Anti-inflammatory agents

Question 1

What are examples of nonsteroidal anti inflammatory drugs (NSAID)?

Answer 1

Aspirin, ibuprofen, naproxen, celecoxib

Question 2

What are example of antihistamines?

Answer 2

diphenhydramine, Fexofenadine (Allegra),

Loratadine (Claritin)

Question 3

What are examples of glucocorticoids?

Answer 3

hydrocortisone, dexamethasone, prednisone

Question 4

What are examples of disease modifying anti-rheumatic drugs?

Answer 4

anti TNF antibodies: adalimumab (humira), infliximab (remicade), etanercept (enbrel)

Question 5

What is the mechanism behind NSAIDs?

Answer 5

• prostaglandin H2 synthesis inhibitors

- Block cyclooxygenases (COX1 and COX2)

Question 6

What is the role of prostanoids?

Answer 6

-Vasodilation 
Prostacyclin (PGI2), PGE2
-Vasoconstriction
Thromboxane A2
-Sensitize spinal neurons to pain (hyperalgesia)
 PGE2
-Acts on thermoregulatory center of hypothalamus to produce fever
PGE2

Question 7

What are some problems associated with non-selective COX inhibitors?

Answer 7

• 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

Question 8

What is the role of histamine in the body?

Answer 8

A mediator of immediate allergic and inflammatory reactions
Controls gastric acid secretion and mucus production
Functions as a neurotransmitter and neuromodulator

Question 9

What are the effects of antihistamines?

Answer 9

Block histamine-triggered:
Vasodilation
Increased permeability of blood vessels

Reducing:
Redness and swelling
Runny nose and watery eyes

Question 10

What is the mechanism of antihistamines?

Answer 10

• block H1 receptors

- are inverse agonist

Question 11

What are side effects of antihistamines?

Answer 11

• drowsiness

- dizziness and dry mouth

Question 12

What are the functions of glucocorticoids in the body?

Answer 12

• 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.

Question 13

What is the mechanism behind glucocorticoid immunosuppression?

Answer 13

-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

Question 14

What are the adverse events associated with glucocorticoids?

Answer 14

• 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

Question 15

What is the role of TNF in inflammation?

Answer 15

-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

Question 16

What are TNF blockers used for? (DMARD)

Answer 16

Chronic inflammatory diseases
Rheumatoid arthritis
inflammatory bowel diseases (Crohn’s disease, ulcerative colitis)
Psoriasis

Question 17

What are the side effects of TNF blockers?

Answer 17

increases risk of:

certain infections, particularly chronic diseases involving granuloma formation (e.g., tuberculosis)
cancer, particularly certain types of lymphoma
anaphylaxis

Question 18

Describe the ADME of aspirin? (absorption, distribution, metabolism, elimination)

Answer 18

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.

Question 19

Describe the ADME of ibuprofen?

Answer 19

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

Question 20

Describe the ADME of diphenhydramine?

Answer 20

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.

Question 21

Describe the ADME of dexamethasome?

Answer 21

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.