Aspiring, NSAIDs, and Acetaminophen Flashcards Preview

Pharmacology > Aspiring, NSAIDs, and Acetaminophen > Flashcards

Flashcards in Aspiring, NSAIDs, and Acetaminophen Deck (61):
1

function of NSAIDs

inhibit COX-1 and COX-2

2

how does aspirin inhibit function of COX-1 and COX-2

it covalently modifies the enzyme

3

how does NSAIDs inhibit COX-1 and COX-2

competes for the active site of cyclooxygenase (competitive inhibitor)

4

how does Acetaminophen inhibit COX-1 and COX-2

-interfers with the oxidative state of cyclooxygenase site
-inhibition impaired by "peroxide tone"

5

acetaminophen metabolites can form a conjugation with arachidonate acid in the brain to yield

a neuroactive metabolite
-or inhibition of the nitric oxide pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate and substance P

6

general properties of NSAIDs

-anti-inflammatory
-analgesia (inability to feel pain)
-antipyresis
-gastric erosion
-cause renal dysfunction, impair renal function
-variable effect on platelet aggregation; increase cardiovascular pathologic events due to COX-2 inhibition

7

side effects of NSAID therapy

-gastric and intestinal ulceration
-anemia from resultant blood loss
-local irritation from drugs (organic acids) plus removal of PGE2 and PGI2 cytoprotective effects (less mucous covering GI)

8

how should patients at risk of GI toxicity be managed

-given celecoxib or other NSAID co-administered with a proton pump inhibitor or the PGE1 analong misoprostol

9

All NSAIDs have what effect on the cardiovascular system

-prothrombotic effects that increase risk of stroke, TIA, symptomatic coronary artery disease
-symptomatic peripheral vascular disease (COX-2 inhibition)

10

All NSAIDs can exacerbate

hypertension

11

what is the safest NSAIDs

naproxen bc it has the lowest cardiovascular toxicity effects

12

what are the adverse effects of NSAIDs on the renal system

-decrease renal blood flow and GFR in patients with congestive heart failure, liver disease (ascites); chronic renal disease; or those who are hypovolemic or dehydrated
-promote salt and water retention by producing PG-induced inhibition of both the reabsorption of chloride and the action of ADH
-may cause increased intravascular volume/edema
-analgesic nephropathy
-idiosyncratic and dose-related hepatic injury

13

symptoms of aspirin "intolerance"

-vasomotor rhinitis, generalized urticaria (hives), and bronchospasm, laryngeal edema and bronchoconstriction, flushing, hypotension and shock

14

aspirin "intolerance" occurs in pts with

-nasal polyps, asthma, and chronic urticaria
-asthma may be induced or exacerbated in such patients

15

what is the mechanism of aspirin intolerance

-defect in mast cell histamine storage/shunting or arachidonic acid to lipoxygenase pathway
-nonimmunologic mechanism

16

effects of aspirin in pregnancy

-prolong labor
-promote premature closure of ductus arteriosus

17

common drug interactions of NSAIDs

-prolong bleeding time (warfarin; heparin)
-increase the ulcerogenic effects of glucocorticoids
-reduce effects of diuretics and other antihypertensive agents
-reduce lithium clearance; also methotrexate; cyclosporine; aminoglycosides

18

therapeutic uses of NSAID

-relief pain and inflammation
-reduce body temp in febrile states
-closure of ductus arterioles
-with antihistamines, in pts with systemic mastocytosis
-adjunct in cancer-related hypercalcemia
-Bartter's syndrome
-moderate cutaneous rxns in pts receiving niacin

19

aspirin in a --- dependent pharmacokinetics

dose

20

MAO of aspirin

acetylates COX

21

what type of inhibitor is aspirin (salicylic acid)

competitive inhibitor

22

dose-dependent therapeutic effects of aspirin

-anti-platelet effects
-analgesia; reduction in febrile responses
-anti-inflammatory

23

aspirin metabolism

-aspirin is metabolized in plasam to yield salicylic acid
-salicylic acid is biotransformed in liver and mitochondria

24

therapeutic uses of aspirin

-antipyretic, analgesic, anti-inflammatory

25

aspirin can be used as a prophlaxis of disease assocaited with

-platelet hyperaggreability (CAD; unstable angina; post_MI or stent; postoperative deep vein thrombosis; risk of stroke)
-pre-eclampsia and hypertension indued by pregnancy

26

adverse effects of aspirin

-gastric irritation, ulceration, erosion, hemorrhage
-increased bleeding time (2X for 4-7 days)
-decreased renal function in patients at risk
-hepatic injury (usually with larger doses associated with treatment of RA)

27

low doses of aspirin inhibits

uric acid excretion

28

large doses of aspirin promotes

uric acid excretion

29

10 mg/dl of aspirin causes

analgesia, antipyretic, anti-platelet; gastric intolerance/bleeding, hypersensitivity

30

10-49 mg/dl of aspirin causes

anti-inflammatory, uricosuric

31

50-80 mg/dl of aspirin causes

mild intoxication; tinnitus, central hyperventilation

32

80-100 mg/dl causes

moderate intoxication; fever, dehydration, metabolic acidosis

33

110-160 mg/dl of aspirin causes

severe intoxication; hypoprothrombinemia, vasomotor instability; coma

34

>160 mg/dl of aspirin causes

lethal blood levels; renal and respiratory failure

35

what is salicylism

aspirin overdose

36

effects of salicylism

-confusion; tinnitus, dizziness

37

how does salicylism affect respiration

-contributes to acid-base disturbances
-stimulation via uncoupling of oxidative phosphorylation
-direct stimulation of respiratory centre
-toxic doses suppress respiration

38

what metabolic effects does salicylism have

-increases uncoupling
-inhibit aerobic respiration
-release epinephrine
-reduces lipogenesis
-large doses stimulate glucocorticoid secretion

39

uncoupling of oxidative phosphorylation causes

increase of O2 consumption and CO2 production

40

toxic doses of aspirin inhibit aerobic respiration leading to

accumulation of pyretic, lactic and acetoacetic acids

41

aspirin promotes epinephrine release which promotes

hyperglycemia and depletes muscle and hepatic glycogen

42

aspirin reduces lipogenesis which causes

increase in oxidation of F/A

43

full therapeutic dose of aspirin produces respiratory alkalosis, how does compensation occur

-increase renal excretion of bicarbonate, accompanied by increased Na+ and K+ excretion

44

extreme metabolic acidosis is caused by

-salicylate accumulation
-renal dysfunction with accumulation of organic acids
-derangement of carbohydrate metabolism

45

what is Acetaminophen (Tylenol)

an effective antipyretic and analgesic

46

does Acetaminophen have anti-inflammatory effects

very little

47

Acetaminophen does not effect the --- and ---

GI tract
platelets

48

main toxicity of Acetaminophen is directed toward

liver

49

mechanism of action of Acetaminophen

-inhibits cyclooxygenase, by altering oxidate state of active site

50

ability of Acetaminophen to inhibit cylooxygengase is impaired in the presence of

peroxides (ie. inflammation)

51

ability of Acetaminophen to inhibit cylooxygenase is enhanced in the presence of

high [ ] of antioxidants (ie. brain)

52

experimental demonstration of novel metabolite of acetaminophen in

CNS which inhibits COX and stimulates TRPV1 receptor or possible interference with nitric oxide pathway and interface with central neurotransmitters

53

Large dose of Acetaminophen (>7.5 g) may cause

hepatotoxicity

54

hepatotoxicity of acetaminophen is mediated by

a metabolite formed by P450, which is normally inactived by glutathione

55

hepatotoxic dose may be substantially smaller in individuals with

preexisting liver disease or who consume alcohol regularly

56

acetaminophen over dose is the most common cause of

-acute liver failure
50% of adults
13% of pediatric cases

57

treatment of acetaminophen toxicity

N-Acetylcysteine

58

administration of N-Acetylcysteine is based on

a nonogram derived from time-dependent acetaminophen [ ] data generated in adults with a single, acute ingestions of drug who presented to medical centres with 24 h of the overdose

59

FDA issued manufactuers of TC pain delivers and fever reducers to revise their labelling to include warnings about potential safety risks. Products covered by the FDA action included

-acetaminophen (in a class by itself)
NSAIDs
-aspirin
-ibuprofen
-naproxen
-ketoprofen

60

acetaminophen prescription products limited to

325 mg per dose

61

what were the changes in Aceaminophen dosing regulations and warnings

-require boxed warning highlighting the potential for liver injury, as well as allergic runs
-used in many combination products; label abbreviations are currently not standardized