Narcotic Analgesics Flashcards

Morphine
Terms Definitions
NSAID
aspirin; musculoskeletal pain; inhibition of PG synthesis; both antiinflammatory and antipyretic; central or peripheral action; no tolerance or dependence.
Morphinans
similar structure to morphine- levorphanol- L isomer- 4-5x more potent than morphine and effective orally-dextomorphan- D isomer- not analgesic but good anti-tussive effects
The following describes this specific analgesic:-use for postoperative pain, severe pain-injection routes main use-oral bioavailability can be erratic-good choice for patient-controlled analgesia
Morphine
LAAM
analgesic and used instead of methadone in treating heroin addicts
Partial mu agonist
Buprenorphine(ceiling effect due to partial agonist properties)
what characterizes narcotic OD?
miosis, hypotension, bradycardia, cardiac arrest, hypothermia, oliguria, pulmonary edema, severe respiratory depression, coma
what opioid receptors does buprenorphine interact with?
partial mu agonist
-chronic pain
usually oral- first pass effect; rectally, spinally, or IV once can't swallow anymore; slow release forms like ms-contin; diarrhea; acute pulmonary edema
Phenylpiperidine derivatives1. meperidine
aka Demerol; less potent; normeperidine is toxic metabolite that lowers CNS seizure threshold; interactions with MAOI's and TCA's, etc; short duration of withdrawal
Morphine
well absorbed by many routes; large first pass effect; large BBB effect; met in liver--glucuronidated and some sulfation; active metabolites excreted in urine; 3 and 6 C's; also demethylation.
Moderate and Low Efficacy opiates for analgesia
OxycodoneHydrocodoneCodeine, DihydrocodeinePropoxyphene
Treat opiate overdose with:
Naloxone-opiate antagonist that is very lipophilic (fast onset) and short acting-breathing restored in minutes
what hypersensitivity ADRs are associated w/narcotics?
urticaria (possibly hemorrhagic), pruritis, wheal/flare at injection site, sneezing, and edema
what characterizes fentanyl?
this phenylpiperidine has the same pharmacological profile as morphine, but is 100x more potent. it has significantly greater lipid solubility as well - shorter acting: 30-60 min (extended action available as a skin patch). 22% of pts will develop pruritus.
what characterizes methadone?
this phenylheptane has good PO absorption and limited biotransformation. t1/2 in most pts: 15 hrs. t1/2 in narcotic addicts: 24 hrs (increased plasma proteins; albumin & globulins). *danger: duration of respir. depression > duration of analgesia.
what is the benzomorphan agonist-antagonist?
pentazocine (prevents complete activation of the receptor)
3. diphenoxylate and loperamide
GI drugs to treat diarrhea
Name three very lipophilic (and hence rapid onset of action) Opiate ANTAGONISTS.
Naloxone, Naltrexone, MethylnaltrexoneNaloxone: useful for overdoseNaltrexone: alcohol treatment, maintain detoxificationMethylnaltrexone Alvimopan: peripherally active mu antagonists, useful to counteract constipating effect of analgesic opioids
what is pentazocine (benzomorphan agonist-antagonist)?
originally developed as a 'non-addictive' opioid but both psychological and physical dependence can develop. adverse psychological reactions: nightmares/hallucinations can occur, esp in hepatic/renal pts. this has more recently been combined w/naloxone which doesn't reduce analgesia PO - but will if injected (then may cause withdrawal rxn - similar to buprenorphine combination).
what are the 2 types of morphinans?
agonist: levorphanol, agonist-antagonist: butorphanol
what opioid receptors does butorphanol interact with?
mu: antagonist, kappa: agonist
what CV ADRs are associated w/narcotics?
bradycardia, hypotension, flushing, syncope, phelbitis
mechanism of action
bind to and activate opiod receptors; alter the perception of pain; inhibit synaptic transmission (presynaptically); affect intracellular transduction (inhibit cAMP production and block Ca++ channels).
Treatment for opiate withdrawal
Clonidine (alpha 2 agonist - to decrease NE hyperactivity)-mu receptor activity normally inhibits NE neurons (NE hyperactivity causes withdrawal symptoms)-alpha 2 agonist targets autoreceptors on NE neurons to decrease NE release
what generally characterizes the narcotic agonist-antagonists?
these activate the kappa receptors, have antagonistic activity at mu receptors, less respiratory depression than w/pure narcotic agonists (mu), and can precipitate withdrawal in pts mu-opioid agonists.
what characterizes biotransformation of morphine?
there is significant first pass effect, morphine is biotransformed into glucuronides, one of which is: morphine-6-glucuronide (m-6-g) which has a high affinity for the mu receptor, analgetic activity, higher potency than morphine, is highly polar and has CSF levels after chronic administration higher than a single dose (does not readily exit blood). m-3-g is the other metabolite which may cause seizures w/high dose morphine (200 mg/hr IV)
what characterizes the emesis effect of opioids?
narcotics increase sensitivity to motion
what are the IM/PO equianalgesic doses for morphine, codeine, heroin, hydromorphone, levorphanol, meperidine, methadone, and oxycodone?
hydromorphone (IM/PO: 1.5/7.5), levorphanol (2/4), heroin (5/60), methadone (10/20), morphine (10/60), oxycodone (15/30), meperidine (75/300), codeine (130/200), hydrocodone (--/30)
what defines a "narcotic" (opioids)?
requirements: ring structure, a carbon chain connected to it, an oxygen, and a nitrogen.
peripheral actions of opiods
GI effects- enteric NS in gut- decreased secretion, increased muscle tone--constipation; morphine constricts sphincter of Oddi in gallbladder; urinary retention; prolongs labor; little effect on CV system (alkaloid character causes some hypotension b/c mast cells release histamine); immunosuppression
what is the primary action at the opioid receptor subtype sigma?
dysphoria, hallucinations, cardiac stimulation
therapeutic use of morphine-acute
very severe pain; post op; MI pain; sickle cell vaso-occlusive crisis
what are other reported effects of naltrexone?
dysphoria, anorexia, and wt loss (during chronic use)
what are the reported effects of naltrexone on alcoholics?
fewer drinks per day, alcoholic beverages tasted less pleasant, experienced less of a 'high' from alcohol, improved compliance, reduced relapse, lower dropout rate, longer time to relapse, more successful in coping with relapse when it occurred
what may explain the difference in potency ration between acute and chronic morphine administrations?
accumulation of m-6-g. therefore acute PO doses are usually 60 mg and chronic doses are 20-30 mg.
how should switching between opioid in a chronic pt be handled?
calculate dose based on acute potency difference, then reduce dose and make upward dosage adjustments as needed. this is b/c cross-tolerance is incomplete.
what is the aminotetralin agonist-antagonist?
dezocine
-poor choice as analgesic because kappa effects are dysphoric-useful for addicts
Pentazocine
High efficacy, Lipophilic opiates for Analgesia, Pre-anesthetic medication (ultrashort duration of action)
Fentanyl (IV)SufentanilAlfentanilRemifentanil
what are the phenylheptanes?
levomethadyl, methadone and propoxyphene (off market)
what is naltrexone?
similar to naloxone (oxymorphone derivative) which is used in narcotic addiction tx. it is longer acting than naloxone and dose dependent.
2. propoxyphene
les efficacious than morphine; rough analgesic effect
morphine toxicity
coma; pinpoint pupils (may dilate some b/c of CO2); depressed respirationGIVE NALOXENE to diagnose if heroin overdose or barbiturates
morphine derivatives...1. hydromorphone
2-4x more effective; orally effective; aka dilautid
The following describes these 2 specific analgesics:-higher efficacy than codeine-combination w acetaminophen permits lower dose of both-used as sustained release: have become a popular drug of abuse
Oxycodone, hydrocodone(semisynthetic narcotics)- oxycodone somewhat more efficacious of the two
Name 3 opiates used for treating diarrhea
LoperamideDephenoxylateAcetorphan (Racecadotril)(use drugs that do not cross bbb)-Loperamide is better than morphine, doesn't get into brainDephenoxylate and its metabolite difenoxin: have some CNS activity, marketed in combi w atropineAcetorphan (Racecadotril): prodrug for enkephalinase inhibitor Thiorphan- useful mainly in infants
what other ADRs are associated w/narcotics?
sweating and porphyria
what are the agonist phenanthrenes?
*naturally-occurring opium alkaloids: codeine, morphine. *semisynthetic derivatives of morphine: hydromorphone, oxymorphone. *semisynthetic derivatives of codeine: hydrocodone, oxycodone.
what characterizes tramadol?
this centrally-acting analgesic is a synthetic codeine analog w/less affinity for opioid receptors. it is a mu receptor agonist and 5-HT uptake inhibitor - providing analgesia equal to codeine but less than acetaminophen. it has reduced chance for abuse/respiratory depression than other opiate agonists and is only partially reversed by naloxone.
what characterizes levomethadyl?
this phenylheptane is a long-acting methadone derivative w/a t1/2 of 48-72 hrs. it is only FDA-approved for addiction tx and maintenance doses are given 3x/week.
endogenous opiods
1. enkephalins- target delta and mu2. beta endorphin- target delta and epsilon3. dynorphins- target kappa4. endomorphin- activated by endomorphins*no current therapeutic use for opiod peptides
Diphenylheptane derivatives1. methadone
effective orally; long half life active metabolite; more bioavailable; cheap; avoid stigma!
Opiods
morphine; any type of pain, esp dull and continuous; stimulate opiod receptors; no antiinflammatory or antipyretic effects; central site of action; develop tolerance and dependence
treatment of narcotic addiction
1. substitute another narcotic (methadone)2. detox3. narcotic antagonists (naloxene and naltexone)4. clonidine (not an opiod, but cuts down on withdrawal symptoms)
High efficacy opiates for Analgesia
Methadone (V long- 24h)Hydromorphone (Medium to Long)Morphine (Medium)Levophanol (Medium)Meperidine (Short; poor choice due to side effects)
what is nalmefene?
a naltrexone derivative, only IV and has a longer t1/2: 8-10 hours.
what is heroin?
di-acetyl-morphine - made by the Bayer company in the late 1800s to develop a better analgesic - good drug, rapidly deacetylated & crosses BBB. if a drug test is done on this patient, won’t find heroin, but will find mono-acetylated morphine or morphine itself.
what characterizes morphine?
this phenanthrene is the most widely used narcotic, taken orally or by pump often for CA pain.
side effects of morphine treatment
respiratory depression; nausea and vomiting; constipation; dizziness and mental clouding; dysphoria; hypotention; urinary retention; tolerance and physical dependence; interaction with other drugs; additive with other CNS depressants; enhanced action via antidepressants, amphetamines, antihistamines, etc;
Via what mechanisms do opiates treat Diarrhea?
-antisecretory (increase water reabsorption)-decrease motility via constriction of circular muscle
what are contraindications for naltrexone?
pts recieving or physically dependent upon opioids, pts in withdrawal, pts w/a positive opioid urine test, and acute hepatitis/liver failure.
what CNS ADRs are associated w/narcotics?
h/a, nausea, dizziness, sedation, disorientation, delirium, incoordination, transient hallucinations, agitation, tremor, seizures, and euphoria/dysphoria
what are other uses for opioids?
relief of non-productive cough (codeine), relief of severe diarrhea, immediate (short term) relief of dyspnea associated w/pulmonary edema and left ventricular failure (decreases workload), and improved respiration in pts on mechanical ventilators (pts less likely to fight).
what is opiophobia?
this is due to fear of addiction, decreased cognition (less able to prepare for death), and decreased suffering (less spiritual growth). this leads to more restrictive narcotic regulations and less use of narcotics.
what are the endorphins?
beta-endorphin, a 31 AA peptide (split from a larger peptide which also yields ACTH) which is found primarily in the pituitary and binds predominantly on mu/delta sites. precursor: propiomelanocortin. beta-endorphin produces various behavioral and physiological responses to pain.
what narcotic ADRs do pts develop tolerance to?
n/v, sedation, respiratory depression
opiods with mixed agonist and antagonist activities
pentazocine--causes increase in bp and heart rate**; component of "Ts and blues"nalbuphine--less respiratory depressionbuprenorphine--now treats heroin addiction b/c longer retraction of withdrawal symptoms, safe, and more potentnalorphine--not used muchbutorhanol--nasal spray for migraine
what is nalbuphine (agonist-antagonist phenanthrene)?
similar to butorphanol in regard to lack of parallelism between analgetic dose and degree of respiratory depression.
what characterizes the endocrine effects of opioids?
pts receiving daily opioid therapy for > 1 a month may undergo reductions in cortisol, sex hormones & DHEA.
2. fentanyl, sufentanyl, and alfentanyl
much more potent and very lipophilic; fast onset and short duration; effective; maintenance of anesthesia and post op analgesia; fentanyl can cause muscle rigidity in high doses (chest); patch form is slow release and good for chronic pain or radiation patients.
what ADRs are associated w/naltrexone?
hepatoxicity (esp at doses of 300 mg+, narrow therapeutic index), confusion, and hallucinations
what characterizes the CV effect of opioids?
hypotension. directly: depression of vasomotor center. indirectly: histamine release (peripheral vasodilation - mostly w/morphine).
Use this narcotic for cough (name 2)
Codeine-do not use chronically or in the presence of cough of unknown etiologyDextromethorphan-available OTC-weak agonist but may not act through opiate receptors but via unique mechanism
what characterizes the respiratory depression effect of opioids?
this is the primary cause of death in OD, but therapeutic doses should have a minimal effect on respiration.
what are the uses for methadone?
CA pain tx: only in compliant pts who will not deviate from dosage (should have shorter acting rescue opioid for episodic or breakthrough pain). narcotic addiction tx: PO efficacy decreases focus on injection process and long t1/2 decreases need for frequent dosing. mechanism for addiction tx: >18 y/o, >2 years of addiction, failed other modalities, and volunteer.
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