3.4 - COX2 and Acetaminophen

What are the 2 subtypes of the cycooxygenase enzyme?

• COX-1

• COX-2

What is the first COX-2 Inhibiting drug?

Celecobix (Cerebex)

What are the cardiovascular problems seen by inhibiting the COX-2 enzyme?

• Evidence they promote MI cause heart attack and stroke

• All except celebrex were recalled

Why does COX-2 inhibition cause myocardial infarction?

PGs that promote vasodilation and vasoconstriction are usually in balance, some COX-2 selective inhibiting drugs stop vasodilation sparing COX-1 vasoconstrictors causing balance to lead towards infarction

What is a COX-1 enzyme?

• Normal in certain cells

• Synthesizes PGs to protect the cells and maintain their function

• Can be found in stomach, kidneys, platelets

What is a COX-2 enzyme?

• Synthesizes when cells are injured

• Cells promote inflammation and mediate pain

• Ex: RA, other pathologies

What is a acetaminophen?

• Has analgesic and anti-pyretic effects

• Not an NSAID

• Causes no gastric irritation

• Has no anti-inflammatory or anti-coagulant effects

• In high doses can cause liver toxicity

How can acetaminophen cause liver toxicity?

• Acetaminophen passed through the liver and forms N-acetyl-benzoquinominine

• Typically GSH attached to N-acetyl-benzoquinominine and form metacpturic acid which is expelled through the urine

• When there is too much N-acetyl-benzoquinominine, GSH cannot keep up and causing toxic levels of drug to build up and damage liver proteins

What are the common signs of hepatotoxicity?

• Jaundice

• Loss of appetite

• Abdominal pain

• Severe nausea/vomitting

• Fever

• Sore throat

• Malaise/lethargy

• Weakness

• Unusual bleeding and bruising

Why are acetaminophen and opioid combos used?

Combination can allow for pain to be more controlled with less use of an opioid

What is a tradeoff of using acetaminophen and opioid combos?

Opioid dose may be under prescribed and not manage the pain of patient

What are examples of acetaminophen and opioid combos?

• Ultracet

• Lortab, vicodin, lorcet

• Endocet, roxicet, primalev