Paracetamol + Aspirin Flashcards Preview

Musculoskeletal > Paracetamol + Aspirin > Flashcards

Flashcards in Paracetamol + Aspirin Deck (34):
1

list paracetamol formulations

tablet
capsule
liquid suspension
suppository
IV
IM

2

When is paracetamol used

Headache +/or fever (antipyretic+analgesic)

3

is paracetamol classified as a NSAID

NO!

4

describe paracetamol structure

Benzene ring core with an acetamide on C1 and a hydroxyl group in the para position

5

describe the 3 iso-enzymes of COX

COX-1 : present in most cell types
COX-2 : Undetected in healthy tissue, induced by inflammation
COX-3 : splice variant/ mutated version of COX-1 with no functionality in humans

6

Describe Arachidonic Acid sturcture

Arachadonic acid is a 20-carbon fatty acid chain w/ 4 double bonds. Polyunsaturated fatty acid found in phosopholipids of cell membranes

7

How is Arachidonic Acid liberated from the cell membrane

Phospholipase (A2)

8

Explain how prostaglandins are formed from free AA

COX-1/COX-2 convert AA to PGG2, PGG2 is then reduced to PGH2 using the enzyme peroxidase, Different cells and tissues contain different prostaglandin synthase enzymes, PG are cell/tissue specific

9

what is the known paracetmol MOA

paracetamol is a weak inhibitor of COX activity, it is HIGHLY selective to COX-2. it produces an analgesic and antipyretic effect.

10

If paracetamol is a COX inhibitor suggest why it does not have an anti-inflammatory effect.

High levels of peroxides in inflammatory lesions may cause oxidation of paracetamol, blocking its action at these active sites.

11

How might paracetamols analgesic effect work?

2011 a study suggested that paracetamols analgesic effect may be through one of its metabolites NAPQI. NAPQI acts on TRPA1 receptors in the spinal cord thus reducing sensitivity to pain

12

Name paracetamol metabolism methods

Glucuronidation(40-65%)
Sulphation(20-40%)
N-hydroxylation and rearrangement, then GSH conjugation(<15%)

13

what is the main metabolic pathway of paracetamol in children?

Sulphation

14

What is the main metabolic pathway of paracetamol in adults

Glucuronidation

15

Why are children under 1 unlikely to form NAPQI by product?

CYP2E1 enzyme expression in children of this age is very low

16

paracetamol dosage?
+ onset of analgesia?

0.5-1G every 4-6 hours do not exceed 4G in a day. Analgesia onset is over 15 minutes after oral administration.

17

paracetamol t1/2

1-4 hours

18

paracetamol strength of pain relief?

mild to moderate

19

how is paracetamol metabolised?

metabolised through hydroxylation, conjugated mainly as glucuronide

20

how does paracetamol exhibit toxicity at high doses?

Hepatic cytochrome P450 can metabolise paracetamol to form NAPQI, NAPQI reacts with sulfhydral of GSH and is detoxified. At high doses this detoxification pathway becomes saturated and therefore toxic NAPQI builds up in the liver and causes toxicity, NAPQI has toxic reactions with proteins and nucleic acids.

21

Side effects of paracetamol?

Liver damage, Kidney damage and brain damage.

22

Advantages of using paracetamol rather than another analgesic?

beneficial to patients with coagulation issues, can be used as an alternative to aspirin as its not anti-thrombotic
No gastric irritation- NSAIDs

23

What is aspirin derived from?

Salicylic acid

24

What is aspirins chemical name?

Acetylsalicylic acid

25

What are aspirins uses?

(Analgesic,Anti-pyretic and Anti-inflammatory) unique to aspirin it is Anti-thrombotic

26

what is the MOA of aspirin

like all NSAIDs aspirin is an inhibitor of COX, it binds at the active site of the enzyme obstructing access for arachidonic acid. Aspirin is an irreversible inhibitor, it acetylates COX on the serine residue 530.

27

Explain how aspirin acts as:
1)Analgesic
2)Anti-Pyretic
3)Anti-inflammatory
4)Anti-thrombotic

1)Inhibition of PGE2 (sensitize pain receptors)
2)Inhibits PGE2, thermoregulation of hypothalamus
3)inhibits PGE2/D2 (which cause vasodilation), causes reduction in blood supply and fluid extravasation
4)reduced TxA2 production in platelets

28

How much pain relief from aspirin?

mild to moderate

29

Dose of aspirin

300-900mg every 4-6 hours MAX dose 4G

30

aspirin onset of analgesia

>15mins after oral administration

31

How is aspirin metabolised? and what is the main metabolite?

Aspirin is rapidly hydrolysed by esterases within plasma and tissues within 30 mins, 75% metabolised in the liver.
The main metabolite is Salicylic acid (pka 3.0)

32

Aspirin t1/2
>500mg
1G
2G

3hrs
5hrs
9hrs

33

side effect of aspirin? and how does this occur?

Ulceration and bleeding of GI tract.
1)Aspirin inhibits PG synthesis in stomach
2)PG help form protective barrier against stomach acid
3)reduced PG = reduced protection against acid.
4)results in peptic ulcers,bleeding

34

Does aspirin have any interactions and if so explain?

Aspirin interacts with warfarin.
Warfarin is an anticoagulant used to prevent blood clots (THROMBOSIS). warfarin inhibits Vitamin K reductase (synthesis), vitamin K is an important clotting factor. Aspirin displaces warfarin from plasma protein binding site and free warfarin conc. in blood increases (higher risk of bleeding)