk for MI or CVA)

20
Q

Describe renal concerns of NSAID use

A

NSAID renal concerns

  • BP elevation and diuretic interaction: altering prostaglandin levels leads to Na+/H2O imbalance
  • Ischemic acute tubular necrosis: by preventing prostaglandin afferent blood vessel dilation in low perfusion states (e.g. hypovolemia, CHF)
21
Q

Describe hematologic effects of NSAIDs

A

NSAIDs hematologic effects

  • NSAIDs reversibly bind COX: half life normal after a few half lives
  • ASA irreversibly acetylates COX-1: need to make more COX to recover, platelets have no nuclei to make more COX, takes 7-10 days to make new platelets
  • Low dose ASA is cardioprotective while NSAIDs (even at high dose) are not
22
Q

NSAIDs block formation of ____ from ____, ____ clotting

A

NSAIDs block formation of TxA2 from COX-1, decreasing clotting

(note COX-2 selective blockers do not)

23
Q

Describe NSAID hepatic toxicity

A

NSAID hepatic toxicity

  • Uncommon and not severe
  • Idiosyncratic: not dose or duration related, exception is ASA
24
Q

Contraindications to NSAID use are ____, ____, ____, ____, and ____

A

Contraindications to NSAID use are ulcer, coagulopathy, renal disease, hepatic disease, and pregnancy

(low dose ASA is acceptable in CV disease)

25
Q

Describe COX-2 specific inhibitors

A

COX-2 specific inhibitors

  • Celecoxib
  • GI ulcer rate reduced by half (same as adding PPI to NSAID)
  • Still increases BP and risk of MI/CVA
  • No effect on platelets: can use during surgery, no interference with low dose ASA
26
Q

Describe IV NSAIDs

A

IV NSAIDs

  • Ketorolac: generic potent analgesic, anti-inflammatory effect, worthless orally, limited to 5 days due to toxicity
  • Ibuprofen: potent analgesic, anti-inflammatory effect, limited to 5 days due to toxicity
  • Acetaminophen (not NSAID): more potent, less toxic when IV
27
Q

Describe topical NSAIDs

A

Topical NSAIDs

  • Diclofenac: gel, ointment, or patch
  • Useful on superficial joints
  • Less toxic: no platelet effects, minimal GI effects, warnings are the same as for oral
28
Q

____ are used when something other than opioids is required during an operation

A

Perioperative NSAIDs are used when something other than opioids is required during an operation

  • Opioids slow GI tract via peristalsis via direct action on gut, cause constipation in outpatients, can mean longer stay due to inability to take orals / leave hospital with ileus / slowed GI function due to pain