Opioid Analgesics (finished) Flashcards
Describe the ways in which drugs can relieve pain Compare and contrast the terms opioid, opiate and narcotic Discuss the advantages and disadvantages (limitations) of opioids and NSAIDs in terms of type and level of pain, adverse effects and drug dependence Describe and distinguish among the subtypes of opioid receptors Define the terms agonist, antagonist, mixed agonist-antagonist and partial agonist in terms of opioids and give examples of each type of drug List the advantages a
Describe the ways in which drugs can relieve pain
Eliminate cause of pain:
Anti-inflammatory (NSAIDs)
Chemotherapy (including antimicrobials)
Antiulcer
Prevent transmission:
Local anesthetics
Affect the way pain is perceived:
General anesthetics
Opioids
Affect patient’s reaction to pain:
Anxiolytics
Opioids
Compare and contrast the terms opioid, opiate and narcotic
Opiate: drug derived from opium poppy
Opium, morphine, codeine
Opioid: more generic term; all substances, endogenous and exogenous, that bind opioid receptors
Endorphins (endogenous)
Morphine, also an opiate
Fentanyl, synthetic so not an opiate
Narcotic: originally meant sleep inducing (Greek “narcos”
Now a legal term encompassing illicit drug use
Includes opioids, cannabinoids, stimulants, etc.
Discuss the advantages and disadvantages (limitations) of opioids and NSAIDs in terms of type and level of pain, adverse effects and drug dependence
be able to do this
Describe and distinguish among the subtypes of opioid receptors
Mu (μ) Analgesia Respiratory depression Decreased gastrointestinal motility Physical Dependence
Kappa (κ)
Analgesia
Sedation
Decreased gastrointestinal motility
Delta (δ)
Modulates μ activity
ORL1 – Orphanin opioid receptor-like 1
Structurally similar to μ but insensitive to opioid ligands
Give examples of opioids with active and toxic metabolites and the significance of this information in the treatment of pain
Pharmacologically Active
Morphine-6-glucoronide (morphine metabolite)
Excreted in urine, so can impact morphine’s effect and duration if renal function is compromised
Toxic metabolites
Normeperidine, a metabolite of meperidine
Excitotoxic: tremor, twitching, convulsions
Meperidine should only be used acutely
List the clinical uses of opioids and how they relate to their sites of action centrally
Cortex:
Pain perception, reaction to pain, euphoria, sedation
Medulla: Respiratory depression Antitussive effects Nausea, vomiting Thermoregulation
Spinal Cord:
Depresses pain reflexes
Stimulates non-pain reflexes
Eye, occulomotor nerve:
Miosis (pinpoint pupils) – little tolerance so good indicator of opioid use
Vagus nerve:
Bradycardia
Increased GI tone
Mu (μ)
Analgesia
Respiratory depression
Decreased gastrointestinal motility
Physical Dependence
Kappa (κ)
Analgesia
Sedation
Decreased gastrointestinal motility
Delta (δ)
Modulates μ activity
ORL1 – Orphanin opioid receptor-like 1
Structurally similar to μ but insensitive to opioid ligands
Opioid Receptor Signal Transduction
Presynaptic inhibition of afferent neurons:
Receptor activation blocks voltage-gated Ca2+ channels
Reduced release of glutamate and substance P
Postsynaptic inhibition:
Receptor activation opens K+ channels
Inhibit excitation of postsynaptic neuron
Enhanced inhibition of ascending pathway:
Pain inhibitory neuron indirectly activated
Opioid receptor activation blocks release of GABA from inhibitory interneuron
Greater inhibition of nociceptive processing in dorsal horn of spinal cord
Agonist
Receptor binding produces effect
Examples: Morphine Methadone Oxycodone Heroin
Antagonist
Receptor binding produces no effect
Reverses effect of morphine-like opioids
Examples:
Naloxone
Naltrexone
Partial Agonist
Less efficacy than full agonist
Lower abuse potential
Example:
Buprenorphine
Often used with naloxone, an antagonist (Suboxone)
Mixed Agonist-Antagonist
Agonist at one receptor
Antagonist at another
Example:
Pentazocine
Agonist at Kappa
Antagonist at Mu
Clinical relevance:
can initiate withdrawal symptoms
Routes of Administration:
Oral
Convenient, but high first pass metabolism can be limiting
Slower onset, delayed peak effect, longer duration (relative to parenteral routes)
Better for chronic treatment
First pass metabolism: drugs absorbed from GI tract go to liver, are rapidly and efficiently metabolized
Oral morphine clinically effective, just requires 3-6x higher dose (relative to parenteral)
By contrast, methadone less impacted by first pass metabolism (1.5-2x higher dose)
Altered liver function – Clinical relevance?
Routes of Administration:
Intravenous
Precise and accurate dosing
Rapid onset, but increased risk of adverse effects
Bolus versus continuous
Can be patient controlled (PCA)
Routes of Administration:
Intramuscular/Subcutaneous
Rapid onset
Duration between oral and IV
Routes of Administration:
Spinal
Longer duration at lower doses than systemic
Can avoid some brain-mediated adverse effects
Respiratory depression
Routes of Administration:
Rectal suppository
Administration may be easily discontinued
Routes of Administration:
Buccal/Sublingual
Faster onset than oral, avoids first pass metabolism
Convenient (no injection)
Example: Fentanyl “lollipop”
Routes of Administration:
Transdermal
Convenient, avoids first pass metabolism
Better for chronic treatment
Examples: Fentanyl, Buprenorphine
Sites of action and effects outside CNS
GI Tract:
Constipation, decreased gastric emptying, cramping, spasm
Slow tolerance, so always an issue with opioid therapy
Bronchiolar constriction (high doses)
Uterus – prolongs labor
Ureters – difficulty urinating
Causes histamine release
Flushing and itching of the skin
Therapeutic uses
Analgesia
Especially severe pain
Cancer, chronic illness
Obstetric labor
Crosses placental barrier (neonatal respiratory depression)
Slows progress of labor
Anesthesia Pre- and post-surgery Sedative, anxiolytic, analgesic Cardiovascular surgery Minimizes CV depression
Cough
Codeine, dextromethorphan (non-opioid)
Diarrhea GI effect (constipation) All opioids effective Loperamide (Imodium) Doesn’t cross BBB Diphenoxylate + Atropine (Lotomil) Atropine – anticholinergic to discourage abuse
Acute overdose
Naloxone
Short duration of action
Single dose – could relapse after 1-2 hrs
Injection to avoid first pass
Addiction
Naltrexone
Orally effective
Single dose, alternate days blocks heroin effects
Prevent relapse in opioid addiction and alcohol addiction
Opioid tolerance
Reduction in effect over time with repeated delivery
Increase in dose required for equivalent response
Rate of tolerance varies with endpoint
Opioid dependence
Removal of drug, or administration of antagonist (e.g., naloxone) leads to withdrawal syndrome
Physical Dependence
Psychological Dependence
Addiction: Compulsive use, drug seeking behavior
Driven by euphoria, indifference to stimuli, sedation, “rush”
Methadone treatment: orally effective, long t1/2, low cost
Buprenorphine + naloxone (Suboxone)
Partial agonist + antagonist, can precipitate withdrawal
Lower abuse potential
Opioid withdrawal
Unpleasant but not life threatening
Rhinorrhea, lacrimation, yawning, chills, gooseflesh (piloerection), hyperventilation, hyperthermia, mydriasis, muscular aches, vomiting, diarrhea, anxiety, and hostility
Onset, intensity and duration determined by drug used and degree of physical dependence
Reintroduction of opioid eliminates withdrawal symptoms
