NSAIDs Flashcards
What does NSAID stand for
Non steroidal anti-inflammatory drugs
Define NSAIDs
class of drugs that relieve pain, reduce inflammation, redness and swelling and bring down high temperature (fever)
What conditions require NSAIDs
Headaches
painful periods
toothaches
sprains and strains inf
common cold /flu
inflammation of the joints (arthritis)
How do NSAIDs work
blocking the production of prostaglandins, which are chemical messengers that are responsible for pain / swelling of inflammatory conditions
What is the difference between narcotic analgesics and non-narcotic analgesics
Narcotic -> CNS effect
Non-narcotic -> no CNS effect
Most NSAIDs are reversible or irreversible COX inhibitors
Most NSAIDs are irreversible cyclooxyrgenase inhibitors
-> prevent formation of prostaglandins -> lowering signs and symptoms of inflammation
What are prostaglandins
family of chemicals that are produced by the cells 1. in response to injury/illness
2. prostaglandins promote inflammation/pain/fever
3. Prostaglandins support blood clotting func of platelets
4. prostaglandins protect the lining of the stomach from the effects of acid
What is the chemical structure of prostaglandins
Unsaturated carboxylic acids
20 carbon skeleton
+ 5 member ring
Where are prostaglandin biochemically synthesized from
Fatty acids, arachidonic acid
Prostaglandins in COX 1 ARE
Thromboxane A2
Prostaglandins in COX2 are
Prostacyclin PG12
COX 1 is called
Constitutive
COX 2 is called
inducibile
Salicylates are derived from
Salicylic acid (monohydroxybenzoic acid
Salicylic acid is also known as
2-hydroxybenzoic acid
Does salicylamide have analgesic and inflammatory action
No,
Salicylamide has analgesic but not inflammatory action
In salicylates, the hydroxyl group should be on the ______ position
Ortho
T/F: Halogen substitution enhances activity however makes them toxic as well
True
In salicylates, substitution with a hydrophobic aryl group at 5 position improves anti inflammatory activity
True
Phenacetin is available in united states
No
Acetaminophen is an effective analgesic and antipyretic
True
Is acetaminophen an anti-inflammatory?
No, due to its weak inhibition of cyclooxygenase -> weak inhibition of prostaglandin synthesis
Acetaminophen toxicity
Hepatotoxicity -> depletion of glutathione pool
What is the antidote of acetaminophen
Acetylcycsteine
When was phenylbutaxone introduced
1949 -> treatment of arthritis
although not a first line drug
T/F: phenylbutazone is an NSAID effective for treatment of fever, pain and inflammation in the body
True
Phenylbutazone has analgesic and antipyretic effects and enhanced antiinflammatory effects -> RA
True
Pyrazolone is a drug that has analgesic, anti inflammatory, and anti pyretic properties
True
What condition is assosiated with pyrazolone
Leukopenia (low white blood cell count)
What is fenamates derived from
N-phenylanthranilic acid
What major side effect of fenamates
Diarrhea
T/F: Fenamates are N containing analouges of salicylates
True
Mefanaic acid is used as
- Anti-inflammatory
- arthritis
- menstrual pain
- pain after surgical conditions
Is mefanamic acid an inhibitor of what type
COX1 AND COX2 competitive inhibitor
which are responsibile for the first step of prostaglandin biosynthesis
What are heteroaryl acetic acids and propionic acid derivatives used for
RA
Is Sulindac a prodrug
Yes
In ibuprofen, the S-isomer is more active than the R-isomer
True
What was the first member of propionic acid class of NSAIDs to come to general use
Ibuprofen
Is naproxen widely used
One of the most widely used NSAIDs
Diclofenac is what type of derivative
Phenyl acetic acid derivative
Is diclofenac potent?
Yes, it is one of the most potent NSAIDs known clincially
What is under the oxicam family
piroxicam
meloxicam
tenoxicam (under study)
Is piroxicam equivalent to aspirin, indomethacin , or naproxen for long term treatment of RA or OA
yes
Is there a difference between COX1 AND COX 2
yes, x-ray crystals structure analysis show difference in amino acid sequence
What is the difference in structure between COX 1 and COX 2
COX 2 has a smaller valine in the active site
COX 1 has a larger isoleucine
COX 2 inhibitors lack what
A carbonyl group
Simple competitive inhibiton of COX 1 AND COX 2 inhibitors is thought to occur becuase of …?
Lack of access to the side pocket
In COX2 selective drugs, the heterocycles could include
furan
pyrrole
thiazole
oxazole
imidazole
isoxazole
pyrimidine
thiophene
Coxibs are _______ COX 2 inhibitors
selective
What effects do selective COX 2 inhibitors give
antiinflammatory
analgesic
antipyretic
low ulcerogenic potential
Primary indication of celecoxib
pt who need long and regular pain relief
no advantage for using celecoxib for a short term or acute pain relieve over conventional NSAIDs
Prostaglandin inhibition in kidney after using COX2 can affect what
renal blood flow -> retention of water and sodium ( edema)
a risk encountered in all NSAIDs except aspirin
In order to fight inflammation we either use:
Steroids or NSAIDs
Do some NSAIDs target 5-LOX? which ones?
Yes, ibuprofen and indomethacin can inhibit activity of 5-LOX
What do we call COX 1 and COX 2
ISOENZYMES
identical yet differ in their distripution
What is the % identical between COX 1 AND COX 2
99% identical
only point mutation -> different selectivity
COX 1 is housekeeper which COX 2 is only release in inflammation
True
Which has a larger active site? cox 1 or cox 2
COX 2 has a larger active site, due to it containing valine an a.a that is small
Since COX 2 has a larger active site, where does large drugs and small drugs fit?
Large drugs -> COX 2
Small drugs -> both COX 1 AND COX 2 (non selective)
Salicylic acid is also known as …?
Vitamin S
Is salicylic acid selective?
Non selective because its small
Is salicylic acid reversible (not aspirin)
Yes
reversibile binding
Which is more stable, salicylic acid or ASA
Salicylic acid
when ASA degrades -> vinegar smell
Which is more acidic, Salicylic acid or ASA
same acidity
Is aspirin a prodrug?
No, becuase the ester is active before and after it’s broken down
Is aspirin reversible
No, Aspirin is irreversible
the only NSAID that inhibits clotting of blood for 4-7 days is
Aspirin
Why does aspirin have antipyretic activity
because its able to interfere with the production of prostaglandin E1 in the brain
At low doses, aspirin is used as
Anti-platelet
Does Aspirin reach the brain?
Yes via transporters
Aspirin should be stopped how long before surgeries?
A week
What are some off-label uses of aspirin
- shiny hair
- plant illness (basic soil -> neutralize it)
What are side effects of aspirin
- bleeding
- stomach ulcer
- allergy (bronchostriction)
- reye’s syndrome
Since all NSAIDs are acids and they must contain COOH, that makes them
irritants
What is bufferin
A buffering solution to reduce the COOH irritation to the stomach wall
What is Reyes syndrome
if you give a child <16 yr with a viral infection, aspirin
Symptoms:
1. swelling of the brain
2. liver dysfunction
3. breathing difficulties
4. fever -> coma
Is Aspirin C/I in children with viral infections
Yes, reyes syndrome
Is diflunisal reversible
Yes
Is diflunisal small/large/selective/nonselective
Small
Non selective
Which is more potent, aspirin or diflunisal
Aspirin is more potent than diflunisal
One of the strongest/most potent NSAIDs
Dicolfenac
Is diclofenac used for chronic pain management
NO
What is the MAO of diclofenac
blockage of voltage-dependent sodium channels -> freezes the nerve -> no action potential
Is diclofenac pure COX 2 inh
no, because its small it can bind to both cox 1 and cox2 bit it prefers cox 2
Is diclofenac effective as an antipyretic
Yes
Is diclofenac effective against all strains of multi drug resistant E. coli with a MIC of 25 mcg/mL
Yes
Drug repurposing
The methyl in ibuprofen was orignially an H but they changed it to methyl. why
H -> Hepatotoxic
CH3 -> safer
What is the painkiller of choice for pregnant woman
Paracetamol
avoid in first trimester -> ADHD
What is the pain killer of choice for babies
None <3 months
1. no liver dysfunction -> paracetamol
2. ibuprofen
Which is more tolerated, ibuprofen or aspirin
Ibuprofen is more tolerated, less GI irritation, reversible COX inhibitor
What is the prophylaxic use of ibuprofen
Prophylaxis of alzeheimer and parkinson
Is indomethacine reversible?
Yes, reversible COX inhibitor
Is indomethacine potent
VERY
مرصد
What is the indication of using indomethacine
acute gout arthritis (severe pain)
Is indomethacine selective
No , least selective among all NSAIDs
Is sulindac selective
Not selective. however, more selective than indomethacine
Why is naproxen mostly prescribed by dentists
because it distributes to low perfusion tissues like lungs and gum?
Is naproxen selective
NO
Piroxicam, is it short acting or long acting
Long acting , once daily
Does dosing alter selectivity in piroxicam
YES
low doses -> COX 2
high doses -> no selectivity
How is piroxicam excreted
h.philic -> urine -> dose adjusments in kidney injurt
Why does COX 2 have cardiotoxic
inhibiting all COX 2 -> body produced more COX 1 -> INC thromboxane A2 -> INC platelet aggregation
What is the black box warning on celecoxib
NOT TO BE GIVEN FOR PATIENTS WITH CARDIOVASCULAR RISK, DM, MI PTS
Does acetaminophen have platelet function
No
Is acetaminophen an NSAID
NO, but it functions on COX 3 centrally
How does acetaminophen reach the CNS knowing that it doesnt have a transporter
it’s unionized -> passive diffusion
Why does acetaminophen toxicity occur
because acetaminophen already has an OH group, it bypasses phase 1 metabolism in the liver and you suddenly shock the liver with a high amount of acetaminophen ready for phase 2
if the liver does not have enough glucuronic acid needed for conjugation -> acetaminophen accumulation in the liver
NAPQI is a very toxic intermediate
What is the toxic dose of acetaminophen
up to 4g
or up to 1 g in cases of reduced liver function
