Inflammation

Question 1

What is an antacoid?

Answer 1

Mediators of inflammation produced locally around the site of stimulus to inflammation

Question 2

What are the conceptual challenges in developing new anti-inflammatory drugs?

Answer 2

Cost

Lack of oral availability

Question 3

How do histamine a fulfil Dale’s criteria for a pharmacological mediator?

Answer 3

Present in histaminergic neurones
Store in granules
Upon antigen-IgE cross-linking, granules are released
Effects shown at H receptors
Terminated by histaminase

Question 4

How does histamine contribute to a local inflammatory response?

Answer 4

Causes vasodilation of the small arteriolar and precapillary sphincters
Causes the release of CGRP and other vasodilatory by anti-dromic impulses in sensory nerve fibres

Question 5

How does histamine contribute to anaphylaxis?

Answer 5

Causes smooth muscle contraction in bronchi

Question 6

Name 3 chemical mediators which regulate acid secretion from parietal cells

Answer 6

Histamine (+)
Gastric (+)
Prostaglandins E(2) and I(2) (-)

Question 7

Describe ranitidine.

Answer 7

H(2) antagonist

Heals duodenal ulcers

Question 8

Describe terfenidine.

Answer 8

H1 non sedative antagonist

No entry to CNS

Question 9

Describe diphenhydramine.

Answer 9

H1 antagonist
Used to treat motion sickness
Can cross BBB

Question 10

What is an eicosanoid?

Answer 10

Locally produced lipids
Work in the 10(-12)M range
Small t(1/2) 
Metabolised into active prostaglandin

Question 11

Describe the biosynthesis of PGE(2)

Answer 11

Phospholipid is converted into arichidonic acid by phospholipase A(2)
arichidonic acid is converted to PGG(2) by cyclooxygenase
PGG(2) converted to PGH(2) by cycloendoperoxides
PGH(2) converted to PGE(2) by PG isomerise reductase

Question 12

How is the biosynthesis of PGE(2) targeted by anti-inflammatory drugs?

Answer 12

Lipocortin inhibits phospholipase A(2)

NSAIDS inhibit cyclooxygenase

Question 13

What are the main side-effects of NSAIDs?

Answer 13

Gastro-intestinal bleeding

Question 14

What is the biological mechanism behind NSAID gastrointestinal bleeding?

Answer 14

NSAIDs block cox-1, inhibiting PGE(2) production
Reducing PGE(2) increases acid production
Acid irritates gastrin mucosa increasing susceptibility to ulceration
They prolong bleeding by reducing the platelet stickiness

Question 15

How do cox-2 inhibitors avoid gastrointestinal bleeding?

Answer 15

Cox-2 doesn’t affect platelet stickiness

Question 16

Why is aspirin used for platelet inhibition and not other NSAIDs?

Answer 16

Aspirin is the only NSAID which irreversibly inhibits cyclooxygenase. This means much lower doses can be used and less frequently

Question 17

Uses of prostaglandin analogues.

Answer 17

Abortion
Labour induction
Postcoital contraception
Peptic ulcer treatment

Question 18

Main causative agents of peptic ulcer formation.

Answer 18

H. pylori
NSAIDs
Stress
Diet

Question 19

What is the HPA axis?

Answer 19

Hypothalamic- pituitary- adrenal axis
A complex set of direct feedback interactions among the 3 endocrine glands
Regulates glucocorticoids i.e cortisol

Question 20

How does the HPA axis contribute to the regulation of inflammation?

Answer 20

Glucocorticoids are anti-inflammatory
They suppress the production of antacoids
Inhibitor of induction and effector phases of immune response

Question 21

Omeprazole

Answer 21

Proton pump inhibitor
Treats peptic ulcers
Inhibits H/K ATPase of parietal cell
Decreases gastric acid secretion

Question 22

Aluminium hydroxide.

Answer 22

Antacid

Neutralises gastric acid

Question 23

Sucralfate.

Answer 23

Coating agent

Provides protection to GI epithelium

Question 24

Misoprostol.

Answer 24

Prostaglandin

Inhibits acid production

Question 25

Dicyclomine.

Answer 25

Anti cholinergic agent mAChR inhibitor Decrease acid secretion

Question 26

How do steroidal anti-inflammatory drugs affect prostaglandin production?

Answer 26

Inhibit the expression of cox-2, reducing the amount of PGE(2)

Question 27

How do NSAIDs affect prostaglandin production?

Answer 27

Inhibits cox-2, reducing the amount of PGE(2)

Question 28

List the 5 cardinal signs of inflammation

Answer 28

``` Pain- dolor Redness- rubor Immobility- functo leasa Swelling- tumor Heat- calor ```

Question 29

Describe the mechanism of action of glucocorticoids.

Answer 29

Bind to intracellular receptors, causing them to dimerise and move to the nucleus The complex inhibits the transcription of genes for cox-2 and NO synthase, cytokines, interleukins, and cell adhesion molecules

Question 30

What are the therapeutic affects of glucocorticoids?

Answer 30

Hydrocortisone: Decreases egress of neutrophils from blood vessels and reduced activation of neutrophils, macrophages, and mast cells Decreased activation of T(helper) cells

Question 31

What are the adverse effects of glucocorticoids?

Answer 31

Decreased fibroblast function, reduced healing and repair | Reduced activity of osteoblasts but increased activity of osteoclasts, develop osteoporosis

Question 32

What effects are encounter after administration of high doses and cessation of glucocorticoid treatment?

Answer 32

``` Suppression of the response to infection Osteoporosis Hyperglycaemia Muscle wasting Acute adrenal insufficiency ```

Question 33

List the pathological characteristics of asthma

Answer 33

Inflammation of airways Bronchial hyperactivity Reversible airways obstruction

Question 34

Give two symptomatic relievers

Answer 34

Salbutamol- beta 2 agonist- bronchodilation | Theophylline- activates PKC- bronchodilation

Question 35

Give two pathology modifying drugs

Answer 35

Cromoglycate | Nedocromil

Question 36

What is a biologic?

Answer 36

A medicinal preparation created by a biological process

Question 37

Discuss the use of therapeutic antibodies to treat inflammatory diseases.

Answer 37

Treats patients who do not respond to glucocorticoids Do not need glucocorticoids, avoiding side effects High cost Requirement of long term administration Has to be injected

Question 38

Compare infliximab with etanercept (TNF- alpha blockers)

Answer 38

Etanercept cannot neutralise receptor bound TNF when infliximab can Infliximab can also lyse cells in the inflammatory process