Opioid Analgesics Flashcards
Name the 9 strong opioid analgesics, and what receptor they block.
Mu agonists
– *morphine
– *codeine
– *fentanyl
– *heroin
– *hydrocodone (Vicodin, Lortab, Zohydro ER)
– *hydromorphone (Dilaudid)
– *meperidine (Demerol)
– *methadone
– *oxycodone (Percocet, OxyContin ER)
Name the 5 partial and mixed agonist / antagonists Analgesics.
*pentazocine (Talwin)
*buprenorphine (Buprenex, Subutrex, Suboxone)
*butorphanol (Stadol)
*tramadol (Ultram)
*tapentadol (Nucynta)
Name 5 Opiod Antagonists
*naloxone (Narcan)
*naltrexone (ReVia)
*methylnaltrexone (Relistor)
*alvimopan (Entereg)
*naloxegol (Movantik)
Where are Mu receptors located and what do they mediate?
brainstem, spinal cord, and limbic areas
thought to mediate supraspinal analgesia, some spinal analgesia, sedation, respiratory depression, euphoria and dependence.
Where are Kappa receptors located, and what do they mediate?
Located mainly in the brainstem and spinal cord,
and to a lesser extent, the limbic system.
They are thought to mediate some spinal analgesia, some supraspinal analgesia, miosis, sedation, and dysphoria.
Differences between definitions of opiate, opioid and narcotic.
– opiate - derived from opium
– opioid - having properties similar to drugs
derived from opium
– narcotic – technically means “sleep inducing”
but is commonly taken to mean “opioid”
What are the pharmacologic actions of morphine
Analgesia - uncouple physical and emotional awareness from the physical sensation
Sedation and mental clouding - floating dream-like state where people can be aroused
Relief of anxiety and apprehension - especially in people with pain
Euphoria (usually) / Dysphoria (more common in females and pain-free individuals)
Antitussive effect - depression of cough control center in medulla
- may aggravate asthma or COPD due to release of histamine
- can also cause itching (relieve with histamine antagonists (benadryl)
Name some adverse effects of opioids
Nausea
Depression of Respiration
Contriction of pupils - pin-point pupils is one tell-tale sign of opioid poisoning
Lowering of seizure threshold
Endocrine disturbances
decreased intestinal motility - constipation
urine retention
bronchoconstriction
increased biliary pressure
skeletal muscle rigidity and immunosuppression
How does morphine cause nausea?
What population is it more common in, and can tolerance develop?
– due to stimulation of the chemoreceptor trigger zone (CRTZ) in medulla, also may involve vestibular system.
– more common in ambulatory patients than in recumbent patients
– tolerance develops - with chronic use, the CRTZ may actually become de-sensitized
What is the major toxic effect of morphine?
Depression of respiration
- decreased sensitivity to CO2 at chemoreceptors in medulla
- use with caution in resp impaired patients
How does morphine help patients with pulmonary edema?
Treatment of pulmonary edema. Morphine gives partial relief in acute pulmonary edema by alleviating the patient’s conscious awareness of respiratory distress.
How does morphine disturb the endocrine system?
– decreased secretion of gonadotropins, corticosteroids and prolactin
– menstrual disturbances in females and impotence in males are common in chronic opioid users
Identify effects of morphine on smooth muscle and some results.
What can block some of these effects?
– decreased intestinal motility - constipation is a common side effect
– urine retention - often have to catheterize patients who received opioids
– bronchoconstriction - may cause serious problems in asthmatics and patients with obstructive pulmonary
disease.
– increased biliary pressure due to constriction of the bile duct
Some effects can be blocked by atropine or similar antimuscarinic drugs
Identify some cardiovascular effects of morphine
– postural (orthostatic) hypotension due to release of histamine and interference with hemostatic reflexes
– cutaneous vasodilation - due to release of histamine, causes a warm flushing of the skin. Some patients may experience pruitis that can be alleviated by H-1 histamine antagonists.
– increased CSF pressure due to buildup of CO2 and resulting cerebral vasodilation use only with caution in patients with head injuries
Pharmacokinetics of Morphine
route, onset, duration, metabolism, excretion, placental barrier, dose
Route: traditionally IM, SC and IV for patients
Onset: Rapid after parenteral admin; maximal analgesic action within one hour
Duration: analgesia 4-6 hours
-t1/2 = 2-3 hours (longer in elderly)
metabolism: liver
excretion: 90% urine as metabolites in 24 hours, 7-10% in feces
readily crosses placental barrier and can affect fetus (resp depression or dependence)
Dose: standard therapeutic dose of morphine is 10 mg
SC or IM. This is the dose to which all other analgesic
drugs are compared.
Major drug interactions of morphine
additive effects with other CNS depressants (alcohol, barbiturates, benzodiazepines, antipsychotics, antidepressants, antihistamines)
MAO inhibitors - meperidine
abuse with amphetamines and cocaine - speedball
used in combo with other analgesics (aspirin, acetaminophen or ibuprofen) acting through different mechanisms has enhanced effect
Certain antihistamines (hydroxyzine)- can enhance analgesic effects
Tricyclic antidepressants and SNRI’s (serotonin / norepinephrine re-uptake inhibitors) can enhance analgesic effects
Symptoms and treatment of opioid poisoning.
Symptoms - characteristic triad
– CNS depression - stupor or coma
– depressed depth and rate of respiration
– pin point pupils
Note: If the patient is severely hypoxic (i.e. very close to
death) the pupils may be dilated.
Treatment
– Support respiration - be prepared to mechanically ventilate the patient. Be aware that administration of O2 may remove the hypoxic drive for respiration and cause apnea.
– Administer a narcotic antagonist such as naloxone
(NARCAN).
Common uses of morphine and related drugs
Moderate - severe pain
Treatment of chronic pain
Adjuncts to surgical anesthesia
Antitussives
Antidiarrheals
Dyspnea of left heart failure and pulmonary edema
Abuse
Usual dose of Morphine
usual dose is 10 mg SC or IM; or 10-30 mg P.O., although with severe, chronic pain, higher doses
may be needed.
3 important developments of opioid use in healthcare
– infusion and autoinjector systems
– PCA (patient controlled analgesia)
– spinal analgesia
Codeine
route, dose, metabolism, uses
route: orally effective
dose: 30-60 mg (1/12 as potent as morphine)
Metabolism: metabolized to morphine in most patients. genetic differences may explain individual differences in sensitivity
use: analgesic for mild-moderate pain and antitussive
hydromorphone
similar to morphine but more potent
oxycodone (Roxicodone, percocet, oxycontin
- similar to both morphine and
codeine, but used orally (usually in combination with acetaminophen) for mild-moderate pain.
OxyContin is a sustained release oral preparation for the management of severe chronic pain.
Hydrocodone (vicodin, norco, lortab, zohydro ER)
similar both to morphine and codeine; used orally for mild-moderate pain and as an antitussive; is currently one of the most
widely prescribed opioids.
On 10/8/14, it was reclassified as Schedule-2 from Schedule-3, which has complicated prescribing.
Zohydro ER is a sustained release product that does not contain acetaminophen.
Meperidine
route, potency, smooth muscle, use, newborns, duration
synthetic drug
route of administration - oral and parenteral
1/10 the potency of morphine
weaker effects on smooth muscle than morphine - less constipation and urine retention, although the evidence to support this is weak.
has been used for moderate to severe pain
has been commonly used in obstetrics - may cause less
respiratory depression in the newborn than morphine
relatively short acting 1-3 hours; not appropriate for chronic pain because of the buildup of an active metabolite (normeperidine) that can cause seizures.
falling into disfavor in many circles.
Heroin
potency, route, duration
more potent and more euphoric than
morphine; duration of action about 4-6 hours.
available for medical use in some
countries, but not in the US
abuse
commonly taken by injection, snorting or smoking
Methadone
duration, use, dosage
less euphoric and longer duration of action (12- 24 hours) than heroin or morphine (4-6 hours)
used as an analgesic and in treating opioid addiction (stigma in use for this)
dosing can be tricky and needs to be done carefully, with close monitoring of the patient.
- When used acutely as an analgesic, duration of action = 4-6 hours.
When used chronically (as in methadone maintenance for the treatment of opioid dependence,
or for the management of chronic pain), it has a duration of action of 12-24 hours.
Fentanyl
very potent mu agonist (about 100 x more potent than morphine) - given
parenterally to supplement surgical anesthesia.
A transdermal preparation (Duragesic) is available for the management of chronic pain.
Lozenge/lollipop preparations are also available for the treatment of severe “breakthrough” pain in chronic pain patients.
-controversy regarding this due to fear of kids finding
Whats one major problem with opoid / acetaminophen combination products?
Contain a lot of acetaminophen, and can lead to liver toxicity / damage
Pentazocine
receptors, effective, sedation, CNS, dependence,
– agonist effects are dominant - acts as an agonist at κ (kappa) receptors, but only as a partial agonist at µ (mu) receptors; it acts as a µ antagonist at high doses.
– less effective than morphine for severe pain
– sedation and respiratory depression are less than with morphine
– CNS stimulation and hallucinations are more common than with morphine
– with chronic use, the potential for physical dependence is less than morphine, but still significant
- can precipitate withdrawal syndrome in opioid addicts
Buprenorphine
receptors, analgesic effect / abuse, naloxone effect, route, treatment
– acts as a partial agonist at µ-receptors and possibly κ-receptors.
– analgesic effects may be slightly less than that of morphine, its abuse potential is much lower.
– Buprenorphine is the primary agent used for the so-called “office based” treatment of opioid addiction.
– reduces drug craving in heroin addicts and is being used in the treatment of heroin addiction.
–Suboxone is a new combination product containing buprenorphine plus nalaxone designed for sublingual use. When taken as directed, the naloxone does not reach a therapeutic blood level and the buprenorphine can produce its effects. However, if the user tries to inject the drug to achieve a high, the naloxone will block the effects of the buprenorphine.
– Although it is usually given by injection, it is also effective when
administered sublingually, intranasally, or transdermally.
Tramadol
use, receptor / inhibition, effects, side effects. manufacturer claim
newer drug for use in mild-moderate pain.
It supposedly is a weak mu agonist and inhibits the synaptic reuptake of norepinephrine and
serotonin, much like the tricyclic antidepressants.
It produces good analgesia, with only mild side effects.
In general, the side effects resemble those of other opioids (dizziness, sedation, nausea, constipation).
The manufacturer has claimed that the drug has a very
low abuse and addiction potential. However, there are a
significant number of reports indicating that the drug has
opioid-like abuse potential.
Key facts of tramadol abuse and dependence.
dependence, abuse, tolerance, withdrawal symptoms / relief of
Tramadol may induce psychic and physical dependence of
the morphine-type (µ-opioid)
Dependence and abuse, including drug-seeking behavior
- not limited to prior hx
- higher risk with prior hx
Tramadol is associated with craving and tolerance development.
Withdrawal symptoms may
occur if tramadol is discontinued abruptly.
- anxiety, sweating, insomnia,
rigors, pain, nausea, tremors, diarrhea, upper respiratory
symptoms, piloerection and rarely hallucinations
- relieved by reinstitution of opioid therapy and gradual dose reduction
Tapentadol
receptors, inhibits, effectiveness, what type of pain
Newer drug that is similar to tramadol, except that it has stronger agonist activity at mu receptors.
-It also inhibits reuptake of NE and 5-HT.
More effective for pain than tramadol, but also greater abuse potential.
Classified as Shedule II drug.
Tramadol is Schedule IV.
May have some special benefits for“neuropathic pain”.
Naloxone (Narcan)
use, route, abuse prevention, duration, withdrawal
drug of choice for opioid
poisoning, can reverse the respiratory depressant effects of opioids
– not effective orally, because of first pass metabolism, usually given parenterally in Ed or intranasaly by first responders.
– sometimes included in combination with oral narcotic
analgesics (eg. Talwin NX) to prevent abuse (i.e. injection of the drug)
– relatively short duration of action (i.e. only about 1-2
hours)…….agonists have longer actions
– patients must stay in hospital for this reason as opioid effects will return when naloxone wears off
– can precipitate withdrawal in addicts, which is not pleasant for patient or care givers!!!
Naltrexone
route and duration, adverse effect, when is therapy begun, alcoholism
orally effective, long acting antagonist (24 hours)
used in “immunizing” addicts (ie. preventing the high
produced by opioid agonists)
risk of hepatotoxicity is a serious drawback
its effectiveness in the long-term treatment of opioid dependence is not clear
patient compliance is a major problem
Keep in mid that an opioid addict must first be detoxified
(ie. brought through withdrawal) before naltrexone therapy can be initiated.
It has been shown to decrease the craving for alcohol in alcoholics. It is now approved for use in the treatment of alcoholism
Methylnaltrexone
type / use, route, when used,
Quaternary analog of naloxone approved for the treatment/prevention of opioid-induced constipation.
Must be given parenterally, usually SC
Only appropriate for serious constipation resulting from use higher doses of opioids for
more severe pain.
Alvimopan (Enterig) is a similar agent but can be given orally.
Naloxegol
New drug approved for opioid-induced constipation.
It consists of a naloxone molecule conjugated to short chain polyethylene glycol-like molecule.
Taken orally, it has few systemic effects.
May be more useful than similar agents for use in out patients
Describe pattern of tolerance in opioid use
– tolerance - develops to some effects more than others. For
example, there can be a high degree of tolerance to the
analgesic, euphoric and sedative effects of opioids whereas
there is usually little tolerance to opioid-induced miosis or
constipation.
– withdrawal syndrome
Characteristics of Acute Withdrawal Syndrome
8 symptoms
– craving for drug
– anxiety, insomnia
– dilation of pupils
– severe GI hypermotility
– hypertension and tachycardia
– “goose flesh”
– yawning and sweating
Duration and intensity of acute withdrawal
short acting drugs, long acting, and what follows
– short acting drug (e.g. heroin) - intense symptoms, short duration (2-3 days)
– long acting drug (e.g. methadone) - moderate symptoms, long duration (4-7 days)
– Note: The acute withdrawal phase is often followed by prolonged syndrome consisting of mild anxiety irritability, sleep disturbances and autonomic excitability that may last for several weeks - months.
Treatment of Dependence
– “cold turkey”
– weaning patient off the drug
– methadone
– substitution - wean patient off drug
– maintenance - maintain patient on drug
– buprenorphine is also being used
– naltrexone (Trexan) - long acting opioid antagonist
– clonidine (Catapress) - will suppress some withdrawal symptoms; lofexidine (Lucemyra)
is a newer alpha 2 agonist for opioid detox.
Identify some keys to effective use of opioids without abuse.
Healthcare provider must maintain control
Define outcomes and develop a
therapeutic plan to achieve
Monitor patient to insure compliance with the plan and efficacy
Periodic drug holidays to monitor level of pain and look for signs of dependence
Patient contracts
Drug screening
