Smith - Prostanoids And Anti-Inflammatory Drugs Flashcards
Acute inflammation is what?
Body’s normal protective response to an injury, irritation, or even surgery
Protective response
Eliminate initial cause of cell injury, clear out necrotic cells and damaged tissues
What are 5 signs of acute inflammation?
LPHaRTS
Loss of function
Pain
Heat
Redness
Tenderness
Swelling
What are some non-selective NSAIDS?
Aspirin
Ibuprofen
Acetominophen
Naproxen
What are NSAIDS?
Nonsteroidal anti-inflammatory drugs
What do NSAIDS do?
Inhibit cyclooxygenase enzymes
What is an example of a selective NSAID?
COX2 - Celecoxib
What are glucocorticoids?
Inhibit phospholipase A2
- Prednisone
- Cortisone
What are DMARDs?
Disease modifying anti-rheumatic drugs
What are the 2 types of DMARDs?
Traditional (non-biologic)
Biologic
Where do a lot of our inflammatory mediators originate from?
Breakdown of arachidonic acid
T/F - Glucocorticoids affect the pain process flow at a higher level than the NSAIDS target.
TRUE
What are eicosanoids?
Oxygenation products of poly-unsaturated long-chain FAs
- G-coupled proteins
- Auto and paracrine fxs
What are prostanoids?
Sub-class of eicosanoids
What are 3 prostanoids?
Prostaglandins
-Mediate inflammatory and anaphylactic rxns
Thromboxanes
-Mediate vasoconstriction
Prostacyclins
-Active in resolution phase of inflammation
Prostanoids have major effects on what?
Smooth muscle
Platelets and blood cells
Nerve terminals
Endocrine organs
Adipose tissue
Aspirin and other NSAIDs provide non-specific ___________ of the cyclooxygenase (COX) enzymes.
Inhibition
T/F - Non-selective COX inhibitors have both positive (anti-inflammatory) and adverse effects (upset stomach)
TRUE
Tell me about COX-1.
Constitutive (platelets, kidney, GI)
Inhibition by classic NSAIDS increases risk for GI ulceration
Tell me about COX-2.
Constitutive in kidney
-Inducible elsewhere by hormones, GFs, and inflammatory mediators
Inhibition by NSAIDs or by selective Coxibs
COX-2 selective inhibitors do NOT inhibit platelet aggregation or cause GI upset/ulceration
Tell me about Aspirin.
Only NSAID that inhibits both COXs in an IRREVERSIBLE manner
Tell me more about Aspirin.
Nonselective COX-1 and COX-2 inhibition
Anti-platelet aggregation effects
Rarely used for anti-inflammatory purposes (Dose for those effects is way too high)
What are contraindications of Aspirin?
NSAID allergies
Avoid children with viral-induced illness (REYE SYNDROME)
Gout, hemophilia, blood thinners, ACE inhibitors, pregnancy near term
Tell me about Ibuprofen.
Analgesic and antipyretic and antinflammatory
Interferes with the antiplatelet effect of low-dose aspirin
Tell me about Naproxen.
Same as most other NSAIDs, but available in slow-release formulation (Aleve)
When does a fever get to be too high?
103 degrees F
What are some adverse effects common to all NSAIDs?
CNS - headache Cardiovascular - Edema *GI - Pain, dysplasia, nausea, vomiting, ulcers, bleeding Hematologic Hepatic Pulmonary - asthma Skin - rashes Renal insufficiency REYE SYNDROME
Tell me about Celecoxib (Celebrex).
COX-2 selective inhibitor
Analgesic, antipyretic, and anti-inflammatory, like Aspirin
No effect on platelet aggregation
10-20x more selective for COX-2 than COX-1
- Lower GI adverse effects
- No cardioprotective effects
- Increased risk of edema, hypertension, MI, and stroke
Tell me about acetaminophen (Tylenol).
NON-ASPIRIN pain reliever
-Central-action effect on hypothalamus to cause vasodilation and sweating (reduces fever)
—Analgesic mechanism thru elevation of the pain threshold
Tell me more about acetaminophen.
Alternative to NSAIDs in pts with allergies, ulcers, bleeding problems, or taking blood thinners (warfarin)
Adverse effects
-Rash, chest pain, bone marrow suppression
—Contraindicated for pts with liver disease and insufficiency due to alcoholism
T/F - Acetaminophen is NOT an NSAID.
TRUE
T/F - Acetominophen should NOT be taken as an anti-inflammatory drug.
TRUE
Tell me about glucocorticoids.
Steroid hormones
Prevents conversion of membrane phospholipids to arachidonic acid by inhibiting the phospholipase A2 enzyme
-Decrease inflammation
What are the short to medium-acting glucocorticoids? 3 of them
Hydrocortisone
Cortisone
Prednisone
What is the long-acting glucocorticoid?
Dexamethasone
What is a major side effect of overdosing on acetominophen?
Hepatotoxicity
-Days->weeks->liver failure->death
Tell me about prednisone.
Blocks phospholipase A2, and thus shuts down immune responses
Used for
- Asthma
- COPD
- Crohn’s
Tell me about non-biologic DMARDs
Suppress the progression of the disease by acting against the underlying immunological abnormalities
What are 2 non-biologic DMARDs?
Methotrexate
Azathioprine
What are the main adverse effects of glucocortcoid use?
Bone weakening
Skin thinning
Heart risks
Cataracts and glaucoma
What is the 1st line DMARD for rheumatoid arthritis?
Methotrexate
Inhibits transformylase and thymidylate synthetase enzymes
Adverse:
-Nausea, GI ulcers, stomatitis, hepatotoxicity
—CONTRAINDICATED IN PREGNANCY
—RISK OF LIFE-THREATENING EFFECTS IF TAKING NSAIDS SUCH AS ASPIRIN, NAPROXEN, OR OTHER SALICYLATES.
Tell me about azathioprine.
PRODRUG that acts thru main metabolite, 6-thioguanine
-Suppresses DNA synthesis and production of rapidly proliferating cells (B and T cell fxs)
Used for:
-rheumatoid arthritis
Adverse:
-Bone marrow suppression, GI upset, increased infection risk, increased lymphoma risk
Tell me what the two biologic DMARDs are. (Larger molecules than non-biologics).
Proteins produced by recombinant DNA tech:
-T-Cell modulators
—Abatacept
- TNFalpha-blocking agents
- Adalimumab
Tell me about abatacept.
Acts as fusion protein to prevent activation of T-cells
Use:
-Rheumatoid arthritis for those that are not responding well to anti-TNFalpha therapy
Adverse:
-Increased risk of lymphomas, infections, congestive heart failure, lupus-like syndrome
MONTLY COST: $3500-$3800
Tell me about adalimumab.
Prevents ligand from binding TNFalpha receptor
Use:
-Rheumatoid arthritis, psoriasis, refractory asthma
Adverse:
-Increased risk of lymphomas, infections, lupus-like syndrome
5 different TNFalpha inhibitors
- Infliximab
- Adalimumab
- Certolizumab pegol
- Golimumab
- Etanercept (This one is a circulating receptor fusion protein)
