SM_244a: Pharmacology, Opioids, and Pain Concepts III Flashcards Preview

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Flashcards in SM_244a: Pharmacology, Opioids, and Pain Concepts III Deck (28)
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1

NSAIDs are related only because ____ and ____

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

 

 

(different structures)

2

Describe prostaglandins

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)

3

NSAIDs block ____, preventing formation of ____ from ____

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

 

 

(note arachidonic acid also converted into leukotrienes via lipooxygenase)

4

Describe the types of COX

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

5

COX __ is inflammatory

COX 2 is inflammatory

 

(COX-2 specific inhibits such as celexocib)

6

Describe the systems prostaglandins affect

Prostaglandins affect

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

7

Describe role of prostaglandins in pain

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)

8

Describe peripheral mechanisms of pain mediated through COX-2

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

9

Prostaglandins ____ the inhibitory pathway and ____ the ascending pathway

Prostaglandins inhibit the inhibitory pathway and upregulate the ascending pathway

 

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

10

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

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

11

NSAIDs ____ but do NOT ____

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

 

(able to prevent self injury)

(analgesia is peripheral and central)

12

NSAIDs cause GI toxicity via ____ and ____

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

13

GI ulcers after NSAIDs are often ____

GI ulcers after NSAIDs are often asymptomatic

14

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

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

15

Enteric coating protects against NSAID GI toxicity by ____

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

16

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

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

17

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

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

 

(causes diarrhea, sold as combo drug)

18

Discuss prostaglandins in the kidney

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

NSAIDs ____ BP in treated hypertensives but not normotensives

NSAIDs increase BP in treated hypertensives but not normotensives

 

(increases risk for MI or CVA)

20

Describe renal concerns of NSAID use

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

Describe hematologic effects of NSAIDs

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

NSAIDs block formation of ____ from ____, ____ clotting

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

 

(note COX-2 selective blockers do not)

23

Describe NSAID hepatic toxicity

NSAID hepatic toxicity

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

24

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

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

 

(low dose ASA is acceptable in CV disease)

25

Describe COX-2 specific inhibitors

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

Describe IV NSAIDs

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

Describe topical NSAIDs

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

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

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

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