Opioid analgesics Flashcards
Difference between analgesia and anesthesia
Analgesia - Block pain transmission
Anesthesia - Block sensory neurotransmission
What does qd mean?
Once daily
What does bid mean?
Twice a day
What does Q12 mean?
Every 12 hours
What does tid mean?
three times each day
The _____ in the brain assigns aversive or pleasurable qualities to pain
Nucleus Accumbens
The ____ in the brain is involved in fear/pain expectation
amygdala
Name the key brain regions expressing opioid receptors
Periaqueductal Gray
Rostral ventral medulla
Dorsal Root Ganglion/Dorsal Horn
Opium contains two types of alkaloids, name them.
Phenanthrenes
Benzylisoquinolines
Phenanthrene opoids primarily show differences at
3 and 6 positions
Phenanthrene partial antagonism is conferred by….
bulky side groups
Significance of knowing which drugs are Phenanthrene and which are non-Phenanthrene?
Some patients respond better to one type than the other, so in patients struggling with pain or side effects of one, the other may help a lot.
Three examples of Phenanthrenes
Morphine
Hydrocodone
Buprenorphine
Four examples of non-Phenanthrene
Tramadol
Meperidin
Fentanyl
Methadone
Name a Phenanthrene antagonist
Naloxone
How are Phenanthrene opioids metabolized
Glucorinidation at the 3, 6 position
With morphine-6-glucoronide, the metab. is still active
Which organ(s) runs opioid metabolism
Metab. is largely hepatic, impaired with liver disease
Metabolites are excreted through the kidneys
Name the different types of Opioid receptors
G Protein Coupled (Family A/Gio coupled) Mu Kappa Delta Nociceptin, orphanin FQ receptor
Natural agonists of mu opioid receptors
Beta endorphins (endogenous morphine)
Why target mu opioid receptors therapeutically
Analgesia (NOT for sharp localized, neuropathic pain)
Sedation
Antitussive (suppresses the cough reflex)
Important sid effects of mu opioid drugs
Resp. Depression Constipation, Pruritis Tolerance/Dependence Urinary Retention Nausea/Vom Muscle Rigidity Miosis
Significance of the kappa opioid receptor
Involved in negative feedback loop, inhibiting the release of dopamine. The first dopamine causes dynorphin transcription. Its release activated presynaptic kappa receptors on dopaminergic terminals, inhibiting further release
Name the endogenous kappa agonist
Dynorphin
Delta opioid receptors are being considered for treatment of…
Anxiety, Depression, OH Abuse
Ischemic Damage
Why are delta opioid so interesting in the context of chronic pain?
They are upregulated with chronic stimulation
Natural ligand for delta opioid receptor?
Enkephalins (preproenkephalin)
Why do we care about the orphanin opoid receptor like subtype 1
Debate on activity, opposes classic mu effects and mediates pain
Describe the molecular signalling of opioids
opioid binds to GPCR. They’re all Gi/o coupled, which causes them to inhibit ACyc, and thus decrease cAMP. They also turn on GIRK, causing hyperpolarization and inhibiting NT release.
Presynaptic inhibition of neurotransmitter release is mediated by…
Inhibition of calcium uptake
Postsynaptic inhibition of pain transmission is medicated by…
hyperpolarization through GIRK channels
Which two opioids are typically used in surgical mu analgesia
Fentanyl
Sufentanil
Remifentanyl
Which opioid can be used via IV, Patch, or Lollipop
Fentanyl
Other name for hydromorphone
Dilaudid
Why is morphine most common
Covered by medicare
Other names for hydrocodone
Lortab
Vicodin
Norco
Other names for oxycodone
Oxycontin, Percocet
Name as many clinically used opioids as you can
Sufentanil, Remifentanyl, Fentanyl Morphine, Hydromorphone Codeine, Hydrocodone, Oxycodone Meperidine, Methadone Tramadol, Loperamide, Propoxyphene
Other name for meperidine
Demerol
Other name for tramadol
Ultram
Negative effect of methadone
Prolonged QT
Meperidine is used to treat…
Problems with meperidine?
Rigors Its metabolite (normeperidine) is neurotoxic (tremors, twitches, seizures)
Loperamide is used for…
diarrhea
How do Tramadol and Tapentadol work?
Mild opioid analgesic
SNRI properties
Help with management of mild neuroathic pain
Which patients is Meperidine especially dangerous in?
Patients with decreased renal function
Important details for Methadone
Primarily used for opioid dependence
It has a long duration of action/half life (15-60 hrs)
NMDA antagonist to help Chronic pain treatment
Important details on Levorphanol
Long half life (16 hr)
NMDA antagonist for neuropathic pain
Two receptors upregulated by chronic pain
AMPA, NDMA
Which opioids are known for NMDA action
Methadone and Levorphanol
Which drug is a partial mu agonist
Buprenorphine
Which drugs are mu antagonists
Naloxone (Narcan)
Naltrexone
When to use Buprenorphine
Used to treat opioid withdrawl in addiction therapy
Combined with naloxone for maintenence therapy
Which opioids are used for postop, epidural. Why?
Hydromorphone, Morphine
4-5X the half life of fentanyl
Which opioids are used for pain maangement. Why?
Oxycodone, Hydrocodone, Oxycontin, Zohydro
Oral bioavailability, longer halflife
Which opioid is used for terminal cancer pain? Why?
Morphine
Cost, History of Knowledge, No worries about dependence
Which opioid is used for patients with a history of trouble tolerating opioids?
Meperidine (Demerol)
