Transcript OTC Analgesics Lecture nsaidONLYx

Review- Opiate addiction:
1. Can be life threatening to
break (quitting can kill you)
2. Is treated with opiate
antagonists
3. Results, in part, from loss of
opiate receptors
4. Results, in part, from loss of
CYP2D6
What is the relationship between
hyperpolarization and ligand-gated
potassium channels?
1. A neuron becomes even more negative
because these channels open
2. A neuron becomes positive because
these channels open
3. A neuron becomes even more negative
because these channels close
4. A neuron becomes positive because
these channels close
5. There is no relationship between
hyperpolarization and potassium
channels
• Analgesics
– Opiates
– OTC pain killers - Non steroidal antiinflammatory drugs - NSAIDs
• Ethanol
• Cannabis
Pain reviewSubstance P
Prostaglandin
Pain stimulus picked up by
peripheral nervous system
Pain signal amplified by
central nervous system
What’s the chemistry of pain?
BLOCK COX  BLOCK PAIN
Cyclo-oxygenase
prostaglandins
1
How do prostaglandins worsen pain?
BLOCK COX  BLOCK
INFLAMMATION
prostaglandins
2
What conditions are associated with inflammation?
•
•
•
•
•
Arthritis
Crohn’s disease
Psoriasis
Alzheimer’s disease
Multiple sclerosis
Activity 2
What are NSAIDs?
When did we meet the acetyl group
before?
1. It made MDMA difficult to
metabolize
2. It made codeine less potent
than morphine
3. It made prozac have a lower TI
than zoloft
4. It made heroin more lipid
soluble
5. It was removed in the
metabolism of nicotine
Activity 3
NSAID administration?
Wikimedia commons
NSAID Dosage?
Drug
Recommended
adult dosage
Approximate lethal
dosage
Acetaminophen
(paracetemal)
325 - 650 mg every
6 hours
6-12 grams per day
Aspirin (acetylsalicylate)
325 – 650 mg every 24-30 grams per day
4 hours
Ibuprophen (methyl 200 - 400 mg every
propyl proprionic
6 hours
acid)
6-12 grams per day
Activity 4
NSAID metabolism?
CYP2D6
2C8 and 2C9
1/2 life between 2
and 4 hours
Notable – metabolite
of acetaminophen is
liver toxic
Vicodin is acetaminophen plus opiate
analgesic. The components:
1. Are both metabolized by
the same enzyme
2. Both impact prostaglandins
3. Both impact substance P
4. Both are addictive
5. Both are most effective if
taken orally
Activity 5
How do NSAIDs block COX?


COX enzymes
NSAIDs
Acetyl group
http://www.time.com/time/covers/1101050228/map/
Activity 6
NSAID addiction?
• No
• But do they do good? Activity 7
Headaches are
special – why?
Increase blood volume in limited
space
Action?
Medicine type
Success?
Anti-inflammatory meds
Reduce swelling
Fair
Caffeine-including meds
Vasoconstrict
Moderate
Opiates
Reduce pain perception
Tranquilizers (depakote)
Calm neurons that call
from blood delivery
Better (addictive)
Best (side effects)
Aspirin Benefits (besides Pain relief)
• Protect against heart attack – why?
http://health.upenn.edu
http://www.aurorahealthcare.org
Thromboxane is produced by platelets – allowing them to
clump together to form a clot. Aspirin interferes with this.
Are all NSAIDs equal?
Cox 1
Enzyme’s job
Aspirin
Acetaminophen
Vioxx and
Celebrex
Cox 2
General,
Pain and
including GI inflammation
Cox 3
Unknown
(brain
function)
When did we previously meet a drug
category that tried to minimize side effects
by optimizing binding specificity?
1.
2.
3.
4.
Antidepressants
Opiates
Amphetamines
Inhalents
Activity 8 OTC
Aspirin
analgesic side effects?
Acetaminophen Cox2 blockers
hybridmedicalanimation.com
Canadianparents.com
beliefnet.com
sccollege.edu
50,000 ER visits
500+ deaths
PER YEAR
Noaw.com
Individual experience may vary…
CYP2D6
Food in gut
State of health
Degree of pain
Age
Strength of COX