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Flashcards in NSAIDs Deck (18):
1

what are the pharmacological actions of NSAIDs

-Antipyretic
-Analgesic:pain of mild to moderate intensity, painj associated with inflammation.
-Anti-inflammatory effect

2

How do NSAIDs work

Inhibiting the enzyme cyclooxygenase from converting AA to PGG2 and therefore inhibits prostaglandin synthesis associated with inflammatory factors.

3

How does the NSAID anti-inflammatory effect work?

COX inhibition results in inhibition of PGE2+PGI2 synthesis, these prostaglandins have a significant role in vasodilation therefore less vasodilation results in reduction of redness, pain and swelling

4

How do NSAIDs reduce fever?

Fever is caused by the presence of endotoxins in the blood these pyrogenic substances cause an onset of events that leads to the hypothalamus, when the hypothalamus is in the presence of PGE2 the core body temp. is elevated, NSAIDs inhibit synthesis of PGE2 therefore inhibit the pyretic effect of the prostaglandin on the hypothalamus

5

How do NSAIDs produce an analgesic effect?

PGE1+PGE2 sensitise nociceptive afferent nerve terminals to mediators such as bradykinin, inhibition of these prostaglandins results in bradykinin levels being of too low concentraion to cause pain on their own.
Relief of headache is a result of a reduction in vasodilation in the cerebral vasculature due to inhibition of PG synthesis.

6

Describe pharmacokinetics of ibuprofen?

-Rapidly absorbed following administration
-Peak CONC. 1-2 hours
-t1/2-2 hours
dosage-tid

7

describe the pharmacokinetics of piroxicam?

-Peak CONC. 2-4 hours
-t1/2: 50-100 hours
-Dosage: once or twice daily

8

List the NSAID interactions?

1)oral anticoagulants
2)Hypotensive agents
3)ACE inhibitors + Angiotensin II antagonists
4)Diuretics
5)lithium
6)Methotrexate

9

How do NSAIDs affect the gastric mucosa?

PGE2+PGI2 promote blood flow and increase thickness of mucous barrier. Inhibiton results in decreased thickness of this barrier and susceptibility to ulceration + bleeding.

10

How do NSAIDs affect renal function?

PGE2 is involved in maintaining renal cortical blood flow and electrolyte balance. Inhibition of PGE2 adversely affects kidney function.

11

How do NSAIDs affect platelet function?

inhibition of TXA2 affects platelet function and thus increases bleeding time.

12

How do NSAIDs affect uterine contraction?

Inhibition of PGF2alpha results in intiation and progression of labour and delivery.

13

list the general NSAID side effects?

GI complications
reversible renal failure
Platelet dysfunction
Bronchospasm
Skin reactions

14

list the GI side effects?

nuisance symptoms:
heart burn
nausea
dyspepsia
abdominal pain 10-12%

mucosal lesions-ulcers

serious GI side effects:
Perforated ulcers
bleeding
death 0.5-2%

15

describe the use of the 2 main COX isoforms?

COX 1-
constantly present responsible for basal PG synthesis, responsible for critical homeostatic function such as stomach-mucosal protection, thromboxane in platelets and kidney-modulating intrarenal bloodflow and electrolyte balance
COX 2-
induced by inflammatory mediators and suppressed by steroids. CONC. increased in inflamed tissues, results in increased production of IL-1, TNFs and growth factors in the rheumatoid joint. there are basal levels in kidney brain and ovarian tissue, its involved in development of kidney, salt and water regulation + ovulation and parturition.

16

list these in order of most
COX-2 selective and least risk of GI side effects: Indometacin,ibuprofen,piroxicam,
sulindac,diclofenac.

Diclofenac
Ibuprofen
Sulindac
Indometacin
Piroxicam

17

Explain the methods used to determine how a NSAID receives its COX classification

Enzymatic/biological:
COX-1 IC50/COX-2 IC50 = selectivity ratio.
Biologic and pharmacologic:
Human whole blood assay
Clinical:
No effect on GI mucosa/platelet function + decrease incidence of PUBs

18

list the 4 classifications of COX inhibitors

1)COX-1 specific inhibitor: low dose aspirin
2)Non specific COX inhibitor: diclofenac + ibuprofen
3)preferential COX-2 inhibitors: meloxicam, nabumetone + etodolac
4)COX-2 specific inhibitors: rofecoxib + celecoxib= 1st gen
etoricoxib,parecoxib,valdecoxib= 2nd gen