Pharm: Anti-Inflammatories_Dmards

Front 1

What is the purpose of the Arachidonic Acid pathway?

Back 1

Production of inflammatory mediators (including Eicosanoids).

Front 2

Name the main products of the arachidonic acid pathway.

Back 2

The arachidonic acid pathway produces:
1. Leukotrienes
2. Thromboxanes
3. Prostacyclin
4. Prostaglandins

Front 3

Which enzyme liberates Arachidonic Acid
from membrane phospholipids?

Back 3

Phospholipase-A2

Front 4

What two enzymatic pathways exist in respect of Arachidonic Acid?

Back 4

Arachidonic Acid may either be acted on by:
- 5-lipoxygenase, or
- cyclo-oxygenase enzymes

Front 5

The 5-lipoxygenase pathway produces mediators called ___________

Back 5

Leukotrienes

Front 6

The cyclooxygenase (COX) pathway produces which three inflammatory mediators?

Back 6

The cycloxygenase pathway produces:
1) Thromboxanes
2) Prostacyclin
3) Prostaglandins

Front 7

When arachidonic acid is acted upon by COX enzymes, what intermediate is produced?

Back 7

Cyclo-endoperoxides

Front 8

Thromboxanes are produced where?

Back 8

Thromboxanes are produced by platelets.

Front 9

Prostacyclin is produced where?

Back 9

Prostacyclin is produced in the Endothelium.

Front 10

Where are prostaglandins produced?

Back 10

Smooth muscle

Front 11

Which cycloxygenase enzyme is found in most cells?

Back 11

COX 1 is found in most cells. It is "constitutive".

Front 12

What is necessary to stimulate expression of COX2 ?

Back 12

An inflammatory stimulus is necessary to induce expression of COX 2.
(COX-2 is stimulated only by such stimuli)

Front 13

True or false?
COX 1 is particularly abundantly expressed by platelets.

Back 13

True.
COX 1 is particularly abundantly expressed by platelets.

Front 14

At a site of inflammation, which type of COX enzyme would you expect to encounter?

Back 14

Both types.
COX 1 is present in most cells, and
COX 2 is induced by inflammatory stimuli.

Front 15

What is kwn about COX 3?

Back 15

Not a great deal, but it is thought to be the site of action for paracetamol.

Front 16

Define cyclo-oxygenase (COX).

Back 16

Cyclo-oxygenase is an enzyme that converts Arachidonic Acid into eicosanoids (inflammatory mediators).

Front 17

How do the inflammatory mediators produced in the arachidonic acid pathway exert their effects?

Back 17

They act on receptors in local body cell membranes.

Front 18

What are the main functions of the eicosanoids?

Back 18

-circulation changes (via vasoconstriction and dilation)
-mediate platelet aggregation
-stimulate pain receptors

Front 19

List the cardinal signs of inflammation.

Back 19

Inflammation cardinal signs:
1. heat
2. swelling
3. redness
4. pain
5. loss of function

Front 20

State the three main events in inflammation.

Back 20

Inflammation involves increased:
1. Vasodilation
2. Blood Flow
3. Capillary Permeability

Front 21

What is the action of thromboxane?

Back 21

ThromboXane causes platelet aggregation and is an vasoconstrictor.

Front 22

What is the action of Prostacyclin?

Back 22

ProstacyclIN INhibits platelet aggregation and
is a vasodilator.

Front 23

What do the Prostaglandins do?

Back 23

Prostaglandins:
- Activate PAIN receptors
- increase vasodilation and Permeability

Front 24

Name some substances that control the inflammatory response.

Back 24

Inflammatory response controlled by:
a) histamine
b) bradykinin
c) substance-P
d) cytokines
e) eicosanoids

Front 25

Inflammation is...?

Back 25

A set of vascular and cellular responses to tissue insult or injury

Front 26

Name some substances that control the inflammatory response.

Back 26

Inflammatory response controlled by:
a) histamine
b) bradykinin
c) substance-P
d) cytokines
e) eicosanoids

Front 27

Inflammation is...?

Back 27

Vascular and cellular changes that occur in response to
tissue insult or injury.

Front 28

Most anti-inflammatory therapy is based on what?

Back 28

....manipulation of eicosanoid synthesis

Front 29

State the main types of anti-inflamm drugs.

Back 29

Main anti inflamm drugs are:
-NSAIDs
-Steroidal anti-inflamms (glucocorticoids)

Front 30

Name a common feature of NSAIDs and Glucocorticoid drugs.

Back 30

Both NSAIDs and glucocorticoids inhibit synthesis of eicosanoids.

Front 31

What causes most adverse effects of NSAIDs and why?

Back 31

Inhibition of COX-1

(its necessary to maintain integrity of the GI epithelium).

Front 32

What accounts for the analgesic and anti-inflammatory effects of NSAIDs?

Back 32

COX-2 inhibition.
Prostacyclin and prostaglandin production is inhibited.

Front 33

Compare and contrast 2 different NSAIDs

Back 33

-

Front 34

Name one mild and one potent NSAID.

Back 34

Mild NSAID = Ibuprofen
Potent NSAIDs = Celecoxib, Piroxicam

Front 35

Give 3 licensed indications for use of diclofenac sodium.

Back 35

Indications for diclofenac sodium:
1.
2.
3.

Front 36

Outline the pharmacodynamics of aspirin

Back 36

-

Front 37

Why should NSAIDs and Warfarin not be taken together?

Back 37

NSAIDs increase the anti-coagulant effects of Warfarin.
Mixing them poses the risk of a fatal bleed.

Front 38

In what situations would a COX-2 inhibitor
NSAID be indicated?

Back 38

where non-selectives cannot be used, i.e:
- where risk of GI complications exists
- where bleeding risk exists
- if max NSAID already prescribed

Front 39

On what basis does the BNF say NSAIDs should be chosen?

Back 39

on the basis of the incidence of GI and other side effects. (p.505)

Front 40

State the category, MOA, indications, contrainds, interactions and SEs of Ibuprofen.

Back 40

-

Front 41

State the category, MOA, indications, contrainds, interactions and SEs of voltarol.

Back 41

-

Front 42

Name one reason why methotrextate is cytotoxic?

Back 42

Methotrexate is cytotoxic because it is potent folate antagonist. Folate is necessary for synthesis of purines and pyramidines (the two types of bases from which DNA is constructed), without which DNA synthesis is not possible. Without folic acid, cell death occurs.

Front 43

True or false?
NSAIDs inhibit synthesis of all inflammatory mediators.

Back 43

False.
NSAIDs only inhibit the products of the cyclooxygenase pathway, and have no effect on the lipoxygenase pathway which results in Leukotrienes.

Front 44

Name one reversible and one non-reversible COX inhibiting drug.

Back 44

Reversible COX inhibitor = ibuprofen

Irreversible COX inhibitor = Aspirin

Front 45

What 2 main actions do NSAIDs share with Paracetamol?

Back 45

Both NSAIDs and Paracetamol are:
- analgesic [Pain Relieving]
- antipyretic [Reduce Fever]

Front 46

Why is a patient's Prothrombin Time important if NSAIDs are being considered?

Back 46

All NSAIDs can induce life-threatening bleeds in
patients with prolonged Prothrombin Times.

Front 47

What is the main drug interaction with Aspirin?

Back 47

Aspirin should never be given with Warfarin. Aspirin has an antiplatelet action and increases the bleeding time.

Front 48

Is Aspirin safe for asthmatics?

Back 48

No. Aspirin may induce asthma in some patients.

Front 49

Is Aspirin excreted from the body unchanged?

Back 49

No. Aspirin is hydrolysed and conjugated before excretion.

Front 50

Is Indomethacin a weak or potent NSAID?

Back 50

Indomethacin is a potent NSAID.

Front 51

Name 2 unwanted side effects of Indomethacin.

Back 51

Indomethacin can:
- cause water and salt retention
- cause GI bleeding

Front 52

True or false?
Indomethacin and Aspirin interact to the same extent with Warfarin.

Back 52

False.
Aspirin interacts with Warfarin, but Indomethacin reacts little with Warfarin.

Front 53

Why might simultaneous prescription of thiazide diuretics and Allopurinol not be a good idea?

Back 53

Thiazide diuretics elevate plasma urate, so are contraindicated in gout.

Front 54

Why should Aspirin and Ibuprofen not be taken together?

Back 54

Both are non-selective NSAIDs, inhibiting COX-1 and its GI protective effect.
Taken together there is a risk of GI bleeding and ulceration.

Front 55

Example of COX-2 selective inhibitor drug.

Back 55

Celecoxib

Front 56

Short notes on Celecoxib.

Back 56

Class - COX2 selective NSAID
MOA - selectively inhibits COX2 production thereby inhibiting pain and inflammation - inducing prostaglandins. Does not inhibi thromboxane.
Indications - pts at high risk of GI effects (elderly), pts already on long-term max NSAID doses
Contras - heart disease, stroke, PAD
Interactions - Aspirin (increased risk of adverse GI effects)
Side effects - increases thrombotic risk

Front 57

Name a topically applied NSAID

Back 57

topical NSAID = ibuprofen

Front 58

Tx options for gout?

Back 58

Gout Tx:
Acute = Indomethacin (potent NSAID)
Prophylaxis = Allopurinol (decreases uric acid excretion)

Front 59

What is gout?

Back 59

Gout is due to overproduction of purines. Sodium urate crystals form in the joints and evoke an inflammatory response.