Drugs To Treat Autoimmune Disease

Question 1

Clinical uses of non-steroidal anti-inflammatory drugs

Answer 1

Ani-inflammatory effects
Analgesic effects (pain reduction)
Antipyretic effects (reduction of body temperature)

Question 2

Pharmacological effects of non-steroidal anti-inflammatory drugs relates to their ability to inhibit what enzyme?

Answer 2

Cyclooxygenase

Question 3

What happens if you inhibit cyclooxygenase?

Answer 3

You inhibit the production of prostaglandins

Question 4

Effects of prostaglandins include:

Answer 4

Powerful vasodilation
Decrease in blood flow

Question 5

2 types of cyclooxyrgenase

Answer 5

COX-1 and COX-2

Question 6

COX-1

Answer 6

Expressed in most fissures
Housekeeping role involved in tissue homeostasis

Question 7

COX-2

Answer 7

Expression induced in activated inflammatory cells
Expression induced by cytokines IL-1 and TNF-alpha
Anti-inflammatory action of NSAIDs is dues to inhibition of COX-2

Question 8

Examples of older, non-selective NSAIDs

Answer 8

Aspirin, ibuprofen, paracetamol

Question 9

COX-2 inhibitors play a significant part in reducing

Answer 9

Vasodilation
Oedema
Pain

Question 10

Common adverse effects of NSAIDs

Answer 10

Gastric irritation
Effect on renal blood flow
Prolong bleeding through inhibiting platelet function
Increases likelihood of thrombotic events including myocardial infarction

Question 11

Immunosuppressants

Answer 11

Interact directly with the immune system and either inhibit T-cell production or block the release of mediators from phagocytes

Question 12

Clinical uses of immunosuppressants include

Answer 12

Suppressing rejection of transplanted organs
Treating a variety of autoimmune diseases

Question 13

Cyclosporin

Answer 13

Immunosuppressant
Cyclic peptide of 11 amino acids

Question 14

Cyclosporin mechanism of action

Answer 14

Binds to a cytosolic protein in T-cells called cyclophilin, inhibiting transcription factor activation for the activation and synthesis of IL-2

Question 15

Glucocorticoids - Adrenal steroids

Answer 15

Endogenous substance that maintain a low level of anti-inflammatory actions

Question 16

Glucocorticoids examples

Answer 16

Hydrocortisone
Prednisolone
Dexamethasone

Question 17

Actions of glucorticoids on inflammatory cells

Answer 17

Reduced activity of macrophages by decreasing gene transcription of cytokines
Decreased action of helper T-cells by decreased proliferation
Decreased production of cytokines
Decrease production of nitric oxide, histamine, and prostanoids

Question 18

Glucocorticoids - mechanism of action

Answer 18

Bind intracellular receptors that then dimerise, migrate to the nucleus, and interact with DNA to modify gene transcription and protein synthesis

Question 19

Azathioprine

Answer 19

Interferes with purine synthesis & is cytotoxic
Widely used for immunosuppression for control of tissue rejection in transplant surgery

Question 20

Azothioprine as a prodrug

Answer 20

Metabolised from azothioprine to mercaptopurine, which is an analogue of purine that interferes with natural DNA synthesis and therefore prevents the division of T-cells

Question 21

Anti rheumatoid drugs

Answer 21

Immunosuppressants
Glucocorticoids
NSAIDs (reduce symptoms but do not slow progression of disease)
Disease modifying anti rheumatoid drugs

Question 22

What do disease modifying anti rheumatoid drugs do?

Answer 22

Improve symptoms and reduce disease activity

Question 23

Examples of disease-modifying anti-rheumatoid drugs

Answer 23

Sulfasalazine
Gold compounds
Anti-cytokine therapy

Question 24

Sulfasalazine

Answer 24

Produces remission in RA
Thought to work via reducing activity of phagocytes by scavenging ROS and/or NO

Question 25

Gold compounds

Answer 25

Effects develop slowly (over 3-4 months) Pain and joint swelling subsides Mechanism of action unknown

Question 26

Anti-cytokines therapy

Answer 26

Greatest conceptual breakthrough in treatment of chronic inflammatory disease Treatment aimed at specific-aspects of the immune response Drugs are “biopharmaceuticals” Recombinant engineered antibodies specific for human protein THUS – difficult to produce and expensive They are administered in the UK to patients resistant to other DMARDs

Question 27

Anti-cytokines therapy - infliximab

Answer 27

Monoclonal antibody against TNF-alpha Binds to TNF-alpha and prevents its action

Question 28

Anti-cytokines therapy - basiliximab

Answer 28

Monoclonal antibody against IL-2 receptor Binds to IL-2 receptor and prevent effective T-cell proliferation

Question 29

Anti-cytokines therapy - anakinara

Answer 29

IL-1 beta receptor antagonist