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Flashcards in NSAIDs Deck (16):
1

NSAIDs GI adverse

Due to inhibition of COX-1 and *ulceration* of the mucosa

TX: misoprostol, PPI's, H2 blockers

Lowest risk = COX-2 (celecoxib)
**High risk = Piroxicam**

2

NSAID cardiovascular adverse

Imbalance between TXA2 and PGI2 -> **vasoconstriction, platelet aggregation and thrombosis**
**Selective COX-2** inhibitors have higher CV risk, but fewer GI adverse effects

3

NSAID Renal adverse

***Decrease renal blood flow, AIN, analgesic nephropathy***
Decrease PGE2 -> Na+ and H2O retention (via a decrease in GFR)
Decrease PGI2 -> hyperkalemia and ARF

NSAIDs & ABx are most common cause of AIN (Type 1HS)
Chronic use-> analgesic nephropathy & papillary necrosis

4

NSAID adverse other

*Uricosuric effects** are dose dependent -> low dose *reduces secretion* while high dose *inhibits reabsorption*

5

Aspirin hypersensitivity (NSAIDs)

Rhinitis, edema, asthma, etc
Due to **excess LT synthesis**

NOT a typical HS reaction

6

NSAID drug interactions

ACE-I's -> have vasodilator effects due to increased kinin -> increase PG synthesis which is blocked by NSAIDs

Corticosteroids-> when combined with NSAIDs may increase frequency and severity of **GI ulcers**

Warfarin and NSAID use can increase the risk of *bleeding*

7

Aspirin/Salicylates

*Irreversible acetylation* of COX (other NSAIDs are reversible)

**Uncouple oxidative phosphorylation** -> increase CO2 and increased respiration
High dose stimulates respiratory center -> hyperventilation
Toxic levels-> respiratory paralysis

Decrease TXA2 platelets (lack nuclei), but endothelial PGI2 is unaffected -> increased bleeding time -> **cardioprotective** due to decrease aggregation

High dose-> zero order elimination by kidney
**Chronic use can cause hepatic injury**
**Salicylism -> HA, confusion, ***Tinnitus***, dizziness**
Respiratory alkalosis and metabolic acidosis

8

NSAIDs and colon cancer

Aspirin decreases risk by 50%

Fun fact: aspirin also inhibits the flushing associated with niacin used to lower serum cholesterol (PGD2)

9

NSAIDs and GOUT

DOC -> *Indomethacin*

**Do NOT use aspirin** because it inhibits urate excretion and may increase risk for stones
**Tolmetin** is also ineffective

10

NSAID contraindications

Aspirin use in children -> **Reye's syndrome** (use acetaminophen or ibuprofen instead)

Pregnancy is a relative contraindication
Aspirin is Category D in 3rd trimester

Fun fact: Acetaminophen -> DOC in OA & pregnancy but is not antiplatelet or anti inflammatory

11

NSAID Nonselective Drugs

Aspirin
Diclofenac
Ibuprofen
Indomethacin
Ketorolac
Naproxen
Piroxicam
Tolmetin
Acetaminophen (not technically an NSAID)

12

NSAID COX-2 selective

**Celecoxib**
Etoricoxib
Meloxicam (not as selective as coxibs)

13

NSAID mechanism

*Antipyretic, Analgesic and Anti-inflammatory* properties
**Inhibition of COX -> decrease PG and TXA synthesis**

COX-1 = constitutive enzyme involved in homeostasis (cytoprotective PG formation in gastric cells)

COX-2 = induced by growth factors, tumor promotors and cytokines -> inflammation and cancer
Constitutive in Kidney and brain
*Endothelial COX-2 -> source of vascular prostacyclin*

Most NSAIDs inhibit both isozymes; most antiinflammatory effects are due to inhibition of COX2 while *gastric damage is due to blockade of COX-1*

PGE2 *sensitizes nerve endings* to pain -> NSAIDs are better than opioid for inflammatory pain
PGE2 also responsible for *fever*, mainly from COX-2

14

NSAID uses

Better than opioids for inflammatory pain

Useful in treatment of RA, OA and acute gouty arthritis
Indomethacin -> DOC for closure of ductus arteriosis
Celecoxib is a sulfonamide that may cause HS reactions

15

Celecoxib adverse NSAID

Is a sulfonamide -> may cause HS reaction

**Cardiovascular** imbalance between TXA2 and PGI2 -> vasoconstriction, platelet aggregation and thrombosis

16

Indomethacin is DOC for what?

Closure of ductus arteriosus