analgesics

1. Narcotics and Analgesics
Pharmacology
By Linda Self

2. Pain
 Universal, complex, subjective
experience
 Number one reason people take
medication
 Generally is related to some type of
tissue damage and serves as a
warning signal

3. Scope of the Problem
 Increases as Baby Boomers age
 25 million people suffer acute pain
related to surgery or injury
 Chronic pain affects 250 million
Americans
 Is a multibillion dollar industry
 Much ignorance exists about this
complaint

4. Gate Control Theory of Pain
 Gate control theory of pain is the idea
that physical pain is not a direct
result of activation of pain receptor
neurons, but rather, its perception is
modulated by interaction between
different neurons

5. Gate Control Theory of Pain
 Nerve fibers (A delta (fast channels))
and C fibers (slow channels) transmit
pain impulses from the periphery
 Impulses are intercepted in the dorsal
horns of the spinal cord, the
substantia gelatinosa
 In this region, cells can be inhibited
or facilitated to the T-cells (trigger
cells)

6. Gate Control Theory of Pain cont.
 When cells in the substantia
gelatinosa are inhibited, the ‘gate’ to
the brain is closed
 When facilitated, the ‘gate’ to the
brain is open

7. Gate Control Theory of Pain
 Similar gating mechanisms exist in
the nerve fibers descending from the
thalamus and the cortex. These areas
of the brain regulate thoughts and
emotions. Thus, with a pain stimulus,
one’s thoughts and emotions can
actually modify the pain experience.

8. Pathophysiological Response
 Tissue damage activates free nerve
endings (nociceptors) of peripheral
nerves
 Pain signal is transmitted to the
spinal cord, hypothalamus, and
cerebral cortex
 Pain is transmitted to spinal cord by
A-delta fibers and C fibers

9. Pathophysiological Response
 A-delta fibers transmit fast, sharp,
well-localized pain signals
 C fibers conduct the pain signal
slowly and produce poorly localized,
dull, or burning type of pain
 Thalamus is the relay station for
incoming stimuli, incl. pain

10. Pain Fibers and Pathways
 A delta fibers found in the skin and muscle,
myelinated, respond to mechanical stimuli.
Produce intermittent pain.
 C fibers distributed in the muscle as well as
the periosteum and the viscera. These
fibers are unmyelinated, conduct thermal,
chemical and strong mechanical stimuli.
Produce persistent pain.

11. Inhibitory and Facilitatory
Mechanisms
 Neurotransmitters—chemicals that exert
inhibitory or excitatory activity at post-
synaptic nerve cell membranes. Examples
include: acetylcholine, norepinehprine,
epinephrine, dopamin, and serotonin.
 Neuromodulators—endogenous opiates.
Hormones in brain. Alpha endorphins, beta
endorphins and enkephalins. Help to relieve
pain.

12. Opioid Receptors
 Opioid receptors—binding sites not
only for endogenous opiates but also
for opioid analgesics to relieve pain.
Several types of receptors: Mu,
Kappa, Delta, Epsilon and Sigma.

13. Mu Receptors
 Location: CNS incl. brainstem, limbic
system, dorsal horn of spinal cord
 Morphine sulfate and morphine
sulfate agonists bind to Mu receptors

14. Sources of Pain
 Nociceptive—free nerve endings that
receive painful stimuli
 Neuropathic –damaged nerves

15. Narcotic Analgesics
 Relieve moderate to severe pain by
inhibiting release of Substance P in
central and peripheral nerves;
reducing the perception of pain
sensation in brain, producting
sedation and decreasing emotional
upsets associated with pain

16. Narcotic Analgesics
 Can be given orally, IM, sub q, IV or
even transdermally
 Orally are metabolized by liver,
excreted by kidney—caution if
compromised
 Morphine and meperidine produce
metabolites
 Widespread effects: CNS, Resp., GI

17. Narcotics—Mechanisms of Action
 Bind to opioid receptors in brain and
SC and even in periphery

18. Indications for Use
 Before and during surgery
 Before and during invasive diagnostic
procedures
 During labor and delivery
 Tx acute pulmonary edema
 Treating severe, nonproductive cough

19. Contraindications to Use
 Respiratory depression
 Chronic lung disease
 Chronic liver or kidney disease
 BPH
 Increased intracranial pressure
 Hypersensitivity reactions

20. Changing Philosophy on Pain
 Undermedicated
 Titrate to comfort

21. Management Considerations
 age-specific considerations
 Morphine often drug of choice—non-
ceiling. Other nonceiling drugs
include: hydromorphone, levorphanol
and methadone
 Use non-narcotic when able
 Combinations may work by different
mechanisms thus greater efficacy
(e.g. Tylenol w/codeine)

22. Route selections
 Oral preferred
 IV most rapid—PCA allows self
administration. Basal dosage. More
effective, requires less dosing.
 Epidural, intrathecal or local injection
 Can use rectal suppositories or
transdermal routes

23. Dosage
 Dosages of narcotic analgesics should
be reduced for clients receiving other
CNS depressants such as other
sedative-type drugs, antihistamines
or sedating antianxiety medications

24. Scheduling
 Give narcotics before encouraging
turning, coughing and deep breathing
in post-surgical patients
 Automatic stop orders after 72h
 In acute pain, narcotic analgesics are
most effective when given
parenterally and at start of pain

25. Individual Drugs
 Agonists have activity on mu and
kappa opioid receptors
 Agonist/antagonists have agonist
activity in some receptors;
antagonists in others. Have lower
abuse potential than pure agonists;
because of antagonism—can produce
withdrawal symptoms
 Antagonists are antidote drugs

26. Agonists
 Alfenta (alfentanil)—short duration
 Codeine
 Sublimaze or Duragesic (Fentanyl)—short
duration
 Dilaudid (hydromorphone)
 Demerol (meperidine)—preferred in urinary
and biliary colic, less resp. depression
newborns
 Morphine
 OxyContin

27. Agonists cont.
 Darvon (propoxyphene)
 Ultram (tramadol)
 Methadone

28. Agonists/Antagonists
Have lower abuse potential than pure
agonists
 Buprenex (buprenorphine)
 Nubain (nalbuphine)
 Talwin (pentazocine)
 Stadol (butohanol)—also in nasal
spray

29. Antagonists
 Revex (nalmefene)—longer duration
of action than Narcan
 Narcan (naloxone)
 ReVia (naltrexone)-used in
maintenance of opiate-free states in
opiate addicts

30. Dietary and Herbal Supplements
 Zostrix (capsaicin)—from cayenne
peppers; topical indicated for post-
herpetic neuralgia, neuropathic
pain=Substance P

31. Cancer
 Give on a regular schedule
 Oral, rectal and transdermal are preferred
over IV
 Oxycodone and a non-narcotic analgesic
may have additive effects
 MS or other for severe pain
 Long acting for chronic pain with fast acting
meds for “break-through pain”
 May use TCAs, anti-emetics, stool regimen

32. Management of Withdrawal
Symptoms
 Methadone
 Clonidine (norepinephrine)
 Gradually decrease dosing so not to
cause withdrawal s/s

33. Analgesic,Antipyretic, and Anti-
inflammatory Drugs
 Mechanism of action—inactivate
cyclo-oxygenases, enzymes required
for the production of prostaglandins
 ASA and traditional NSAIDs
inhibit both COX 1 and COX 2
 COX 1 is present in all tissues esp.
GI, kidneys, endothelial cells and in
platelets

34. Cox 1 cont.
Prostaglandins important in:
1. Protection of kidneys and stomach
2. Regulate vascular tone and platelets
in CV system

35. COX 2
 Found in brain, bone, kidneys, GI
tract, and the female reproductive
system
 Overall, prostaglandins produced by
COX 2 are associated with pain and
inflammation

36. Actions of the COX’s
 Act on hypothalamus to decrease response
to pyrogens and reset the thermostat
 Prevent prostaglandins from increasing the
pain and edema produced by other
substances released by damaged cells
 COX 1-Antiplatelet activity for life of
platelet—7-10 days plus interfere w/blood
coagulation and increase risk for bleeding

37. Indications for Use
 Treat mild to moderate pain or
inflammation
 Musculoskeletal disorders; HA;
dysmenorrhea, minor trauma and
surgery
 Low dose ASA for risk of MI or stroke
 Celebrex is indicated for familial
polyposis

38. Contraindications to Use
 PUD
 GI or bleeding disorders
 Hypersensitivity reactions
 Impaired renal function
 If allergic to ASA
 In children, ASA contraindicated in
presence of viruses=Reye’s syndrome
 Celebrex if allergic to sulfonamides

39. Reye’s
 Seen in children under 15 after an
acute viral illness
 Results in encephalopathy, fatty
infiltration of the liver, pancreas,
kidneys, spleen, and lymph nodes
 Cause is unknown

40. Contraindications
 Toradol (ketoralac) not used in labor
and delivery or during any major
surgery
 OTC preps contraindicated in
alcoholics due to possible liver
damage

41. Aspirin (ASA)
 Home remedy for headaches, colds,
influenza and other respiratory
infections
 For fever
 For inflammation
 ASA and COX 2 are ok, COX 2 have
little effect on platelet function

42. ASA cont.
 Poisoning can occur with large doses.
Saturate the metabolic pathway, slow
elimination and cause drug accumulation
 If overdose, measure serum levels
 Recognize s/s: N/V, fever, fluid and lyte
deficiencies, tinnitus, decreased hearing,
hyperventilation, confusion, visual
changes>>>>delirium, stupor and coma

43. ASA salicylism
 Gastric lavage
 Activated charcoal
 IV bicarbonate so more rapid
excretion
 hemodialysis

44. NSAIDS
 Propionic acid derivatives such as
ibuprofen, ketoprofen (Orudis),
naproxen and fenoprofen (Nalfon)
 Acetic acid derivatives include
indomethacin (Indocin), sulindac
(Clinoril) and tolmetin (Tolectin)---
these drugs have more severe
adverse reactions than the proprionic
acid derivatives

45. NSAIDS
 IV indomethacin is approved for the
tx of patent ductus arteriosus in
premature infants.
 Remember: patent ductus is a
communication between the
pulmonary artery and the aorta

46. NSAIDS
 Toradol (ketoralac) is used only for
pain. Is the only NSAID that can be
given by injection. Use limited to 5
days as can cause bleeding.
 Oxicam drugs include Mobic
(meloxacam) and Feldene (piroxicam)
 Celebrex (celecoxib)
 Affect bleeding only while drug is still
in the system

47. Effects of Nonsteroidals on Other
Drugs
 Decrease effects of ACEI, beta
blockers and diuretics
 Affect sodium and water retention
 Inhibit renal prostaglandin synthesis

48. Acetaminophen
 Equal in effectiveness to ASA in
analgesic and antipyretic effects
 Lacks anti-inflammatory actions
 Ethanol induces drug-metabolizing
enzymes in liver. Resulting rapid
metabolism of acetaminophen
produces enough toxic metabolite to
exceed glutathione. Need glutathione
to inactivate toxic metabolites. P. 114

49. Acetaminophen Poisoning
 Toxicity occurs with 20g or more.
 Creates toxic metabolite that is inactivated
by glutathione.
 OD supply of glutathione is depleted and
toxic metabolite damages liver cells
 Not to exceed 4g/day
 Treatment—gastric lavage, charcoal,
antidote is Mucomyst (acetylcysteine).
Provides cysteine, a precursor to
glutethione.

50. Drugs used in Gout and
Hyperuricemia
 Zyloprim (allopurinol)—prevents or
treats hyperuricemia
 Uric acid is formed by purine
metabolism and an enzyme xanthine
oxidase. Allopurinol prevents
formation by inhibiting xanthine
oxidase.

51. Antigout Medications
 Colchicine—used to treat or prevent acute
attacks of gout. Drug of choice for acute
attacks. Decreases inflammation by
affecting leukocytes.
 Benemid (probenecid) increases urinary
excretion of uric acid. Not effective in acute
attacks.
 Anturane (sulfinpyrazone) uricosuric similar
to Benemid. Not for acute attacks.

52. Guidelines for Treating Gout
 Maintenance drugs are Zyloprim,
Benemid and Anturane
 Colchicine needed for several weeks
to prevent acute attacks while serum
levels are being lowered
 Need high fluid intake, alkaline urine
to prevent renal calculi

53. Drugs Used for Migraines
 Selective serotonin 5-HT1 receptor
agonists
 Increase serotonin in the brain
 Constrict blood vessels
 Contraindicated in patient’s with
history of MI,, angina, uncontrolled
htn.

54. Drugs used for migraines
 Drugs vary in onset with sub q
sumatriptan acting the most rapidly
and starting within 10 minutes; most
clients get relief within 1-2 hours
 Drugs are metabolized in the liver by
monoamine oxidase or by cytochrome
p450 enzymes; sub q administrations
causes more adverse effects than the
oral drugs

55. Migraine Meds
 Ergotamine tartrate—ergot alkaloid
used only in tx of migraine
 Work by constricting blood vessels
 Most effective when given sublingual
or by inhalation
 Contraindicated in pregnancy, htn,
PVD, CAD, renal or hepatic disease
and even in severe infections

56. Guidelines for Treating Migraine
 Start out with acetaminophen,
aspirin, or other NSAIDs
 Moderate to severe migraines,
sumatriptan or other related drugs
are useful
 For severe and frequent migraines,
prophylaxis is indicated. Use ASA and
NSAIDs.

57. Guidelines for Treating migraines
 For menstrual migraines, start tx one
week before and during menses
 Other drugs indicated for tx include
beta adrenergic blocking agents such
as Inderal

58. Guidelines for Treating Arthritis
 Control pain and inflammation
 Rest, exercise,and PT
 Osteoarthritis—COX1, COX2,
glucosamine, intraarticular injections
of corticosteroids or hyaluronic acid
(Synvisc) to act as shock absorber

59. Rheumatoid Arthritis
 NSAIDs
 Corticosteroids
 Immunosuppressants—methotrexate
 Enbrel, Remicade and Arava. Affect
tumor necrosis factor and other
cytokines.

60. Questions or Discussion