Anti-inflammatory agents Flashcards
What are examples of nonsteroidal anti inflammatory drugs (NSAID)?
Aspirin, ibuprofen, naproxen, celecoxib
What are example of antihistamines?
diphenhydramine, Fexofenadine (Allegra),
Loratadine (Claritin)
What are examples of glucocorticoids?
hydrocortisone, dexamethasone, prednisone
What are examples of disease modifying anti-rheumatic drugs?
anti TNF antibodies: adalimumab (humira), infliximab (remicade), etanercept (enbrel)
What is the mechanism behind NSAIDs?
- prostaglandin H2 synthesis inhibitors
- Block cyclooxygenases (COX1 and COX2)
What is the role of prostanoids?
-Vasodilation Prostacyclin (PGI2), PGE2 -Vasoconstriction Thromboxane A2 -Sensitize spinal neurons to pain (hyperalgesia) PGE2 -Acts on thermoregulatory center of hypothalamus to produce fever PGE2
What are some problems associated with non-selective COX inhibitors?
- COX 1 expressed constitutively in many cell types
- disrupts clotting
- blocks prostaglandin production in gastric mucosa: stomach issues
- Cardiovascular events (esp COX 2), assoc with hypertension and MI
What is the role of histamine in the body?
A mediator of immediate allergic and inflammatory reactions
Controls gastric acid secretion and mucus production
Functions as a neurotransmitter and neuromodulator
What are the effects of antihistamines?
Block histamine-triggered:
Vasodilation
Increased permeability of blood vessels
Reducing:
Redness and swelling
Runny nose and watery eyes
What is the mechanism of antihistamines?
- block H1 receptors
- are inverse agonist
What are side effects of antihistamines?
- drowsiness
- dizziness and dry mouth
What are the functions of glucocorticoids in the body?
- naturally produced by adrenal cortex
- modulate glucose metabolism
- Part of a normal endocrine feedback mechanism turning immune responses down or off
- Cause effects by binding to the glucocorticoid receptor (GR) and immune mediator expression.
What is the mechanism behind glucocorticoid immunosuppression?
-upregulation of annexin-A1 (annexin-1 or lipocortin-1) synthesis
-Annexin-A1 suppresses expression of prostaglandins by inhibiting enzymes in eicosanoid synthesis:
Phospholipase A2
Cyclooxygenase/PGE isomerase
-also interferes with transcription factors, NF-kB: inhibits T cell development, inhibits B cell maturation
Summary: blocks innate and cell mediated immune response
What are the adverse events associated with glucocorticoids?
- increases risk of certain infections, cancer, anaphylaxis
- causes increase in glucocorticoid levels and long term use can lead to atrophy of adrenal cortex, hypertension, cushing syndrome
What is the role of TNF in inflammation?
-produced by mainly macrophages
-In acute, innate responses, TNF:
Initiates release of pro-inflammatory cytokines and vasoactive compounds
Facilitates recruitment of macrophage and neutrophils
Triggers apoptosis in neutrophils
In cell-mediated immune responses, TNF:
Involved in regulation of T- and B-lymphocytes
Is essential for granuloma formation
Induces activation and proliferation of fibroblasts
What are TNF blockers used for? (DMARD)
Chronic inflammatory diseases
Rheumatoid arthritis
inflammatory bowel diseases (Crohn’s disease, ulcerative colitis)
Psoriasis
What are the side effects of TNF blockers?
increases risk of:
certain infections, particularly chronic diseases involving granuloma formation (e.g., tuberculosis)
cancer, particularly certain types of lymphoma
anaphylaxis
Describe the ADME of aspirin? (absorption, distribution, metabolism, elimination)
A: rapidly absorbed in small intestine and converted to salicylic acid. 1-2hr
D: 90% bound to albumin, distributed in all tissues, can cross placenta
M/E: salicylic acid metabolized by liver to metabolites excreted by kidney. T1/2: 2-4.5 hrs. Shifts to zero order at high doses.
Describe the ADME of ibuprofen?
A: absorbed mostly in small intestine. Not prodrug. Tmax=2hr.
D: 98% bound to albumin. widely distributed. can cross placenta. low levels in breast milk.
M: metabolized in liver. T1/2=2hr.
E: excreted through kidney as metabolite
Describe the ADME of diphenhydramine?
A: small intestine. Tmax 2-3hrs. 60% dose reaches blood.
D: 80% bound to albumin. widely distributed. crosses blood brain barrier. “safe”during preg.
M: in liver. T1/2=8h.
E: little unmodified excreted by kidney.
Describe the ADME of dexamethasome?
A: 70-90% oral absorption. small intestine. Tmax=1-2hr. Cmax 65% of intramuscular dose.
D: 70% albumin bound.widely distributed, including CNS.
M: metabolized by liver.T1/2=2-3.5 hr
E: excreted by kidney as intact drug and metabolite.
