15) NSAIDS

Question 1

What 3 Therapeutic Effects are NSAIDs used for ?

Answer 1

1) Analgesia - Local Peripheral action at the site of pain
- Decreased PGE2 synthesis in dorsal horn => Reduced Neurotransmitter release => Reduced Excitability of Neurons in pain relay pathway

2) Anti Inflammatory - Reduction in Prostaglandin Productions released during injury
3) Antipyretic Effects - Inhibition of Hypothalamic COX - 2

Question 2

What is the role of Prostaglandin ?

Answer 2

Enhances the effect of other autacoids such as Histamine and Bradykinin during an inflammatory response.
=> Vasodilation
=> Fever
=> Hyperalgesia

Question 3

Outline the synthesis of Prostaglandin

Answer 3

1) Inflammatory response when there is tissue damage Phospholipase A2 converts Phospholipids in the membrane in the Cell Membrane to Arachidonic Acid

2) Acid is then converted into Prostaglandins by COX 1 and 2
COX 1 = Constantly expressed in various tissues therefore most ADRs are due to blockage of COX 1
COX 2 = Expression is increased during expression therefore NSAIDs target this

Question 4

List ADRs of using NSAIDs
> GI
> Renal
> CVS

Answer 4

GI:
> Bleeding and Perforation 
> Peptic Ulceration 
> Dyspepsia 
> Nausea 

Renal:
> Reduce GFR
leading to water and Na+ Retention
> ADRs are more likely to occur in CKDs and Heart Failure

CVS:
> Vasconstriction occurs through the reduced antagonism of ADH by prostaglandin

Question 5

What are some risk factors of ADRs occurring ?

Answer 5

> Elderly patients
Long term usage
Organ failure
- Heart, Kidney, Liver

Question 6

How does Selective COX - 2 Inhibitors work ?
> Give an examples
> Uses

Answer 6

CeleCOXIB, Ibruprofen, Naproxen, Diclofenac

> Avoid inhibition of homeostatic functions mediated by COX 1
- Meaning less ADRs

Question 7

How does NSAIDs interact with other drugs

- Protein Binding

Answer 7

NSAIDs are heavily bound to plasma proteins, so will compete with other drugs, this results in the loss of binding of the drug meaning there is a higher plasma concentration.
> Sulphonyurea => Hypoglycaemia
> Warfarin => Increased Bleeding `

Question 8

What happens in a Paracetamol Overdose ?

> Treatment

Answer 8

Normally paracetamol is conjugated with sulphate for excretion - however, if the conjugated enzymes are saturated in an overdose it cannot be excreted => Build up of NAPQI which is toxic to cells
> NAPQI is conjugated with Glutathione

If quick activated charcoal
IF not give N - Acetyl Cysteine

Question 9

Why is Acetylcysteine given instead of just Glutathione

Answer 9

Acetylcysteine can be absorbed into hepatic cells

Question 10

What Homeostatic Functions does COX 1 have ?

Answer 10

> GI protection
Platelet Aggregation
Vascular Resistance
Renal Blood Flow

Question 11

What Homeostatic functions does COX 2 have ?

Answer 11

> Renal Homeostasis
Tissue Repair and Healing
Uterine Contractions
Inhibition of platelet aggregation

Question 12

What pathogenic functions does COX 1 have ?

Answer 12

> Chronic Inflammation
Chronic Pain
Raised BP

Question 13

What pathogenic functions does COX 2 have ?

Answer 13

> Chronic Inflammation 
> Chronic Pain 
> Fever
> Tumour Cell growth 
> Vascular Permeability