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Flashcards in NSAIDs Deck (71):
1

Acetyl Salicylic Acid [Aspirin]

Salicyclic Acid Derivatives
(don't know chemical groups)

salicylate ester of acetic acid

*irreversibly* acetylates/inactivates COX in platelets, megakaryocytes

(4-7 days, life of platelet)

anti-inflammatory, antithrombotic effects (inactivates platelets)

2

Mesalamine (5-amino salicylic acid) [Apriso®]

Salicyclic Acid Derivative

*reversible inhib COX-1 and COX-2

toxicity: GI, CNS, nasophary., hypersn

used for UC

3

Diflunisal

Salicyclic Acid Derivative

*reversible* inhib. of COX

analgesic, anti-inflammatory

little antipyretic activity

long 1/2 life (8-12 hrs), inc. pt compliance

less GI SEs, don't use in pts with anti-ASA sn.

tox: GI (mild), ha, renal, hypersn

4

Indomethacin [IndocinR]

Acetic Acid Derivative

rev. inhib COX 1 and 2

tox: GI, bleeding, CV, CNS

use: RA (NOT JRA), OA, tocolytic agent

5

Etodolac

Acetic Acid Derivative

more COX-2 selectivity

tox: GI, less sev.

use: FA, OA, postop analgesic

6

Diclofenac

Acetic Acid Derivative

rev. inhib COX 1 and 2

tox: GI, CNS

use: RA, OA, anagesia/dysmenorrhea

7

Tolmetin

Acetic Acid Derivative

rev. inhib COX 1 and 2

tox: GI, CNS, anaphylaxis!

use: RA, JRA*, OA

8

Ketorolac

Acetic Acid Derivative

rev. inhib COX 1 and 2

tox: GI, CNS

use: mod sev, acute pain, NOT for RA/OA

9

Ibuprofen [MotrinR, AdvilR]

Propionic Acid Derivative

rev. inhib COX 1 and 2

tox: GI (less than ASA, indometh.), ocular disturbs, hypersn rash, avoid during preg/breast feeding

uses: RA, OA, analgesia, dysmenorrhea, fever

10

Naproxen [AnaproxR, NaprosynR, AleveR]

Propionic Acid Derivative

rev. inhib COX 1 and 2

tox: GI

11

Ketoprofen

Propionic Acid Derivative

rev. inhib COX 1 and 2

tox: GI, CNS

use: RHA, OA, analgesia, dysmenorrhea

12

Oxaprozin [DayproR]

Propionic Acid Derivative

rev. inhib COX 1 and 2
(1x/day)

tox: GI

use: RA, OA

13

Piroxicam (FeldeneR)

Enolic Acid Derivative: Oxicam

rev. inhib COX 1 and 2

tox: GI

use: RA, OA

14

Meloxicam (MobicR)

Enolic Acid Derivative: Oxicam

rev. inhib COX 2 > 1

tox: GI

use: OA

15

Nabumetone

Non acidic compound (Alkanones)

rev. inhib COX 2 > 1
activated by liver

tox: GI, CNS

use: RA, OA


16

Acetaminophen [TylenolR]

Para aminophenol derivative

weak inhibition COX-1,2,3

antipyretic by acting on hypothalamic heat-regulating center

tox: *hepatotoxicity, *nephrotoxicity, hypersn

uses: antipyretic, analgesic, OA

17

platelets only have..

COX-1 (not COX-2)

18

Celecoxib (CelebrexR)

COX-2 INHIBITOR

19

Acetyl Salicylic Acid [Aspirin] GI absorption mechs

more non-ionized ASA in stomach (where it's acidic)-->can be absorbed by gastric mucosa cell

in mucosa cell: it's ionized-->stuck there

*ionized in sm. int. BUT larger surf. area so absorbed*

20

Acetyl Salicylic Acid [Aspirin] pharmkin

widely distributed through tissues, binds plasma proteins

*can diffuse through placenta and BBB-->CNS effects*

21

Acetyl Salicylic Acid [Aspirin] metab/elim

urinary pH changes from 5 to 8 in kidneys (alkalinization with sodium bicarbonate)

*ASA in ionized state, does not diffuse back, excreted), the renal clearance of free ionized salicylate increases from 2-3% of the amount excreted to about 80%

(The opposite happens in acidic urine)

22

Acetyl Salicylic Acid [Aspirin] GI SEs

dyspepsia, heartburn, epigastric distress, nausea

less frequently vomiting, anorexia, abdominal pain
inc. with high doses/pre-existing ulcer

occult bleeding, gastric mucosal damage, iron def. anemia (case)
reactivate latent gastric and duodenal ulcers

*most freq. with ASA than other salicylates

23

case: iron def. anemia
enteric-coated reg. strength ASA
1 mg warfarin
INR 1.15
tablet in ulcer of gastric antrum
tx w. endolcac and ASA -DON't DO: synergy

tx w. lasoprazole (PPI)

24

Misoprostol (Cytotec®)

prostaglandin E1 analogue

can protect stomach by lowering gastric acid production, anti ulcer with ASA tx

25

ASA otic effects

tinnitus and hearing loss- *reversible

200-300 μg/mL for anti-inflammatory effects, appearance of tinnitus
indicates adequate plasma concentrations have been reached

26

ASA hepatic effects

reversible, particularly with previous hepatic impairment and high dose salicylates
-must monitor

27

ASA renal effects

renal medullary ischemia as a result of inhibition of renal prostaglandin synthesis

28

ASA CV effects

noncardiogenic pulmonary edema, HTN
CI: CHF pts (esp. w. Na)

29

ASA hematologic effects

(high doses) decrease hematocrit and plasma
iron concentrations

reduce RBC life span
inc. risk of bleeding

CI in patients with bleeding disorders

*discontinue ASA 5-7 days before sx

30

ASA hypersensitivity rxns

ASA triad?

*Type 1*
Urticaria and /or angioedema:

aspirin sensitivity
asthma
nasal polyps
(small doses: 20-30mg)
*in asthma pts*

foods with salicylate-->hypersn

31

ASA ped cautions (also teenagers)








symptoms ??

varicella infections (chicken pox) or influenza-like illnesses is reportedly associated with an increased risk of developing *Reye's syndrome*

sudden vomiting, violent headaches and belligerence that may progress to delirium and coma

32

what to use in peds for an anti-pyretic instead of ASA?

ACETAMINOPHEN

33

ASA Pregnancy, fertility, lactation

safe use has not been established

*can diffuse thru placenta and BBB*

could be teratogenic, congenital abnormality associations, use only when potential benefits>possible risks to fetus

caution to nursing mothers

maternal and fetal hemorrhagic complication

34

ASA intoxication

Chronic salicylate intoxication is also known as salicylism

> than 100 mg/kg daily for 2 days or longer

Acute salicylate OD results from ingestion of a single toxic dose
lethal:
10-30g adults
4g kiddos


35

ASA intox manifests

Tinnitus and hearing loss

Hyperventilation and CNS effects (kiddos)

metabolic acidosis and respiratory alkalosis

CNS stimulation (salicylate jag), then CNS depression-->resp. failure or CV collapse-->coma/death

principal: *acid-base and electrolyte disturbances, dehydration, hyperpyrexia, and either hyperglycemia or hypoglycemia*

36

ASA OD tx

immediately!
symptomatic and supportive

enhance salicylate elimination: lavage

prevent further absorption: activated charcoal (2hr)

correct fluid, e-lyt, A/B disturbances

alkalinize urine to
pH 7.5 or greater enhances salicylate excretion (will be neg. charged): IV sodium bicarbonate:

37

ASA drug interactions

Protein-bound drugs: compete for binding site

don't use with anticoagulants/thrombolytic agents-->inc. risk bleeding

corticosteroids inc. clearance of ASA

*NSAIDs* DON'T used in conjunction with other NSAIDs: synergy (GI effects)

38

ASA dosage for RA, OA, etc

2.4-3.6 g daily
(gram-level! at risk for toxicity)

39

NSAIDs adverse effects: CV

HTN: dose-dependent, from inhibition of *COX-2 in the kidney*

(use w. caution in HTN, dec. cardiac function pts)

fluid retetion and peripherial edema

40

NSAIDs adverse effects: CNS

diffuse thru BBB and placenta

dizziness, ha (indomethacin, fenoprofen, ketorolac)
psych
somnolence/drowiness

41

NSAIDs adverse effects: dermatologic

rashes

42

NSAIDs adverse effects: elderly

ulcers
spontaneous bleeding

43

NSAIDs adverse effects: GI

gastric/duodenal ulcers
inhib. PG production (gastric cells have COX1)

*can occur anytime, with or without warning symptoms in patients receiving NSAID therapy chronically

44

factors assoc. with inc. risk GI ulcer

smoking, etOH
bleeding

45

NSAIDs adverse effects: hematologic

autoimmune hemolytic anemia (Type II drug allergy)-IgG, IgM with Tolmetin, *reversible
-remove offending drug, tx with corticosteroids

platelet (COX1) aggregation less and dec. duration than with ASA
*reversible

NSAIDs may prolong bleeding time-affect coagulation cascade

46

NSAIDs hypersn. rxns

rare in ASA (3 hrs after)
manifests as asthma, anaphylaxix, acute resp. distress, rapid fall in BP- shock-like, angioedema, dyspnea, angiitis

47

NSAIDs adverse effects: lactation

DON'T use NSAIDS in nursing mothers because the potential effects on the infant's cardiovascular system

48

NSAIDs adverse effects: renal

*COX 2 constitutively expressed*
NSAIDs inhibit COX-2-->inhibit renal PG synthesis:

progressive renal impairment

Acute renal insufficiency

Interstitial nephritis

hyper Na+, K+

Papillary necrosis (chronic renal injury)

49

NSAIDs adverse effects: pregnancy

-inhibit prostaglandin E2 synthesis may induce the closure of the fetal ductus arteriosus

-can prolong labor (*avoid, esp during 3rd trimester*)

use: FDA-labelled NSAIDS for closure of patent ductus arteriosus in
premature infants, are either indomethacin (ha) or ibuprofen

50

NSAIDs drug interaxns

All NSAIDs bind to plasma proteins

51

Celecoxib, last COX-2 standing

inhibition of prostaglandin synthesis, via inhibition of cyclooxygenase-2 (COX-2)

*Metabolism is via cytochrome P450 2C9* (drug interactions)
Elim by hepatic metabolism

52

celecoxib CIs


not for pts who have allergic-type reactions to sulfonamides

OR experience asthma, urticaria or allergic-type reactions after taking aspirin or other NSAIDs

53

celecoxib adverse effects

GI: less since not COX 1 inhib, but still some GI
CNS
resp
skin
psych

54

endothelial cells have

COX-1 and *COX-2*-->PGI2
vasodilaiton and declumping

55

platelets have

COX-1-->TXA2
vasoconstriction and aggregation (via TXA2)

*not inhib. by selective COX-2 inhibitors, had to remove from market exc. celecoxib (milder)

56

acetaminophen affects

paracetamol

affect on fever by action on hypothalamic
heat-reg center

weakly inhibits COX1, 2, 3? (spliced)

57

acetaminophen pharmkin

metabolized by the hepatic microsomal
enzymes to acetaminophen sulfate and acetaminophen glucuronide (typ. excreted)

*small amount metab by cytP450 to *N-acetyl-p-benzoquinoneimine*, which is highly reactive to cellular proteins and thus becomes toxic to both liver and kidney (norm. detox by glutathione)
*toxicity in large amounts*

58

acetamin SEs

hepatotoxicity*** (reversible) potentially fatal hepatic centrilobular necrosis

nephrotoxicity

59

acetominophen OD


antidote?

gastric lavage

oral N-acetylcystein (Mucomyst)- restores glutathione levels-neutralizes toxic metabolites

use w.in 8 hrs post-ingestion

60

ASA used for

mild-mod pain, fever, inflamm. disease

also: prevention of arterial and venous thrombosis

61

NSAIDs

*mostly used as anti-inflammatory agents*

both analgesic and antipyretic properties

reversible inhibition of COX 1 and 2

absorbed rapidly and completely, pKa 3.5-6.3 (acidic)
protein bound, variable half life

62

NSAIDs for RA

all except Ketorolac, Meloxicam, Mefenamic acid

63

NSAIDs for OA

all except Ketorolac and Mefenamic acid

64

JRA tx

Tolmetin and naproxen

65

Ibuprofen hypersensitivity

severe rxns w. fever, rash, abd pain, ha, N/V, liver damage and meningitis in pts w. SLE or other collagen diseases

may not start immediately

66

celecoxib uses

OA, RA, acute pain, dysmenorrhea, familial adenomatous polyposis

67

why other selective COX 2 drugs were taken off the market

CV problems from uninhibited COX-1-->platelets-->prod. TXA2-->vasoconstriction and aggregation

68

COX-1 inhibitor:
ibuprofen-->inhib COX1-->prevents TXA2 release-->inhibits platelet aggregation and vasoconstriction

endothelium cells (COX-2) NOT inhibited by ibuprofen-->still releases PGI2-->unopposed vasodilation and declumping

69

COX-2 inhibitors: celecoxib
affects endothelial cells (COX-2)-->NO release PGI2-->inhibits vasodilation and decamping

BUT
platelets (COX-1) still release TXA2-->*vasoconstriction and aggregation UNOPPOSED*-->CV problems

all COX-2s removed except celecoxib: milder effects

70

don't take more than ?? g acetaminophen/day
alcoholics?

71

acetominophen uses

analgesic
antipyretic
weaker anti-inflammatory than ASA

mild-mod pain
OA