Analgesics, Antipyretic and Antinflammatory Drugs Flashcards Preview

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Flashcards in Analgesics, Antipyretic and Antinflammatory Drugs Deck (23)
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1

NSAIDS

 Aspirin

 Ibuprofen ( Advil®, Motrin®) 

 Naproxen (Aleve®)

 And many others of differing chemical classes

 Acetaminophen (Tylenol®)  Celecoxib (Celebrex®)

 N-acetylcysteine

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NSAID major actions

ANALGESIA

ANTIPYRETIC

ANTI-INFLAMMATORY (Except acetaminophen)

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prostaglandin actions

• INFLAMMATION

• SMOOTH MUSCLE TONE

• HEMOSTASIS

• THROMBOSIS

• PARTURITION

• KIDNEY FUNCTION

• GI SECRETION

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inflammation

• COX-1 PRODUCTS IN INITIAL PHASE

• COX-2 UPREGULATED HOURS LATER

• PGI₂ AND PGE₂ MEDIATE INFLAMMATION Sensitize nociceptors

• PGE₂ CONTRIBUTES TO CENTRAL SENSITIZATION WITH HYPERALGESIA & ALLODYNIA

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pain

• PGI2 & PGE2 formed during inflammation sensitize peripheral receptors

• NSAIDs Reverse peripheral PG-induced sensitization to induce analgesia Central actions to alleviate hyperalgesia and allodynia

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fever

• IL-1β, IL-6, TNF-α ,& interferons

Endogenous pyrogens to elevate hypothalamic set-point via COX-2 & PGE₂ synthase induction in endothelial cells PGE₂ enters brain to act on thermosensitive neurons to ↑heat production and ↓heat loss

NSAIDs suppress PGE2 production

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NSAID classifications

• t NSAIDs - Non-selective Reversible Inhibitors of COX-1 & COX-2 (Ibuprofen & Naproxen) 

• Coxibs & some tNSAIDs - Inhibit COX-2

• Aspirin - Irreversible COX-1 & COX-2 inhibition

• Acetaminophen – COX inhibition but different than with NSAIDs

• COX SELECTIVITY

NON-SELECTIVE ASA, IBUPROFEN NAPROXEN

COX-2 SELECTIVE CELECOXIB

ACETAMINOPHEN MECHANISM ?

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NSAID uses

NSAID USES

• ANTI-INFLAMMATORY *

• ANALGESIC

• ANTIPYRETIC

• IN NEONATES TO CLOSE PDA

• CARDIOPROTECTION - ASPIRIN ONLY

* Except acetaminophen

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ASPIRIN / NSAID - ADRs (NOT ACETAMINOPHEN)

 GASTROINTESTINAL

 BLEEDING  PREGNANCY

 RENAL

 ASPIRIN/other NSAID SENSITIVITY

All due to alteration of normal prostaglandin/leukotriene physiology

 THROMBOSIS,STROKE,&MI (except low dose ASA)

ASA USE IS AVOIDED IN CHILDREN with viral illness

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NSAID GI ADVERSE EFFECTS RISK FACTORS

 Age > 70 years (6X)

 Multiple NSAID use (7-9 X)

 Hx peptic ulcer (6X)

 Heavy alcohol use

 Warfarin (12X)

 Helicobacter pylori infection COX-2 selective NSAIDs for high risk patients (This did NOT work)

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NSAIDs MECHANISM of GI EFFECTS

 LOSS of CYTOPROTECTIVE ACTIONS of GASTRIC PROSTAGLANDINS

Acid secretion is unabated Decrease in protective mucus Decrease in mucosal blood flow

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CV RISK of NON-ASPIRIN NSAIDs

 Risk of MI or stroke↑ 30-50 % or MORE

 Risk ↑ for those with/without CV disease or risk factors

 May occur early in use and ↑with use

 Is dose related

 Occurs with and without heart disease or risk factors

 Use after 1st MI more likely to die

 ↑ risk HF

 Not known if risks are similar for all NSAIDs

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NSAIDs -RENAL EFFECTS

 Little effect on normal kidneys

 When renal blood flow is impaired as in: Heart failure Dehydration Kidney disease Normal aging

 Prostaglandins maintain renal function, they block Cl⁻ reabsorption & action of ADH

 With NSAIDs there is salt/water retention

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NSAIDs on GESTATION and DELIVERY

 BLEEDING Antepartum and postpartum

 Transfusion requirement is increased

 Gestation is prolonged

 Premature closure of the ductus

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ASPIRIN/OTHER NSAID SENSITIVITY REACTIONS

 Non-immunologicaly mediated

 Signs and symptoms

Rhinitis

Nasal polyps

Asthma

Urticaria

Laryngeal edema

Bronchospasm

AVOID ALL SALICYLATES/NSAIDs (ex: acetaminophen)

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ASPIRIN & CHILDREN

 AVOID IN FEBRILE ILLNESS

The risk is that of Reyes’ syndrome with liver injury and encephalopathy

 USE: IBUPROFEN NAPROXEN ACETAMINOPHEN

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ASPIRIN PHARMACOKINETICS

 DOSE-DEPENDENT

HALF LIFE ASPIRIN 15 MINUTES

SALICYLATE

low dose 2-3 hours

high dose 12-15 hours

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ASPIRIN OVERDOSE

Combined metabolic acidosis & respiratory alkalosis

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OTHER NSAIDs(IBUPROFEN et al)

 Several distinct chemical classes

 Kinetics and potency vary

 COX-1 and COX-2 inhibition

 COX inhibition is reversable

 Adverse event profile is like aspirin

 Great variability in individual response

 Change to another NSAID

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ACETAMINOPHEN(TYLENOL®)

 Analgesic and Antipyretic

 Poor antiinflammatory

 Little antiplatelet activity

 Little GI toxicity

 Potentially hepatotoxic

 Maximum safe dose - 2600 mg

 Maximum safe single dose- 600mg

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ACETAMINOPHEN TOXICITY

 Hepatotoxic when dose >4 gm/day

 Hepatotoxicity may occur @ doses 1000 units

 Treat with n-acetylcysteine orally

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ACETAMINOPHEN ACUTE LIVER FAILURE

 55% of ALF in US

 Median dose 24 gm

 Unintentional OD 48%

 Intentional(suicide) 44%

 Survival 65%

 Death 27%

 Tx 8% Rx N-acetylcysteine (Mucomist®)

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ACETAMINOPHEN /ALF RISK FACTORS

 Depression

 Chronic pain

 Alcohol or narcotic use

- same Cytochrome P450 metabolizes both acetaminophen and alcohol

-makes toxic NAPQI, which is neutralized by glutathione

-alcoholics don't have good nutrition and lack glutathione

-antidote: N-acetylcysteine

 Simultaneous use of multiple preparations of acetaminophen

 Pediatric overdose (DOSE ERRORS)