Flashcards in L18 Deck (47)
What is your first anti-inflam drug class choice for RA? Second choices?
2. Aspirin (salicylates)
What anti-inflams would you use for AS and psoriatic arthritic?
NSAIDs or aspirin (salicylates)
What is your first choice anti-inflams for osteoarthritis? Other options?
1. Acetaminophen (Tylenol)
What is your first choice anti-inflam for lupus and Crohn's? Second choice?
1. Steroids or DMARDs
2. Aspirin (salicylates)
What are the 3 main functions of NSAIDs? What don't they do? Do they cure?
1. Non-narcotic pain reduction (analgesic)
2. Reduce fever (anti-pyretic)
NO immune suppression
NO cure - suppress inflammation
Where do NSAIDs act?
Membrane phospholipids --> PLA2 --> arachidonic acid --> COX1/2 --> eicosanoids
= COX (cyclo-oxygenase) inhibitors
When COX1/2 breaks down eicosanoids (PGH2), what are the 3 main products?
Thromboxane - makes TXA2 (thromboxane)
Prostacyclin - makes PGI2
- from PGF & PGE synthase enzymes
Which ones are made is due to cell specific enzymes
What are the 4 prostaglandins you should know?
Describe COX 1. Where is it found?
- Can be induced
@ platelets: thromboxane
@ GI and to prevent clots: prostacyclin (PGI2)
@ Kidneys & fever: prostaglandin E2
Describe COX 2. What upregulates it? What is the main metabolite produced?
Upregulated by IL1, shear stress, own products (feed forward)
PGE2 = metabolite, feed forward (fever)
What are the 5 types of NSAIDS?
1. Salicylates (aspirin - Bayer)
2. Propionic acid derivatives (Advil, Aleve)
3. Indole derivatives (indomethacin)
5. COX2 selective inhibitors
What is the active ingredient in aspirin? What is the natural source?
Willow tree leaves/bark
How does aspirin interact with COX enzymes?
COVALENT - permanent inhibition
Low dose = preferential inhibit COX 1
High dose = inhibit both COX1/2
AKA dose-dependent mechanism for fever and inflammation reduction
Which COX enzymes is found on platelets? What does this enzyme prefer to make? What do you take for it?
COX1 --> thromboxaine
Take low dose aspirin - preferential inhibition
No platelet aggregation - no clots (baby aspirin prevents against heart attack, take 1 Bayer a day)
What are side-effects of aspirin use?
What is the mechanism of propionic acid derivatives?
Non-specific, both COX1 & 2
What is Advil?
Ibuprofen = propionic acid dervative
Shorter lasting, 3-4hrs
OTC - pain & fever
RX - anti-inflam
- Slow to act because ti enters synovium slowly
What is Aleve?
Naproxen = propionic acid derivative
Longer lasting, 12 hrs
What is the use of indole derivatives (indomethacin)?
Used to close patent ductus arteriosis
Contra-indicated with GI disease - high side effect risk
What are 3 common oxicams?
1. Prioxicam (!!!!) - OA & RA
- Use only for chronic pain, NOT acute (post-op)
COX2 selective (NOT specific)
What are phenyl acetic acid derivatives used for?
Rx - severe pain
What is the COX2 inhibitor you need to remember?
COX2 selective inhibitor
Inhibits p450 enzymes
Interacts with ACE inhibitors - monitor
No GI - but watch for CARDIOVAS
- COX1 alone = sticky platelets, heart attacks (on the news!)
What is Reye's syndrome?
Virus host reaction
Hepatic encephalopathy & steatosis
May be due to taking aspirin/other NSAIDs - why don't give kids Advil
NOT seen with acetaminophen
Can you be allergic to aspirin?
Edema, skin rashes, bronchoconstriction & spasm
- B/c increases AA --> leutorienes --> spasm
Why don't you use aspirin (salicylates) for RA?
Helps the pain
Doesn't help the inflammation
Side effects too great
What is the major consequence of aspirin OD?
Uncouple oxidative phosphorylation
- Accelerate glycotic and lipolytic pathways
- More O2 consumed
- More CO2 made
- Use up all liver glycogen
Why would you use NSAIDs for gout?
Creates dose-dependent excretion of ureic acid --> can't form in joints
What are unexpected benefits of NSAID use?
CVD protection if inhibit both COX1&2
↓Colon cancer risk
What is the mechanism by which NSAIDs protect against colon cancer?
- X COX2 and/or thromboxane, TGF beta
- NO PGE2
- Remove angiogenesis, decreased apoptosis and cell proliferation associated with inflammation --> cancer
Which NSAIDs do you use OTC for acute decrease inflam/pain?
Which NSAID do you use OTC for chronic pain?
Which NSAIDs do you use Rx for acute inflam/pain?
Phenyl acetic acid derivatives
Which NASIDs do you use Rx for chronic pain?
Meloxicam (oxicam for arthritis)
Celebrex (COX2 inhibitor)
Ibuprofen & naproxen (at higher doses)
Which NSAIDs are selective for COX2 but still have COX1 affinity?
What are the benefits of aspirin, ibuprofen, and naproxen? Negatives?
↑GI side effects
How are NSAIDs metabolized? Where?
No toxic metabolites
Often bound to albumin
Why are there different ways to take aspirin - in water vs pill etc?
Changes how fast absorbed
What are the big 5 negative side effects of NSAIDs?
↑bleeding time b/c ↓TXA
Gastritis & ulceration b/x ↑PGI2
Fluid retention ↓PGE2
Delayed labor ↓PGE2
What is SCARS? What NSAID is most commonly associated?
Severe cutaneous adverse reactions
= Whole body blisters
Celecoxib - (Celebrex) suggests disease mechanism linked to COX2 inhibition
What Stevens-Johnson syndrome?
A type of SCAR
Epidermis separates from dermis
Why? medications (NSAIDs)
No trxt - ride it out
Why don't we give pregnant women NSAIDs?
What are the normal effect of thromboxane?
What are the normal effects of PGI2 (prostacyclin)?
Inhibit platelet aggregation
What is the normal effect of PGF 2 alpha (prostaglandin)?
Contract uterus to induce delivery
What is the normal effect of PGE2?
What is the normal effect of PGDS?