7.1 - NSAIDs Flashcards Preview

ESA 5 - Pharmacology > 7.1 - NSAIDs > Flashcards

Flashcards in 7.1 - NSAIDs Deck (16):
1

What are prostaglandins? How do they exert their actions?

Prostaglandins are signalling agents which are produced by the COX-1 and COX-2 enzymes. They act to induce pain and pyrexia:

  • Sensitive peripheral nociceptors - Bind to EP1 in C-fibres to inhibit K channels, increase Na channel expression, increase neurotransmitter release, and increase neuronal sensitivity to bradykinin. Results in increased C fibre activity.
  • Sensitising central nociceptors - Binds to EP2 in dorsal horn of spinal cord. Increases cAMP and therefore PKA activation. This reduces activation of glycine (inhibitor), leading to increased pain reception.
  • Pyrexia - Release of IL-1 by macrophages acts on hypothalamus to stimulate PGE2 release. This acts on EP3 which decreases cAMP and increases calcium levels in neurones regulating temperature. Results in increased heat production and reduced heat loss

2

What are the 2 types of COX enzymes? Explain how they are different. Where does the main therapeutic effect of NSAIDs come from?

COX-1 - Expressed in nearly all tissues constitutively. Cytoprotective role in gastric mucosa, myocardium, renal parenchyma.

COX-2 - Expressed only via induction of inflammatory mediators. Main therapeutic effect of NSAIDs

3

What are the 3 properties all NSAIDs share?

analgesics, anti-inflammatories, anti-pyretics

4

Describe the pharmacokinetics of most NSAIDs. How does aspirin differ?

Most NSAIDS - first order elimination

Aspirin - low doses are first order, high doses zero order.

5

Describe the ADRs associated with NSAIDs.

Due to inhibition of COX-1:

  • GI - PGE2 inhibits acid secretion and stimulates mucus production. Inhibiting therefore leads to ulceration, haemorrhage, and perforation, esp in long term usage and elderly.
  • Renal - In HRH compromised individals, reduces GFR and perfusion of kidneys as PGE2 maintains adequate blood flow.
  • Vascular - Increased risk of prolonged bleeding, increased bruising, increased risk of haemorrhage. NSAIDs inhibit platelet aggregation.
  • Hypersensitivity - Skin rashes can occur. Asthmatic bronchospasm can occur.

6

What are the side effects of selective COX-2 inhibitors?

increased risk of hypertension and cardiac and renal failure

7

What are the therapeutic DDIs of NSAIDs?

Used with low dose opiates to reduce ADRs and extend the therapeutic range for treating pain

8

Why do NSAIDs show DDIs?

NSAIDs can interefere with drugs binding to plasma proteins, resulting in higher free concentration of other drugs

9

What drugs do NSAIDs show DDIs with? What effects does it have?

  • Increased sulphonylurea - hypoglycaemia
  • Increased Warfarin - Increased bleeding
  • Increased methotrexate - Increased ADRs

10

How does Aspirin exert its effects? How do other NSAIDs exert their effects?

Irreversibly inhibits COX enzymes via acetylation as opposed to competitive blocking.

11

What other therapeutic uses does aspirin have?

  • Athero-thrombotic disease prevention - acts as antiplatelet
  • Gi cancer prophylaxis - reduces risk of colon cancer

12

Why is paracetemol not considered an NSAID?

no anti inflammatory action

13

What is the therapeutic dosing of paracetemol?

No more than 4g per day

14

Describe the metabolsim of paracetemol under normal doses.

90% enters phase 2 metabolism. 10% enters phase 1 oxidation to produce NAPQI. NAPQI then detoxified by phase 2 conjugation with glutathione.

15

Describe the metabolism of paracetemol at toxic doses

Phase 2 saturated and therefore more drug enters phase 1 metabolism. Increase in NAPQI which depletes glutathione levels and increases levels of unconjugated NAPQI.

Unconjugated NAPQI damages hepatic cells,

16

What is the time frame needed to treat paracetemol overdose?

0-4 hours, activated charcoal to reduce uptake by up to 90%

0-36 hours give IV-acetylcystein to increase glutathione levels.