Antipyretic-analgesic and Anti-inflammatory Drugs

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??????? Antipyretic-analgesic and
Anti-inflammatory Drugs
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Pain Treatment

• Analgesics
• Antipyretic-analgesic and anti-inflammatory drugs

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Pain
An unpleasant experience associated with actual
or potential tissue damage.
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Pain Physiology
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(No Transcript)
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Neurochemistry
Ion Fluxes (H/ K)
Tissue Injury
To brain
Bradykinin
Prostaglandins
Leukotrienes
Dorsal horn
Sensitized Nociceptor
Mast Cell
Histamine
Aspartate, Neurotensin, Glutamate, Substance P
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Pain Transmission
Pain perception
Enkephalin inter-neuron
Descendingpathway
Ascendingpathway
Spinal cord
Nociceptor
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Descending Pain Control Pathways
Descending impulse
Enkephalin
Opioid receptor
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Opportunities for Pain Treatment

• At the receptor
• Along the nerve
• At receptors in spinal column and brain

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• Acute vs chronic
• Nociceptive vs Neuropathic

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Acute vs. Chronic Pain
Dorsal root ganglion
To brain
A-delta fibers sharp,shooting pain
C fibers dull, aching, burning pain
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Nociceptive Pain
Ascending pain pathway
Spinal cord
Tissue injury
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Neuropathic Pain
Ascending pain pathway
Nerve injury
Spinal cord
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Principles of Pain Management

• Gold standard patient determines severity
• Tradition pain has been undertreated
• Prevention or early treatment best
• Pain kills
• Pain is real
• Balance pain relief with side effects of drugs

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Antipyretic-analgesic and Anti-inflammatory Drugs

• Non-steroidal anti-inflammatory drugs, NSAIDs.
• Aspirin-like drugs.

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Mechanism of NSAIDs
phospholipid
PLA2
NSAIDs
Arachidonic acid, AA
Prostaglandin, PG
Leukotrienes, LTs
PGE2
PGF2?
PGI2
TXA2
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Salicylates Aspirin and NSAIDs

• Anti-inflammatory
• Inhibits cyclooxygenase pathway for breakdown of
  arachidonic acid to prostaglandins and
  thromboxane
• Ibuprofen, Naprosyn naproxen
• COX-2 inhibitors

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Acetaminophen

• Inhibits synthesis of prostaglandin in CNS but
  not in periphery.
• No anti-inflammatory or anti-platelet effects but
  good for mild pain and to reduce fever
• Adverse reactions rare. Overdose may cause liver
  disease esp in persons who regularly consume
  alcohol.

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Other Pain Management Drugs

• Antidepressants in neuropathic pain
• Ergotamine in migraine headache
• Anticonvulsants in neuropathic pain or migrane
  headache
• NMDA antagonists for neuropathic pain
• Centrally acting alpha2 agonists such as
  clonidine
• Anesthetics (lidocaine or bupivicaine) (ketamine)
• Radiopharmaceuticals for cancer bone pain

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Nerve
NMDA
Memantine blocks the NMDA receptor. Phase II
study diabetic subjects with neuropathic pain
experienced 29 less pain than placebo-treated
subjects.
N-methyl-D-aspartate (NMDA) receptor opens
channel for Ca influx. This can lead to nerve
damage and pain.
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An Alpha 2 Agonist?
Reuptake pump
a R
Post-synaptic cell
NE
NE
NE
Alpha 2 presynaptic receptor
b R
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When stimulated, they inhibit nerve transmission.
a R
Post-synaptic cell
NE
Alpha 2 presynaptic receptor
b R
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Clonidine given epidurally or orally blocks pain
messages from neuropathic origin.
a
Post-synaptic cell
NE
Alpha 2 presynaptic receptor
R
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A highly lipid soluble drug, what is the chance
that epidurally-placed clonidine would get into
the blood stream?
a
R
Post-synaptic cell
NE
Alpha 2 presynaptic receptor
b
R
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What would the SNS blockade do to the blood
pressure?
a
R
Post-synaptic cell
NE
Alpha 2 presynaptic receptor
b
R