Pharmacology of anti-inflammatories and immune suppression

Question 1

Cardinal signs of inflammation

Answer 1

Rubor 
Tumor 
Calor
Dolore 
Functio laesa

Question 2

causes of acute inflammation

Answer 2

Infections (viral, bacterial, parasitic)
Trauma and foreign bodies
Chemical, physical, endogenous agents -> cell death
Acute immune reactions (Allergy

Question 3

causes of chronic inflammation

Answer 3

Persisting infections
Chronic exogenous or endogenous toxicity
Chronic immune reactions
(Autoimmunity & transplant rejection)

Question 4

examples of the immune driven inflammation

Answer 4

Allergies
Contact dermatitis
Celiac disease
Autoimmune disease
Organ rejection
Clearing bacterial and viral infections 
Graft vs Host disease

Question 5

name 5 NSAIDS

Answer 5

Aspirin, Indomethacin, Paracetamol, Ibuprofen, Diclofenac

Question 6

when are NSAIDS taken

Answer 6

Prescribed for pain & chronic inflammation

OTC for minor aches and pains.

Question 7

what symptoms do NSAIDS treat

Answer 7

anti-inflammatory
analgesic
antipyretic

Question 8

what are the significant adverse effects of NSAIDS on the GI tract

Answer 8

abdominal discomfort, dyspepsia
Stomach / duodenal ulceration
Myocardial infarction

Question 9

which is the only NSAID to irreversibly inactivate both isoforms of the COX enzymes (COX-1 and COX-2)

Answer 9

Aspirin

Question 10

which NSAID Acetylates the catalytic serine residue in position 529.

Answer 10

Aspirin

Question 11

at which levels does aspirin affect COX2 expression

Answer 11

at both transcriptional and posttranscriptional levels

Question 12

in what way does COX-2 acetylation modifies the enzyme

Answer 12

enzyme in such a way that it performs an incomplete reaction ultimately resulting in the generation of lipoxins

Question 13

what else does Aspirin do?

Answer 13

Inhibits IκB kinase and prevents NF-κB activation

Acetylates many proteins and RNA

Question 14

what are the two COX inhibitors

Answer 14

Aspirin and Ibuprofen

Question 15

how does ibuprofen block the antiplatelet effect?

Answer 15

by blocks the activity of aspirin

Question 16

Side effect of asprin

Answer 16

Nausa Stomach pain Heart burn Vomitting

Question 17

more serious side effects of Aspirin

Answer 17

swelling of eyes, face,lips,tongue,throat
wheezing, difficulty breathing, horseness, fast breathing
fast heart beat
cold clammy skin
hives rash
bright red blood in stools, black or tarry stolols
ringing in the ears, loss of hearing
bloody vomit, vomit resembling coffee grounds

Question 18

what are coxibs

Answer 18

family of drugs more targeted to COX-2

Selective anti-inflammatory

Question 19

example of a coxibs

Answer 19

Celecoxib

Question 20

where is cox 2 found

Answer 20

in cancer cells/Vascular endothelium/kidney

Question 21

why were coxibs made?

Answer 21

to minimise gastric problems

Question 22

what concurrent use of celecoxib increase the risk of

Answer 22

Hyponatraemia low sodium
Nephrotoxicity
Hyperkalaemia high potassium
bleeding

Question 23

what are NO-NSAIDs (nitric oxide-donating NSAID)

Answer 23

New class of NSAIDs having a gastro-protective effect and increased anti-inflammatory activity.

Question 24

SAIDS:glucocorticoids examples

Answer 24

hydrocortisone, prednisolone and dexamethasone

Question 25

what are SAIDS based on

Answer 25

Based on adrenal steroids

Question 26

what are SAIDS synthesized from

Answer 26

synthesized from cholesterol

Question 27

when are SAIDS released

Answer 27

released as needed under the influence of ACTH

Question 28

when are SAIDS used

Answer 28

Used clinically in many inflammatory disease

Question 29

when are SAIDS used Topically

Answer 29

low toxicity

Question 30

when are SAIDS used Acutely

Answer 30

acceptable toxicity

Question 31

when are SAIDS used Chronically

Answer 31

severe side effects and toxicity.

Question 32

when do you normally experience side effects of glucocorticods

Answer 32

Occurring mainly with prolonged systemic use as anti-inflammatory or immunosuppressive

Question 33

side effects of glucocorticoids

Answer 33

Suppression of response to infection Suppression of endogenous glucocorticoid synthesis. Metabolic actions (effecting carbohydrate and proteins metabolism) Iatrogenic Cushing’s Syndrome Osteoporosis

Question 34

Lewis triple response of histamine

Answer 34

Reddening -> Vasodilatation -small arterioles and pre-capillary vessels Wheal -> Increased permeability of post- capillary venules Flare -> antidromic stimulation of local nerve resulting in the release of vasodilators

Question 35

what receptors does Histamine affect?

Answer 35

H1, H2, H3 and H4 GPCRs

Question 36

what cells release histamine

Answer 36

mast cells

Question 37

when are histamines released

Answer 37

by exocytosis during inflammatory and allergic reactions

Question 38

what do histamines cause

Answer 38

``` Stimulation of gastric secretion Contraction of smooth muscle (other than that of blood vessels) Cardiac stimulation Vasodilation Increased vascular permeability ```

Question 39

Sedating Antihistamines H1, H2

Answer 39

Chlorphenamine | promethazine

Question 40

Non Sedating Antihistamines H1, H2

Answer 40

Cetrizine | fexofenadine

Question 41

what do antihistamines do

Answer 41

Reduce the increased vascular permeability caused by histamine

Question 42

when are antihistamines used

Answer 42

Allergic rhinitis (hay fever), urticaria, insect bites, drug sensitivitiesTopical preparations (e.g. for eye, nose)As a adjunct to adrenaline in emergency treatment of anaphylaxis

Question 43

other effects of antihistamines

Answer 43

5-hydroxytryptamine (5-HT) receptors, α!-adrenoreceptors and ACH muscarinic receptors

Question 44

Immunosuppression

Answer 44

Tissue rejection Psoriasis Rheumatoid arthritis Corticosteroids +

Question 45

Immunosuppressive drugs

Answer 45

Cyclosporine A Tacrolimus (F506) Rapamycin

Question 46

Two therapies for rheumatoid arthritis, psoriasis, asthma, Crohn’s, MS

Answer 46

Monoclonal Antibody therary | Disease Modifying Anti-Rheumatic Drugs (DMARDs):

Question 47

whar are monoclonal antibodies

Answer 47

Humanized or human monoclonal antibodies. Inhibit cytokines, receptors, adhesion molecules

Question 48

da foq

Answer 48

``` TNF: Cimzia, Humira, Remicade, Simponi IL6: Actemra IL12 and IL23: Stelara IL1α: Illaris IgE: Xolair α4 and α4β7: Tysabri, Entyvio CD11a: Raptiva CD20: Rituxan, Mabthera Other biologics: Anakinra, recombinant human IL-1RA; Enbrel, Human TNFR2–Fc fusion protein ```