Non-Opioid Pain Relievers Flashcards
Local ___ is the body’s response to injury.
inflammation
What is the point of inflammation?
- identify injury
- remove noxious materials
- ward off infection
- repair damage to tissue/restore function
Injured cells release certain chemicals called ___. ___ ___ can produce ___ of resident immune cells called ___ cells.
alarmins; Alarmin IL33; degranulation
___ is released by mast cells and acts through ____ to produce local ___ and render the ___ ‘leaky’. This will allow more immune cells to enter the injury site and also produce ___.
Histamine; GPCR; vasodilation; capillaries; edema
Where is the histamine receptor found and what does it do upon activation?
Histamine-H1 receptor activity on vascular endothelium and increases Ca2+
What are the two major effects that Histamine stimulated increase in Ca2+ cause?
- NO produced in endothelial cells travels to smooth muscle. Once there, NO relaxes the smooth muscle (vasodilation)
- MLCK mediated contraction of the capillary endothelium makes the capillary leaky
T/F. Inflammation adds to the pain felt at the injury site and excessive inflammation is not beneficial to the host.
True.
What is the goal of anti-inflammatory drugs?
- attenuate the inflammatory response
2. attenuate pain
The anti-inflammatory properties and pain relief comes from attenuating the production of ___, which are involved in pain ___ and more ___.
prostaglandins; sensitization; inflammation
Prostaglandins are derived from ___ ___. What are the four principle prostaglandins?
arachidonic acid
PGE2, PGD2, PGF2, PGI2
T/F. Prostaglandins are not stored prior to signal but instead made in response to cell signal.
True.
Which is more important in inflammation, COX-1 or COX-2? Which COX is constitutively active?
cox-2
COX-1 is constitutive. COX-2 is induced
The action of the enzymes ___ and ___ sends the arachidonic acid down the path leading to production of the ___.
COX1; COX2; prostaglandins
What does COX stand for?
cyclooxygenase enzyme
What are the undesirable affects of inhibiting COX-1?
COX-1 is involved in homeostatic functions so its inhibition affects the following: GI tract Renal tract Platelet function Macrophage differentiation
The 4 different prostaglandins interact with ___ different GPCRs. PGE2 interacts with ___ different GPCRs, therefore some effects are in direct opposition to each other.
8; 4
T/F. Prostaglandins play a key role in generating and maintaining the inflammatory response and in pain sensitization.
True.
Where do prostaglandins act to sensitize pain responses?
via their GPCRs at peripheral nerve endings
___ mediated activation of G-alpha-___ leads to increased activity of PKA. PKA mediated ___ of the ___ type nociceptor enhances its activity leading to a sensitized pain response.
PGE2; s; phosphorylation; TRP
T/F. Prostaglandins can only sensitize pain via peripheral nerve endings.
False, they can also work via central mechanisms which could make things feel more painful
How do all NSAIDS work?
by inhibition of COX enzymes and diminishing the production of prostaglandins
___ acid or aspirin is a ___ inhibitor that works 100X better on ___-_. It is the ___ selectivity of the commonly used NSAIDS. COX-2 inhibition produces __-____ acid after inhibition.
Acetylsalicylic; irreversible; COX-1; worst; 15-hydroxyeicosatetraenoic
Which drugs are the reversible inhibitors of COX-1 and -2? Which one is more selective for COX-2 (inducible form)?
Ibuprofen, Naproxen, and Acetaminophen
Naproxen
All inhibit COX-1 at lower concentrations than COX-2 except naproxen
What are the therapeutic effects of acetylsalicylic acid (aspirin)?
analgesia
anti-pyretic (fever)
anti-inflammatory
anti-thrombolytic
