NSAIDS Flashcards
Which prostaglandins necessary for GI protection
PGE2 and PGI2 produced by COX1
• Limits activity of proton pumps
• COX1 Inhibition
o Excess acid production in stomach
o Proton pump inhibitors can mediate this effect
Platelet effects
- COX1 present on platelets
- Produces thromboxane A2 which mediates clotting
- Inhibition of COX1 – permanent inactivation of COX1
Renal effects of
COX1
COX2
PGE2 & PGI2
• COX1: GFR rate • COX2: Na and H2O excretion (inducible) • Inhibition • PGE2 & PGI2: regulates renal blood flow & GFR • Inhibition o Decreased PGE2 Na & H2O retention Increased BP Increased weight Congestive heart failure (this is rare) o Decreased PGI2 Hyperkalemia Acute renal failure
Prostaglandins responsible for fever & pain
PGE2
5 uses of NSIADS
Antipyretic • Inhibition of IL-1 Anti-inflmatory • Saliciystes used as scavangers of free oxygen radicals Antithrombotic • Irreversiabel for apsirn Analgesic • Decrease PGE2 IV & IM • Ketorolac Ductus arteriosus closure • Indomethacin
NSAID excretion
- Renal excretion is primary mode of clearance
- Small amount of biliary excretion & reabsorption
- Organic acids
- Hepatic metabolism via CYP3A or CYP2C
NSAID excretion (5)
• Anaphylactic shock (Excess arachidonic acid gets shunted into leukotriene production)
• Contraindicated in 3rd Trimester
o PGE2/I2 maintain patency of ductus arteriosus
o Use in 3rd trimester can cause premature closure
• Reyes Syndrome especially in children following viral fever
• CDV Risk in COX2 Selective Inhibition
o COX2 inhibitors block prostacyclin synthesis causing vascular constriction
o Because COX1 is not inhibited, patient become hypercoaguable
• Salicylism: Acute asprin toxicity, ringing in ears, nausea 7 vomiting
NSAID drug drug interactions (5)
- Caffeine enhances analgesic effects
- Reduce effectiveness of diuretics
- Nephrotoxicity: anti-viral & NSAIDs so must discontinue NSAIDS 7 days prior to taking antiviral drugs (cidofovir)
- Cimetidine (PPI) alter metabolism of NSAIDS
- Reduce excretion of Li
3 treatment strategies for chronic inflammation
o Ablation of Immune Modulation (DMARDs)
o Suppression of expression of cytokines and immune cell activity (corticosteroids)
o Disruption of cytokine activity (anti-TBF alpha biologics)
Methotrexate Use Mechanism Kinetics Side Effects Contraindications
Use
• 1st line for rheumatoid artheritis
Mechanism (low dose)
• Inhibits folate metabolism
• Immunospuressive to revleaves acute inflamtion
Kinetics
• 3-6 weeks
Side effects • GI distress • Oral ulceraltion • Dose dependent hepatoxicity • Pulmonary/hepatic fibrosis • Severe hypersensitive pneumonitis in pre-existing lung disease • Hair loss • Headaches • Skin pigmentation
Contraindications
• Preganc
• Lactation
• Alsoholisms
Leflunomide
Mechanism
Side effects
Kinets & dosage
Mechanism
• Inhibits dihydrooroate dehydrogenase to inhibit pyriidine biosythesi
• Prevents histamine release & COX2 expression
Side Effects
• GI
• Hepatic (more than methotrexate)
Kinetics & Dosage
• Oral
• Long half life
Sulfasalazine
Mechanism
Use
Toxicity
Mechanism
• Prodrug containing sulfapyridine and 5-aminosalicylic acid (mesalamine) which is metabolized by colonic bacteria
• 5-aminosalicylic acid accumulates
• Mesalamine: Inhibits leukotriene synthesis (anti-inflamatory)
• Sulfapyridine: Free oxygen radical scavenger at the joint
Use • Ulcerative colitis • Crohns disease • Juvenile rheumatoid artheretis • Analgesic in pregnancy
Toxicity
• More toxic than methotrexate or leflunomide
• Sulfa or salicyte allergies
• Leuopenia
• Rahs, nausea, vomiting, dizziness, headache
GLUCOCORTICOIDS Mechanism Toxicities Monitor Contraindications
Mechanism
• Cross cell membrane and bind glucocorticoid receptors
o Inhibit leukocyte infiltration
o Suppress humoral immune response (suppress inflammatory mediators)
o Inhibits expression of COX2 & IL-2
o Activate phospholipase A2 inhibitory proteins (lipocortins) which prevent release of arachidonic acid
• Reduce edema & scar tissue
• Reduce circulatin leukocytes & lympholytic
Toxicities
• Cushing-like syndrome
• Hyperhidrosis
• Telangectasia
• HPA suppression leading to adrenal supression
• Insulin resistance (Protein catabolism and amino acids used in gluconegensis)
• Peptic ulces
• Acute psychosis & depression
• Mineralcortoid receptor agonist (Na & H2) retention
Monitor (7) • Hyperglycemia • Glycosuria • Na retention • Hypokaleia • Peptic ulcers • Osteoporosis • Immune suppression
Contraindications (5) • Peptic ulcer • Heart disease or HTN • Infection • Psychosises Hepatic dysfunction
TNF-alpha pathology
- Central cytokine in chronic inflammation
- Cell surface receptorsTNF1 & 2
- Produced in macropahges & stimulates activation of T-lymphocytes & pro-inflmatory events
- Expression of extracellular
Name 3 TNF alpha antagonists
o Infliximab (Remicade) o Adalimumab (Humira) o Etanercept (Enbrel) 2 TNF receptors
