NSAIDS and paracetamol

Question 1

mediators that can induce pain

Answer 1

prostaglandins
leukotrienes
substance P
bradykinin

Question 2

Traditional NSAIDS examples

Answer 2

aspirin
diclofenac
ibuprofen
naproxen

Question 3

Cox 2 inhibitors examples

Answer 3

celecoxib

meloxicam

Question 4

NSAIDS are used in conditions including

Answer 4

backache, headache, toothache
muscular aches and pains
osteoarthritis, rheumatoid arthritis
dysmenorrhoea, gout, some cancer pain-thrombotic events (low dose aspirin)

Question 5

NSAIDS exert the following activities

Answer 5

-analgesic
anti-inflammatory
antipyretic 
anti-platelet 
Block the production of prostaglandins by inhibiting the enzyme cyclooxygenase

Question 6

Cyclooxygenase exists in two forms

Answer 6

cyclooxygenase 1 (COX 1) -cyclooxygenase 2 (COX 2)

Question 7

COX 1

Answer 7

found in most cells
A consistutive enzyme which synthesizes the production of prostaglandins which are involved in homeostasis – housekeeping or good prostaglandins

Question 8

cox 2

Answer 8

induced by inflammatory stimuli and synthesis prostaglandins which are involved in pain and inflammation bad prostaglandins

A constitivue enzyme in some areas eg kidney vascular tissue

Also thought to be involved in some cancers

Question 9

NSAIDS

Answer 9

produce vasodilation

potentiate the increased permeability of blood vessels caused by substances such as histamine and bradykinin

sensitise nerve terminals and potentiate the pain producing effects of substances such as bradykinin and 5-hydroxytrypamine (they do not directly produce pain themselves)

Traditional NSAIDS (e.g. aspirin, diclofenac, ibuprofen, naproxen) inhibit both COX 1 and COX 2•Traditional NSAIDS block the production of all prostaglandins

Question 10

prostagladins

Answer 10

The prostaglandins are a group of lipids made at sites of tissue damage or infection that are involved in dealing with injury and illness.

Prostagldins act on prostaglandin G protein coupled receptors DP FP IP EP TP
Prostaglandins such as PGE2 and PGI2 are involved in pain and inflammation

Question 11

The stomach

Answer 11

• Digestion of proteins by pepsin
• Gastric juice very ph
• The stomach mucosa is exposed to some of the harshest conditions
• The gastric mucosal barrier from bicarbonate and mucus protect tissue from acids and enzymes in the lumen of the stomach
• Prostaglandins formed by cox1 eg PGE2 help maintain this barrier
o Increase bicarbonate ion secretion
o Increase mucosal secretion and mucosal blood flow
o Reduce gastric acid secretion
• Traditional NSAIDS can reduce these effects causing bleeding

Question 12

prostagladins in stomach

Answer 12

formed by COX 1 e.g. PGE2 help maintain this protective barrier 
increase bicarbonate ion secretion
increase mucus secretion
increase mucosal blood flow 
reduce gastric acid secretion

Question 13

Blockage of good housing keeping prostaglandins results in

Answer 13

• GI bleeding and ulcers
• Increased tendency to bleed
• Reduced renal function
• Sodium and water retention
• Early miscarriage and prolongation of labour
• Asthma symptoms

Question 14

Other house keeping prostaglandins include those that

Answer 14

o Help maintain renal function eg PG12 PGE2 (COX2 )
o Help maintina airway function in some patients with asthma
o Assist implantation of fertilized ovum
o Maintain patent ductus arteriosus (PGE1) and contract the uterus during labor eg PGF

Question 15

Low Dose Aspirin

Answer 15

In platelets the enzyme cyclooxygenase 1 (COX 1) converts arachidonic acid to thromboxane A2

Thromboxane A2induces platelet aggregation and vasoconstriction

Aspirin irreversibly inhibits COX 1, inhibits the production of thromboxane A2 and reduces platelet aggregation

Question 16

Patients with caution for NSAID are

Answer 16

• Pervious ulcer
• Cardiac failure
• Hypertension
• Renal impairment
• Asthma
• Pregnancy
• Elderly patients are more adverse effects with NSAIDs

Question 17

Traditional NSAIDs exert the antipyretic (used to prevent or reduce fever) effect by

Answer 17

inhibiting the synthesis of prostaglandins in the hypothalamus they do not lower normal temperature
A number of important drug interactions may occur

Question 18

COx inhibitors vs NSAIDS

Answer 18

COX 2 inhibitors are claimed to produce less gastrointestinal bleeding and ulcers than traditional NSAIDS

COX 2 inhibitors produce the same analgesic and anti-inflammatory effects as traditional NSAIDS -they are no more effective than traditional NSAIDS

COX 2 inhibitors produce the same adverse renal effects as traditional NSAIDS -use with caution in patients with renal impairment, hypertension or cardiac failure

A number of important drug interactions may occur with COX 2 inhibitors. Examples include angiotensin converting enzyme inhibitors, angiotensin 2 receptor antagonists, anti-hypertensives, diuretics, lithium and fluconazole

Question 19

Rofecoxib (Vioxx)

Answer 19

Removed from market increased risk of heart attack and stroke

Question 20

Only give NSAIDS

Answer 20

• When necessary
• In the lowest dose
• For the shortest amount possible

Question 21

Possible Mechanism for Adverse Cardiovascular Events

Answer 21

increased risk of heart attack

stroke

Question 22

Paracetamol aka acetaminophen

Answer 22

• Exerts analgesic and antipyretic
• May be used where NSAIDS are contraindication
o Previous ulcer
o Cardiac failure
o Hypertension
o Asthma
o Renal impairment
• Does not exert anti inflammatory activity
• Does not block cox2 or cox1
• Possible interaction with warfarin monitor INR
• Undergoes glucuronidation and sulphation with a small amount being converted to NABQI by CYP450 2E1
•

Question 23

paracetamol overdose

Answer 23

• Can cause toxicity and overdose
• When taken in overdose the normal glucuronidation and sulphation pathways can become depleted

Antidote is acetylcysteine
Give quick