Lecture 6 - NSAIDS/DMARDs

Question 1

NSAIDs:
\_\_\_\_ is a salicylate.
ibuprofen and naproxen are \_\_\_\_\_ acids.
\_\_\_\_\_ and meloxicam are enolic acids.
indomethacin, diclofenac, etodolac are \_\_\_\_\_ acids

Answer 1

aspirin;
arylpropionic;
piroxicam;
arylacetic

Question 2

COX ____ is induced by inflammation. prostaglandins contribute to increased neural ____ and pain

Answer 2

2;

firing

Question 3

Thromboxane A 2 is produced by COX ____. COX ___ enzymes, prostaglandins, and prostacyclins serve a protective role in the GI tract

Answer 3

1, 1

Question 4

COX2 is present constitutively in the ___ and ____. Cox 1 is always expressed in platelets, _____ and kidney. Prostacyclins promote mucus secretion and inhibit _____ in the stomach

Answer 4

brain, CNS;
stomach;
acid production

Question 5

Aspirin _____ inhibits COX 1 and 2 via ____.

Answer 5

irreversibly (as opposed to other NSAIDS which are reversible), acetylation

Question 6

there is a risk of Reye syndrome when using aspirin in ____ who have a ____ infection. Reye’s causes ____ and ____ problems

Answer 6

kids, viral;

encephalopathy, hepatic

Question 7

aspirin has a ____ half life. its metabolite, _____, has a ____ half life

Answer 7

short, salicylate;

long

Question 8

a mild aspirin overdose causes vertigo and ____.

Answer 8

tinnitus

also fever, nausea, vomiting

Question 9

aspirin overdose:
early \_\_\_\_\_ (acid base problem) due to \_\_\_\_. late \_\_\_\_\_\_

Answer 9

respiratory alkalosis, hyperventilation;

anion gap metabolic acidosis

Question 10

treatment of aspirin overdose:

_____ or ____ to cause _____ of urine

Answer 10

dextrose, NaHCO3;

alkalinization

Question 11

which arylpropionic acid has a longer half life, naproxen or ibuprofen?

Are they better or worse tolerated than aspirin?

Answer 11

naproxen (14 hours vs 2);

better

Question 12

arylacetic acid derivatives such as diclofenac are especially useful in combating ____ pain. they are ____ inhibitors of prostaglandins and have a ____ risk of ulcer formation. what is often given along with these meds?

Answer 12

osteoarthritic; strong, high;

misoprostol

Question 13

misoprostol is a _____

Answer 13

PGE1 analog

Question 14

enolic acids such as meloxicam and piroxicam are used to treat ____ due to high ____ penetration. do they have high or low amounts of GI side effects? do they have long or short half lives?

Answer 14

arthritis, joint;
low;
long (ie 50 hours)

Question 15

NSAID side effects:
inhibition of renal _____ synthesis causes _____ of the ______ arteriole, leading to an increased risk of renal disorder.

Answer 15

PGE2;

vasoconstriction, afferent

Question 16

acetaminophen is highly effective as a ____ and ____, but has limited _____ activity

Answer 16

analgesic, antipyretic;

anti-inflammatory

Question 17

what is acetaminophen’s effect on platelet aggregation? what about the GI?

Answer 17

none, none

Question 18

acetaminophen ____ inhibits COX in the ____

Answer 18

reversibly, CNS (ie can cross BBB)

Question 19

Acetaminophen usually undergoes ____ metabolism. However, overdose or use of acetaminophen along with _____ causes some acetaminophen to be metabolized via ____

Answer 19

phase 2 (glucuronidation, sulfation);
alcohol (CYP inducer);
CYP450 enzymes

Question 20

Metabolism of acetaminophen via CYP produces _____. This metabolite can lead to depletion of _____ and forms toxic metabolites. Overdose causes ______ necrosis

Answer 20

NAPQI;
glutathione;
hepatic

Question 21

what other side effect can acetaminophen cause? why?

Answer 21

renal toxicity due to vasoconstriction via inhibition of PGE2

Question 22

_____ is the only COX2 selective inhibitor still on the market. why were most removed??

Answer 22

celecoxib;

inhibition of PCI plus no inhibition of TXA = heart attacks, thrombotic problems

Question 23

all NSAIDS at high doses can interfere with ____ healing

Answer 23

bone

Question 24

methotrexate, cyclophosphomide, and azathioprine suppress _____ cell proliferation and function

Answer 24

B and T

Question 25

____ causes G1 arrest, inhibiting T cell proliferation and B cell autoantibody production

Answer 25

leflunomide

Question 26

_____ is an IL1 blocking agent. It inhibits ____ function. ____penia and pre-existing malignancy are contraindications

Answer 26

anakinra; MQ;

neutro

Question 27

Methotrexate, cyclophosphomide, azathioprine, anakinra, TNFalpha blocking agents are collectively called ____.

Answer 27

disease modifying antirheumatic drugs

Question 28

_____ and _____ are anti-TNFalpha antibodies used to treat RA

Answer 28

infliximab, adalimumab

Question 29

____ is a TNF receptor fusion protein.

Answer 29

entanercept

Question 30

entanercept, infliximab, and adalimumab cause downregulation of ____ and T cell function by inhibiting TNF alpha acctivity. they increase the risk of ____ and llegionella.

Answer 30

MQs, listeria

Question 31

TNFalpha inhibitors are contraindicated in ___ and ____ due to potential for reactivation

Answer 31

Tb, HepB