Opiate Analgesics Flashcards
What drugs do you start with to manage pain? what are the drugs after that? What are the strongest drugs you can use for pain?
Start with: Non opiod drugs solo or with others
-NSAIDS, COX-2 Inhibitors, Paracetamol
Next ones:
-Weak Opiods ie Tramadol & Codeine
Strongest Ones:
-Strong Opiods ie Morphine, Fentanyl, Pethidine
Define Nociceptive Pain
Define Inflammatory Pain
Define Pathological Pain
How long does acute pain last? Chronic?
Nociceptive: acute response to a mechanical insult
Inflamm: Pain caused by tissue damage and infiltration of immune cells
Path Pain: Damage to Nervous System
Acute: 2-3 mos. Chronic is more than 2-3 months
What are enkaphalins
Endogenous opiates. There are two of them
What are the opiod receptors in the body and what is their MOA?
There are 3 GPCRs (u-delta-kappa; ir MOR, DOR, KOR). They are Gi coupled and inhibit adenylyl cyclase (think they inhibit pain so they inhibit AC)
Morphine acts mainly at the u or MOR type receptor.(you want MOR MORphine…)
What is the course that the pain signal travels
Pain signal is carried to:
Interneurons in the spinal cord (DRG). Then to cells in Ascending Tract: -Medulla (parabrachial nuclei) -Ventral Caudal thalamic neurons -Neurons of the cerebral cortex
Once the brain has processed this pain signal, it sends the signal of pain to cells of the descending tract, then to:
- Midbrain (periaquaductal grey)
- Medulla Pons
- Interneurons of the spinal cord that ultimately relays the pain formation back to the spot that was injured
What is the role of opioid receptor in the descending path?
Opiates (ie Morphine) act to Inhibit GABA release, and enhance inhibition of nociceptive transmission
Opioid receptors are found on the ascending, descending, dorsal root ganglion, periaquaductal grey pretty much everywhere
What are the “wanted” effects of the opiates?
CNS: Analgesia Euphoria Sedation Miosis (Tolerance-->Dx for overdosing this is constriction of the pupil)
Periphery:
Anti-diarrheal
Unknown:
Cough Suppression
What are the SEs of opiates?
CNS:
Respiratory Depression (Main cause of death among addicts)
Nausea
Addiction
Periphery: Constipation Urinary Voiding Uterus (prolong labor) Pruritis
What are the pharmacokinetics for Opiates?
Anything you can think of ie oral, IM, subcu, mucosally, rectal
Distribution varies by organ. Binds to plasma proteins in the blood but leaves the blood rapidly
Can’t really cross the BBB easily, but diacetylmorphine (heroin) can bc has two acetyl groups
How are opiates metabolized?
Opiates are converted to polar metabolites with two rounds of esterase and the glucoronidase. the final product is
MORPHINE 6-GLUCURONIDE
This is then excreted thru the kidneys
How are opiates used as an analgesia? what should you be careful about when giving these for pain?
Severe constant pain NOT INTERMITTENT
Pain with terminal diseases and cancer
Give slow dosage to provide more stable pain relief
Be careful!
Transmits over intact, not damaged pathway
Only for constant, not intermittent pain
In labor, could cross placenta, poison baby and cause fetal respiratory depression->Use Naloxone as an antidote
How are opioids used for pulmonary edema
IV morphine which provides great relief thru unknown mechanism
Can opiates be used as a cough suppressant? If so what are the two most common opiates prescribed for this?
They are potent antitussives, but MOA is unclear.
Drugs:
Codeine–>suppresses at lower doses than those needed for analgesia. so cough needs less than pain relief
Dextromethorphan–> Is not an opiate drug per se. No pain relief or addictive properties. ONLY ANTITUSSIVE
What opiates are used for diarrhea?
Phenylpiperidines.
These are: Morphine Derivatives
GI Selectivity
Few CNS effects
How are opiates used for anesthesia? Can they be used with other anesthetics?
Opiates used as pre-meds before anesthesia
Can be used as adjuncts with other anesthetics or if highly potent can be the main anesthetic in high risk surgeries where you need to MINIMIZE CARDIO DEPRESSION. But, you must make sure there is mechanical ventilation.
Opioids can be a regional anesthetic as well bc they have direct action on spinal cord. For ex, EPIDURAL FENTANYL in combo with low dose anesthetics lowers pain in pts with major upper abdominal surgery
When does the maximal effect of respiratory depression occur after the admin of morphine?
10-15 mins after you give it
Describe tolerance and addiction to opiates
Tolerance begins with the very first dose, but you dont see this until 2-3 WEEKS OF FREQUENT EXPOSURE
Reduction in response after repeated admins
Tolerance develops more when large doses given at short intervals, RATHER THAN short doses given over long intervals
T or F:
Tolerance to one opiate leads to a simultaneous tolerance to other opiates.
T. This is called cross tolerance
Which effects have a high degree of tolerance to opiates? Low degree?
High: Low: E. RACES Miosis Constipation Emesis Respiratory Drive Analgesia Cough Suppressant Euphoria Sedation
What are the withdrawal symptoms of Opiates?
Behavioral restlessness, hyperactivity, irritability, INCREASED SENSITIVITY TO PAIN, n/v, cramps, muscle aches, piloerection, insomnia, anxiety
Time scale: (for morphine and heroin) 6-8 hrs after last dose...(wowzers) 36-48 hrs is the peak 5 days done
Is opiate withdrawal life threatening? After withdrawal is over, what disappears? What can withdrawal symptoms be precipated by?
No.
Tolerance.
Antagonists
In the case of overdose, what can you give?
Give an ANTAGONIST called NALOXONE IV. It reverses coma due to overdose, or resp dep in newborns
What are contraindications of opiates?
Pure and partial agonist mixed ie morphine (pure) and pentazocine (partial)
Head injuries bc the resp depression will cause INCR CO2 Levels. These patients may have had elevated IC pressure, and the increased CO2 could be lethal
Pregnancy bc fetus may become dependent
Impaired pulmonary function bc of resp depression capability of opiates
Renal or hepatic issues bc opiates are metabolized in liver and excreted in kidneys
Drug Interactions
Which drug groups don’t play well with Opiates?
Sedatives/Hypnotics: Increases resp depression capability
Antipsychotics: Increase Sedation, variable effects on resp depression
MAO Inhibitors: Fevers, Seizure, Coma
Which is the biggest risk in overdosing opiates?
Respiratory Depression!!!!
What are the 5 categories of opiates? How long does analgesia effects last? What are 4 classes of drugs
5 categories: Strong Agonists Mild to moderate agonists Mixed agonist/antagonist Antagonist Antitussive
4-6 hours
Classes: Phenathrenes Phenylpiperidines Morphinans Benzomorphans
What are the strong opiate AGONISTS?
Hint…MMM, He Overly Likes Honey Fish
Morphine Meperidine Methadone Hydromorphone/Oxymorphone Levorphanol Heroin Fentanyl
Describe Morphine as far as category, efficiency, analgesia.
Its scientific name is PHENATHRENE Strong Agonist High Efficiency High abuse potential GOLD STANDARD IN ANALGESIA
Describe Heroin as far as category, efficiency, analgesia.
Its scientific name is Diacetylmorphine Strong Agonist High Efficiency High Abuse potential BETTER AT CROSSING BBB EXTREMELY HIGH ABUSE POTENTIAL Illegal
Describe Hydroxymorphone and Oxymorphone as far as category, efficiency, analgesia.
Phenanthrene
EXTREMELY SOLUBLE, RAPID ONSET
6-8x stronger than morphine
USE FOR CHRONIC PAIN
Describe Levorphanol as far as category, efficiency, analgesia.
Morphinan Strong Agonist High Efficiency High abuse potential LESS N/V THAN MORPHINE
Describe FENTANYL as far as category, efficiency, analgesia.
Phenylpiperadine Anesthetic in high risk surgeries High abuse potential 80x MORE POTENT THAN MORPHINE HIGHLY LIPID SOLUBLE SO BRIEF DURATION
Describe MEPERIDINE as far as category, efficiency, analgesia.
Phenylpiperidine
Older drug
Antimuscarinic (tachycardia) disadv compared to Morphine
BUT HAS FEWER W/DRAWAL SYMPTOMS
Describe METHADONE as far as category, efficiency, analgesia.
Phenylpiperadine
High Efficiency
High Abuse Liability
Adv over Morphine: Long half life (15-60 hrs)
Chronic pain treatment at low cost
Slow developing tolerance and addiction
Milder w/drawal symptoms so used for detox
What are the moderate Opioid agonists?
Hint…The cod and Ox eLOPEd
Codeine, Oxycodone, Loperamide
Describe Codeine as far as category, efficiency, analgesia.
Phenanthrene
Treat moderate pain
Medium abuse potential
Can use with Asp or Acetaminophen (Tyl with Codeine)
ANTITUSSIVE
Adv over Morphine: Greater oral efficacy, Less abuse potential
Describe Oxycodone as far as category, efficiency, analgesia.
Phenanthrene Moderate Pain High Abuse Potential Adv over Morphine: Greater oral efficacy (same as codeine) Greater nasal efficacy
Describe Loperamide as far as category, efficiency, analgesia.
Phenylpiperidine
Moderate Agonist
No BBB crossing
USED FOR DIARRHEA
What are the weak agonists?
Trick question…there’s only one.
TRAMADOL.
Very weak u-Agonist
Blocks serotonin & NE transporters
Can serve as adjuvant to PURE u-AGONIST IN CHRONIC PAIN
so give the strong one a little boost with the weak one
What are the mixed agonist/antagonists?
Buprenorphine & Nalbuphine
Describe Buprenorphine as far as category, efficiency, analgesia.
Partial u agonist and k antagonist (mixed remember so it will have both agonist and antagonist properties)
Slow dissoc from u-receptor
Naloxone only partially reverses its effects
TREAT CHRONIC PAIN
Long half life (20-73 hrs)
REALLY GOOD SAFETY PROFILE, no resp depression (ceiling effect
Can be USED FOR DETOX. BETTER THAN METHADONE BC ONLY HAVE TO DOSE EVERY 2-3 DAYS
Describe Nalbuphine as far as category, efficiency, analgesia.
u-Antag, k Agonist (opposite of Buprenorphine)
CEILING EFFECT TO RESP DEPRESSION
Resistant to Naloxone!!!
What are the Opioid antagonists?
Naloxone, Naltrexone
Describe Naloxone as far as category, efficiency, analgesia.
Phenanthrene No abuse potential USE FOR OPIATE OVERDOSE Short duration of action (1-2hours) -this is important bc if you give to a coma patient, they may wake up for 1-2 hours and then go back into a coma bc not all of the original drug is cleared yet
Describe Naltraxone as far as category, efficiency, analgesia.
Used for EtOH and Opioid dependence
What are the anti-tussives?
Codeine, Dextromethorphan
Describe Dextromethorphan as far as category, efficiency, analgesia.
Morphinan
d-isomer of Levorphanol
No opioid activity, analgesia, addiction potential…only for cough
Just as good as codeine w/fewer GI side effects, and no abuse potential
