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.
17
Q
DMARDs - disease modifying anti-rhumatic medications
A
Drugs that reduce the progression of RA and prevent joint destruction. They are slow acting and with long duration of action.
Methotrexate, Chloroquine, Hydroxychloroquine, Sulphasalzine, Leflunomide, Gold salts….
18
Q
Methotrexate
A
- Analog of folic acid. Used for immunosuppresion and anti-rheumatic effects.
- It interferes with production of cytokine and nucleotides.
- It has a rapid onset compared to other DMARDs.
- Has side effects: mucosal ulceration, nausea, cytopenias, liver cirrhosis, acute pneumonia like syndrome.
But Leucovorin can be taken after methotrexate to reduce SE. - Is contraindicated in pregnancy.
19
Q
Cyclophosphamide
A
- Has a strong benefit in RA, but less than methotrexate. It’s highly toxic!
- Useful in severe RA and systemic lupus.
20
Q
Leflunomide
A
- Inhibits pyrimidine synthesis by inhibiting DHODH enzyme (dihydroorotate dehydrogenase). This will decrease RNA synthesis and eventually lead to cell arrest.
- It’s teratogenic - so is contraindicated in pregnancy.
- Cyclosporin A
- Tacrolimus - is x100 times more effective than leflunomide.
21
Q
Chloroquine + Hydroxychloroquine
Antimalarials
A
- Have anti-inflammatory and immunosuppressive effects. They do so by stabilisation of lysosomes and decreasing cytokines.
22
Q
Gold salts - Sodium Aurotiomalate
A
- Has immunosuppressive effect. By decreasing ESR and C-reactive protein, increasing histidine+sulfyhdryl serum levels, decreasing Ig, rheumatoid factor and C1q-binding activity. (????)
- Can have side effects like blood disorders.
23
Q
D-penicillamin
A
- Analog of AA cysteine.
- Decreases proteosynthesis and DNA synthesis so slows bone destruction and RA.
24
Q
Sulphasalazine
A
- Effects GALT (gut associated lymph tissue).
- Used in RA with fast onset, or in non-specific inflammatory bowel diseases.
25
Q
Adalimumab
A
- TNF - alpha inhibitor
- Recombinant monoclonal antibody, binds to TNF-alpha receptor this inhibiting its activity.
26
Q
Infliximab
A
- TNF-alpha inhibitor
- Chimeric monoclonal antibody, that binds to TNF-alpha and inhibits it.
- Long term treatment with infliximab will lead to synthesis of Anti-infliximab antibodies, so methotrexate is given to prevent their formation.
27
Q
Etanercept
A
- TNF-alpha inhibitor
- Human monoclonal antibody, binds 2 molecules of TNF-alpha and block their function.
- Is more effective in combination with methotrexate.
- Is dangerous in patients with life threatening infections.
28
Q
Golimumab
A
- TNF-alpha inhibitor.
- Human monoclonal antibody, forms stable complexes with TNF-alpha preventing its effect.
- Is also more effective together with methotrexate.
29
Q
Rituximab
A
- B-cell depletor
- Chimeric monoclonal antibody, directed against CD20 on B cells resulting in their depletion.
- Other B-cell depletors include: Ofatumumab, Belimumab, Atacicept and Tabalumab.
30
Q
Anakinra
A
- IL-1 antagonist.
- Recombinant antagonist protein of IL-1 receptor, binds to this receptor and prevents its function.
- Other IL-1 antagonist: Canalonumab and Rilonacept.
31
Q
Tocilizumab
A
- IL-6 antagonist.
- Recombinant monoclonal antibody, directed against IL-6 and inhibits it.
32
Q
Abatacept
A
- T-cell modifying agent.
- Recombinant fusion protein that competes with CD28 for binding with CD80/CD86 (takes the place of CD28). This will decrease the activation of T cells.
- Other T-cell modifying agent: Belatacept
33
Q
Secukinumab + Ixekizumab
A
- IL-17 inhibitors
34
Q
Denosumab
A
- RANKL inhibitor
35
Q
Tofacitinib
A
- JAK1 + JAK3 inhibitor
36
Q
Baricitinib
A
- JAK1 + JAK2 inhibitor
37
Q
Colchicine
A
- Has no effect on uric acid metabolism, but acts against inflammatory response to urate crystals so relieves gout pain.
- It binds to tubilin causing it to depolymerize, this will reduce migration of granulocytes to site of inflammation and decreases inflammatory response.
- It’s contraindicated in pregnancy.
38
Q
Allopurinol
A
- XO (Xanthine oxidase) inhibitor
- The most common drug used to decrease uric acid levels in gout.
- Another XO inhibitor is Febuxostat.
39
Q
Rasburicase
A
- Converts uric acid to allantoin, increasing its excretion.
40
Q
Probenecid
A
- Blocks urisuric and renal tubular transport, decreases reabsorption of urate so increases its excretion.
41
Q
Lesinurad
A
- Blocks URAT1 and OAT4 which are transporters responsible for uric acid reabsorption. So it increases urinary excretion of uric acid.
