Opioids & Antagonists Flashcards
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
