L47 - L48: Opioids Flashcards
Spinal cord (dorsal horn)
Reflex withdrawal
Spino-thalamic
Conscious perception
Spino-hypothalamic
Endocrine response
Visceral response
Spino-reticular
General arousal
Visceral response
Spino-mesencephalic
Major pain processing center
Primary sensory cortex
Conscious perception
Emotional response
What is mood alteration (euphoria, tranquility) attributed to?
Mu receptor activation in ventral tegmental area (one of the ‘pleasure’ or ‘reward’ centers of hypothalamus
Why does nausea and vomiting occur?
Opioids activate brainstem chemoreceptor trigger zone (CTZ) stimulating nausea and vomiting
Symptoms may be worse during ambulation - may have vestibular contribution
What are the hormonal effects of opioids?
Opiates modify release of many hormones from hypo-thalamic-pituitary-adrenal axis
Reproductive hormones (LH, FHS testosterone) and beta-endorphins - female addicts have irregular cycles and males have reduced sex drive
Oxytocin and ADH - can cause hypotension
Body temperature - decrease body temp by action on hypothalamic heat regulating centers; high dose to chronic users may cause temperature elevation
What are the motor system effects of opioids?
Opioids block neurotransmitter release in the basal ganglia, e.g. stratium
Mixed effects - relaxation and rigidity; eyelid droop, speech slurred, “heaviness in limbs”, walking is slow
High doses - catatonia, muscular rigidity
Effects of opioids on GI tract
High density of opioid receptors in GI tract
Constipation, increased muscle tone, inhibition of smooth muscle contraction and propulsive activity
Effects of opioids on biliary tract
Opioids constrict biliary smooth muscle and may result in colic causing pain
Effects of opioids on ureter and urinary bladder
Opioids increase urethral and bladder tone
Produce sense of urinary urgency
Increased sphincter tone causes urinary retention, particularly in postoperative patients
Effect of opioids on pupillary constriction
Opioids produce miosis (pinpoint pupils)
Act on parasympathetic pathways from oculomotor complex (cranial nerve III); blocked by atropine
Tolerance doesn’t develop to this
What can precipitate opiate withdrawal syndrome?
Antagonists can precipitate opiate withdrawal within a few minutes of administration
What is addiction of opioids due to?
Action on reward center in hypothalamus
Psychological dependence on state of euphoria, indifference
Wish to avoid withdrawal symptoms
Why does heroin have to be injected?
First pass effect
How are opioids metabolized and excreted?
Most converted to polar metabolites in the liver by addition of something like glucuronide to it
These metabolites can have significant pharmacological effects themselves
M6G and M3G excreted by kidneys
Heroin
Diacetylmorphine
Most lipophilic of all opioids - acetyl groups at 3 and 6 hydroxy positions
Cross blood-brain barrier rapidly since very lipophilic
In brain, quickly hydrolyzed to morphine; builds up high concentration in brain
3 -4 times analgesic potency
Withdrawal symptoms more intense than morphine
Overdose frequent
Codeine
Orally effective
Antitussive - drug of choice for cough
Analgesic: used for relief of dull, continuous pain in ambulatory person
Has respiratory depressant and sedative effects
1/10 potency of morphine
Side effects are like morphine, but toned down
Tolerance can develop
Takes a while for physical dependence to occur
Oxycodone
Chemical modification of codeine
Good oral efficacy
Primary use: oral analgesics and antitussive
Similar to morphine in important pharmacology
Percodan
Oxycodone + aspirin
Percocet
Oxycodone + acetaminophen
OxyContin
Longer lasting dosage
Pill had high drug content and was crushed and injected
Now reformulated w/ abuse-resistant polymer making pill more difficult to crush
Methadone
Similar to morphine: analgesia, sedation, respiratory depression, miosis, constipation, antitussive effects
Good oral absorption
Duration: single dose - 6 hours; repeated doses - 16 to 20 hours (long acting)
Used as replacement for heroin in “methadone treatment” of addition - potent; orally effective; high persistent effect when given repeatedly (unlike morphine) even though single dose has same duration of action; can be used as single daily dosage to suppress withdrawal symptoms
Useful for treatment of chronic pain
Fentanyl
Sublimaze of china white
Potent analgesic with relatively short durations of actions: 80 - 100x more potent than morphine; more lipid soluble than morphine, which accounts for more rapid onset and shorter duration of action; onset = 5 min; duration = 0.5 to 1 hour
Intravenous supplements to general anesthesia and induction of anesthesia
Major advantage - cardiovascular stability
Highly absued (china white is street name) bc of immediate rush; there is a lot of mixing a little bit of fentanyl w/ heroin
Duragesic
Fentanyl patch
Delivers fentanyl for ~3 days: used only for severe pain, not treated by less potent drugs
Diphenoxylate
Lomotil
Therapeutic use: antidiarrheal
Not an analgesic, not an anti-tussive
CNS depression action, some euphoric effects
Lomotil is combination w/ atropine; diphenoxylate is potentially addictive, but atropine makes abuse unlikely (if you try to up the dose, atropine kicks in and makes you sick so you’ll stop)
Tramadol
Synthetic codeine analog
Weak mu receptor agonist
Also acts as norepinephrine and serotonin uptake inhibitor
Used for moderate to moderately severe pain
Side effects may include seizures
Nalbuphine
Strong kappa receptor agonist, mu receptor antagonist
Used for moderate to severe pain
May have ‘ceiling’ to respiratory depression
But may be additive with some mu receptor agonists at lower doses
Buprenorphine
Partial mu receptor agonist and antagonist
Less euphoria and respitaroy depression than heroine or methadone
At moderate doses reach ‘ceiling’ effect
Injected: Rapid onset 2 - 3 min, 15 min IM
Analgesic duration 3 - 6 hours (pretty long-lasting)
Very slow release from receptor (which is why, at high doses, is an antagonist)
Use in ‘methadone’ opiate replacement therapy
Naloxone
Perfect antagonist - no action or cross-antagonism
Requires IV admin
Almost immediate onset: 1 - 2 min for response
Relatively short duration of action (b/w 1 -4 hours); have to re-inject
Once stabilized, use naltrexone
Naltrexone
Effective orally
Remarkably long duration of action
Single oral dose blocks opioid agonists for 48 - 72 hours
Can’t use for acute toxicity if need rapid onset
Very useful for treating morphine overdose - patient does not need to be monitored for relapse of respiratory depression
Reduces alcohol and opioid cravings - probably by acting on pleasure centers in hypothalamus
What is the benefit of packing naloxone with an orally absorbed agonist?
Co-packaging to prevent abuse
Taken orally, agonist works as pain medication
Injected, nalaxone prevents agonist action
(E.g. oxycodone and naloxone)
Taken orally, naloxone has no effect
Crushed and injected, naloxone blocks receptors
