DH206: Pharmacology Chapter 5 Nonopioid (Nonnarcotic)
Analgesics Lisa Mayo, RDH, BSDH Copyright 2011, 2007 Mosby, Inc.,
an affiliate of Elsevier. All rights reserved.
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Slide 4
Tissue Injury & Prostaglandins When tissues damaged =
release substances such as histamine, bradykinin, prostaglandins,
serotonin = vasodilation = increase permeability of capillary walls
Prostaglandins are mediators of the inflammatory response Formed in
cell membranes of most organs Cell membrane phospholipids forms the
parent of all prostaglandins (arachidonic acid or fatty acid)
Slide 5
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Tissue Injury & Prostaglandins Slight trauma
to a nerve fiber enzyme phospholipase stimulated & break off
arachidonic acid Arachidonic acid enters into 2 metabolic pathways
1. Enzyme CYCLOOXYGENASE breaks down arachidonic acid into
prostaglandin PGE 2 & PGI 2 (next slide) 2. Enzyme LIPOXYGENASE
breaks down arachidonic acid into leukotrienes (cover in resp
chapter)
Slide 6
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rights reserved.
Slide 7
Tissue Injury & Prostaglandins 1. Enzyme CYCLOOXYGENASE
breaks down arachidonic acid into prostaglandin PGE 2 & PGI 2
Prostaglandins capable of : Stimulating peripheral pain receptors
Constricting/dilating vessels Elevating body temp Bronchodilation
& constriction Relax & contract smooth muscles of bladder,
intestines in the production of erythema, edema, uterine
contraction Inhibit platelet clot formation
Slide 8
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rights reserved.
Slide 9
Tissue Injury & Prostaglandins Cyclooxygenase (COX) Family
of enzymes required to make prostaglandins from arachidonic acid 3
subtypes (book outdate info on this says there are 2) 1.COX-1:
available in all cells, responsible for tissue homeostasis, called
housekeeping enzyme Protect GI tract Maintain normal platelet
function Regulate renal flow 2.COX-2: produced during inflammation,
found in low amounts in tissues 3.COX-3 Ideally drugs should
inhibit COX-2 & leave COX-1 alone NSAIDs/Aspirin are
non-selective: affect COX-1&2 where adverse effects of drugs
come from (GI upset)
Slide 10
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.NBQ As apprehensive dental patient comes in and
states he already took ibuprofen for the pain he anticipates from
the appointment today. As you know, tis inhibits the synthesis of
prostaglandins. All of the following statements are TRUE about
prostaglandins EXCEPT which one? a. They have a very short half
life b. They generally act locally on or near the tissue that
produced them c. They are synthesized only in the liver and the
adrenal cortex d. The common precursor of prostaglandins is
arachidonic acid e. Their synthesis can be inhibited by a number of
unrelated compounds, including aspirin and cortisol
Slide 11
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.NBQ As apprehensive dental patient comes in and
states he already took ibuprofen for the pain he anticipates from
the appointment today. As you know, tis inhibits the synthesis of
prostaglandins. All of the following statements are TRUE about
prostaglandins EXCEPT which one? a. They have a very short half
life b. They generally act locally on or near the tissue that
produced them c. They are synthesized only in the liver and the
adrenal cortex d. The common precursor of prostaglandins is
arachidonic acid e. Their synthesis can be inhibited by a number of
unrelated compounds, including aspirin and cortisol
Slide 12
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.NBQ From which of the following substances are
prostaglandins formed? a. Arachidonic acid b. Endorphins c.
Enkephalins d. Norepinephrine
Slide 13
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.NBQ From which of the following substances are
prostaglandins formed? a. Arachidonic acid b. Endorphins c.
Enkephalins d. Norepinephrine
Slide 14
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Slide 15
Pain Analgesic: selective decrease of pain perception Pain
originates from CNS while stimulus comes from peripheral nervous
system (PNS) 2 components of pain: 1. Perception/Sensory (physical
component) 2. Reaction (psychological component)
Slide 16
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Pain Types Orofacial pain 1. Nociceptive /
Neuropathic pain 2. Acute / Chronic pain Nociceptive Pain that
arises from a stimulus out the CNS Ex: exposed dentin, post-surgery
pain Nociceptors are stimulated by pain transmit to A & C
fibers - transmit pain feeling to the brain Dental LA interfaces
with A & C fibers Analgesics can block pain Nociceptors within
the peripheral nervous system (CH5) Nociceptors within the central
nervous system (CH6)
Slide 17
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Slide 18
Classification Site of action Nonopioid analgesics act on
peripheral nerve endings Opioids act primarily in the central
nervous system (CNS) Mechanism of action Nonopioid analgesics
inhibit prostaglandin synthesis Opioids affect the response to pain
by depressing the CNS
Slide 19
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Classification Nonopioids divided into the
following grps: 1. Salicylates 2. Nonsteroidal anti-inflammatory
drugs (NSAIDs) 3. Acetaminophen **Drugs used in tx of mild to
moderate nociceptive dental pain**
Slide 20
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Classification Analgesics used for Dental
PainNotations Salicylates aspirin(Ecotrin, Bayer)
diflunisal(Dolobid) NSAIDs ketorolac(Toradol) ibuprofen(Advil,
Motrin) ketoprofen(Orudis, Actron) flurbipropfen(Ansaid) naproxen
sodium(Anaprox, Aleve) etodolac(Lodine)
celecoxib(Celebrex)Selective for COX-2
Slide 21
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Salicyclates Aspirin(ASA) is the prototype
salicylate Many references refer to aspirin as an NSAID but it is
NOT CDC says it is a nonarcotic analgesic, not an NSAID
Slide 22
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Slide 23
Salicylates Outline Acetylsalicylic acid (aspirin) Mechanism of
action Pharmacokinetics Pharmacologic effects Adverse reactions
Toxicity Drug interactions Other salicylates Diflunisal
Slide 24
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Aspirin Mechanism of Action Effects related to the
ability to inhibit prostaglandin synthesis by blocking COX
pathway
Slide 25
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Aspirin Pharmacokinetics Administration: oral,
rectal ABSORPTION: small intestine, stomach DISTRIBUTION: Widely
distributed into most body tissues Peak effect on empty stomach =
30min Half-life small dose aspirin (81mg): 2-3hrs Half-life large
dose aspirin (325mg): 15-30hrs METABOLISM: liver to salicylic acid
BOOK CORRECTION: salicylates are readily bound to plasma PRO
(80-90%), PLEASE CHANGE!! P.51, last paragraph EXCRETION: kidney
via urine
Slide 26
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. 4 As 1.Analgesic: blocks COX pathway
2.Antipyretic: increases heat loss through sweating
3.Antiinflammatory 4.Antiplatelet (next slide) 5.Uricosuric:
excretion of uric acid in the urine, thus reducing the
concentration of uric acid in blood plasma (used as a tx for
GOUT)
Slide 27
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Aspirin Pharmacologic Effects Antiplatelet:
irreversibly binds to platelets Inhibitor of platelet aggregation
Useful for MI, stroke, cardio disease Aspirin breaks down to
salicylic acid & acetic acid Acetic acid irreversibly binds to
COX-1 in platelets Prevents formation thromboxane body ability to
form clots and bleeding times This lasts for the life of the
platelet because it is now incapable of resynthesizing new COX (New
platelets form every 7 days)
Slide 28
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Aspirin Pharmacologic Effects Antiplatelet Effects
dependent on DOSE taken: aspirin has a (+) effect on 2 substances
involved in blood clotting 1)Thromboxane A 2 Substance promotes
clotting Aspirin inhibits (stops) its action = reduces clotting
Will occur in LOW-dose aspirin 2)Prostacyclin Substance inhibits
(stops) clotting Aspirin enhances this substance = reduces clotting
HIGH dose aspirin: no major effects on bleeding times or
thromboxane because high doses prevent formation of
prostacyclin
Slide 29
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved. Aspirin Adverse Reactions GI: most common (ulcers,
bleeding) To reduce these effects take with antacids, milk,
meals(NBQ) Avoid alcohol enhance adverse GI issues Hypoglycemia
Aspirin inhibits PGE 2 which insulin Bleeding Interferes with
clotting mechanism by reducing platelet adhesiveness Reye syndrome
Primarily kids, but can occur any age Using aspirin to tx viral
illness (chickenpox, flu) & given aspirin have been associated
with Reye syndrome Can be fatal US Surgeon General: no aspirin for
kids
