Mon Test Week 5 Day 2 Anti-inflam pharma Flashcards
2 ways the immune “malfunctions”?
Deficiency or Over Responsiveness
2 types of immune deficiencies?
Primary which is genetic and congenital and Secondary which is developed later in life due to disease, mutations or drugs
2 types of immune system over responsiveness?
Autoimmunity- self tolerance fails and body attacks itself\
Hypersensitivity- body over reacts to stimulus, usual an exogenous antigen
List innate system components (9)?
- Dendritic Cell
- Eosinophils
- Basophils
- Neutrophils
- Monocytes
- Macrophages
- Complement Proteins
- Mast Cells
- NK cells
List of Adaptive immune components? And the Common pathway cells?
T-cells which include CD4 and CD8
Cytokines
B-cells
Antibodies
Common Pathway
NK T cells
Gamma T-cells
Which side of the immune system innate or adaptive goes wrong with autoimmune diseases?
The adaptive
Do we always want to use anti-inflammatories?
No, inflammation is complex and a part of the human process of healing and defense. By suppressing it we can suppress and delay healing.
2 types of anti-inflammatory drugs and the major difference between them?
NSAIDs and Corticosteroids
NSAIDs inhibit a one pathway COX or cyclooxygenase and Corticosteroids inhibit a pathway above it- the conversion of phospholipids to arachidonic acid so they inhibit a lot more
Details on next few cards
What do NSAIDs inhibit and what do they not affect?
Inhibit inflammation due to mediators such as
prostaglandin, prostacyclin and thromboxane production.
Do not affect leukotriene, tumor necrosis factor (TNF), or interleukin
production.
What do corticosteroids inhibit?
Inhibit prostaglandin, prostacyclin, thromboxane, plus leukotriene, and
interleukin production
A lot more including 10-20% of protein making of a cell. mRNAs don’t get translated.
2 major types of NSAIDs and which of the 3 she asked us to know are which kind? A major difference in what they inhibit?
Non-Selective COX1 and COX2 Inhibitors- Ibuprofen and Naproxen
Selective COX2 Inhibitor- Celecoxib
Non-selective inhibit prostaglandin productuction- COX1 makes prostaglandin in the GI tract, kidneys and platelets. Prostaglandin protects the gi tract lining
Non selective inhibitor (Ibuprofen and Naproxen) adverse drug reactions?
epigastric pain, heartburn, nausea—avoid use in patients with known or history of gastroesophageal reflux disease (GERD) or peptic ulcer due to risk of GI bleed; can worsen pre-existing edema; tinnitus rare; increases risk of adverse cardiovascular event in patients with pre-existing heart disease (unstable angina, heart failure, prior MI)
Non selective inhibitor (Ibuprofen and Naproxen) drug interactions?
Many. Can prolong bleeding time in patients on oral antiplatelet or anticoagulant agents. Can also affect kidney function—use carefully in patients taking ACE inhibitors and thiazide diuretics as incautious use can lead to acute kidney injury
Ibuprofen dosing and comments?
Product options. OTC 200 mg tablet, 200 mg/5 mL oral liquid, 100 mg/mL oral liquid; 100 mg chewable tablet; Rx 400 mg, 600 mg, 800 mg tablets; 10% cream (topical)
Typical dosing. adults, for pain: 400 mg three or four times daily; doses for dysmenorrhea or arthritis are typically higher, e.g., 600-800 mg three or four times daily
Comments. Has antipyretic, analgesic properties as well as anti-inflammatory properties
Naproxen dosing and comments?
Product options. OTC naproxen 220 mg capsule, 125 mg/5 mL liquid; Rx 250 mg, 375 mg, 500 mg, 550 mg; also comes in delayed/extended-release formulas; 10% cream (topical)
Typical dosing. adults, for pain: 400 mg two or three times daily; doses for dysmenorrhea or arthritis are typically higher
Comments. Available as a base and sodium salt. 200 mg naproxen base = 220 mg naproxen sodium. Has antipyretic, analgesic properties as well as anti-inflammatory properties
Celecoxib adverse drug reactions?
Diarrhea, dyspepsia, upper respiratory tract infection;
may increase risk of adverse cardiovascular event in patients with pre-existing heart disease (unstable angina, heart failure, prior MI), but evidence points to risk among the lowest of all NSAIDs
Celecoxib drug interactions?
Moderate CYP 2C9 substrate, weak 3A4 substrate. Weak 2D6 inhibitor. Many, but hard to distinguish from non-selective NSAIDs
Celecoxib dosing and comments?
Product options- Rx only 50 mg, 100 mg, 200 mg, 400 mg capsules, 120 mg/4.8 mL oral solution
Typical dosing- 100 mg twice daily or 200 mg once daily; can be dosed at 200 mg twice daily for short term intense pain; max daily dose 400 mg
Comments- Probably a better candidate for patients with a history of GERD or peptic ulcer than non-selective NSAID
What is diclofenac?
An NSAID that in the 3% gel form may be effective for treating aphthous ulcers aka canker sores.
In ingestible form there are many serious potential reactions and interactions.
3 corticosteroids and their slightly different modes of action?
All- Blocks protein synthesis of interleukins (late phase inflammation) and the arachidonic acid pathway so blocks production prostaglandins and leukotrienes;
Prednisone- some mineralocorticoid activity
Dexamethasone- no mineralocorticoid activity
Triamcinolone- minimal mineralocorticoid activity
Prednisone and Dexamethasone adverse drug reactions?
Short-term: glucose intolerance, hypertension, dysphoria (dose related), GI toxicity, fluid retention, weight gain.
Long-term: cataracts, glaucoma, osteopenia/osteoporosis, impaired wound healing, skin thinning, striae (particularly with topical use), moon face, edema, buffalo hump and other abnormal fat deposits, anemia
Prednisone and Dexamethasone drug interactions?
Many. Major CYP 3A4 substrate, so any inducer will decrease serum concentrations of prednisone.
Concomitant administration will enhance GI toxicity of NSAIDs. May enhance immune suppression effect of other immunotherapies.
Triamcinolone oral paste adverse reactions and drug interactions?
Adverse drug reactions. Less than with prednisone because topical or intra-articular administration
Drug interactions. Minimal
Prednisone dosing and comments?
Product options- 1 mg, 2.5 mg, 5 mg, 10 mg 20 mg 50 mg tablets; 1 mg/mL and 5 mg/mL oral solutions; 1 mg, 2 mg, 5 mg delayed release tablets
Typical dosing- Dose depends on what is being treated. Long-term dosing at more than 5 mg daily is avoided whenever possible. Short-term treatment for immune hypersensitivity or another acute inflammatory condition can involve doses of 20 mg or more daily. If on longer than 2 weeks, will need to taper therapy. Patients on more than 5 mg/day may need extra stress dose on day of oral surgery.
Comments- 5 mg daily equals physiologic cortisol production
