Exam 4 - NSAIDS/Non-Opiods/Opiods Flashcards
What are NSAIDS?
Examples?
Non-steroidal Anti-Inflammatory Drugs that relieve pain and fever by supressing inflammation via COX-1, COX-2, and/or LOX inhibition
Aspirin, ibuprofen, ketorolac, naproxen
Diagram the cell damage pathways (COX and LOX)
Describe the two different COX isoforms?
- COX-1 – Always present allows for important homeostatic functions in the GI tract, renal tract, platelet function, and macrophage differentiation. Inhibition undesirable
- COX-2 - expressed due to stimulation and leads to inflammatory response
What are the pharmcokinetics of NSAIDS?
- Weak acids
- Well absorbed
- Highly metabolized
- Highly protein bound
- Renally and hepatically cleared
What are the major side effects of NSAIDS?
- Gastic irritation by decreasing gastic mucous production leading to ulcers
- Nephrotoxicity
- Hepatotoxicity
- Thrombosis
- Rare hypersensitivity reactions
Describe the MOA of aspirin’s irreversible inhibition?
Irreversibly blocks COX-1 by acetylation of serine 529.
This prevents arachidonic acid interacting with COX.
Categorize the NSAIDS based on selectivity of COX and LOX inhibition.
Describe the MOA of NSAIDS to reduce fever?
Mediated by inhibition of COX and IL-1
PG inhibition in the hypothalamus leads to peripheral vasodilation causing dissipation of heat.
NSAIDS cause cerebral vasoconstriction
Describe the MOA of GI upset that occurs with all NSAIDS?
Inhibits GI protective prostaglandin produced by COX-1, causing irritation of gastric mucosa
What is the black box warning for NSAIDS?
Increased risk of cardiovascular events (MI, stroke) and GI bleeding
What would the toxicity of aspirin be at a level of 70 24 hours after ingestion?
Severe toxicity
What are the benefits and drawbacks of COX-2 selective inhibitors?
Drug?
Benefits: No effect on COX-1 functions (less GI upset, no impact on platelet aggregation)
Drawbacks: Increased risk of serious CV events due to inhibition of PGI2
Celecoxib
What are the indications for diclofenac and indomethacin?
Indomethacin
* Rheumatism
* Gout
* Patent ductus arteriosus
Diclofenac
* Reduce arthritic pain
* Comes in a topical form
Why is acetaminophen not an NSAID?
It selectively inhibits COX-2 in the CNS and does not have much effect on the arachidonic acid pathway in the periphery
It has no anti-inflammatory effects
Describe the selection criteria for NSAIDS?
All are roughly equal in efficacy, comes down to:
* Personal factors
* Cost
* Toxicities
- Most: Indomethacin, meclofenamate
- Least: Aspirin and ibuprofen
- COX-2 better for patients high risk for stomach bleeding
Describe the acute and chronic effects of glucocorticoids?
Acute is good, chronic is bad
Attributed to cortisol levels
What is the MOA of glucocorticoids?
- Inhibit immune response by blocking transcription/translation
- Increases Annexin-1 which suppresses phospholipase A2 and leukotriene response
- Increases secretory leukoprotease inhibitor (SLPI)
- Increases IL-10 - immunosuppressive enzyme
- Decreases NFkB which is proinflammatory
What are DMARDs?
Disease Modifying Anti-Rheumatic Drugs
Used to reduce inflammation and decrease damage to bones and joints
List the 3 biologic DMARDs and their MOA?
- Abatacept (Orencia) - Blocks T cell activation
- Rituximab (Rituxan) - Depletes B-lymphocytes
- Adalimumab (Humira) - anti TNF-alpha
What are the endogenous opiods and their receptors?
- Endorphins – highest affinity for mu opioid receptors
- Enkephalins – highest affinity for delta receptors
- Dynorphins – Highest affinity for kappa receptors
All ligands can bind to each receptor, they differ in affinity
What are the components of pain and pain signaling?
- Components: Sensory and emotional
- Pain is sensed by nociceptors (free nerve endings) with specialized receptors that when bound, initiate an action potential in an afferent neuron.
- Pain signals arrive at the dorsal horn of the spinal cord where they ascend to the somatosensory cortex.
Describe the 3 main fibers for sensation transmission?
- A beta fiber (myelinated) – transmits non-noxious mechanical stimuli
- A delta fiber (myelinated) - transmits noxious heat and mechanical stimuli like sharp pain. Produces initial reflex response.
- C fiber (unmyelinated) - transmits noxious heat, chemical, and mechanical stimuli (slow, burning pain).
Describe the 3 tracts in the CNS?
- Spinothalamic - (primary pain pathway) transmits signal through the thalamic nuclei to the somatosensory cortex.
- Spinoreticular - (emotional sensation) transmits signal through the reticular formation of the pons, then thalamus, then somatosensory cortex.
- Spinomesencephalic - Mu opiod receptors in the periaqueductal (PAD) grey matter of the brainstem can release endorphins to supress pain signaling.
What are the pharmacokinetics of opiods?
A: well absorbed, many routes
D: Highly perfuses tissues; accumulates
M: Varies
E: mainly urine (drug tests)
