Analgesics, Antipyretic and Antinflammatory Drugs Flashcards
NSAIDS
Aspirin
Ibuprofen ( Advil®, Motrin®)
Naproxen (Aleve®)
And many others of differing chemical classes
Acetaminophen (Tylenol®) Celecoxib (Celebrex®)
N-acetylcysteine
NSAID major actions
ANALGESIA
ANTIPYRETIC
ANTI-INFLAMMATORY (Except acetaminophen)
prostaglandin actions
- INFLAMMATION
- SMOOTH MUSCLE TONE
- HEMOSTASIS
- THROMBOSIS
- PARTURITION
- KIDNEY FUNCTION
- GI SECRETION
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
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
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
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 ?
NSAID uses
NSAID USES
- ANTI-INFLAMMATORY *
- ANALGESIC
- ANTIPYRETIC
- IN NEONATES TO CLOSE PDA
- CARDIOPROTECTION - ASPIRIN ONLY
* Except acetaminophen
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
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)
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
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
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
NSAIDs on GESTATION and DELIVERY
BLEEDING Antepartum and postpartum
Transfusion requirement is increased
Gestation is prolonged
Premature closure of the ductus
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)
