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OPIOID ANALGESICS

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Learning Outcomes
19.1 Explain the pathway for pain recognition and how opioids produce analgesia. 19.2 Describe the sources of opioid analgesics. 19.3 Discuss the pharmacological effects of these drugs. 19.4 Discuss administration, absorption, and metabolism of these drugs.
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Learning Outcomes
19.5 List the adverse effects of these drugs. 19.6 Explain acute opioid poisoning. 19.7 Discuss the actions of opioid antagonists. 19.8 List drug interactions. 19.9 Discuss the specific terms associated with pain, analgesia, addiction, cough, and opioid receptors.

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Pain
The sensation of pain consists of at least two elements:
The local irritation (stimulation of peripheral nerves) The recognition of pain (within the CNS)

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Nociceptors
Free nerve endings Located in the skin, muscle, joints, bones, and viscera. Nociceptors respond to tissue injury and painful stimuli. Prostaglandins, histamine, bradykinins, serotonin, and Substance P are among the peripheral neurotransmitters released that trigger nociceptors.
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Nociceptors
Alert the brain to the intensity of the pain by increasing the frequency of signals sent to the spinal cord and then to specialized areas within the CNS. Signals arrive in the spinal cord through Adelta nociceptor and C-nociceptor fibers
A-delta fibers (myelinated), the pain is consciously experienced as sharp C fibers (unmyelinated), dull, aching pain is felt
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Pain

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Pain
There are two different types of pain:
Nociceptive pain: can only occur when all neural equipment is working properly Neuropathic pain: abnormal signals or nerves damaged by entrapment, infection, amputation, or diabetes

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Pain Duration
Acute: usually appears in association with an observable injury and disappears when the injury heals Chronic: persists for weeks, months, or years even with analgesic therapy Nociceptive pain can be either acute or chronic. Neuropathic pain is chronic, even though it may be intermittent
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Neuropathic
Hyperalgesia sensitization within the spinal neurons observed as over responsiveness Prolonged pain Referred pain is the spread of pain to an uninjured area

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Pain
No matter what type of pain is present, relief from pain (analgesia) is the therapeutic goal. Selection of the most appropriate analgesic depends upon the type and duration of pain.
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Pain Management
Opiods Nonopioid analgesics: NSAIDS, Acetaminophen, COX-2 inhibitors (will be discussed in Ch. 20) Meds in adjunct therapy:
Antiepileptic drugs Tricyclic antidepressants

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Opioid Analgesics
Opioid analgesics, in their natural plant form, have been medicinally used for 5000 years. Opioids are considered first-line therapy for:
Pain associated with procedures (bone marrow biopsy) Pain due to trauma or cancer (burns) Visceral pain (appendicitis)
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Opioid Analgesics
Majority used to relieve acute or chronic pain. Few, such as fentanyl (Sublimaze, Duragesic), alfentanil (Alfenta), and sufentanil (Sufenta), are primarily indicated for preoperative sedation to reduce patient apprehension. Also used to suppress cough and treat diarrhea
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Opioid Analgesics
Also used to suppress cough: codeine (III and V), hydrocodone (III), and dextromethorphan (OTC)

And treat diarrhea: difenoxen (Motofen) and loperimide (Immodium) (schedule V)

CNS Opioid schedule pg. 272

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Opioid Analgesics
Opioid analgesics were previously called narcotic analgesics. The term opioid is used today for any molecule, natural or synthetic, that acts on the opioid receptors. The naturally occurring opiates include morphine and codeine.
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Opioid Analgesics
Site of Action:
Opioid Receptors (brain, spinal cord, GI)
Endogenous Opioids Endorphin, enkephlin, dynorphin, nociceptin, and nocistatin

Important to survival, decreases pain so that the injured can remove themselves from a harmful situation, enzymes break down endorphins and then pain returns and person seeks help for the pain.
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Opioid Receptors
Three opioid receptors are the most clinically important mu, kappa, and delta. There are two types of mu receptors.
Mu 1, located outside the spinal cord (CNS), interprets pain. Mu 2, found throughout the CNS, is responsible for respiratory depression, analgesia, euphoria, and physical dependence.
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Opioid Analgesics
Tolerance: ability of the body to alter its response (to adapt) to drug effects so that the effects are minimized over time. Dependency: drug required to prevent onset of withdrawal symptoms Because of the potential for abuse, opioid analgesics are federally restricted (controlled) substances.
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Opioid Analgesics
Opioids are called central analgesics because they work in the CNS.
Selectively act within the CNS to reduce the reaction to pain Do not impair the function of peripheral nerves Pain is still present, but patients respond as though they can tolerate the pain

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Opioid Analgesics
Morphine is the standard for showing the potency of all other opioid analgesics. Vary
Potency Onset of action Incidence of opioid side effects

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Opioid Analgesics

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Opioid Analgesics
Opioid analgesics act by binding to opioid receptors and mimicking the effects of the analgesic peptides.

Opioids influence CNS activity:

Decrease mental alertness Euphoria Dysphoria Respiratory depression
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Opioid Analgesics
Opioids have direct action on smooth muscle in the GI tract, which can lead to constipation.

They can also cause:

Bronchoconstriction Decreased urination

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Opioid Analgesics
Opioids do not depress cardiac function.

Most opioids cause miosis (pin point). Meperidine causes mydriasis.

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Drug Administration
Opioids are available in oral and parenteral dosage forms. (capsule or IV/injection)

Opioids are given on a repeated schedule to avoid intense pain.

Specialists are now using aggressive treatment schedules in which dosing is often under patient control.
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Drug Administration
Because opioid analgesics are CNS depressants at any dose, patients should be closely monitored for overdose. Opioid analgesics are metabolized by the liver and then excreted by the kidneys.
Anything that causes alkaline urine increases the concentration of opioids in the blood.
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Adverse Effects
Adverse effects of opioid analgesics:
Mental confusion (decreased mental alertness) Nausea Vomiting (chemoreceptor trigger zone) Dry mouth Constipation (increased smooth muscle tone) Urinary retention Respiratory depression (suppressed medulla)
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Adverse Effects
Opioid analgesics are contraindicated in patients with:
Bronchial asthma or heavy pulmonary secretion (spasmogenic and release of histamine) Convulsive disorders Biliary obstruction (spasm of the common bile duct) Head injuries Pregnancyrisk to benefit must be assessed

Opioids should not be given if a nonopioid analgesic will work.

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Tolerance and Physical Dependence

Tolerance may develop due to changes in the opioid receptors. Physical dependence can develop with chronic use of opioids. Addiction is a complex interaction of several factors that lead to a lack of control over drug use.
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Tolerance and Physical Dependence

Methadone is used in the treatment of opioid addiction:
Satisfies opioid hunger Does not produce severe withdrawal symptoms

Buprenorphine:
Pushes opioids out of receptors Blocks attachment of opioids to receptors Reverse respiratory depression
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Opioid Antagonists
Opioid poisoning presents with coma, depressed respiration, cyanosis, and hypotension. Antagonists are drugs that attach to opioid receptors and displace the analgesic, rapidly reversing poisoning. Pure: competitive Partial: reverse respiratory depression
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Opioid Antagonists

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Opioid Antitussives
Antitussives are drugs that suppress the cough reflex:
Codeine Hydrocodone Dextromethorphan

Expectorants are commonly combined with antitussives to aid in the removal of mucus.
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Drug Interactions
Opioid analgesics potentiate the effects of CNS depressants. Meperidine and dextromethorphan should not be given with MAO inhibitors. Rifampin and phenytoin have caused withdrawal symptoms when administered with methadone.
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Tramadol = Ultram Merperidine = Demerol Butorphanol = Stadol Hydromorphone = Dilaudid Pentazocine = Talwin Propoxyphene = Darvon Hydrocodone/APAP = Norco Fentanyl = Duragesic
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Methadone = Dolophine Naltrexone = ReVia Naloxone = Narcan Nabumatone = Relafen Etodolac = Lodine Diclofenac = Voltaren Indomethacin = Indocin Meloxican = Mobic
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Top 200
1 Vicodin / Lortab Hydrocodone / APAP Analgesic - Narcotic 26 Darvocet N Propoxyphene-N / APAP Analgesic - Narcotic 36 Percocet / Roxicet / Endocet / Tylox Oxycodone W/APAP Analgesic - Narcotic 45 Tylenol #3 Codeine W/APAP Analgesic - Narcotic 55 Ultram Inc ER Tramadol Analgesic Non-narcotic
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Top 200
129 Endocet Hydrocodone / Ibuprofen Analgesic - Narcotic 130 Ultracet Tramadol / APAP Analgesic Non-narcotic 159 Oxycontin Oxycodone SR Analgesic Narcotic 195 Morphine / MS-Contin Morphine Analgesic - Narcotic

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