NSAIDS Flashcards
1
Q
COX enzymes
A
Cyclooxygenases - enzymes responsible for synthesis of prostaglandins, thromboxanes and prostacyclins, all of which are needed during inflammation.
COX 1 - constitutive - meaning always expressed.
COX 2 - inducible - meaning expressed only when needed (during disease and inflammation)
2
Q
NSAIDS
A
Non steriodal antiinflammatory drugs that have antiinflammatory, anti-pyretic and analgesic properties.
These are drugs that inhibit COX enzymes, by that decrease synthesis of prostaglandins and decrease the inflammatory response.
3
Q
Side effects of NSAIDS
A
- GIT: inhibition of COX 1 causes decreased PGE2 which leads to peptic ulcers or GI bleeding.
- Renal: inhibition of COX 1+2 causes decreased PGE2 and PGI2 which leads to Na and water retention, hypertension and hemodynamic acute kidney injury.
- CVS: inhibition of COX 1 in platelets causes decreased TAX2 so inhibits vasoconstriction and platelet aggregation.
inhibition of COX 2 in vessels causes decreased PGI2 so inhibits vasodilation and allows platelet aggregation.
*So drugs inhibiting COX 2 more will lead to a “prothrombic state” which will allow more formation of clots, increasing the risk for stroke or myocardial infarction.
4
Q
Which NSAIDS are selective COX 2 inhibitors?
A
Lumiracoxib > Rofecoxib > Etodolac > Diclofenac > Celecoxib
5
Q
Paracetamol (Acetaminophen)
A
- Antipyretic and analgesic effect. No anti-inflammatory effect.
- The ONLY centrally acting analgesic-antipyretic. So is less active in the periphery and as a result has less side effects.
- Is mostly metabolized in the liver by conjugation (glucuronidated or sulfated) and excreted by urine. But a small percentage is hydroxylated to NAPQI which is toxic. Normally, NAPQI reacts with glutathione and is then excreted.
- In case of overdose, the metabolism of paracetamol shifts to NAPQI which will react with hepatic proteins and cause hepatotoxicity.
- N - Acetylcysteine is life saving in cases of paracetamol overdose because it mimics glutathione.
6
Q
Aspirin (Acetylsalicylic acid)
A
- The only IRREVERSIBLE NSAID. It irreversible acetylates COX enzymes non-selectively, so inhibits both COX 1+2.
- It has anti-inflammatory, antipyretic and analgesic effect. These are due to inhibition of COX 2, but inhibition of COX 1 mostly lead to the typical side effects.
- Used for analgesia - headache, arthralgia, myalgia.
- Used for anti-inflammatory - osteoarthritis, gout, RA. But only in higher does (4-6gr per day).
- Used for anti-aggregatory - preventing thrombus formation and reduce risk of CVS problems. But only in low doses (160mg every other day).
- Used to facilitate closure of the patent ductus arteriosus.
- Is contraindicated in children with viral infection because it can lead to Reye’s syndrome. Paracetamol is used instead.
- Has typical NSAIDs side effects. A mild toxicity of aspirin is called Salicylism.
- Diflunisal is a derivative of aspirin, it’s 3-4 times more potent as analgesic and anti-inflammatory, but has NO antipyretic effect. This is because it doesn’t reach the CNS, and as a result doesn’t cause salicylism.
7
Q
Ibuprofen
A
- A non-selective COX inhibitor. Has antipyretic, anti-inflammatory, analgesic and anti-aggregatory effect.
- Derivative of propionic acid.
8
Q
Ketoprofen
A
- A non-selective COX inhibitor. Has antipyretic, anti-inflammatory, analgesic and anti-aggregatory effect.
- Derivative of propionic acid.
9
Q
Which NSAIDs are derivatives of propionic acid?
A
Ibuprofen, Ketoprofen, Naproxen, Fenoprofen, Flurbiprofen, Oxaprozin.
*Naproxen is the least harmful NSAIDs in patients with CVS diseases.
10
Q
Indomethacin
A
- A non-selective COX inhibitor. Has antipyretic, anti-inflammatory, analgesic and anti-aggregatory effect.
- Derivative of acetic acid.
- Its use is limited because it can be toxic.
11
Q
Sulindac
A
- A non-selective COX inhibitor. Has antipyretic, anti-inflammatory, analgesic and anti-aggregatory effect.
- Derivative of acetic acid.
- Similar to indomethacin but has less severe side effects.
12
Q
Piroxicam + Meloxicam
A
- Are non-selective COX inhibitors. Derivatives of oxicam.
- Have long half-lives, and their excretion in urine interferes with excretion of lithium.
- Used to treat RA, Ankylosing spondylitis, osteoarthritis.
Meloxicam can be relatively COX 2 selective in low doses.
13
Q
Phenylbutazone + Metamizole
A
- Are non-selective COX inhibitors.
- Have strong anti-inflammatory and weak analgesic effect (except of metamizole) and antipyretic effects.
- Have serious side effects (other than the typical ones) agranulocytosis and aplastic anemia.
14
Q
Celecoxib
A
- A selective COX 2 inhibitor, so doesn’t inhibit COX 1.
- Has typical side effects. But DOESN’T have anti-aggregatory effect, so doesn’t prolong bleeding.
- Contraindicated in patients with allergy to sulfonamides.
- Contraindicated in patients taking CYP2CP inhibitors. Like Fluconazole, Fluvastatin and Zafirlukast.
- Since it doesn’t have an anti-aggregatory effect, it’s not used in patient with ischemic heart disease or stroke.
15
Q
Diclofenac
A
- A selective COX 2 inhibitor, so doesn’t block COX 1.
- Can cause GIT problems, so can be given in combination with Misoprostol to prevent GIT problems.
- Can lead to prenatal closure of the ductus arteriosus.
16
Q
Nimesulid + Nabumetone + Tolmetin
A
- Are preferentially COX 2 inhibitors, meaning they prefer being selective to COX 2.
- Nimesulid is a strong analgesic, and anti-inflammatory, has low effects on platelet aggregation and rarely causes GIT problems.
