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Pharmacology > NSAIDs > Flashcards

NSAIDs Flashcards

1
Q

NSAID General Indications

A 
Reduce inflammation (RA/OA/Gout)
Pain Relief (Mild/moderate pain, muscle strains, headache/migraine, surgery)
Fever reduction (viral infection, common cold/flu)
Promote closure of patent ductus arteriosus
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2
Q

ASA specific

A

Stroke/MI prevention

Inhibition of platelet activation

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3
Q

NSAID MoA

A

Tissue Damage -> affected tissue -> inflammatory mediators (cytokines and prostaglandins) -> pain, inflammation, fever

NSAIDs act on PG, bind to cyclooxygenases and inhibit

Phospholipase A2 -> Arachidonic acid -> cyclooxygenases -> PG/Tx synthases -> Inflammatory and homeostatic response

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4
Q

Differences in MoA

A

All NSAIDs except ASA are competitive COX enzyme inhibitors (bind to active site)

ASA is irreversible non-competitive inhibitor, covalently modifies COX in active site

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5
Q

COX1 and COX2

A

Both catalyze rate-limiting conversion of AA to PG and Tx

COX1: constitutive, expressed in most tissues, general housekeeping (platelet reg, kidney function, stomach and mucous production), inhibited by ASA and tNSAIDs NOT CELECOXIB

COX2: Inducible to proinflammatory stimuli, induced by macrophages/monocytes/chordro/osteo/fibro, constitutive low-level in kidney/endothelium/brain/ovaries/uterus, inhibited by ASA, tNSAIDs AND celecoxib

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6
Q

COX1 Housekeeping

The GI tract

A

COX1 expressed in stomach, produces PG contitutive (are cytoprotective)
Inhibit gastric acid secretion, increase HCO3 production, Increase gastric mucous production, increase vasodilation/gastric blood flow

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7
Q

COX1 Housekeeping

CV System

A

Platelets express only COX1 and produce TXA2 (vasoconstriction, platelet aggregation)

Endothelial cells express COX1 and 2 but no TXA2 synthase so only PGI2 (vasodilator, inhibits platelet aggregation)

The TXA2/PGI2 balance regulates BP and thrombogenesis, imbalance leads to hypertension, ischemia, thrombosis, MI and stroke

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8
Q

COX1 Housekeeping

The Kidney

A

COX 1 and 2 constitutively expressed in the kidney

PGs promote vasodilation, glomerular filtration rate, water and Na excretion

In disease states there are increased vasoconstrictors thus if NSAIDs are present they decrease the PG/vasodilatory protection and pt gets renal ischemia

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9
Q

COX1 Housekeeping

Female Reproduction

A

PGs play role in stimulating uterine contraction and birth, NSAIDs may delay labor

NSAID treatment during pregnancy may prematurely close fetal ductus arteriosus and adversely affect fetal circulation

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10
Q

Low dose ASA

A

Treatment of CVD and prophylactic stroke/MI prevention
ASA acetylates COX1 in platelets PERMANENTLY inhibiting its activity and TXA2 (7-10 day lifetime)
Enothelial cells are able to keep making PGI2
This promotes an anti-thrombogenic environment
High dose starts affecting PGI2 and negates the beneficial effect

Other NSAIDs do inhibit COX1 in platelets but it is reversible so the action is not as effective/long lasting as ASA

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11
Q

Major adverse effects of ASA and salicylates

A

Increased risk of GI complications (ulcers)
Increased risk of bleeding (hemophiliacs)
High dose ASA: Exacerbation of pre-existing hypertension/ heartfailure
Salicylates are 50-90% protein bound, will kick drugs off of plasma proteins and cause drug side-effects
Airway hypersensitivity
Reye’s syndrome (rare and fatal liver degenerative disease, encephalitis, occurs in young children/adolescents during febrile viral infection)
Increased risk of gout (inhibits renal uric acid excretion)

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12
Q

Major adverse effects of traditional NSAIDs

A

Nonselective for COX1 and COX2
Clinical effect is from inhibition of COX2, adverse effects are from inhibition of COX1
GI toxicity
Kidney impairment
CV, antiplatelet effect, bleeding (the more selective you are for COX2, the more risk of MI/stroke)
Exacerbation of pre-existing hypertension/ heartfailure
NSAID hypersensitivity (not from immune system)
Pregnancy-related adverse effects

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13
Q

Major adverse effects of selective COX2 inhibitors

Coxibs

A

Good for patients with GI and bleeding complications
Can exhibit similar renal toxicity as other NSAIDs
Increased risk of CV events, especially at higher doses
CONTRAINDICATED FOR PATIENTS WITH/AT RISK FOR CVD
Inhibits COX2 and thus PGI2 in endothelial cells, creates pro-thrombotic vasoconstrictory environment

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14
Q

NSAID Contraindications

A

History of GI ulcer (not celecoxib)
Renal disorders
Bleeding disorders, anti-coagulants (not celecoxib)
Hx of CVD/hypertension/heart failure (especially celecoxib)
Hypersensitivity to an NSAID
Pregnancy
Hx of gout (ASA/salicylic specific)
Children with febrile viral infections (ASA/salicylic specific)

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15
Q

ASA/ Salicylate toxicity

A

High dose: zero order kinetics, serum half life dramatically increased

Hyperventilation, metabolic acidosis, hypoglycemia, confusion, tremors, seizure, cerebral edema, respiratory depression, coma, death

Tx: alkalinzation of the urine with HCO3 (traps and excretes ASA)

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16
Q

Non-NSAID analgesic

Acetaminophen

A

Pain and fever
No anti-inflammatory activity
No anti-platelet activity
Principally acts on CNS: pain and thermoregulatory centers
Preferred for children with febrile viral infections, peptic ulcer disease, hemophilia, hypersensitivity to ASA or NSAIDs
FEWER ADVERSE EFFECTS THAN ASA AND NSAIDs

17
Q

Acetaminophen toxicity

A

High concentrations metabolic enzymes are overwhelmed
NAPQI metabolite builds up while it detox agent Glutathione is depleted
Alcohol exacerbates NAPQI production, causes hepatic cells to start dying
Give antidote N/acetyl cysteine to increase glutathione levels to detox NAPQI levels

18
Q

Ibuprofin

A

tNSAID
Equipotent with ASA
Rapid onset, ideal for fever and acute pain
Less GI and bleeding than ASA

19
Q

Naproxen

A 
tNSAID
aka aleve
20x more potent than ASA
Rapid onset, ideal for anti-pyretic
Long serum half life, 2x daily dosing
Low GI and bleeding, considered safest NSAID
20
Q

Oxaprozin

A

tNSAID
Slow onset ~6hrs
Long serum half life, daily dosing
Increases uric acid secretion, useful for gout

21
Q

Indomethacin

A

tNSAID
10-40x more potent than ASA, anti-inflammatory
Not as well tolerated as ibuprofin, 50% experience side effects
Promote closure of patent ductus arteriosus

22
Q

Ketorolac

A

tNSAID
Weak anti-inflammatory
Used as IV analgesic for post-surgical pain
Used as a replacement for opioid analgesics

23
Q

Diclofenac

A 
tNSAID
More potent anti-inflammatory than indomethacin and naproxen
Somewhat better tolerated
Relatively selective for COX2
INCREASED RISK OF MI/STROKE

Pharmacology (44 decks)

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