``` Ibuprofen = propionic acid dervative Shorter lasting, 3-4hrs OTC - pain & fever RX - anti-inflam - $$$ - Slow to act because ti enters synovium slowly ```

L18 Flashcards by Logan Kolakowski

What is your first anti-inflam drug class choice for RA? Second choices?

DMARDs
Aspirin (salicylates)
NSAIDs
Steroids

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What anti-inflams would you use for AS and psoriatic arthritic?

NSAIDs or aspirin (salicylates)

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What is your first choice anti-inflams for osteoarthritis? Other options?

Acetaminophen (Tylenol)
NSAIDs
Aspirin (salicylates)

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What is your first choice anti-inflam for lupus and Crohn’s? Second choice?

Steroids or DMARDs

2. Aspirin (salicylates)

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What are the 3 main functions of NSAIDs? What don’t they do? Do they cure?

Non-narcotic pain reduction (analgesic)
Reduce fever (anti-pyretic)
Anti-inflam
NO immune suppression
NO cure - suppress inflammation

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Where do NSAIDs act?

Membrane phospholipids –> PLA2 –> arachidonic acid –> COX1/2 –> eicosanoids
= COX (cyclo-oxygenase) inhibitors

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When COX1/2 breaks down eicosanoids (PGH2), what are the 3 main products?

Thromboxane - makes TXA2 (thromboxane)
Prostacyclin - makes PGI2
Prostaglandins 
- from PGF &amp; PGE synthase enzymes 
Which ones are made is due to cell specific enzymes

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What are the 4 prostaglandins you should know?

PGE 1
2
PGD2
PGF alpha

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Describe COX 1. Where is it found?

ALWAYS on
- Can be induced 
@ platelets: thromboxane 
@ GI and to prevent clots: prostacyclin (PGI2)
@ Kidneys &amp; fever: prostaglandin E2

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Describe COX 2. What upregulates it? What is the main metabolite produced?

Inducible form
Upregulated by IL1, shear stress, own products (feed forward)
PGE2 = metabolite, feed forward (fever)

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What are the 5 types of NSAIDS?

Salicylates (aspirin - Bayer)
Propionic acid derivatives (Advil, Aleve)
Indole derivatives (indomethacin)
Oxicams
COX2 selective inhibitors

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What is the active ingredient in aspirin? What is the natural source?

Acetyl-salicylic acid

Willow tree leaves/bark

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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

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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)

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What are side-effects of aspirin use?

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What is the mechanism of propionic acid derivatives?

Non-specific, both COX1 & 2

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What is Advil?

Ibuprofen = propionic acid dervative
Shorter lasting, 3-4hrs
OTC - pain &amp; fever
RX - anti-inflam
- \$\$$
- Slow to act because ti enters synovium slowly

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What is Aleve?

Naproxen = propionic acid derivative

Longer lasting, 12 hrs

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What is the use of indole derivatives (indomethacin)?

Delays labor
Used to close patent ductus arteriosis
Contra-indicated with GI disease - high side effect risk

What are 3 common oxicams?

Prioxicam (!!!!) - OA & RA
Tenoxicam
- Use only for chronic pain, NOT acute (post-op)
Meloxicam
COX2 selective (NOT specific)
Arthritis

What are phenyl acetic acid derivatives used for?

Rx - severe pain
Ketorlac
Tolmetin
Diclofenac

What is the COX2 inhibitor you need to remember?
Mechanism
Contra-indications
Uses

CELE-COX-IB
= Celebrex 
COX2 selective inhibitor 
Inhibits p450 enzymes 
Interacts with ACE inhibitors - monitor 
For RA
No GI - but watch for CARDIOVAS
- COX1 alone = sticky platelets, heart attacks (on the news!)

What is Reye’s syndrome?

KIDS!!! 
Virus host reaction 
Hepatic encephalopathy &amp; 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?

YES
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 ↓Alzheimer's/dementia (neuroinflam)

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?

Ibuprofen (Advil) | Naproxen (Aleve)

Which NSAID do you use OTC for chronic pain?

Aspirin (Beyer)

Which NSAIDs do you use Rx for acute inflam/pain?

Indomethacin Phenyl acetic acid derivatives - Ketolac - Diclofenac

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?

Meloxicam Indomethacin *CV risk*

What are the benefits of aspirin, ibuprofen, and naproxen? Negatives?

↓CVD | ↑GI side effects

How are NSAIDs metabolized? Where?

p450 enzymes 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 Liver toxic 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 Life threatening! Epidermis separates from dermis Why? medications (NSAIDs) No trxt - ride it out ```

Why don't we give pregnant women NSAIDs?

Spontaneous abortion!!!

What are the normal effect of thromboxane?

Platelet aggregation | Vasocontrict

What are the normal effects of PGI2 (prostacyclin)?

Inhibit platelet aggregation Vasodilator GUT!!!!!

What is the normal effect of PGF 2 alpha (prostaglandin)?

Contract uterus to induce delivery

What is the normal effect of PGE2?

Fever

What is the normal effect of PGDS?

Non-REM sleep

What is common between all prostanoid receptors?

7 TM GCPR - Lots of cross talk b/c similar structure Prostanoids = molecules made from the membrane to act back on the membrane