Non opioid analgesics

Question 1

ketorolac (toradol): class, use

Answer 1

• non-steroidal anti-inflammatory drug (NSAID)
• only IV NSAID in US

Question 2

ketorolac (toradol): MOA

Answer 2

• blocks cyclooxygenase (COX) 1 & 2 which reduces inflammatory response
• inhibits prostaglandin synthesis causing anti-inflammatory effects & analgesia effects
• inhibition of COX-1 also blocks synthesis of thromboxane A2 causing REVERSIBLE inhibition of platelet aggregation

Question 3

ketorolac (toradol): PK

Answer 3

• Onset: 10 min
• Peak: 2-3 hrs
• Duration: 6-8 hrs
• E1/2t: 5 hrs (prolonged by 30%-50% in elderly)
• PB: > 99%
• Metabolism: by the liver, principally by glucoronic acid conjugation
• Elimination: 60% excreted unchanged in urine

Question 4

ketorolac (toradol): SE

Answer 4

• PULM: bronchospasm in asthmatics or aspirin-sensitive patients d/t inc. leukotrienes
• GI: GI bleed, ulcerations, perforation
• GU: renal toxicity/ ARF
• HEME: prolonged bleeding time, decreased plt aggregation, anaphylaxis, Steven-Johnson Syndrome, impaired bone healing

Question 5

ketorolac (toradol): cautions/contraindications/drug interactions

Answer 5

• CAUTIONS/CONTRAINDICATIONS
  
  • BLACK BOX: do not use in peri-op in CABG, can cause inc CV effects like MI & stroke
  • pregnancy (3rd trimester, cat D - d/t premature closure of DA)
  • hypersensitivity/aspirin allergy
  • GI bleeding
  • coag defects
  • asthma
  • Do not use in hypovolemic patients or patients who rely on renal prostaglandins for renal function (CHF, renal failure, hepatic cirrhosis) as this may precipitate renal failure/toxicity
• DRUG INTERACTIONS
  
  • displaces other highly protein bound drugs
    
    • increases levels of warfarin, phenytoin, sulfonylureas, sulfonamides, digoxin
  • reduces effect of diuretics, beta blockers, ACE inhibitors via suppression of renal PGs
  • increases lithium levels
  • increased risk of GI bleed when combined with anti-coagulants
  • probenacid increase levels of most NSAIDs - avoid ketorolac
  • do not use with methotrexate - severe bone marrow supp

Question 6

ketorolac (toradol): dose

Answer 6

• 30 mg IV x1 or q6hrs
• max dose: 120mg
• elderly: cut dose in 1/2 if you use at all
• do not exceed 5 days of use

Question 7

acetaminophen (tylenol): class, use

Answer 7

• class
  
  • Non-opioid analgesic
  • Antipyretic
• good choice in
  
  • PUD
  • pediatric patients
  • pts who need well functioning platelets

Question 8

acetaminophen (tylenol): MOA

Answer 8

• Central anti-prostaglandin effect
  
  • NMDA receptor blockade in CNS
  • Blocks Substance P in spinal cord
  • lacks peripheral effects (thus weak anti-inflammatory agent)

Question 9

acetaminophen (tylenol): PK

Answer 9

• IV peak: 15 min with max fever reduction at 30 mins
• PO peak: 30-60 min
• Rectal peak: 1-2 hrs
• Metabolism: conjugated and hydroxylated to inactive metabolites in liver
• Elimination: Little excreted unchanged by kidney

Question 10

acetaminophen (tylenol): SE

Answer 10

• renal toxicity, (but NSAIDs higher risk)
  
  • renal papillary accumulation of metabolites can cause renal cell necrosis
• hepatic injury

Question 11

acetaminophen (tylenol): cautions/contraindications/drug interactions

Answer 11

• CAUTIONS/CONTRAINDICATIONS
  
  • liver disease
  • renal disease
  • alcoholic cirrhosis (↓ dose)
• OD can cause serious hepatic injury
  
  • Hepatotoxic metabolite N-acetyl-p-benzoquinone outnumbers glutathione

Question 12

acetaminophen (tylenol): dose

Answer 12

• 1 g IV q 6 hours
• 325 - 650 mg PO q 4-6 hours
• do not exceed 4 g/day