Pharmacology of inflammation

Question 1

What do NSAIDs stand for?

Answer 1

Non-steroidal anti-inflammatory drugs

Question 2

How do NSAIDs work?

Answer 2

Inhibiting the activity of cyclooxygenase enzymes (COX-1 or COX-2).

Question 3

What is the role of COX enzyme?

Answer 3

COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid

Question 4

What is arachidonic acid generated from?

Answer 4

Phosphatidylinositol

Question 5

How is arachidonic converted from phosphatidylinositol?

Answer 5

Via phospholipase A2

Question 6

What are prostaglandins involved in?

Answer 6

Inflammation

Question 7

What are thromboxane’s involved in?

Answer 7

Haemostasis

Question 8

What are non-selective NSAIDs?

Answer 8

Ibuprofen, Naproxen, Diclofenac, Aspirin

Question 9

What are COX2 selective NSAIDs?

Answer 9

Celecoxib, Rofecoxib

Question 10

What coverts arachidonic acid to the leukotriene pathway?

Answer 10

Lipoxygenase

Question 11

Why is aspirin taken by stroke vulnerable patients?

Answer 11

Reduced blood clotting

Question 12

What is the role of thromboxane A2?

Answer 12

Thromboxane that is produced by activated platelets during haemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation.

Question 13

What steroid drugs are used for inflammation?

Answer 13

Glucocoticosteroids

Question 14

Why are glucocorticosteroids the most powerful anti-inflammatories?

Answer 14

Capable of inhibiting virtually all the components of inflammation.

Question 15

What do glucocorticosteriods upregulate?

Answer 15

Annexin-1

Question 16

What does annexin-1 do?

Answer 16

Suppresses phospholipase A2, thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events (epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst).

Question 17

Why are glucocorticosteroids good for treating asthma but NSAIDs don’t have a huge effect?

Answer 17

Steroids target earlier in the AA pathway, inhibit prostaglandin and leukotriene production

Question 18

What are the most prominent glucocorticoids?

Answer 18

Cortisol (hydrocortisone), Cortisone, Prednisone, Prednisolone, Methylprednisolone and Dexamethasone.

Question 19

Side effects of glucocorticoids?

Answer 19

Immunodeficiency is the main side effect: increasing susceptibility to viral infection

Hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance (“steroid diabetes”); caution in those with diabetes mellitus

Increased skin fragility, easy bruising

Steroid-induced osteoporosis: reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)

Weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; see corticosteroid-induced lipodystrophy

Hypertension through effects of fluid and electrolyte balance.

Question 20

What is histamine synthesised from?

Answer 20

Decarboxylation of histidine

Question 21

First generation antihistamines are..

Answer 21

Not specific to the H1 receptor, inverse agonists

Question 22

Second generation antihistamines, are…, they were synthesised because..

Answer 22

Modifications of the First Generation Antihistamines to eliminate side effects resulted in the Second Generation Antihistamines

More selective for peripheral H1 receptors

Question 23

What are side effects of first generation anti-histamines?

Answer 23

Because they can cross the BBB, they cause drowsiness, as H1 receptors are also involved in the CNS in the sleep-wake cycle.

Question 24

Types of first generation anti-histamine

Answer 24

Ethylenediamines, Ethanolamines, Alkylamines - Chlorphenamine, Piperazines and Tricyclics.

Question 25

Examples of second generation anti-histamines

Answer 25

Terfenadine, loratadine and cetirizine

Question 26

What are DMARDs

Answer 26

Disease-modifying antirheumatic drugs

Question 27

What is does methotrexate do?

Answer 27

Stimulates adenosine release from fibroblasts, reduces neutrophil adhesion, inhibits leukotriene B4 synthesis by neutrophils, inhibits local IL-1 production, reduces levels of IL-6 and IL-8, suppresses cell-mediated immunity, and inhibits synovial collagenase gene expression.

Question 28

What are biological DMARDs?

Answer 28

Biologic DMARDs are highly specific and target a specific pathway of the immune system

Question 29

Biological DMARD examples

Answer 29

Some biologic agents include infliximab (TNFalpha), adalimumab, etanercept, rituximab, abatacept, rituximab, tocilizumab (IL-6), tofacitinib, among others.