Pharm exam 4 - meds for pain

What are the two types of non-steroidal anti- inflammatory drugs (NSAIDs)

First generation and second generation

First generation NSAIDs (classical)

• Non-selective COX inhibitors

  • Aspirin

  • Ibuprofen

  • Naproxen

• Inhibit COX-1 & COX-2

• Increase of peptic ulcers

• Increase of bleeding

Second generation NSAIDs (new)

• Selective- COX-2 Inhibitors

  • Celecoxib

• Decrease risk of peptic ulcers

• Increase risk of clotting

What is COX?

Cyclooxygenase, an enzyme
COX 1 & COX 2
Found in all tissues

What does COX regulate?

Regulates multiple processes using prostaglandins

• Stomach → COX-1 protects gastric mucosa
• Platelets → COX-1 stimulates aggregation
• Uterus → COX-1 causes contractions for delivery
• Kidney → COX-1 & 2 maintain renal blood flow
• Tissue injury → COX-2 promotes inflammation & pain
• Vessels → COX-2 causes vasodilation
• Brain → COX-2 mediates fever & perception of pain
• Colon → COX-2 promotes colorectal cancer

COX Inhibitors uses:

 mild-moderate pain
 inflammation
 fever
 pre-menstrual symptoms
 protection against colon cancer

COX Inhibitors adverse?

Relatively safe, but possible adverse effects

What are the two major categories of COX inhibitors?

 Anti-inflammatories
- NSAIDs - aspirin, ibuprofen, naproxen, celecoxib

 Non anti-inflammatories
- acetaminophen

What is Aspirin?

First gen NSAID

Aspirin uses:

reduction of pain, fever, inflammation, MI prevention

Aspirin MOA:

irreversibly inhibits COX-1 and COX-2

Aspirin pharmacokinetics:

 Absorption
PO: plain, buffered, enteric-coated
 Metabolism
Short T1/2, is quickly converted to salicylic acid (SA), an active metabolite
SA’s T1/2 is concentration-dependent
 Distribution
SA is highly bound to albumin, crosses all membranes easily
 Excretion
SA by kidneys; dependent on pH

Aspirin adverse effects:

 GI – gastric distress, bleeding, ulcers
 General excessive bleeding
 Renal impairment
 Salicylism Syndrome
 Hypersensitivity
 Do not give ASA to children (Reye’s syndrome) or pregnant women (risk to mom and baby)

Aspirin contraindicated in patients with:

peptic ulcer disease, bleeding disorders, ASA/NSAID hypersensitivity

Aspirin interactions:

 Other anticoagulants (warfarin, heparin)
 Alcohol
 Other NSAIDs (antiplatelet effect)

What are aspirin toxicities?

Salicylism syndrome

Acute poisoning

What is Salicylism syndrome?

 develops slowly as ASA levels climb above therapeutic range
 s/sx: tinnitus, sweating, headache, dizziness
 withhold aspirin until s/sx resolve, then at reduced dose

What is Acute poisoning?

 s/sx: respiratory alkalosis → respiratory depression, acidosis,
hyperthermia, sweating, dehydration, stupor, coma
 an acute medical emergency, death related to respiratory failure
 treatment is supportive

What is Ibuprofen?

First Gen NSAID

Non-aspirin NSAID

Ibuprofen MOA:

Reversible inhibition of COX-1 and COX-2

Ibuprofen uses:

same as aspirin except:
 does not prevent MIs/CVAs
 may increase CV risk

What is Ibuprofen a good choice for?

dysmenorrhea; is selective for COX in the uterine muscle

What are examples of ibuprofen?

Advil, Motrin

Important factos about ibuprofen:

 Less gastric bleeding than aspirin
 Risk of renal impairment

What is Naproxen?

First Gen NSAID

non-aspirin NSAID

Is Naproxen selective for ?

COX-1, less incidence of GI problems and MI/CVA than other non-ASA NSAIDs

otherwise same as ibuprofen

Naproxen half life time:

12-17 hours, allows less frequent dosing

What is Celecoxib?

Second Gen NSAID
inhibits COX-2 only

• Reduces pain and inflammation

• Causes fewer GI side effects than first-generation NSAIDs

Celecoxib uses:

arthritis, acute pain, dysmenorrhea (period cramps)

What are the major adverse effects and nursing considerations for Celecoxib?

• Increased risk of MI (heart attack) and CVA (stroke)

• Can impair kidney function

• Use the lowest effective dose for the shortest time

• Avoid in patients with heart disease

What are the therapeutic uses of Acetaminophen (Tylenol)?

• Analgesic (pain reliever)

• Antipyretic (reduces fever)

• Preferred fever reducer for children

• Does NOT reduce inflammation

What is the mechanism of action (MOA) of Acetaminophen (Tylenol)?

• Inhibits COX enzymes

• Action is thought to be limited to the CNS (brain and spinal cord)

• Provides pain relief and fever reduction

• No anti-inflammatory effects

How can Acetaminophen (Tylenol) be administered?

• PO (oral)

• PR (rectal)

• IV (intravenous)

How is acetaminophen (Tylenol) metabolized

• Major pathway: Converted directly into nontoxic metabolites

• Minor pathway: CYP450 converts it into a toxic metabolite

• Glutathione converts the toxic metabolite into a nontoxic metabolite

What is the maximum daily dose of acetaminophen for adults?

• Maximum: 4 g (4,000 mg) in 24 hours

• Exceeding this dose increases the risk of liver toxicity

What are the key nursing considerations for acetaminophen (Tylenol)?

• Check for acetaminophen in combination medications (cold/flu products, prescription pain medications)

• Do not exceed 4 g/day in adults

• Glutathione protects the liver by detoxifying the toxic metabolite produced through the CYP450 pathway

Why does alcohol increase the risk of acetaminophen liver toxicity?

Alcohol:

1. Induces CYP450, producing more toxic acetaminophen metabolite.

2. Depletes glutathione, so less toxic metabolite is detoxified.

3. Causes liver damage, reducing the liver's ability to metabolize acetaminophen

What is the maximum recommended dose of acetaminophen for regular alcohol users?

• 2 g (2,000 mg) in 24 hours

• This is half the normal adult maximum (4 g/day) to reduce the risk of liver toxicity

What patient teaching is important for acetaminophen and alcohol use?

• Avoid exceeding the recommended daily dose.

• Regular alcohol use greatly increases the risk of liver toxicity.

• Check combination medications to avoid accidentally taking extra acetaminophen.

What are the early signs and symptoms of acetaminophen toxicity?

• Nausea

• Vomiting

• Diarrhea

• Sweating

• Abdominal pain/discomfort

What are the late signs and symptoms of acetaminophen toxicity?

• Hepatic necrosis (liver damage)

• Liver failure

• Coma

• Death

What is the antidote for acetaminophen overdose?

• Acetylcysteine (Mucomyst)

• Replaces glutathione, allowing the toxic metabolite to be detoxified

• Most effective if given within 8–10 hours of the overdose

What is important to know about acetaminophen toxicity?

• Causes about 50% of acute liver failure cases

• Liver injury (hepatic necrosis) typically appears 48–72 hours after an overdose

• Early recognition and treatment with acetylcysteine can prevent severe liver damage