Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IMED3002 > Non-Opioid Analgesics > Flashcards

Non-Opioid Analgesics Flashcards

1
Q

How can pain transduction be blocked?

A

NSAIDS

COX-2 inhibitors

Topical local anaesthetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How can conduction/transmission of pain signals be blocked?

A

Epidural block

Regional anaesthesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How can pain modulation take place at the level of the spinal cord?

A

Opioids

COX-2 inhibitors

Ketamine

Alpha-2 -Delta ligands

Alpha2 agonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How can pain perception in the brain be reduced?

A

Opioids

COX-2 inhibitors

Paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the classes of analgesics based on?

A

Salicylates (NSAIDs and COX-2 inhibitors these drugs inhibit prostaglandin synthesis)

Opioids (Selective ligands delivery techniques activate inhibitory systems)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the most used analgesic in the world?

A

Paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is paracetamol?

A

A non opioid and non salicylate analgesic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What types of pain is paracetamol used for?

A

First-line therapy for:

Osteoarthritis

Musculoskeletal pain

Renal disease

Cancer pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What other effects beside analgesia can paracetamol be used for?

A

Can be used to lower fever

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does paracetamol work?

A

Unclear mechanism of action.

Theories include:

Interaction with radical prostanoid intermediate

Inhibits COX-3 in the brain without affecting COX-1, and 2

Interaction with serotonin pathway/cannabinoid receptors

Interaction with NMDA receptor/NO synthetase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What sites is paracetamol inactive at?

A

Kidney (no renal impairment)

Gut (No risk of peptic ulcers)

Inflammation (Not anti-inflammatory)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the adverse effects of using paracetamol?

A

In clinical doses of 4 - 6 g/day there are no relevant adverse effects compared to the placebo. Toxicity more common in overdose (to the liver) or predisposed individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why is paracetamol highly toxic in higher doses than clinical doses?

A

In lower doses acetominphen is converted to glucoronides and sulfates which can be excreted by the kidney easily and safely. (glutathione is needed for this)

In higher doses cytochrome P450.2E1 converts paracetamol into NAPQI which is converted to compounds that are hepatotoxic.

If there is too much acetominophen/paracetamol then the excess is converted into NAPQI and the hepatotoxic compounds which need time to be metabolised thus causing liver damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Who is at higher risk of liver toxicity?

A

Overdose

Starvation, malnutrition and low body weight due to low levels of glutathione.

HIV

Alcoholism (but only in overdose.)

Glucose-6-phosphate dehydrogenase deficiency (G6PD) leads to mathaemoglobinaemia and haemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Paracetamol summary:

A

Good efficacy for mild to moderate pain

Limited component of multimodal analgesia

Available intravenously, orally and rectally (low bioavailability rectally)

Minimal adverse effects in therapeutic doses

Risk of liver failure in overdose

Debated risk to induce asthma/allergy

Recommended as a first line analgesic in many conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the key target of NSAIDs?

A

Prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do prostaglandins do?

A

It sensitizes activation of nociceptors (hyperalgesia)

18
Q

How do NSAIDs work?

A

Arachidonic acid forms cyclooxygenase which forms prostaglandins which are important for pain and inflammation.

NSAIDs act on cyclooxygenase nad inhibit its activity thus resulting in less prostaglandin production and less pain.

19
Q

Why must care be taken with use of NSAIDs?

A

Prostaglandins are important for normal GI function and Renal function.

Excess use can result in damage to mucosa of gut and ulcer formation.

Excess use can also cause renal toxicity.

20
Q

What are the 3 important effects of NSAIDs?

A

They are anti-inflammatory

Analgesic

and anti-pyreti`c

21
Q

What are the adverse effects of NSAIDs?

A

Toxicity is dose dependent and effects include:

Intolerability and dyspepsia

GI bleeding

Ulcers

Fluid retention, oedema, hypertension

Renal dysfunction/failure

Heart failure

Contributes to blood loss

Angioedema, bronchospasm

22
Q

Why were COX-2 inhibitor drugs developed?

A

NSAIDs have many adverse effects due to action on all cyclooxygenase (both COX-1 and COX-2). COX-2 inhibitors don’t cause adverse effects because COX-1 is the important enzyme for protection of GI, kidneys, and for platelet aggregation and COX-2 acts on inflammation, pain, and fever.

23
Q

What important structures still require COX-2 for their actions?

A

Brain

Kidney

Endothelium

Ovary

Uterus

24
Q

How are COX-2 inhibitors structurally different to NSAIDs?

A

They are more bulky and that makes them more selective for COX-2 which has a side chain that fits the side pocket of the COX-2 enzyme

25
Q

Name a famous COX-2 inhibitor?

A

Celecoxib

26
Q

What are the normal non-selective NSAIDs?

A

Salicylates (aspirin)

Arylpropionic acids (ibuprofen, naproxen)

Phenylacetic acids (Diclofenac which has lots of side effects so sparingly used)

Oxicam (piroxicam)

27
Q

What are the normal COX-2 selective NSAIDs?

A

Celecoxib

Parecoxib

Etoicoxib

3 other COX-2 inhibitors were banned due to their severe side effects (rofecoxib (associated with hypertension and heart failure), Valdecoxib (skin reaction due to delayed hypersensitivity), and lumiracoxib (associated with liver toxicity)

28
Q

What is the risk of hospitalisation due to GI bleeds in Celecoxib?

A

1%

29
Q

What is the risk of hospitalisation due to piroxicam?

A

9.8%

30
Q

What is the purpose of PPIs?

A

They are proton pump inhibitors that prevent gastric ulcer bleeds in the stomach.

31
Q

How safe is celecoxib?

A

The probability of a stomach ulcer using celecoxib is lower than combining most NSAIDs with PPIs.

PPI+celecoxib resulted in no cases of stomach ulceration and bleeding

Given orally does not cause any bronchospasms in patients with aspirin/conventional NSAID sensitivt asthma.

Risk of acute kidney injury is low.

32
Q

What is the problem with rofecoxib?

A

Associated with cumulative incidence of confirmed thrombotic events.

33
Q

FDA statement on “COX-2 Hypothesis”

A

In various controlled clinical trials, COX-2 selective drugs have been indistinguishable from non-selective NSAIDs in studies of substantial size and duration.

Based upon the available data FDA has concluded that an increase risk of CV events may be a class effects for NSAIDs.

34
Q

Which NSAID/coxib drugs are safer in terms of GI bleeds and which are safer in terms of CV events?

A

All coxibs are better for preventing GI bleeds. CV events occur less in most NSAIDs (celecoxib CV event risk is also low)

35
Q

Conclusion for NSAIDs and Coxibs:

A

NSAIDs and Coxibs are useful non-opioid analgesics, in particular in painful conditions with inflammation.

Adverse effects limit their safe use particularly in:

Elderly

Patients with GI ulcers

People with CV risk factors

People with renal risk factors

They also shouldn’t be used for extended periods of time

36
Q

When should COX-2 inhibitors be used instead of non-selective NSAIDs?

A

Acute pain (rate of ulcers comparable to placebo, less blood loss, less bone healing effects)

Patients with increased risk of GI ulcers

Patients with past history of aspirin induced asthma

37
Q

In which groups is no real difference seen between COX-2 and non-selective NSAIDs?

A

Renal adverse effects (evidence points slightly towards coxibs but not conclusive)

CV adverse effects (evidence suggests celecoxib is safe)

38
Q

What types of conditions can be caused by toxicity with aspirin?

A

Reyes syndrome

Can cause stomach ulceration by inhibiting prostaglandins and creating acidic environment as well further increasing risk of ulceration

39
Q

How does aspirin carry out its NSAID actions?

A

Has a unique mechanism to act on COX with unique activity on platelets and irreversible blockade.

40
Q

How is aspirin eliminated?

A

Some renal elimination, urine pH-dependent which is useful in managing overdose

41
Q

What is reyes syndrome?

A

Common post-viral infection condition which causes rapidly progressive liver damage as well as encephalopathy.

IMED3002 (46 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions