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MANAGEMENT OF PAIN. What is pain? How can pain be treated? Cycle-oxygenase inhibitors Opioids. “ OPIOID ANALGESICS Narcotics”. “Analgesia” = “without pain sensation” Opioids: - reduce pain sensation - reduce concern about pain.

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management of pain
MANAGEMENT OF PAIN

What is pain?

How can pain be treated?

Cycle-oxygenase inhibitors

Opioids

opioid analgesics narcotics
“OPIOID ANALGESICSNarcotics”

“Analgesia” = “without pain sensation”

Opioids:

- reduce pain sensation

- reduce concern about pain

slide3
OPIUM: exudate of seed capsules of Papaver somniferum 10% morphine

OPIUM TINCTURE: laudanum, 10% opium, 1% morphine

PAREGORIC: camphorated opium tincture, 0.04% morphine

history of opioids
HISTORY OF OPIOIDS

4000 B.C. Sumerian pictographs of opium poppy

2000 B.C. Use of opium by Greeks

15th Cent. Laudanum used in Europe

A.D.

18th Cent. Opium smoking popular in Orient

1803 Serturner isolated morphine

1800’s Opium wars in China

Civil war in U.S.A.

1900’s Heroin Methadone

Meperidine Endorphins Naloxone

opiates
OPIATES

Morphine

Heroin

Codeine

opioid drugs
OPIOID DRUGS

Prototype = MORPHINE

morphine
MORPHINE

CNS actions

Cardiovascular actions

Gastrointestinal actions

morphine1
MORPHINE

CNS ACTIONS

  • Mechanism: Acts at brain and spinal opioid receptors (especially mu receptors)
  • Effects

1. Analgesia-selective

2. Euphoria

3. Drowsiness (coma in overdose)

4. Pituitary: increase PRL and ADH, can decrease ACTH

5. Pupils: miosis

6. Respiratory depression

7. Depression of cough center

8. Stimulation of CTZ, depression of VC

9. Depression on multineuronal reflexes

10. Generalized stimulation (rare)

11. Central cardiovascular, GI actions

morphine2
MORPHINE

CARDIOVASCULAR ACTIONS

A. Orthostatic hypotension

1. Peripheral vasodilation (?histamine

release, inhibition of NE release?)

2. Sympathetic inhibition (CNS)

B. Cerebral vasodilation (hypercapnia)

morphine3
MORPHINE

GASTROINTESTINAL ACTIONS

A. Increased incidence and amplitude of

circular muscle contraction

B. Decreased gastric emptying

C. Decreased transit, constipation

D. Spasm of biliary tract, sphincter of Oddi

disposition of opiates
DISPOSITION OF OPIATES

ABSORPTION

DISTRIBUTION

BIOTRANSFORMATION

EXCRETION

slide21

Fig. 1. Effect of route of administration on plasma-free morphine levels.

Means  S.E. are shown.

hazards
HAZARDS

Respiratory depression

GI: nausea, vomiting, constipation

Orthostatic hypotension

Perceptual disturbance

Dependence

heroin diacetylmorphine
HEROIN(Diacetylmorphine)

1. Analgesic

2. Penetrates into brain well, potent

3. Hydrolyzed to monoacetylmorphine

and to morphine

4. Other pharmacology like morphine

codeine methylmorphine
CODEINE(Methylmorphine)

1. Analgesic

2. Effective orally

3. Antitussive

4. Low dependence liability

5. Often stimulatory in overdose

6. Some O-demethylated in vivo

meperidine
MEPERIDINE

Shorter duration of action than morphine

Not an effective antitussive

meperidine1
MEPERIDINE

1. CNS effects

a. analgesia

b. euphoria

c. respiratory depression

d. convulsions (normeperidine)

e. pupil response variable

2. Smooth muscle

a. spasmogenic but not constipating

methadone
METHADONE

1. CNS effects

a. analgesia

b. respiratory

c. antitussive

2. Other actions

a. similar to morphine

methadone1
METHADONE

Disposition

Well absorbed, orally active

Metabolized in liver

Long duration of action

dextromethorphan
DEXTROMETHORPHAN

Antitussive

Not addicting

Not analgesic

opioid antagonists
OPIOID ANTAGONISTS

Prototype: NALOXONE

Naloxone: “pure antagonist”

no agonist actions

Naloxone: short duration of action

opioid antagonists1
OPIOID ANTAGONISTS

(Naloxone, naltrexone)

$ Competitive antagonists at opioid receptors

$ Rapid reversal of opioid agonist effects

- analgesia

- respiratory depression

- miosis

$ Do NOT directly antagonize barbiturates, alcohol, benzodiazepines

mixed agonist antagonist
MIXED AGONIST-ANTAGONIST

Nalorphine (Nalline)

Pentazocine (Talwin)

Nalbuphine (Nubain)

Butorphanol (Stadol)

Buprenorphine (Temgesic)

Cyclazocine

mixed opioid agonists antagonists
MIXED OPIOID AGONISTS-ANTAGONISTS

1. NALORPHINE: not used as agonist, replaced by naloxone as antagonist (can induce respiratory depression).

2. PENTAZOCINE

Used clinically as agonist

Analgesic

Euphoria or dysphoria

Mild respiratory depression

Moderate abuse potential

3. BUTORPHANIL

About like pentazocine

opioid tolerance
OPIOID TOLERANCE

Cellular tolerance

Cross-tolerance with other opioids

No cross-tolerance to other drug classes

opioid dependence
OPIOID DEPENDENCE

Users seek euphoria, freedom from anxiety,

pleasure

Dependence

primary psychological

physical

secondary psychological

opioid dependence1
OPIOID DEPENDENCE

Withdrawal syndrome

abstinent

precipitated with antagonist

heroin morphine withdrawal
HEROIN/MORPHINE WITHDRAWAL

Early abstinence

8 hr lacrimation, rhinorrhea, yawning, sweating

12 hr “yen” (restless sleep), miserable, dilated pupils, anorexia, gooseflesh, restlessness, irritability, tremor

48 hr symptoms peak, severe sneezing, yawning, diarrhea, nausea, vomiting, waves of gooseflesh, alternate chills and sweating, weakness, depression, cramps, bone pain, muscle spasm, tachycardia, hypertension, sexual orgasm, dehydration

7 days acute phase ended

Protracted abstinence

Weeks, months

overdose
OVERDOSE

Triad

Coma

Respiratory depression

Pinpoint pupils

Management

Support of vital functions

Antidotal therapy

Narcotic antagonist