Non-opioid Analgesics Flashcards
What is local inflammation?
The body’s response to an injury
- ID the injury
- remove noxious materials
- ward off infection
- repair damage to tissue/restore function
Injured cells release what?
Alarmins
T/F - pathogens can sneak through an injury site?
True
Alarmin Il-33 can produce what?
Degranulation of mast cells
Histamine
One of the more important initial mediators of the inflammatory response released by mast cells
How does Histamine act?
Through a GPCR to produce vasodilation and render the capillaries ‘leaky’
This allows more immune cells to enter the injury site and produce edema
What is Histamine-H1 receptors activity
Increase intracellular Ca to produce two major effects
What two major effects are the result of the increase of intracellular Ca by Histamine-H1 receptor activity?
1) NO mediated relaxation of smooth muscle, causing vasodilation
2) MLCK mediated contraction of the capilary endothelium
What does MLCK mediated contraction of the capillary endothelium cause?
It makes the capillaries leaky
As more immune cells are recruited to the injury site, what happens?
The inflammatory response is ramped up
What role does inflammation play in nociceptive pain?
Inflammatory mediators interact with receptors and facilitate the transmission of pain signals throughout the nervous system
What are the major inflammatory mediators that can cause pain?
Prostaglandins Substance P TNF-a IL-16 IL-6
T/F - Local inflammation adds to the pain felt at the injury site
True
T/F - Excessive inflammation is not beneficial to the host
True
What’s the goal of anti-inflammatory drugs?
Attenuate the inflammatory response
Attenuate pain
The anti-inflammatory properties and pain relief comes from what?
Attenuating the production of prostaglandins
What are prostaglandins synthesized from?
Arachidonic acid
What are the principle prostaglandins?
PGE2
PGD2
PGF2
PGI2
What do Cox1 and Cox 2 do?
They send arachadonic acid down the path leading to the production of prostaglandins
How do prostaglandins enhance pain sensitization?
They activate Gas, which increases PKA activity, which phosphorylates TRP nociceptors - enhancing pain sensitization
How do NSAIDs wrk?
Inhibiting COX enzymes, diminishing the production of prostaglandins
What is acetylsalicylic acid’s (asprin) mechanism of action?
Irreversible inhibitor of Cox1 and Cox2
About 100x better inhibitor of Cox1
What is Ibuprofen, Naproxen, and Acetaminophen’s mechanism of action?
Reversible inhibitors of Cox1 and Cox2
Naproxen are most selective for Cox2
What are the therapeutic effects of acetylsalicylic acid?
Analgesia
Antipyretic (fever)
Anti-inflammatory
Anti-thrombolytic (clotting)
What are the therapeutic effects of ibuprofen and naproxen?
Analgesia
Antipyretic (fever)
Anti-inflammatory
What are the therapeutic effects of acetaminophen?
Analgesia
Antipyretic (fever)
Why is acetylsalicylic acid able to produce anti-thrombosis?
Because it is an irreversible inhibitor of the Cox enzymes, knocking out ALL enzyme activity
Why is acteaminophen not an anti-inflammatory?
Several possibilities
1) Unique Cox enzyme in the CNS is the target
2) Acetaminophen’s mechanism is different
3) Provides relief through an entirely different mechanism (cannabinoid receptor)
How can NSAIDs disrupt mucosal defense in the stomach?
Prostaglandins (primarily from Cox1) stimulate mucus and bicarbonate secretion to help make the ‘mucus gel’ protecting the stomach from digesting itself
What are some adverse affects of NSAIDs
Decreased mucosal stomach defense Increases bleeding time (acetylsalicylic acid) Kidney problems Increased BP Heart failure (rare)
What are some precaustions and contraindications for acetylsalicylic acid
Ulcer
Diabetes
Gout
Hypocoagulation conditions
What is important to know for combining opioids and non-opioid pain relievers?
It can be done
NSAIDS have a ceiling effect - maximum pain relief achieved is higher for opioids
They work by different mechanisms
What is the most effect analgesia?
Optimum dose of NSAID and an additional opioid
