Chapter 3 CNS - opioid analgesics and antagonists Flashcards
morphine
full agonist
- opiate receptor agonist
- induces analgesia
- sedation, respiratory depression
- n/v
- vertigo
- miosis (excessive constriction of the pupil of the eye.)
- ADH release (Administration of opioids has also been documented in some case studies to cause ADH secretion from the posterior pituitary due to the stimulation of opioid receptors in the hypothalamus)
- GI effects (decreased propulsion, secretions, tonic spasm){
- increases tone in bile duct, brochi, ureters, and bladder (overcompensating and overactive, contracting too much – can cause incontinence // prevent air from entering)
indications:
* severe pain which cannot be alleviated by non-narcotic analgesics or weaker narcotic analgesics
* Drug of choice for severe pain d/t MI
effects
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
IM/PO/PR (per rectum)/SC/IV/epidural/intrathecal (pain pump)
4-6 hr duration
tolerance/dependence
* tolerance develops to analgesic effects but not to constipating effects
* high abuse potential
* withdrawal l/t
1) insomnia
2) pain
3) increased GI activity
4) restlessness
interactions
* enhance CNS depressants
* inc neuromuscular blocker-induced respiratory depression
* Additive with drugs that cause hypotension
analgesic action (3-fold) // perception of pain reduced (increased threshold) // unpleasant psychological response reduced + sleep is incuded even in presence of pain
Levorphanol (levo-dromoran)
oxymorphone (opana)
oxycodone (oxycontin)
hydromorphone (dilaudid)
tramadol (ultram)
full agonist
- opiate receptor agonist
- induces analgesia
- sedation, respiratory depression
- n/v
- vertigo
- miosis (excessive constriction of the pupil of the eye.)
- ADH release (Administration of opioids has also been documented in some case studies to cause ADH secretion from the posterior pituitary due to the stimulation of opioid receptors in the hypothalamus)
- GI effects (decreased propulsion, secretions, tonic spasm){
- increases tone in bile duct, brochi, ureters, and bladder (overcompensating and overactive, contracting too much – can cause incontinence // prevent air from entering)
indication
* moderate to severe pain
effects
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
pharmacokinetic
* better oral absoprtion than morphine
tolerance/dependence
* tolerance develops to analgesic effects but not to constipating effects
* high abuse potential
* withdrawal l/t
1) insomnia
2) pain
3) increased GI activity
4) restlessness
interactions
* enhance CNS depressants
* inc neuromuscular blocker-induced respiratory depression
* Additive with drugs that cause hypotension
analgesic action (3-fold) // perception of pain reduced (increased threshold) // unpleasant psychological response reduced + sleep is incuded even in presence of pain
meperidine (demerol)
full agonist){
- opiate receptor agonist
- induces analgesia
- sedation, respiratory depression
- n/v
- vertigo
- miosis (excessive constriction of the pupil of the eye.)
- ADH release (Administration of opioids has also been documented in some case studies to cause ADH secretion from the posterior pituitary due to the stimulation of opioid receptors in the hypothalamus)
- GI effects (decreased propulsion, secretions, tonic spasm){
- increases tone in bile duct, brochi, ureters, and bladder (overcompensating and overactive, contracting too much – can cause incontinence // prevent air from entering)
indication:
* used to treat rigors (episode of shaking or exaggerated shivering which can occur with a high fever), such as triggered by amphotericin B (an antifungal used to treat fungal infections in neutropenic patients, cryptococcal meningitis in HIV infection, fungal infections, and leishmaniasis [parasite] )
effects
like morphine
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
- OD causes convulsions d/t excitatory actions of metabolite
IM/SC/PO/IV
shorter duration than morphine
metabolite is excitatory to CNS
tolerance/dependence
* tolerance develops to analgesic effects but not to constipating effects
* high abuse potential
* withdrawal l/t
1) insomnia
2) pain
3) increased GI activity
4) restlessness
interactions
* w/ MAO inhibitors => cases severe CNS excitation
* resp depression
* hypotension
analgesic action (3-fold) // perception of pain reduced (increased threshold) // unpleasant psychological response reduced + sleep is incuded even in presence of pain
methadone
full agonist
- full morphine like actions
- opiate receptor agonist
- induces analgesia
- sedation, respiratory depression
- n/v
- vertigo
- miosis (excessive constriction of the pupil of the eye.)
- ADH release (Administration of opioids has also been documented in some case studies to cause ADH secretion from the posterior pituitary due to the stimulation of opioid receptors in the hypothalamus)
- GI effects (decreased propulsion, secretions, tonic spasm){
- increases tone in bile duct, brochi, ureters, and bladder (overcompensating and overactive, contracting too much – can cause incontinence // prevent air from entering)
- weaker sedative
indication:
* detoxification of narcotic addiction
* severe pain in hospitalized pts
effects
similar to morphine
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
IM/SC/PO
excreted more slowly than morphine (withdrawal sx less intense, but prolonged)
tolerance/dependence
* cross dependent w/ morphine (basis for detoxification
* tolerance develops readily
* less psychologically addicting than morphine
Detoxification replaces heroin dependence w/ methadone dependence then slowly reudce that dose to 0
fentanyl (sublimaze{)
full agonist
- more potent than morphine
- respiratory depression less likely
indication
* preoperative med used in anesthesia
effects
* muscle rigidity
* mild bradycardia
IV; rapid; shorter duration than morphine
no tolerance or dependence when used as an anesthetic (anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes)
transdermal, transmucusoal, prepartion available for chronic pain
sufentanil
full agonist
- most potent analgesic
indication
* anesthesia
effects:
little data
IV
alfentanil
full agonist
- more potent than morphine
- respiratory depression less likely
indication
* anesthesia
little data for effects
IV FASTEST ONSET
remifentanil (ultiva)
full agonist
- more potent than morphine
- respiratory depression less likely
indication - anesthesia
effects:
* cause chest wall rigidity if infused rapidly
IV
IV tubing must be changed or cleared after remifentanil
codeine
weak agonist
- prodrug: 10% of dose is converted to morphine
- actions attributd to morphone
&&&&&&&&&
* opiate receptor agonist
* induces analgesia
* sedation, respiratory depression
* n/v
* vertigo
* miosis (excessive constriction of the pupil of the eye.)
* ADH release (Administration of opioids has also been documented in some case studies to cause ADH secretion from the posterior pituitary due to the stimulation of opioid receptors in the hypothalamus)
* GI effects (decreased propulsion, secretions, tonic spasm){
* increases tone in bile duct, brochi, ureters, and bladder (overcompensating and overactive, contracting too much – can cause incontinence // prevent air from entering)
* weaker sedative
&&&&&&&&&
- antitussive
indication:
* minor pain relief
* cough
effects
* similar to morphine but less intense at doses which relieve moderate pain
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
- @ HIGH DOSES — toxicitiy as severe as w/ morphine
PO/SC/IM
10% demethylated to form morhpine, rest conjugated in liver and excreted in urine
&&&
Low risk of abuse
&&&&&
Interactions similar to morphine
* enhance CNS depressants
* inc neuromuscular blocker-induced respiratory depression
* Additive with drugs that cause hypotension\
cough medications combination
propoxphene (e.g. Darvon)
weak agonist
- weak analgesic (less potent than aspirin)
indication
* minor pain
effects:
1) dizziness
2) sedation
3) nausea
4) vomiting
OVERDOSES cause convulsions, CNS depression, coma + death
PO, well absorbed
LOW risk of abuse
similar to morphine
* enhance CNS depressants
* inc neuromuscular blocker-induced respiratory depression
* Additive with drugs that cause hypotension
OD often l/t to death (especially amongst psychiatric pts)
pentazocine (talwin)
mixed agonist-antagonists- lower abuse potential
- similar to morphine but less potent
- antagonized by naloxone (narcan)
- not by nalorphine (It is used as an antagonist to narcotic analgesics. It eliminates suppression of the respiratory center, bradycardia, and vomiting caused by opiate receptor agonists.)
indication
moderate pain; also used as preoperative medication
effects
* respiratory depression
* constipation
* CNS disturbances
* orthostatic hypotension
* cholestasis (Any condition in which the flow of bile from the liver stops or slows.)
* n/v with initial doses
IM/IV/SC – short duration than morphine; well absorbed, highly metabolized
tolerance/dependence
* lower risk of abuse than morphine
* antagonist effects can induce withdrawal in narcotic addicts
TO PREVENT IV ABUSE; it is mixed with naloxone; taken orally only pentazcocine is abosrbed (BY IV; naloxone blocks pentazocine)
nalbuphine (nubain)
dezocine
butorphanol
buprenorphine
mixed agonist-antagonists- lower abuse potential
- similar to morphine but less potent
- antagonized by naloxone (narcan)
- not by nalorphine (It is used as an antagonist to narcotic analgesics. It eliminates suppression of the respiratory center, bradycardia, and vomiting caused by opiate receptor agonists.)
indication
* moderate to severe pain
* preoperative medicine
* combination anesthesia
undesirable effects
* low incidence of resp depression, sedation, dizziness, n/v
tolerance/dependence
* abstinence syndrome upon withdrawal
* lower abuse potential than morphine
drug interactions
* inc CNS depression caused by CNS depressants
Antagonist activity (all below are opioid agonist-antagonist )
* buprenorphine > butrophanol > desocine = nalbuphine > pentazocine
naloxone (narcan)
pure antagonist
- blocks opioid receptor
- no effect on narcotic-free persons
indication
* tx narcotic OD
* eval for addiction in methadone program
* reduce post op resp depression
effects (narcotic withdrawal sx’s)
* appetite loss
* muscle contraction
* fever/chills
* restlessness
* cardiovascular (hypotension, orthostasis, syncope, and bradycardia) + respiratory sx (depression)
* n/v
* diarrhea
IV, rapid onset
tolerance
* induce abstinence syndrome in narcotic-dependent patients
interaction
* reverses narctoic induce depression
naltrexone (revia)
pure antagonist
- similar to naloxone, but longer duration
indication
* tx narcotic OD
* eval for addiction in methadone program
* reduce post op resp depression
* tx alcoholism <========
effects (narcotic withdrawal sx’s)
* appetite loss
* muscle contraction
* fever/chills
* restlessness
* cardiovascular (hypotension, orthostasis, syncope, and bradycardia) + respiratory sx (depression)
* n/v
* diarrhea
PO duration more than 24 hrs
tolerance
* induce abstinence syndrome in narcotic-dependent patients
interactions
* reverses narcotic induced depression
opioid system
- opium => poppies (relieves pain + induce euphoria by binding to opiate receptors in brain
- mimic actions of 3 peptide families in brain
1) endorphins
2) enkephalins
3) dynorphins - these peps + several nonopioid peptides [MSH (Melanocyte-stimulating hormone), ACTH (Adrenocorticotropic hormone ), and lipotropin (a hormone secreted by the anterior pituitary gland. It promotes the release of fat reserves from the liver into the bloodstream.)]
- cleaved from protein precursors pro-opiomelanocortin (POMC), proenkephalin, and prodynorphin
3 types of sub-receptors mu, kappa, and delta mediate effects of drugs + peptides
- constipation likely side effect that stool softner may be necessary
