Pain and Opiods Flashcards
codeine
Opioid Agonist
Pro-drug converted to MORPHINE (demethylated)
- IN combination with ACETAMINOPHEN (Tylenol #3)
Liver Enzyme: CYP2D6
- Effectiveness linked to high or slow metabolizer, genetic variability for this enzyme
Has ACTIVE METABOLITE
Phase 1 metabolism
fentanyl
Opioid Agonist
Opioid/narcotic
Mu Opioid Receptor Agonist
Can be used as Patch, for patients who can’t swalow
Perioperative Use
Oral and Sublingual forms
IV: extremely rapid onset
- Same for Epidural, Intrathecal/subarachnoid
Liver Enzyme: CYP3A family
Phase 1 pharmacokinetics
NO ACTIVE METABOLITES
heroin
Opioid Agonist
- Mu Opioid Receptor
Pro-drug converted to Monoacetyl Morphine (deacetylated) and Morphine in the brain
Rapid onset pharmacokinetics (immediate)
More lipophilic than morphine
Has ACTIVE METABOLITES
- M-6-Glucoronide: 10 x more potent than morphine
hydrocodone
Opioid agonist
Mu Receptor
Combination with Acetaminophen
Metabolized to Hydromorphone
- Active METABOLITE (5X more potent than Morphine)
- Hydromorphone-6-glucoronide: less agonist activity than morphine-6-glucoronide
Liver Enzyme: CYP2D6
- Huge variability
Combination with acetaminophen gives pain relief without severe opioid side effects
Rarely use opioids with NSAIDs/Aspirin
Sustained Released Agonist
- Provide pain relief for 12 hour dosing by producing stable plasma levels
hydromorphone
Opioid Agonist
Mu Receptor
More lipid soluble than Morphine, faster onset
More potent: 5X, less dosage for same effect
Glucoronidation:
- Hydromorphone-6-glucoronide: less agonist activity than morphine-6-glucoronide
- hydromorphone-3-glucoronide (inactive metabolite)
Pretty safe in renal failure
Extended sustained release formula, provide relief in 12 hour dosing regimens
Meperidine
Opioid Agonist
Mu Receptor
More lipid soluble than morphine: faster onset
Less potent: 1/10X
Converted by Liver to NOR-MEPERIDINE (CNS stim, convulsions)
Nor-meperidine has a longer half life in patients that have renal failure due to decreased elimination
Use of drug has decreased
Used as serotonin reuptake inhibitor
- Can produce Serotonin Syndrome (excessive synaptic serotonin), when combined with SSRIs or MAOIs
Active Metabolite: Nor-meperidine
morphine
Opioid Agonist
Mu Receptor
Produces Analgesic via Brain
- Mu agonists influence motivatoinal affective component of pain
Neutral pH: 80% charged so only 20% allowed to cross
- Low lipid solubility so slowly crosses the BBB
Clinical duration of action: 4 hrs
Metabolism: Glucoronidation
Excretion: Glucoronide metabolites via kidney
- morphine-6-glucoronide (10x more potent) 5-10% of morphine
- morphine-3-glucoronide (inactive)
Half life: 2 hours
Liver disease little effect on action of morphine (need severe liver disease)
RENAL DISEASE: greatly affects morphine influence
- morphine-6-glucoronide secreted by organic ion transporters,
- Elimination impaired in RENAL DISEASE
If patient receiving morphine goes into renal Failure has dangerous consequences\
Inexpensive, widely used, measure of familiarity (widely studied)
MS Contin/ Morphine SR: continued release for managing cancer pain
Need to adjust from IV to PO form and vice versa because decreased oral bioavailability
Can be administered spinally (intrathecal/subarachnoid/epidural)
Intrathecally: Chronic
Epidural: Acute
Side Effects: Repiratory Depression, N/V, Sedation, Itching
methadone
Opioid Agonist
Mu Receptor
Oral
Ultra Long Acting
t1/2: 15 to 60 hours
Methadone mainteance used for Opioid Drug Addiction
Highly Variable Metabolism
Pain management
Liver Enzyme: CYP3A
oxycodone
Opioid Agonist
Mu Receptor
In combination with acetaminophen (percocet)
Metabolized: CYP2D6
- Genetic variability not clinically significant
Active Metabolite: Oxymorphone
Caused abuse problems: Not widely used as a result
Extended Release formula (Oxycontin) 12 hour dosing by producing stable plasma level
oxymorphone
Opioid Agonist
Mu Receptor
Major metabolite of oxycodone
Metabolized from CYP2D6
Sustained Release Form: OPANA
buprenorphine
Mixed Agonist/antagonist
Partial Mu agonist and Kappa agonist (associated euphoria)
Higher affinity for the mu receptor, difficult to reverse its mu agonist effect
Difficult to provide analgesia if patient has surgery because mu bound more tightly to this drug
Has utility in Drug Addicition and Abuse
Buprenorphine 7 day patch, must remove before surgery and wean off effects
Metabolized by CYP3A
nalbuphine
Agonist for K receptor
Mu receptor partial agonist
Mu antagonist
Used for management of acute, short term pain, not for management of chronic pain
Used for control of itching
Pentazocine
Agonist for K receptor
Mu receptor partial agonist
Mu antagonist
Used for management of acute, short term pain, not for management of chronic pain
tramadol
Partial Agonist
Mu agonist and monoamine reuptake inhibitor activity (contributes to analgesic activity)
Ultracet (tramadol + acetaminophen)
Metabolized by: CYP2D6 and CYP3A4
CYP2D6 produces active metabolite
tapentadol
Partial Mu agonist
Less pharamacogenetic variability compared to tramadol
Metabolized by CYP2C9, CYP2C19, CYP2D6
CYP2D6 produces active metabolite
Greater mu receptor efficacy
Used for mild to moderate acute/chronic pain
