Steroids and NSAIDs

Question 1

What are the effects of NSAIDS?

Answer 1

Anti inflammatory - NSAIDS reduce the production of COX-2 products.

Analgesic effects - NSAIDS reduce prostoglandin synthesis which in turn decreases the amount of pain felt in response to inflammation and tissue damage

Antipyretic effects - PGE2 acts on pre optic area to increase thermostatic set point. NSAIDS inhibit cox-2 therefore reduce the amount of PGE2 produced which in turn lowers the thermostatic set point and allows heat loss mechanisms to occur. (sweating + vasodilation).

Question 2

What is the target of aspirin?

Answer 2

COX-1

Question 3

What are some additional effects of aspirin?

Answer 3

Reduces platelet aggregation.

Analgesic

antipyretic.

Reduces risk of stroke + thromboembolism

Question 4

How is Aspirin absorbed?

Answer 4

It is a weak acid - it is absorbed from stomach which is facilitated by the low pH.

It is hydrolysed to salycylic acid in plasma and at low theraputic doese most is bound to serum albumin.

Question 5

How is Aspirin metabolized and excreted?

Answer 5

25% excreted unchanged

25% is oxidised

Some is conjugated with glucuronide or sulphate.

Question 6

What are some of the adverse effects of aspirin?

Answer 6

Gastric bleeding due to the inhibition of COX-1 which is responsible for gastric mucosa protection - inhibition of platelets contributes to this effect.

Overdose (salicylism).

Due to viral infecton which causes liver/cns disturbances.

Also caused by chronic toxicity with repeated ingestion of high doses.

Causes altered acid base balance in the body which in turn uncoupled oxidative phosphrylation.

This leads to respiratory and metabolic acidosis

• causes tittinus, dizziness, hearing loss and nausea

Question 7

What is the effects of paracetamol?

Answer 7

Weak antipyretic

Mild analgesic

Weak to no anti inflammatory properties.

Question 8

How does paracetamol work?

Answer 8

Appears to inhibit Cox-1 and Cox-2 through metabolism by the perioxidase function.

Selectively inhibits synthesis of PGs when arachidonic acid and peroxides levels are low. However has little activity when levels of AA and PG are high.

• Does not suppress the severe inflammation for rheumatoid arthritis but will have some help in reducing inflammation following tooth extraction.

Question 9

What are some of the adverse effects of paracetamol?

Answer 9

Overdose

• Can cause fatal liver toxicity due to saturation of normal liver enzymes.
• This causes paracetamol to be broken down by other enzymes which produces NAPQI.
• NAPQI is toxic if it isnt conjugated by glutathione.

Question 10

What is the effects of ibuprofen?

Answer 10

Anti inflammatory

Anti-pyretic

Analgesic

Mild antiplatelet + vasodilation

Question 11

What ways can ibuprofen be administered?

Answer 11

Orally, topically as is stable in solution.

Question 12

What is one of the benefits of using topical ibuprofen compared to oral?

Answer 12

Less risk of gastric problems

Question 13

What is the target of ibuprofen?

Answer 13

Cox- 1 and Cox- 2.

Question 14

What are some adverse effects of ibuprofen?

Answer 14

Nausea dyspepsia, GI ulceration, Raised liver enzymes.

Exacerbate asthma sometime fatal

Question 15

How can COX-1 inhibition cause gastric ulceration?

Answer 15

PGG2 and PGE2 usually protect gastric mucosa. - inhibition of COX decreases PG production.

Some drugs (aspirin) cause damage to mucosal cells directly.

COX-1 inhibitors inhibit platelet aggregation.

GI damage can be increased by concurrent glucocorticoid administration and dehydration and hypovolaemia.

Question 16

What is the risks associated with using Cox-2 selective inhibitors?

Answer 16

Increases the risk of heart attacks and strokes

Question 17

What is the inflammatory effects of Leukotrienes?

Answer 17

Bronchostriction

Vasodilation and oedema

Increased mucus secretion in airway and gut

Recruitment of leukocytes to site of inflammation.

Question 18

What are some common CysLT receptor antagonists?

Answer 18

Zafirlukast

Montelukast.

Question 19

Where are corticosteroids produces?

Answer 19

outer layer or cortex - mineralcorticoids

middle layer - glucocorticoids (hydrocortisone, corticosterone)

Question 20

What is the result of low cortisol levels?

Answer 20

Muscle weakness

Hypotension

Hypoglycaemia

Weight loss

Question 21

What is addisons disease?

Answer 21

Autoimmune destruction of the adrenal cortex .

Causes a decreased levels of glucocorticoids.

Treated by extrinsic hydrocortisone supplementation.

Question 22

What are the anti-inflammatory effects of glucocorticoids?

Answer 22

Stimulate the production of Annexin 1 which inhibits Phospholipase A2- reduced concentration of AA.

When Glucocorticoids bind to their receptor they -

• up regulate the expression of nuclear anti inflammatory proteins.
• Repress the expression of cytosolic pro inflammatory proteins. Such as complement, NO, Histamine, IgG.

Question 23

What are some of the clinical uses of glucocorticoids?

Answer 23

Asthma

Eczma

Rhinits

Hypersensitivty states (severe allergic response).

Misellaneous disease with autoimmune/anti inflammatory components.

Immunosuppression for graft rejection etc.

Question 24

How are glucocorticoids administered?

Answer 24

oral, topical , parenteral (IV IM).

Question 25

Once administered how do glucocorticoids get into cells?

Answer 25

Once in the blood they bind to the corticosteroid binding globulin then enter cells by diffusion.

Question 26

How are glucocorticoids metabolized?

Answer 26

By the liver and secreted in urine.

Question 27

What are some adverse effects of the use of glucocorticoids?

Answer 27

Increased risk of infection

Suppress endogenous cortisol production. - hypocortism.

Cushings disease due to excessive administration.

Question 28

In what case would we not give a patient corticosteroids based upon their patient history?

Answer 28

Renal insufficiency / congestive heart failure.

Drug interactions may increase risk of bleeding and complications during dental surgery.