Opioid analgesics and antagonists Flashcards
Difference between opiate and opioid?
OPIATE – active alkaloids naturally found in opium (Morphine / Codeine)
OPIOID - anything like morphine (opiate, partial/total synthetic)
Where does opium grow in the wild?
poppy plant. Morphine (12%)
o Codeine
semisynthetic opioids
oxycodone, hydromorphone
Fully synthetic opioids
fentanyl, methadone, loperamide
Non Opioid agonists
tramadol
3 types of opioid receptors: (and type)
o μ (mu) (“MOR”)
o δ (delta) (“DOR”)
o κ (kappa) (“KOR”)
GPCRs (Gi or Go)
Which receptor is used in pain meds?
MU
What type of **orphin goes with each type of receptor
mu = endorphins delta = enkaphalins kappa = dynorphins
how do opioids work?
2 Pathways?
bind on presynaptic terminal and interfere with Ca2+ release
Gi-> decrease cAMP-> decrease PKA -> less active Ca channels
Go->increased free betaGamma subunits-> increased K (more common in the post synaptic side)
Central effects of opioids
inhibitions in the periaquaductal gray matter, and in the dorsal horn,
What drug activates kappa receptors as a side effect
morphine
Buprinorphin receptors
Mu activator, kappa and delta ANTAGONIST
Methadone non-opiod receptors
NMDA
Tramadol effects on nonopioid receptors
reduce 5HT (seratonin) uptake
Why are high doses necessary?
because there is a high first pass metabolism
what breaks down parent opioid drugs?
Liver breaks em down, kidney filters metabolites out
Major effects of μ receptor agonists
CNS: analgesia, drowsiness CV: Vasodialation GI: decrease motility/ secretions Gu/Gyn: less pee ( more ADH) Skin: Flushed and warm Immune: altered wbc production
Anti-dyspneic
opiods can be used to help make breathing easier
Morphine: Mechanism and clinical use in analgesia
Full mu agonist (weak kappa agonist)
- Chronic (non-neuropathic pain)
- best for acute trauma and cancer tx pain
Morphine metabolism
low bioavailability
two metabolites morphine6 = potent analgesic and morphine3 interferes with GABA
Adverse effects of morphine
sedation, nausea, constipation, respiratory depression, siezure, dry mouth, urinary retention
Morphine: Precautions and contraindications
GI bugs = may worse due to less motility
Hepatic impairment
Renal Impairment
Respiratory disease or head injury
Codeine mechanism , clinical use, adverse effects, and adverse effects
weak mu agonist
used for analgesia, cough, antiDiarrheal
Adverse = nausea, vomiting , pruritus
metabolism = creates lots of morphine in high metabolizers and not helpful in weak metabolizers
Oxycodone mechanism , clinical use, adverse effects, and adverse effects
weak MU agonist with STRONG metabolite oxymorphone MU agonist
used for analgesia,
Adverse - creates lots of analgesia in high metabolizers and not helpful in weak metabolizers
CYP2D6
Oxycodone
Percocet?
oxycodone plus acetominophen
people with renal and liver disease should get what opiod? why?
Hydromorphone (no active metabolites), Fentanyl, or methadone
Heroin
crosses blood brain barrier rapidly and turns quickly into morphine
Fentanyl safety advantage?
no histamine release and no active metabolites
which drug is bad for dyspnea
hydromorphone
Loperamide has what effect on the CNS? What is it used for?
No effect on the CNS
used to treat diarrhea (could cause gi pain)
Tramadol: mechanism of action 6
MOR agonist (but weak) o Serotonin releasing agent o Norepinephrine reuptake inhibitor o NMDA receptor antagonist o Nicotinic receptor antagonist o M1 and M3 muscarinic acetylcholine receptor antagonist
Adverse effects of tramadol
Nausea/vomiting, sweating, sexual dysfunction, lower seizure
threshold
how is tramadol different than other opiods
NO respiratory depression, sedation,
drowsiness and constipation are less common
what are the low efficacy opioids
codeine
what are the moderate efficacy opioids
oxycodone, tramadol, buprenorphine
What effects never develop tolerance?
sedation/resp. depression constipation Miosis (pupil constriction)
two steps in changing drugs
1 Calculate the equianalgesic dose
2 Adjust the dose for incomplete cross-tolerance by cutting by 50%
Sched 1 drugs
Drugs with no currently accepted medical use in US
HEROINE, LSD, MARY J
Sched 2 drugs
Drugs with a high potential for abuse which may lead to severe psychological or physical dependence
MORPHINE, HYDROMORPHONE, METHADONE, OXY
What pathway is involved in addiction? what is the result
Mesolimbic (REWARD) Pathway
Increased dopaminergic neurotransmission
How do opiods make you feel so good?
They inhibit GABA (which inhibits dopminergic neurons)
How long before you can call a drug problem a opiod use disorder
12 months
Factors affecting probability of addiction
Personal or family history of substance use disorder
Male
Poor social support
History of conviction related to drugs or DWI
Pre-adolescent history of sexual abuse
Comorbid psychiatric disorder
Where did the video stop?
1:49:50
How does methadone work/ mechanism?
Full MU receptor agonist
NMDA glutamate receptor
Great for chronic pain
Help for detox
Delivery of methadone
tablet, liquid, IV
Methadone Pharmacokinetics
varies greatly based on genetics Metabolized by p450 enzymes CYP3A4 in particular LONG LONG HALF LIFE (can persist in liver) renal and fecal excretion
adverse effects due to NMDA agonist?
Confusion
Hallucinations/Paranoia
Depression/Apathy and Suicidal Ideation
Anorexia
Methadone cardiac adverse rxns
Prolonged QTc
Cardiac arrhythmias
Seizures
Which drug has an NMDA agonist ?
methadone
What criteria make someone eligible for methadone? 3
> = 18 yrs
dependent on opioids > 1 year
Enrolled in methadone maintenance program
1 year requirement can be waived for pregnant patients, previously treated patients, or following prison release.
Buprenorphine mechanism
partial agonist (so it is hard to overdose)
Urine drug screening for Opioids
False positives for poppy seeds, rifampin, quinolones
detects morphine, heroin, codeine, methadone
best for identifying chronic users
bUPRENORPHINE delivery
sublingual because of low bioavailability
What is another name of hydromorphone
Dilauted
Nalaxone
opioid antagonist -> will cause withdrawal
reverses opioid depression
short half-life (need to readminister)
Suboxone:
Naloxone + Buprenorphine
decreases likelyhood of abuse
Naltrexone
opioid antagonist ->
may decrease alcohol craving as well
Precipitates severe withdrawal
half life of Naltrexone
Half-life
4 hrs (oral naltrexone)
13 hrs (metabolite of oral naltrexone)
5-10 days (IM Vivitrol)
Naltrexone: Adverse Effects
Adverse effects:
Nausea, headache, anxiety
More rare side effects: Deep vein thrombosis, hepatitis, eosinophilic pneumonia, Depression, suicidal thinking
Who should not get Naltrexone
those with liver failure
