15 NSAIDs Flashcards
What are prostanoids and what do they do?
Prostanoids= a type of eicosanoid
Produced locally on demand
Examples= prostglandins, prostacyclin, thromboxanes
In general terms, how do NSAIDs work?
NSAIDs- inhibit down stream products of arachidonic acid by inhibiting COX (compete with arachidonic acid for hydrophobic site of COX)
Work as:
- Antipyretics
- Analgesics
- Anti-inflammatory
How is arachidonic acid synthesised from linoleic acid?
Linoleic acid obtained from diet- vegetable oils
Linoleic acid= converted hepatically to arachidonic acid (found throughout body- in particualr in muscle, brain and liver)
Differentiate between the 2 functional isoforms of cyclooxygenase enzymes.
(don’t need to learn table- not an exhaustive list)
Through what types of receptor do prostanoids act?
GPCRs
Give examples of 5 prostanoids.
Give 2 examples of substances which can enhance the action of prostanoids.
Local autocoids eg:
- Bradykinin
- Histamine
What effects do thromboxane (TXA2) and prostacyclin (PGI2) have on vasculature?
Thromboxane= vasoconstrictor
Prostacyclin= vasodilator
NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as analgesics?
NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as anti-inflammatories?
Symptomatic relief by COX inhibition- little/no effect on underlying condition
NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as anti-pyretics?
Name 6 NSAIDs and put them in order of increasing COX-2 or increasing COX-1 selectivity.
- Aspirin
- Ibruprofen
- Naproxen
- Diclofenac
- Celecoxib
- Etoricoxib
Differentiate between naproxen and naloxone
Naproxen= NSAID
Naloxone= opioid receptor antagonist (used for overdose)
What is the most common ADR for NSAIDs? Explain why.
GI upset
- Dyspepsia
- Nausea
- Peptic ulceration
- Bleeding
- Perforation
Why?
COX enzymes inhibited, prostaglandin synthesis affected
Less mucus and bicarbonate secretion
More acid secretion
Less mucosal blood flow
Enhanced cytotoxcity and hypoxia
What are the cautions for prescribing NSAIDs?
GI
- Can cause exacerbation of IBD
- Loacl irritation and bleeding from rectal admin
- Caution:
- Elderly
- Prolonged use
- PPIs
- Anticoagulants
- Smoking
- Alcohol
- History of peptic ulceration
- Helicobacter pylori
What effects do NSAIDs have on the kidneys? Explain why.
Who do we therefore need to be careful about prescribing NSAIDs to?
- Decrease GFR (reversible)
- Decrease renal blood flow (reversible)
Prostaglandins required for vasodilation and renal perfusion
Prostaglandins inhibit sodium absorption in collecting duct–> natriuresis
Cautions:
- Underlying CKD
Heart failure - Very young and elderly
Give 2 examples of selective COX-2 inhibitors.
Explain why they generally have less GI ADRs.
- Celecoxib
- Etoricoxib
COX-2 inhibitors avoid inhibition of homeostatic actions mediated by COX-1
eg Platelets only have COX-1
NSAIDs are susceptible to competitive displacement. Explain what this means and give examples of some drugs which compete with NSAIDs for protein binding.
NSAIDs= highly protein bound
NSAIDs–> displace other protein bound drugs–> increase free drug concentration
Examples:
- Sulfonylureas- hypoglycaemia
- Methotrexate- hepatotoxicity
- Warfarin- increased bleeding risk
NSAIDs have lots of indications. List a few of them.
Give some of the contraindications for NSAID use.
CVD risk increase associated with NSAID use
Impaired renal function
GI disease due to NSAID use
Paracetamol is well absorbed from the GI tract. Where is it inactivated?
Inactivated primarily by conjugation in liver
NAPQI (N-acetyl-p-benzoquinoneimine) is a highly reactive metabolite of paracetamol.
Conjugation with what molecule in the liver renders it harmless? How much paracetamol is required to cause irreversible damage?
NAPQI- conjugates with glutathione
150mg/kg= sufficient to cause ireversible damage
If a patient has a paracetamol overdose;
- How will they present?
- How do find out the extent of the overdose?
- How do we treat it? (why do we not just give glutathione?)
- How will they present?
- Can be asymptomatic for hours
- Nausea, vomiting, abdominal pain (first 24hrs)
- How do find out the extent of the overdose?
- Blood after 4hrs- will know extent of overdose
- How do we treat it? (why do we not just give glutathione?)
- Give N-Acetylcysteine
- Drives phase 2 metabolism
- Glutathione- doesn’t get absorbed into hepatocytes
- Give N-Acetylcysteine
