Opioids Flashcards
What is Opioids Mechanism of Action?
Work on everywhere in the pain pathway
- make it harder for a pain fiber to fire by controlling pain on every level
- Hyperpolarization of nerves by opening potassium channels/ Calcium Channels in 1st (receptor to medulla) and 2nd order neurons (medulla to thalmus)
- Inhibition of ascending pathways in the CNS
- Excitation of descending adrenergic and seratonerigic pathways
What are the active ingredients of Opioids?
- Morphine
- Codeine
both natural opioids
Heroin is the “safe” alternative to Aspirin
- goes into brain & converts to morphine in brain to be active (is faster & more dangerous b/c can cross BBB)
What are the pharmacological effects of Opioids (i.e. what do we use them for?
- Inhibition of pain & pain perception
- Sedation & anxiolysis
- Drowsiness & lethargy
- Cognitive impairment
- Relaxation Inhibition of Pain - Depression of respiration
*-main cause of death from opioid overdose (esp alcohol)
- (don’t give to someone with COPD)
- reduces need to breathe - Cough suppression
- Opioids suppress the “cough center” in the brain - Reduction of intestinal motility: Codeine used to treat diarrhea
What is:
By the mouth
By the clock
By the ladder
Mild pain (0-3): Acetaminophen
Moderate pain (4-6): add Codeine (or Tramadol)
Severe pain (7-10): replace with Morphine
What does By the mouth mean?
means you’ll have to give MORE drug
Advantages:
Oral dosing is LESS effective than IV (first pass metabolism) but..
1. Oral dosing has longer term effect requiring less frequent doses
- Oral dosing avoids the “highs” and thus is less addictive (remember, for addiction, timing is critical)
- faster the award is given, the more addictive - Oral dosing is safer in terms of overdose
What does By the clock (not by the pain) mean?
- Uses less drug. It takes more drug to bring pain down than it does to maintain a person
pain-free - Avoids the euphoria associated with release of pain, so less addictive potential
- Avoids the development of chronic pain syndromes (from pain pathway rewiring)
(give drug, & before pain comes back, you dose again - takes about 3 days)
What does By the ladder mean?
- Assures that the safest and least potent drug required for any specific case is used
◼ Avoids addictive potential because opioids (and strong opioids) are not used until required
Codeine:
◼ Weakest commonly used opioid little addiction
- risk (10% the potency of morphine)
◼ Potency is so low, its has its own special step on the pain ladder (possibly now shared with
tramadol)
◼ Used for pain, diarrhea, coughin, & to inhibit breathing (*almost all 5 except to sedation)
Tramadol:
more effective for pain than Codeine
A UNIQUE WEAK opioid agonist
Similar structure to codeine & morphine, so is in the opiate agonist class
Unlike other opioids, Tramadol has 2 complementary mechanisms:
- Like other opioids, activates the μ-opioid receptor
- Weak inhibitor of norepinephrine and serotonin reuptake
LESS potential for addiction, shows greater pain control than can be explained by weak opioid action
When Tramadol is with acetaminophen it’s called…
Tramacet
Morphine’s
Bioavail:
Latency to onset:
Duration of action:
MOST TOXIC EFFECTS - NOT the 1st line anymore –> but some countries still use it as 1st line b/c v. cheap (b/c plant)
ORAL
- Relatively poor availability of 20-30% (first pass metabolism)
➢ latency to onset –(15 – 60 minutes )
➢duration of action – ( 3 – 6 hours)
➢IV: TWICE AS POTENT AS ORAL
➢Duration of action- Almost immediate to ~2 hours (HIGH POPULATION VARIABILITY)
- makes it difficult to control ppl’s pain properly
Oxycodone:
- Has equal or slightly greater potency than morphine (up to 2X)
- Has oral availability of 80% (compared to - Slow With 30%)
- Half-life slightly greater than morphine
- Dosed at half morphine dose for equiv effect
What is the slow-release form of Oxycodone?
OxyContin
When Oxycodone is with Tylenol it’s called…
Percocet
- was most commonly used pain drug in U.S.
- would die from Tylenol overdose b/c it’s with Tylenol (when dosed higher to control pain)
Hydromorphone:
Bioavail:
Peak effect:
- Oral: Latency to onset (15-30 mins)
- emotional effect typ. comes faster
IV: duration of action (3-4 hrs)
Peak effect (30-60 mins)
Which drug is 5x as potent as morphine for pain?
Hydromorphone
When is Hydromorphone used for?
Surgical settings for MODERATE to SEVERE PAIN (cancer, bone trauma, burns, etc)
- pretty much the strongest for pain!
Fentanyl:
Highly lipophilic and VERY POTENT (thin patient/patch)
- just a lil bit is enough
80 times the analgesic potency of morphine and 10 times the analgesic potency of
peaks quick (comes on fast) & leaves quick
used as a long-term pain control
What are the routes of admin for Fentanyl?
Sublingual & transdermal (rarely IV)
When is the Sublingual Fentanyl used?
Sublingual: Latency 7-12 mins, duration 1-2 hours
Used for ACUTE but TEMPORARY PAIN, such as debriding wounds
- breakthrough pain in palliative care
When is the Transdermal Fentanyl used?
latency 12-17 hours, duration 72-96 hrs
Used in MORE SEVERE PAIN (cancer, palliative)
What is Sufentanyl?
is ~10x MORE POTENT than Fentanyl
(~1000x more potent than morphine)
What typ. happens the 1st time taking Opioids?
- Might be v. sensitive to it
- Get v. nauseous (only happens once, & then inhibit it)
Naltrexone:
Oral Opioid Inhibitor
Latency 15-30 min, Duration 24-72 hours (peak 6-12 hrs)
What does Naltrexone do?
REVERSES the psychotomimetic effects of opiate agonists, reverses hypotension and cardiovascular instability
**Is NOT highly effective in treating opioid addiction, but IS effective to some extent in treating alcohol addiction
Naloxone (Narcan):
- POTENT opioid ANTAGONIST (structure almost identical to oxymorphone)
- VERY QUICKLY blocks opioid binding
- Used in EMERGENCY SITUATION - respiratory depression in clinical situation or heroin overdose. Short half life
- BLOCKS ALL MAJOR EFFECTS OF OPIOIDS incl. pain control!
Where does the Placebo effect only work in?
- depression
- anxiety
- pain
completely an endorphine effect
(ex: not psychological - if given Narcan there’s no placebo effect)
Methadone:
- VERY LONG BUT VARIABLE HALF LIFE (up to 5 days) but effective for only 6-12 hrs
- At least 10x MORE POTENT than morphine, but this is also HIGHLY VARIABLE by patient
- Though it is LESS ADDICTIVE, it has GREATER RISK OF ACCIDENTAL OVERDOSE even in medical settings (accumulation)
Which drug requires special training & licensure?
Methadone
When is Methadone used?
primarily for ADDICTION MEDICINE & PALLIATIVE CARE where patient has developed RESISTANCE or toxicity to other opioids
What should you remember when prescribing Opioids?
Titrate the dose of opioid based on response and side effects until maximum analgesia and function are attained with tolerable side-effects.
If possible, switch the short acting opioid to a long-acting opioid at equianalgesic doses. The dosing schedule is based on time, not pain. Long acting opioids reduce the likelihood that patient will ‘watch the clock’ and reduces peaks and valleys of pain control.
List the Opioids in order of lowest to highest potency:
Codeine < Morphine < Hydromorphone < Oxycodone < Methadone < Fentanyl < Sufentanil
?
What is the 50% rule for Opioids?
if going from 1 opioid to another opioid
give half dose of new b/c more sensitive, & then crank it up a bit until it works
When to discontinue opioid therapy?
hard to tell if they’re tolerated or if they might be selling it (ex: high doses of opioids without analgesia)
What is Tolerance?
- Reduced potency of analgesic effects of opioids following repeated administration, i.e., increasing doses are necessary to produce pain relief
- Related to opioid receptor regulation
- Less common in pts with cancer pain
- Often reason pts “save” opioids until terminal phase
(functional tolerance - down reg. amount of receptors)
(take off opioids for 2 weeks to help tolerance)
What is Dependence?
- Physical dependence: normal response to chronic opioid administration
- Evident with opioid withdrawal: yawning, sweating, tremor, fever, increased HR, insomnia, muscle/abdominal cramps, dilated pupils
- Avoided by lower dose 20-30%/day
Nicotine has no physical dependence
Addiction:
Psychological dependence
“A pattern of drug use characterized by a…craving for opioids…manifest…[by] compulsive drug-seeking behaviour leading to…overwhelming involvement in use & procurement of the drugs”
Dealing with Tolerance:
- Prevent Dose Escalation
- Use a medication ‘holiday’ following slow withdrawal
- Plan for this at the beginning of treatment
What are the other effects of Opioids on the body?
- Causes VOMITING by stimulating the chemoreceptor trigger zone in the brainstem (esp. 1st-3x of having it)
- then DEPRESSES VOMITING
- PINPOINT PUPILS - no tolerance
- VasoDILATION - flushing of skin & decrease in blood pressure. Methadone causes sweating
Causes CONSTIPATION
Decreases sex hormones in males a & females - DECREASES LIBIDO & FERTILITY
