Broad spectrum anti-inflammatory and immunosuppressant drugs

NSAIDs

non steroidal anti-inflammatory drug

What enzyme does NSAIDs inhibit?

Cyclooxygenases (COX enzymes)

Main effects of NSAIDs

Analgesic, anti-inflammatory and antipyretic effects

Aspirin

is an analgesic (relieve pain) and antithrombotic (blood thinner)

Common NSAIDs

ibruprofen, naproxen, diclofenac

Main effect of paracetamol

Antipyretic (fever reducing)

How does fever develop

Pyrogens increase PGE2 which raises body temp

Pyrogens

increase PGE2

Side effect of long term NSAID use?

Gastric and duodenal ulceration

Why are uclers formed from NSAIDs

Prostaglandin inhibition causes increased acid secretion as PGs control acid secretion

What is an allergen

A normally harmless substance that triggers an abnormal immune response

Common symptoms of allergic reactions

itching swelling wheezing cramps vomiting

what mediators are released in severe allergic reactions?

Histamine and leukotrienes

treatment for minor allergic reactions

H1 antihistamines

1st generation antihistamine

cross blood brain barrier - cause sedation

chlorphenamine - sedative

2nd generation antihistamine

newer non sedating longer acting

cetrizine, levocetrizine

Treatment for severe allergic reactions

Glucocorticoids

Chronic inflammation phases

Phase 1 - chronic inflammation

Phase 2 - abnormal repair

Ulcerative colitis (UC)

IBD localized to the colon

Severe UC

increased risk of colorectal cancer

Crohn’s disease

affects small and large intestine

severe crohn’s

may lead to strictures which cause inflammation and may need surgical resection

Rheumatoid arthritis

Chronic autoimmune disease causes joint destruction

Effects of RA - rheumatoid arthritis

pain, deformities, loss of funcntion, hinders capacity to work play or participate in sports

Psoriasis

Skin disease - plaques due to thickened skin layers

Autoimmune diseases

immune system attacks own tissues or cells

B cells in autoimmune system

produce auto-antibodies to target own body

Example autoimmune

lupus

Lupus symptoms

joint pain rash idney disease pleuritis pericarditis

Glucocorticoids

Anti-inflammatory and immunosuppressant drugs

Natural source of glucocorticoids

derived from cholesterol - cortisol from adrenal glands

Glucocorticoids: Mechanism of action

bind nuclear receptors and alter gene expression

effects of glucorticoids

• reduce immune cell recruitment

• reduce T cell activity r

• reduce cytokines (IL-1, TNF)

• reduce prostaglandins, histamine, antibodies

Routes of administration of glucorticoids

oral IV topical

USes of glucorticoids

• ra

• ibd

• asthma

• psoriasis

• severe allergens

Side effects of long term use of glucorticoids

• infecitons

• osteoporosis

• muscle wasting

• hyperglycaemia

• poor wound healing

Aminosalicylates

inhibit lipoxygenase and reduce the level of leuktrienes

reduces infiltration of granulocytes

effects of aminosalicylates

reduce granulocyte infiltration

Calcinerin inhibitors

tacrolimus

Mechanism of Tacrolimus

Binds FKBP12 → inhibits calcineurin → ↓ cytokines

uses of tacrolimus

psoriasis, transplant rejection

side effects of tacrolimus

hypertension, tremor insomnia, hyperglycaemia

Cyclosporin

fungal product

mechanism of cyclosporin

binds cyclophilin which inhibits calcineruin

use of cyclosporin

prevent organ transplant rejection

major side effect of cyclosporin

nephrotoxicity

Methotrexate

immunosuppressant

Mechanism of methotrexate

antagonist of folic acid it blocks nucleotide synthesis which prevents cell division

methotrexate effect on immune cells

agonist of folic acid

blocks nucleotide synthesis

immunosuppressant

Use of methotrexate

RA - rheumatoid arthiritis

Side effect of methotrexate

bone marrow suppression