pain

opioids

pain

IASP defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

pain threshold

the point at which that stimulus is experienced as pain

differs from person to person

pain tolerance

the duration of time or the intensity of pain that a person will endure before taking over action to relieve the pain

decreases with repeated exposure to pain

decreased by fatigue, anger, fear, and sleep deprivation

physical dependence

abstinence syndrome with abrupt discontinuation

about 10 hours after last dose: initial reaction is yawning, rhinorrhea, sweating

progresses to: sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasm, kicking movements

lasts 7-10 days if untreated

withdrawal unpleasant but not lethal, as is possible with CNS depressants

NOT equated with addiction

Addiction

behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm

addicts will do anything to get their high

acute pain

less than 6 months

acute somatic, acute visceral, referred pain

acute somatic

arises from connective tissue, muscle, bone and skin

sharp and localized or dull and non-localized

responds best to:

acetaminophen, corticosteroids, NSAIDS, opiates, local anesthetics, ice, massage

acute visceral

pain in the internal organs and abdomen

poorly localized

radiates

most responsive to opiates

may also use: corticosteroids and NSAIDS

referred pain

pain that is present in an area removed or distant from its point of origin

analgesics

drugs that relieve pain without causing loss of consciousness

drugs for acute pain

morphine and other opioid agonists

centrally acting non-narcotic analgesic: acetaminophen

COX inhibitors: NSAIDS, salicylates, COX-2 inhibitors

Drugs for moderate to severe pain

morphine and opiates

oral forms vs IV vs transdermal

moderate pain use: codeine or codeine/acetaminophen, hydrocodone or hydrocodone/acetaminophen

severe pain: morphine, oxycodone

chronic pain

usually defined as lasting at least 3-6 months

response patterns vary

produces significant behavior and psychological changes

common types of chronic pain:

* central pain
* non-neuropathic pain
* neuropathic pain
* psychogenic pain

central chronic pain

CNS lesions or dysfunction

mirgraines

treatment: treat cause, medications

non-neuropathic pain

myofascial pain syndromes:

fibromyalgia

myositis

myalgia

muscle strain

drug choices:

NSAIDS

TCAs

serotonin reuptake inhibitors

neuropathic pain

result of trauma or disease of nerves

most often chronic

diabetic neuropathy

postherpetic neuralgia

deafferentation pain

sympathetically maintained pain

complex regional pain syndromes (CRPS)

central pain

phantom limb pain

(burning and tingling sensation)

drugs for neuropathic pain

anti-epileptics

pregabalin

gabapentin

antidepressants

TCAs

serotonin and norepinephrine reuptake inhibitor

duloxetine (cymbalta)

management strategy

ask about pain regularly

believe the patient and family in their reports of pain and what relieves it

choose pain control options appropriate for the patient, family, and setting

deliver interventions in a timely, logical, coordinated fashion

empower patients and their families

opioid

a general term defined as any drug, natural or synthetic, that has actions similar to those of morphine

endogenous opioid peptides

three families of peptides

* enkephalins
* endorphins
* dynorphins

found in the CNS and peripheral tissues

we know that these peptides serve as neurotransmitters, neurohormones, and neuromodulators, the precise physiological role is not understood

basic pharmacology of the opioids

strong opioid agonists

* morphine
* other strong opioid agonists

moderate to strong opioid agonists

agonist-antagonist opioids

morphine

therapeutic use: relief of pain

* mechanism of analgesic action
* moderate to severe pain
* preoperative treatment of anxiety

adverse effects of morphine

respiratory depression

onset: IV 7 min, IM 30 min, subQ up to 90 min, may persist 4-5 hrs

tolerance to respiratory depression with concurrent use of other drugs that have CNS depressant actions (eg. alcohol, barbiturates, etc.)

can compromise patients with impaired pulmonary function: asthma, emphysema, kyphoscoliosis, chronic cor pulmonale

* constipation
* orthostatic hypotension
* cough suppression
* emesis
* urinary retention
* euphoria/dysphoria
* sedation
* miosis
* intracranial pressure (ICP)
* birth defects

\

pharmacokinetics of morphine

administered by several routes: PO, IM, IV, subQ, epidural, and intrathecal

not very lipid-soluble

does not cross blood-brain barrier easily

only small fraction of each dose reaches site of analgesic action

precautions: decreased respiratory reserve, pregnancy, labor and delivery, head injury

morphine toxicity, treatment, general guidelines, dosage, and administration

clinical manifestations

classic triad: coma, respiratory depression, pinpoint pupils

treatment: ventilatory support, antagonist: naloxone (Narcan)

general guidelines: monitor full vitals before giving, give on a fixed schedule

dosage and routes of administration: oral, intramuscular and subcutaneous, intravenous, epidural and intrathecal

fentanyl

(sublimaze, duragesic, abstral, actiq, fentora, onsolis)

100 times the potency of morphine

five formulations in three routes

parenteral (sublimaze)

* surgical anesthesia

transdermal (duragesic)

* patch - heat acceleration
* iontophoretic system - needle-free

transmucosal

* lonzenge on a stick (actiq)
* buccal film (onsolis)
* buccal tablets (fentora)
* sublingual tablets (abstral)

meperidine

short half-life

interacts adversely with several other drugs

toxic metabolite accumulation

recommend to avoid

methadone

treatment for pain and opioid addicts

hydromorphone (dilaudid)

much more potent than morphine

less nausea than morphine

1\.5 mg of hydromorphone IV= 10 mg of morphine IV

refer to page 268 for equianalgesic dosing

moderate to strong opioid agonists

similar to morphine in most respects

produce analgesia, sedation, euphoria

can cause: respiratory depression, constipation, urinary retention, cough suppression, and miosis

can be reversed with naloxone

different from morphine

produce less analgesia and respiratory depression than morphine

somewhat lower potential for abuse

codeine

actions and uses

10% converts to morphine in liver

pain and cough suppression

preparations, dosage, and administration

usually oral

30 mg produces same effect as 325 mg acetaminophen

oxycodone

analgesic actions equivalent to those of codeine

long-acting analgesic

* immediate-release
* controlled-release (OxyCotin)
* abuse: crushes and snorts or injects medication

hydrocodone

most widely prescribed drug in the United States

combined with aspirin, acetaminophen, or ibuprofen

same side effects as other opioids

agonist-antagonist opioids

Pentazocine - Talwin

Nalbuphine - Nubain

Butorphanol-Stadol

Buprenorphine

* 7-day patch: Butrans
* Sublingual film: Suboxone

clinical use of opioids

pain assessment

* essential component of management
* based on patient’s description

Evaluate:
* pain location, characteristics, and duration; things that improve/worsen pain
* status before drug and 1 hour after
* balance the need to provide pain relief with the desire to minimize abuse
* patient-controlled analgesia
* PCA devices
* drug selection and dosage regulations
* comparison of PCA with traditional intramuscular therapy
* patient education

dosing guidelines

assessment of pain

dosage determination

(no ceiling dose for pure opioids)

dosing schedule

avoiding withdrawal

opioid antagonists

drugs that block the effects of opioid agonists

principal uses:

* treatment of opioid overdose, relief of opioid-induced constipation
* reversal of postoperative opioid effects
* management of opioid addiction

agonist binds to MU receptor

1. analgesia
2. respiratory depression
3. euphoria
4. sedation
5. decreased GI motility
6. physical dependence

(most important for pain relief)

agonist-antagonist opioids binding to Kappa

1. analgesia (not as strong)
2. sedation
3. decreased GI motility

patient-controlled analgesia

PCA devices

drug selection and dosage regulations

comparison of PCA with traditional intramuscular therapy

patient education

opioid antagonists

drugs that block the effects of opioid agonists

principal uses:

* treatment of opioid overdose, relief of opioid induced constipation
* reversal of postoperative opioid effects
* management of opioid addiction

pure opioid antagonists

naloxone (narcan)

other pure opioid antagonists:

* methylnaltrexone (relistor)
* alvimopan (entereg)
* naltrexone (revia, vivitrol)

naloxone

therapeutic uses

reversal of opioid overdose

drug of choice with pure opioid agonist overdose

titrated cautiously with physical dependence

reversal of postoperative opioid effects

titrated to achieve adequate ventilation and to maintain pain relief

reversal of neonatal respiratory depression

opioids given during labor and delivery may cause respiratory depression in neonate

methylnaltrexone

selective opioid antagonist

treatment of opioid-induced constipation in late-stage disease for patients on constant opioids

nonopioid centrally acting analgesics

* relieve pain by mechanisms largely or completely unrelated to opioid receptors
* do not cause respiratory depression, physical dependence, or abuse
* not regulated under the Controlled Substances Act
* ex: tramadol, clonidine (duraclon), ziconotide (prialt), dexmedetomidine (precedex)

tramadol

mechanism of action

combination of opioid and nonopioid mechanisms

drug interactions

CNS depressants

abuse liability - IV (schedule)

preparations, dosage, and administration

immediate-release and extended-release

clonidine

mechanisms of pain relief

alpha 2-adrenergic agonist

analgesic use

used in combination with opioid analgesic

adverse effects

cardiovascular: severe hypotension, rebound hypertension, bradycardia