NSAIDs Flashcards
Swelling changes include what?
Increased capillary permeability
Dilation of blood vessels
- redness and warmth caused
Increased tissue pressure and action of inflammatory mediators
- pain caused
Eicosanoid receptor types
PGD2: mast cells and neurons
- active in Alzheimer’s disease
- controls sleep functions
PGE2: all kinds of tissues
- responds to pain stimuli
- causes fever, vasodilation, mucus production
PGF2a: smooth muscles
- promotes vascular tone
ALL 3 types are G-coupled protein receptors that promote bronchoconstriction
Chemical mediators in causing fever
Prostaglandins
Chemical mediators causing Increased vascular permeability
Histamine
Bradykinin
Substance P
CGRP
Chemical mediators causing pain
Prostaglandins
Bradykinin
Substance P
CGRP
Chemical mediators causing vasodilation
Histamine
Prostaglandins
Bradykinin
Prostaglandins general mode of action
Increase sensitivity of nociceptive neurons to pain by turning on peripherally active PGE2 and PGI2 receptors
Also increase hypothalamus stimulation (Fever) via COX-2 ligands (PGE2) crossing the BBB and acting on EP 1 and 3 receptors on the hypothalamus
- causes hypothalamus to increase body temp
NSAIDs general MOA
- inhibts COX-1 and/or COX-2 action that transforms arachidonic acid to prostaglandins.
- centrally activated PGE2, PGI2 and PGF2 receptors in nociceptive neurons which decreases prostaglandin sensitivity.
- inhibts fever via inhibiting COX-2 action
Indications of NSAIDs
Reduce pain, inflammation and fever
OA general charcterisitcs
Caused by loss of articular cartilage
- presents asymmetrically
- deep aching pain and stiffness
- duration of pain is <30mins
- weather directly affects pain levels
- Herberden and Bouchard nodes present
Non-pharmacological management of OA
Recommend non weight bearing exercise, weight loss and educate patient in OA
Can use heat, sole insoles and walking assistive devices if needed
1st line analgesic for OA management
Acetaminophen
- does have significant risk for hepatotoxicity
COX-1
Gene that encodes COX-1 enzyme
- Considered the housekeeping enzyme and constitutional enzyme
- involved primarily in homeostasis
- direct link to gut integrity, vascular tone, platelet aggregation (clot formation), nerve and brain integrity, kidney integrity
- found pretty much everywhere but ESPECIALLY in the GI mucosa
COX-2
Gene that produces COX-2 enzymes
- also caused the inducible enzymes
- Does some homeostasis management, but also produces pro-inflammatory prostaglandins, regulates temperature and inhibits clot formation
- Induced by cytokines via trauma/ inflammation
- direct link to inflammation, pain, fever, cancer and allergies
- usually found in cardiovascular system (vessels, heart and lungs)
Predominantly pro-inflammatory prostaglandins
PGE2 and PGI2
What prostaglandin mediates clotting?
Thromboxane (TxA2)
- promotes clots
What prostaglandin balances the effects of thromboxane?
Prostacyclin (PGI2)
- reduces likelihood of clotting
What prostaglandin is produced only by Mast cells?
PGD2
What NSAID is a thrombolytic?
Aspirin (decreases TxA2 levels)
What synthetic prostaglandin analogue prevents NSAID induced ulcers?
Misoprostol
What NSAIDs can be taken intravenously?
Ketorolac and ibuprofen
What is the only NSAID that irreversibly inhibits COX activation?
Aspirin
Acetylates the COX enzyme which makes this irreversible
Reye’s syndrome
Caused by giving aspirin to children when they are fighting an infection.
NSAIDs and elderly
- Recommended against chronic pain use but okay with acute pain.
- must use proton pump inhibitors in conjunction with NSAIDs due to renal issues that arise with old age
Celecoxib
Inhibts COX-2 enzyme only
Must be avoided in patients with heart failure or patients on diuretics
Decreases PGI2 which results in unchecked TXA2 levels and increased platelet aggregation
Used to combat GI-bleeding
What is the primary derivative of all prostaglandins?
Arachodonic acid
What is the ADE that is caused by all NSAIDs with chronic use?
Heart issues (especially celecoxib)
Common ADE in all non-selective COX inhibitors
GI ulcers and bleeding
- disrupts gastric mucosa which weakens GI integrity
- patients should take non-selective NSAIDs with food for this reason
What two NSAIDs should not be taken together?
Aspirin and profens/ naproxen
Both compete for the same binding site so its more potential risk for no benefit
What propanoic acid derivative is used the most and why?
Naproxen because it has a super high half-life (18hrs) and is the least likely to have cardio issues compared to all the other propanoic acid derivatives
- contraindicated in breastfeeding women though and not the greatest choice in pregnant women altogether
Which acetic acid derivative is the best used for opioid alternatives
Ketorolac
- however cannot be on this drug for more than 5-7 days since it can quickly cause renal and GI issues
What is bound to the reactive intermediate of acetaminophen that prevents liver damage?
Glutathione: binds the reactive subunit and allows excretion through renal system without harm
- in OD cases, the body is depleted of this because it is all used up already, and the reactive metabolite will cause liver damage
- codeine is prescribed with high doses of acetaminophen to prevent this
