Pain Opioids 3 Flashcards
How does hydromorphone compare to morphine regarding
- lipid solubility
- Onset of action
- Potency
More lipid soluble
Faster onset
5X more potent
What are the 2 metabolites of hydromorphone? How does the active metabolite compare to morphine-6-glucuronide
Hydromorphone-6-glucuronide
Hydromorphone-3-glucuronide
Hydromorphone-6-glucuronide less active at receptor than morphine-6-glucuronide
What is the product of hydrocodone metabolism? What is the enzyme responsible?
Hydromorphone
CYP2D6
When hydrocodone is combined with acetamenophen, you get _ (2)
Vicodin
Lortab
What is oxycodone metabolized to? What us the enzyme responsible?
Oxymorphone
CYP2D6
How is codeine related to morphine? What enzyme metabolizes codeine?
It is a prodrug that is demethylated to yield morphine
CYP2D6
How is heroin related to morphine? What property makes it a drug of abuse?
It is converted to monoacetyl morphine, then into morphine in the brain
Euphoria, Lipid soluble, fast onset
How is methadone administered? What makes it unique? What is it used for (2)?
Orally
Ultra long lasting (half life or 15-60 hrs)
Opioid addiction, pain management
How does meperidine compare to morphine with regards to:
- Lipid solubility
- Potency
More lipid soluble
1/10 X potency
What is the metabolic product of meperidine? Where does this occur? What are 2 potential side effects of this metabolite?
nor-meperidine
Liver
CNS stimulation, convulsions
What patient subpopulation may be at risk for serious meperidine side effects?
Patients with renal failure, not cleared as needed
What are the components of the serotonin syndrome triad?
Neuromuscular hyperactivity
Autonomic hyperactivity
Altered mental status
What mu opioid agonist is associated with serotonin syndrome? This is especially true when combined with _ (2)
Meperidine
SSRIs or MAOs
What is the activity of tramadol at the mu receptor? What other receptor does it function at?
Partial agonist
Inhibitor of the monoamine reuptake inhibitor
What is ultracet? What enzymes metabolize tramadol / ultracet? Which gives its active metabolite?
Utracet = Tramadol + acetamenophen
CYP2D6 and CYP3A4
CYP2D6
What is tapentadol? What enzyme metabolizes it? What advantage does it have over tramadol?
Partial mu agonist and inhibitor of the monoamine reuptake inhibitor
CYP2C9 and CYP2C19
Less pharmacogenetic variability
What is the receptor activity profile for pentazocine, butorphanol and nalbuphine? What are these drugs used for (2)?
Kappa agonists, mu partial agonists or antagonists
Acute short term pain and to manage side effects
What is the receptor activity profile for buprenorphine? How does its affinity for the mu receptor affect its clinical use? What can it be used for?
- Partial mu agonist, full kappa agonist
- Very high affinity at mu receptor, hard to displace, therefore hard to provide analgesia for surgical patients
- Drug abuse and addiction
Regarding pharmacokinetics, where are majority of phase 1 enzymes found? (2)
Gut
Liver
How can a clinician account for the variability of opioid activity from patient to patient?
Titrate to effect
What are 2 mu agonists that can be used to treat diarrhea? What are their unique properties?
Diphenoxylate
Loperamine
Poorly / Not absorbed
What are the 4 examples of opioid antagonists provided?
Naloxone
Naltrexone
Almivopan
Methylnaltrexone
How do naloxone and naltrexone compare regarding duration of action and administration?
Naloxone is administered IV , naltrexone is oral
Naltrexone is also very long lasting
A poorly absorbed orally active opioid antagonist that antagonizes the GI side effects of opioids. This describes _
Almivopan
Quaternary ammonium derivative that is positively charged. IV peripherally restricted opioid antagonist for
constipation. This describes _
Methylnaltrexone
2 opioid formulations designed to provide pain relief by be resistant to abuse is _
ER morphine with sequestered naloxone
Oxycodone-naloxone
A prodrug for oxymorphone is _. The enzyme responsible for metabolism is _
Oxycodone
CYP2D6
Why is acetaminophen, and not NSAIDs, combined with opioids?
Acetaminophen safer than NSAIDs, less side effects, therefore patient can use more of drug without problems. If patient stops an opioid combined with NSAIDs, can get withdrawal
CYP2D6 is involved in the metabolism of a lot of opioids. What is a drug where its pharmacogenomic variability is actually clinically significant?
Dosing of codeine
What is an advantage of the fentanyl patch? What is an advantage of oral fentanyl? Another use for fentanyl beyond pain relief is _
- Hard to abuse patch
- Rapid onset and potent orally
- Sedation
What are 3 plausible explanations for variable responses to opioids between patients?
Mu receptor polymorphisms
Drug metabolisms differences
Increased drug efflux from tissues
** All related to pharamcogenetics **
