Non-Opioid Analgesics

Question 1

Define pain

Answer 1

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Question 2

What are the two types of physiological pain?

Answer 2

Nociceptive pain and inflammatory pain

Question 3

What is nociceptive pain?

Answer 3

Nociceptive pain is a response to a painful (nociceptive) stimulus, often followed by a protective response E.g. autonmomic withdrawal reflex.

Question 4

What is inflammatory pain?

Answer 4

Inflammatory mediators lead to pain hypersensitivity - adaptive, low threshold pain.

Question 5

What is the adaptive purpose of inflamamtory pain?

Answer 5

The tenderness that accompanies inflammatory pain follows promotes rest and repair.

Question 6

Describe the process of prostaglandin synthesis from essential fatty acids

Answer 6

1. Essential fatty acids converted to membrane phospholipids
2. Membrane phospholipids converted to arachidonic acid by phosphplipase A2
3. Arachidonic acid converted to prostaglandin by cyclo-oxygenase (COX)

Question 7

What role do prostaglandins play in inflamamtion?

Answer 7

Prostaglandins create areas of swelling, vasodilating and pain at sites of injury.

Question 8

How do NSAIDs function?

Answer 8

NSAIDs block the formation of prostaglandins by inhibiting cyclo-oxygenase (COX) enzyme.

Question 9

What are the four groups of adverse effects encountered with NSAID use?

Answer 9

1. GI - irritability, bleeding
2. Renal - if renal impairment
3. Platelet - increased risk of bleeding (non-selective NSAIDs)
4. Respiratory - NSAID induced astham in 15% asthmatics

Question 10

What adverse GI effects occur with NSAID use?

Answer 10

Irritability, bleeding, gastric/duodenal ulceration

Question 11

What adverse renal effects can occur with NSAID use?

Answer 11

NSAIDs are generally very well tolerated if renal function is normal.

If impaired, can cause fluid retention, oedema and hypertension.

Question 12

What are the possible platelet related adverse effects of NSAIDs

Answer 12

Non-selective NSAIDs carry an increased risk of bleeding.

Selective COX-2 inhibitors carry an increased risk of thrombotic events.

Question 13

What are the adverse effects that can be seen with NSAID use in asthmatics?

Answer 13

NSAID use can trigger asthma in 15% of asthmatics.

Question 14

Three broad effects of NSAIDs?

Answer 14

1. Anti-inflammatory
2. Anti-pyretic
3. Analgesic

Question 15

Factor that influence choice of NSAID administration?

Answer 15

Route of administration (IM, IV, oral)

Duration of treatment

Patient factors (risk to benefit with contraindications)

Question 16

Four groups of non-selective NSAIDs with an example?

Answer 16

1. Salicylates - Aspirin
2. Propionic acids - Ibuprofen
3. Phenylacetic acids - Diclofenac
4. Oxicams - Meloxicam

Question 17

Name the common intramuscular NSAID and its group.

Answer 17

Ketorolac - A phenylacetic acid.

Question 18

How are COX-2 selective NSAIDs named, giving an example.

Answer 18

-coxib

E.g. celecoxib.

Question 19

What are the advantages and disadvantages of COX-2 selective inhibitors?

Answer 19

Advantages:

• Lower GI adverse events
• Reduced risk of intraoperative bleeding
• Does NOT cause bronchospasm in asthmatics

Disadvantages

• Increased risk of MI and strokes with long term use - thrombotic events

Question 20

What is the main use for aspirin and how does it function?

Answer 20

Aspirin is largely used for anti-platelet effects, in the prevention of MI and stroke.

Aspirin selectively inhibits COX-1 (platelet cyclo-oxygenase), inhibiting thromboxane A2 formation. Thromboxane A2 is responsible for platelet aggregation and clotting.

Question 21

Adverse effects of aspirin at therapeutic dose?

Answer 21

1. GI effects, similar to NSAIDs
2. Bleeding risk
3. Reyes Syndrome - hepatic failure, encephalopathy in children <12 years
4. Long term - hepatic/renal impairment.

Question 22

Adverse effects of aspirin at supra-therapeutic doses?

Answer 22

• Mortality
• Respiratory alkalosis
• Metabolic acidosis
• Renal papillary necrosis

Question 23

What are the analgesic, anti-pyretic and anti-inflammatory properties of paracetamol?

Answer 23

Paracetamol has an analgesic and anti-pyretic effect, but NO anti-inflammatory effects.

Question 24

Why does paracetamol have limited adverse effects?

Answer 24

Inactive at other sites, such as kidney, GI

• No renal impairment (safe to use in kidney disease)
• No ulcer risk in GI

Question 25

GIve examples of situations where paracetamol is a first line analgesic agent

Answer 25

1. Patients with renal disease
2. Osteoarthritis
3. MSK pain
4. Cancer patients

Question 26

Is paracetamol safe to use in pregnant women and children?

Answer 26

Yes

Question 27

Describe the metabolism and toxicity of paracetamol.

Answer 27

Paracetamol is metabolised by the liver via glucuronidation.

Small amounts of a highly toxic compound (NAPQI) produced, but is rapidly inactivated by the liver.

In an overdose / abnormal liver function, NAPQI can accumulate and cause liver failure.

Question 28

WHat are contraindications to using paracetamol>

Answer 28

Abnormal liver function:

• Alcoholism
• HIV
  Malnutrition