B.28.NSAID's, except acetylsalicylic acid. gout+pain

Question 1

list the non-selective NSAID’s

Answer 1

Ibuprofen
Indomethacin 
Naproxen 
Diclofenac
Metamizole
Ketoprofen
Phenylbutazone 
Meloxicam

Question 2

what are the contraindications for NSAID’s?

Answer 2

GI bleeding 
allergy, asthma, angioedema 
impaired renal function 
congestive heart failure (COX- 2 inhibition ↑ effect)
pregnancy (specifically 3rd trimester)

Question 3

what are the uses of Ibuprofen?

Answer 3

analgesic in children

induction of ductus arteriosus closure

Question 4

what is the recommended dose for Ibuprofen?

Answer 4

child :5mg/kg

adult: 400mg
max. 2400 mg per day

Question 5

what is the uses of Indomethacin?

Answer 5

1st line agent for acute gout attack

induction of ductus arteriosus closure

Question 6

what are the side effects of Indomethacin?

Answer 6

1. bone marrow suppression–>thrombocytopenia, agranulocytosis
2. aplastic anemia

*rarely used for inflammation

Question 7

when do we give Naproxen?

Answer 7

menstrual cramps (management of dysmenorrhea)--> uterine relaxation 
control of acute gout

Question 8

how is diclofenac given?

Answer 8

topical or oral

Question 9

what are the functions of diclofenac?

Answer 9

1. accumulates in synovial fluid–> used for musculoskeletal pain (back pain, disc herniation, osteoarthritis)
2. gastroprotective- releases NO

Question 10

what is risk of taking diclofenac?

Answer 10

prothrombotic risk

Question 11

which NSAID causes hematotoxicity (granulocytosis)?

Answer 11

Metamizole (אופטלגין)

Question 12

what is the function of ketoprofen?

Answer 12

inhibit LOX enzyme (↓ leukotrienes)

Question 13

what is Phenylbutazone?

Answer 13

pyrazole derivative

potent anti-inflammatory effect

Question 14

a severe side effect of Phenylbutazone

Answer 14

aplastic anemia

Question 15

what is the inhibitory effect of Meloxicam?

Answer 15

COX-2>COX-1

Question 16

other SE of NSAID’s

Answer 16

1. in combination with ACE inhibitors–> renal papillary necrosis
2. ↑ lithium concentrations
3. hyperkalemia
4. GI bleeding
5. ↑BP
6. ↓GFR

Question 17

What is Celecoxib

Answer 17

selective, reversible inhibition of COX-2 enzyme

Question 18

what are the functions of Celecoxib?

Answer 18

analgesic
anti-pyretic
anti-inflammatory

Question 19

what are the adverse effects of Celecoxib

Answer 19

GI irritation (milder effect compared to the non-selective)
renal damage
prothrombotic effect
sulfonamide hypersensitivity

Question 20

at what doses are acetaminophen safe?

Answer 20

<4g/day (adult)

Question 21

what is the #1 cause of acute liver failure in western countries?

Answer 21

Acetaminophen

Question 22

management of acetaminophen toxicity

Answer 22

N-acetylcysteine

*within 12 hours of overdose

Question 23

indications for Acetaminophen (Paracetamol)

Answer 23

1. analgesic and antipyretic effect (inhibits cyclooxygenases in the CNS)
2. aspirin substitute
3. osteoarthritis and RA–> slight anti-inflammatory effect (no COX inhibition in the periphery)

NO anti-platelet effects

Question 24

what drug for pain can be given to pregnant women?

Answer 24

acetaminophen

*NSAID’s shouldn’t be given!!

Question 25

list the agents used for acute gout attack

Answer 25

1. NSAID's: indomethacin, Naproxen 2. Corticosteroids: prednisone 3. microtubule assembly inhibitors: colchicine

Question 26

how is colchicine given?

Answer 26

oral or parenteral

Question 27

what is the mechanism of colchicine (as a microtubule assembly inhibitor)?

Answer 27

bind to tubulin--> altered microtubular polymerization--> LTB₄ ↓--> altered leukocyte and granulocyte migration

Question 28

what agent has a more potent effect- indomethacin or Naproxen

Answer 28

indomethacin

Question 29

when do we give prednisone in acute gout attacks?

Answer 29

when NSAID'S are contraindicated

Question 30

how is prednisone given for acute gout?

Answer 30

intra-articular injection | oral (up to 5 days course treatment)

Question 31

what are the indications of colchicine other than acute gout

Answer 31

chronic gout-low doses familial Mediterranean fever management of pericardial diseases (pericarditis, pericardial effusion)

Question 32

side effects of colchicine

Answer 32

acute: severe diarrhea, GI pain | longer use: hematuria, alopecia, myelosuppression gastritis, peripheral neuropathy

Question 33

what are the agents used for chronic gout?

Answer 33

1. Xanthine oxidase inhibitors: Allopurinol | 2. recombinant urate oxidase: Rasburicase

Question 34

what are the indications for giving allopurinol and Rasburicase?

Answer 34

chronic gout adjunct to cancer chemotherapy and radiotherapy ('tumor lysis syndrome' may precipitate gout attack)

Question 35

side effects of allopurinol

Answer 35

GI irritation hypersensitivity reaction, SJS syndrome bone marrow suppression

Question 36

what are the side effects of Rasburicase?

Answer 36

anaphylactic reaction | methemoglobinemia in patients with G6PD

Question 37

allopurinol inhibits the metabolism of..

Answer 37

6-MP

Question 38

What is the mechanism of allopurinol?

Answer 38

inhibit xanthine oxidase--> ↓ purine metabolism --> serum uric acid ↓

Question 39

what is the mechanism of Rasburicase

Answer 39

it's a urate oxidase enzyme that catalyzes the metabolism of uric acid to allantoin--> ↓ serum uric acid