Opioids & Antagonists Flashcards
(22 cards)
Opioids - Clinical Uses
• Analgesia
• Acute pulmonary edema
- Relieves dypsnea, mechanism not clear
• Relief of cough
- Codeine and dextromethorphan
•Treatment of diarrhea
- Loperamide (Imodium), diphenoxylate/atropine
(Lomotil)
• Anesthesia
- General- adjunct to control pain
- Spinal- epidural with local anesthetics•Direct access
to dorsal horn decreases some side effects-
but itching worse
Opioids - Drug Interactions
• Sedative hypnotics
- Increased CNS and respiratory depression
• Antipsychotics
- Sedation, maybe respiratory depression
• MAO Inhibitors
- Meperidine, dextromethorphan
- May inhibit serotonin reuptake to some degree
- BUT- best to avoid ALL opioids with MAOIs
• CYP2D6 inhibitors
- Inhibit metabolism of codeine, oxycodone,
hydrocodone to active compounds
• Fluoxetine, paroxetinethe worst for inhibition
Opioids - Contraindications
• Use of partial agonist with full agonist
- Can impair analgesia, cause withdrawal
• Patients with head injuries
- Increase in intracranial pressure
• Pregnancy
- Especially at delivery
• Impaired pulmonary function
• Impaired hepatic or renal function
• Some endocrine diseasesOpioids - Precautions
- Severe liver/kidney disease
- Pulmonary disease
- Biliary tract problems
- Seizures (especially meperidine)
- Pain of unknown cause (esp abdominal)
- Head trauma
- Chronic non-terminal pain?
- Inflammatory bowel disease
- Pregnancy/breast feeding
- Urinary retention/BPH
Heroin
- Schedule 1 drug
- Cannot be legally prescribed in US
- Very potent
- Gets into the brain well
- Can be injected, snorted or smoked
- Commonly abused - produces euphoria
Morphine - MoA
- Stimulates all opioid receptors
- Strong agonist
- Produces all of the effects of opioids
Morphine - Uses
Useful in severe pain
Morphine - Pharmacokinetics
• Can be administered orally, parenterally, rectally,
intrathecally, epidurally
• More effective when injected than oral due to high
first-pass metabolism (~75%)
• Fairly short half-life
• Extended release long-acting oral preparation used in
chronic/terminal pain
• Rapid onset after parenteral administration; maximal
analgesic action within one hour of injection.
• Duration of analgesia is approximately 4-6 hours.
• t½ = 2-3 hours: may be longer in elderly patients.
• Excretion - 90% in the urine primarily as metabolites
in 24 hours. 7-10% in the feces.
• Metabolized in liver by CYP2D6
• Conjugated to glucuronide compounds
• Morphine-6-glucuronide is a very potent analgesic
• Morphine-3-glucuronide (major metabolite) may
cause adverse effects if it accumulates
Morphine - Side Effects
• May cause itching or vomiting when injected
Hydromorphone (Dilaudid)
• Very strong analgesic, more potent than morphine
• Very effective for moderate to severe pain
• Metabolites don’t accumulate, so good if there is
renal dysfunction
• Less likely to cause histamine release and itching
than morphine
- Oral, sc, IV, rectal, IM administration
- Similar duration of action as morphine
Methadone (Dolophine)
• Long half life and duration of action
• Stimulates mu receptors
• May also block NMDA receptors and inhibit NE/5-HT
reuptake
• Traditionally used for maintenance treatment of
addicts
• Low doses used to prevent withdrawal symptoms
• Withdrawal thought to be milder, but very prolonged
• Now commonly used in long-term control of pain
• Effective in hard-to -treat types of pain
Meperidine (Demerol)
• Mu agonist
• Can cause euphoria
• Should not be used for more than 48 hours, in high
doses, or in renal failure due to accumulation of
metabolite, normeperidine
• Normeperidine can cause seizures
• Anticholinergic - tachycardia, pupil dilation
• No cough suppression
• Obstetrics - less respiratory depression in baby
• Less constipation/urinary retention than morphine
• Nausea/vomiting may be less, or worse, than morphine
• Also inhibits NE/5-HT reuptake-serotonin syndrome with MAOIs!!
Fentanyl (Sublimaze)
• Very lipid soluble and highly potent
• Short duration of action and half-life
• High abuse potential!
• Very commonly used in short surgical procedures,
often with midazolam
• Popular in longer surgeries because of good
cardiovascular profile
• May cause truncal rigidity if given rapidly IV
• Available in transdermal patches or lollipops
• Metabolized by CYP3A4 - drug interactions likely
• Alfentanil, sulfentanil, remifantanil similar, with shorter
half-lives, durations of action
Hydrocodone
• Used for moderate to severe pain
• Often combined with acetaminophen
• Generally given orally, well absorbed
• Fairly short half-life, duration of action
• Conversion by CYP2D6 needed for some of the
analgesic effect
- therefore doesn’t work as well in some patients on
SSRIs, esp. fluoxetine and paroxetine
• Schedule II
Oxycodone (Oxycontin)
• Moderate to severe pain
• Often given orally, may be extended release
(Oxycontin)
• Often combined with acetaminophen (Percoset) or
aspirin (Percodan)
• Metabolism by CYP2D6 increases analgesic
effectiveness
• Half life/action about 4 hours unless extended release
• Schedule II, often abused
• Delivery forms modified to decrease abuse potential
• Naloxone or naltrexone added to prevent effect if
injected
• Oxymorphone is similar to oxycodone, also Schedule
II
Codeine
• Good cough suppressant-doses lower than for
analgesia
• Mild-to -moderate pain
• Must be metabolized by CYP2D6 to be active
• Converted to morphine
• Generally given orally, usually combined with
acetaminophen or aspirin
• Some abuse potential
• Shouldn’t be used in small children
- Schedule II- if alone
- III-if less than 90 mg combined with acetaminophen
or aspirin
- V- when less than 2 mg/ ml in cough suppressants
Pentazocine/naloxone (TalwinNX)
• Kappa receptor agonist
• Mu receptor partial agonist
• Moderate pain, oral (w/naloxone) or injected
• May be less sedating that other opioids
• May have less respiratory depression, GI effects than
other opioids (all of these mediated by mu)
• May cause dysphoria (kappa)
• May cause withdrawal in patients dependent on
opioids-partial mu agonist!
• Low abuse potential-Schedule IV
Buprenorphine (Buprenex; Suboxone)
• Partial agonist on mu and maybe on kappa
• Ceiling to the effect- doesn’t cause much euphoria
• Low abuse potential
• Now used for maintenance treatment of opioid addiction-decreases craving for drug
• Can be injected, sublingual or intranasal
• Combined with naloxone
- naloxone not absorbed sublingually, buprenorphine is - if somehow manage to release drug and inject the
combination, naloxone blocks effect of buprenorphine
Tramadol
• Mild to moderate pain; Weak mu agonist
• Inhibits NE/5-HT reuptake, contributes to analgesic
effect
• Side effects generally mild
- dizziness, sedation, constipation, nausea
• Combination with antidepressants: seizures
• Combination with MAOIs, TCAs, SSRIs: may cause
serotonin syndrome!
• Schedule IV
• Tapentadol similar, schedule II
Dextromethorphan
• Not an analgesic-cough suppressant
• Frequently combined with guafenisen (expectorant)
• Not likely to cause constipation
• Blocks NMDA receptors-abuse potential
• Decreases 5-HT reuptake: serotonin syndrome with
MAOIs
• Has become a drug of abuse in teenagers
• Over the counter- cough syrup, tablet/ Internet
concentrated form without Rx
• Has caused some deaths in teenagers (robotripping)
Naloxone (Narcan)
• Drug of choice for opioid overdose
• Can reverse respiratory depression, consciousness,
awareness of pain, miosis, constipation
• Must be injected! Give until pupils dilate
• Short duration of action (2 hours)
• Repeated dosing may be required
• Now being combined with agonists to prevent abuse-
the drug works when oral, not if injected
• Sometimes low doses used to prevent adverse effects
of injected agonists, but still allow analgesia
• Auto-injector now available for high risk situations
Naltrexone (ReVia)
• Effective orally, and long acting (24 hours)
• Used in treatment of opioid addicts, especially health
care professionals
• Long acting preparation injected to treat addiction, but
results may be better with buprenorphine/naloxone
• Will precipitate withdrawal in patient dependent
opioids!
• Decreases craving in recovering alcoholics
• May cause liver toxicity when used chronically;
concern in alcoholics
