WHAT CHEMICAL IS PRODUCED WHEN YOUR TISSUES ARE DAMAGED?
Prostaglandins: cause inflammatory response at site of damage (swelling, redness,
activation of immune cells, heat, caused by more blood flow to the area)
WHAT CHEMICAL IS RELEASED BY A NEURON IN THE PNS TO
COMMUNICATE TO THE BRAIN ABOUT THE PAIN?
Activates release of Substance P, which then sends message to the brain. Limit substance
P release, reduce the action potentials that send perception of pain.
IF SOMEONE HAD VERY FEW RECEPTORS FOR SUBSTANCE P, HOW MIGHT
THEY REACT TO PAIN? EXPLAIN.
Less response, due to less receptor stimulus
IN ORDER TO MAKE PROSTAGLANDINS (WHICH ARE RESPONSIBLE FOR
INFLAMMATION AND THE BEGINNING OF THE PAIN PATHWAY), WHAT
ENZYME MUST YOUR BODY MAKE? Cyclooxygenase (COX) enzymes
SOME NSAIDS (NON-STEROIDAL ANTI-INFLAMMATORY DRUGS) INHIBIT THIS
ENZYME. ARE THESE DRUGS WORKING IN THE BRAIN TO STOP PAIN OR IN
THE BODY? EXPLAIN. They are working primarily in the body, because they are
activated where the damage to cells occurs. If damage was in the brain, these cells would
stimulate COX enzymes there. Headaches are special, due to swelling in a limited space,
therefore caffeine is often added to NSAIDS to vasoconstrict the blood vessels in the brain.
WHICH ANALGESIC (PAIN KILLER) WOULD BE THE HARDEST TO OVERDOSE ON AND
WHY? Ibuprophen would be the hardest, as it has the highest TI of the three drugs.
MOST OVER THE COUNTER ANALGESICS ARE METABOLIZED BY CYP2D6. IN SOME
CASES, THE METABOLITE OF IS ALSO IMPORTANT. FOR EXAMPLE, THE METABOLITE
FOR ACETAMINOPHEN IS CALLED “NAPQ1” AND IS VERY TOXIC TO THE LIVER. WHY
WOULD LIVER DAMAGE BE AMONG THE MOST SERIOUS SIDE EFFECT FOR
ACETAMINOPHEN? The liver not only has to metabolize the drug itself, but the metabolite produced is
also toxic, therefore, the even at therapeutic doses, this over the counter drug can be dangerous.
TI based on data given at station:
Acaetaminophen = 4.6
Aspirin = 5.1
Ibuprophen = 16.3 Higher the TI, harder it is to overdose
Drug
Recommended adult dosage
Acetaminophen
(paracetamal)
Aspirin (acetylsalicylate)
Ibuprophen (methyl
propyl proprionic
acid)
325-650 mg every 6 hours
Approximate lethal dosage for 65 kg
person
7-12 grams per day
325-650 mg every 4 hours
13-20 grams per day
200-400 mg every 6 hours
13-26 grams per day
WHEN YOU GET HURT, CELLS RELEASE A PRECURSOR THAT THEN IS CONVERTED INTO
PROSTAGLANDINS, WHICH IN TURN CAUSE YOU TO FEEL PAIN. CYCLO-OXYGENASE (COX) IS
THE ENZYME THAT IS RESPONSIBLE FOR THIS CONVERSION. THERE ARE ALSO DIFFERENT
VERSIONS OF THE ENZYME.
ASPIRIN AND IBUPROFEN BLOCK COX1 AND COX2. ACETAMINOPHEN INHIBITS COX2.
THERE IS A LOT OF VARIATION IN THESE ENZYMES.
TWO FRIENDS, JOHN AND JANE BOTH GET HURT. JOHN HAS VERY EFFICIENT COX
THOUGH. HOW MIGHT JOHN’S PAIN LEVEL DIFFER FROM JANE’S?
John will produce more prostaglandins, due to more enzyme, therefore he will experience more pain.
WHAT SYMPTOMS WOULD YOU EXPECT FOR A COX ENHANCER? More pain and
inflammation, blood clotting, more mucous in the stomach
PROSTAGLANDINS, WHICH ACTIVATE THE PAIN PATHWAY TO THE BRAIN ARE ALSO
PRECURSORS TO PYROGENS, THUS NSAID ANALGESICS (LIKE TYLENOL AND ASPIRIN),
CAN BE USED AS PAIN KILLERS AND FOR TREATING WHAT ELSE? Lowering fever
NSAIDS, ESPECIALLY ASPIRIN (SALICYLIC ACID) CAN BE QUITE ACIDIC. USING THIS
INFORMATION, COMMENT ON THE RESULTS ABOVE.
High doses of NSAIDS can increase the risk of GI complications (high acidity in the stomach=ulcers, etc),
at a higher rate than the increase in heart attacks (MI) and renal (kidney failure)
Can be helpful (aspirin) by lowering stickiness of platelets (lower clotting capacity), thus protecting
against heart attacks
THE FIRST DIAGRAM REPRESENTS WHICH OTC PAIN KILLERS ARE BEING USED BY
AMERICANS. THE SECOND DIAGRAM REPRESENTS THE BINDING EFFICACY OF THE PAIN
KILLER TO THE KINDS OF COX ENZYMES. BASED ON THE INFORMATION IN BOTH
DIAGRAMS, COMMENT ON WHY PEOPLE MIGHT BE TAKING CERTAIN MEDICATIONS
MORE OFTEN THAN OTHERS.
In the lower graph, acetaminophen has a higher binding rate than the other drugs, which means the
effects last longer. This correlates to the # of Americans taking this drug the most. They are taking the
drug that lasts the longest.