Flashcards in Paracetamol + Aspirin Deck (34):
list paracetamol formulations
When is paracetamol used
Headache +/or fever (antipyretic+analgesic)
is paracetamol classified as a NSAID
describe paracetamol structure
Benzene ring core with an acetamide on C1 and a hydroxyl group in the para position
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
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
How is Arachidonic Acid liberated from the cell membrane
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
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.
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.
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
Name paracetamol metabolism methods
N-hydroxylation and rearrangement, then GSH conjugation(<15%)
what is the main metabolic pathway of paracetamol in children?
What is the main metabolic pathway of paracetamol in adults
Why are children under 1 unlikely to form NAPQI by product?
CYP2E1 enzyme expression in children of this age is very low
+ 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.
paracetamol strength of pain relief?
mild to moderate
how is paracetamol metabolised?
metabolised through hydroxylation, conjugated mainly as glucuronide
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.
Side effects of paracetamol?
Liver damage, Kidney damage and brain damage.
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
What is aspirin derived from?
What is aspirins chemical name?
What are aspirins uses?
(Analgesic,Anti-pyretic and Anti-inflammatory) unique to aspirin it is Anti-thrombotic
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.
Explain how aspirin acts as:
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
How much pain relief from aspirin?
mild to moderate
Dose of aspirin
300-900mg every 4-6 hours MAX dose 4G
aspirin onset of analgesia
>15mins after oral administration
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)
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