NSAIDs, Acetaminophen, DMARDs, and Drugs used in Gout

Question 1

classification of NSAIDs

Answer 1

1. Salicylates: irreversible
2. Non-Selective NSAIDs: reversible
3. COX2 selective

Question 2

prevents uric acid excretion

therefore NOT USED IN GOUT

Answer 2

aspirin/ASA/acetylsalicylic acid

salsalate, sodium salicylate, choline salicylate, magnesium salicylate

Question 3

low range dose of aspirin (<300 mg/d) follow what type of elimination kinetics?

Answer 3

first-order

effective in reducing platelet aggregation

Question 4

intermediate dose of aspirin (300 - 400 mg/d) is effective as?

Answer 4

antipyretic and analgesic

Question 5

high doses of aspirin (2400-4000 mg/d) follows what type of elimination kinetics?

Answer 5

zero-order

anti-inflammatory effect

Question 6

NSAID propionic acid derivatives

Answer 6

Ibuprofen, Naproxen, Fenoprofen, Carprofen, Ketoprofen, Dexketoprofen, Oxaprozin

Question 7

non-selective NSAID
for analgesia
long-term use reduces risk of colon Ca

Answer 7

Ibuprofen
diclofenac, diflunisal, etodolac, fenoprofen, fluribuprofen, ketoprofen, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, mefenamic acid, bromfenac, meclofenamate, suprofen

Question 8

prevents NSAID-induced gastritis

Answer 8

misoprostol

Question 9

non-selective NSAID, IV
inhibits prostaglandin synthesis
post-surgical analgesic control
use generally restricted to 72 hours only

Answer 9

ketorolac

dexketoprofen

Question 10

non-selective NSAID
reversible COX-1 > COX-2 inhibitor
for PDA closure
SE: aplastic anemia, thrombocytopenia

Answer 10

indomethacin

Question 11

highly COX-2 selective NSAID
for analgesia
SE: reduced risk of GI bleeding, MI, stroke

Answer 11

celecoxib
etoricoxib, parecoxib

rofecoxib & valdecoib: withdrawn from market due to MI and stroke development

MELOXICAM IS PREFERENTIALLY COX-2 SELECTIVE INHIBITOR

Question 12

COX-3 inhibitor
analgesic (mild)
SE: hepatotoxicity (increased with alcohol use)
preferred antipyretic in children (does NOT cause Reye Syndrome)

Answer 12

paracetamol
acetaminophen
phenacetin

Question 13

antidote to paracetamol

Answer 13

N-Acetylcysteine

will donate -SH to reduce glutathione and reuse it vs. NAPQI (toxic paracetamol metabolite)

Question 14

stages of paracetamol overdose

time period and manifestations

Answer 14

stage I: 0.5-24 hours: nausea, vomiting, diaphoresis, pallor, lethargy, malaise
stage II: 24-72 hours: elevated liver enzymes, oliguria, azotemia, increased PT, hyperbilirubinemia
stage III: 72-96 hours: jaundice, hepatic encephalopathy, bleeding diatheses, acute tubular necrosis, HAGMA, coma, death
stage IV: 4 days-2 weeks: recovery

Question 15

DMARD
cancer chemotherapeutic drug
DMARD of first choice to treat rheumatoid arthritis
SE: mucosal ulcers, pseudolymphomatous reaction
RESCUE AGENT: LEUCOVORIN (folinic acid)

Answer 15

methotrexate

Question 16

DMARD
binds to TNF alpha
for Crohn's disease, rheumatoid arthritis
SE: reactivation of latent TB
synergistic with methotrexate

Answer 16

infliximab

adalimumab, etanercept, certolizumab, golimumab

Question 17

DMARD
forms 6-thioguanine
for rheumatoid arthritis
SE: bone marrow suppression, increased incidence of lymphoma

Answer 17

azathioprine

CANNOT BE GIVEN WITH ALLOPURINOL
reduces xanthine oxide metabolism of purine analogs
increasing 6-thioguanine nucleotides –> myelosuppression

Question 18

DMARD
anti-malarial
for rheumatoid arthritis
SE: OCULAR TOXICITY

Answer 18

chloroquine

hydroxychloroquine

Question 19

DMARD
forms phosphoramide mustard
for rheumatoid arthritis
SE: bone marrow suppression, HEMORRHAGIC CYSTITIS
RESCUE AGENT: MESNA

Answer 19

cyclophosphamide

Question 20

DMARD
inhibits IL-1 and IL-2 receptor production
inhibits macrophage T-cell interaction and T-cell responsiveness
for rheumatoid arthritis, tissue transplantation
SE: NEPHROTOXICITY, GINGIVAL HYPERPLASIA, HIRSUTISM

Answer 20

cyclosporine

Question 21

DMARD
for SLE nephritis, vasculitis Wegener’s granulomatosis, rheumatoid arthritis
SE: reversible myelosuppression (neutropenia)

Answer 21

mycophenolate mofetil

Question 22

DMARD
for rheumatoid arthritis, IBD
SE: HEMOLYTIC ANEMIA, METHEMOGLOBINEMIA, REVERSIBLE INFERTILTY FOR MEN

Answer 22

Sulfasalazine

Question 23

co-stimulation modulator
inhibits T-cell activation by binding to CD80 and CD86 on APC
for moderate to severe rheumatoid arthritis
NOT RECOMMENDED TO USE WITH TNF-ALPHA BLOCKER: increased incidence of serious infection

Answer 23

abatacept

Question 24

non-biological DMARD

Answer 24

leflunomide

Question 25

anti-gout
microtubule assembly inhibitor
for gout, familial mediterranean fever
SE: diarrhea, hepatic necrosis, acute renal failure, agranulocytosis

Answer 25

colchicine

Question 26

5 agents that can inhibit microtubule function

Answer 26

1. colchicine
2. vinca-alkaloids
3. taxanes
4. griseofulvin
5. azole anti-helminthics

Question 27

commonly used in initial treatment of gout as replacement for colchicine

Answer 27

indomethacin

Question 28

anti-gout
uricosuric agent: competes with uric acid for reabsorption
SE: GI irritation, aplastic anemia
may precipitate acute gout during early phase of drug action (hence co-administer with colchicine or indomethacin)
inhibits secretion of other weak acids (e.g. penicillin, methotrexate)

Answer 28

probenicid

sulfinpyrazone

Question 29

anti-gout
xanthine oxidase inhibitor (irreversible)
1st LINE TREATMENT FOR CHRONIC GOUT, TUMOR LYSIS SYNDROME
SE: CATARACTS
inhibits metabolism of mercaptopurine and azathioprine

Answer 29

allopurinol

withheld for 1-2 weeks after acute episode of gouty arthritis

Question 30

anti-gout
xanthine oxidase inhibitor (reversible)
NONPURINE REVERSIBLE INHIBITOR OF XANTHINE OXIDASE (MORE SELECTIVE THAN ALLOPURINOL)
for chronic gout, tumor lysis syndrome

Answer 30

Febuxostat