Types of Opioids

Mild Opioids

Mild opioids have weak potency. These opioids are generally available as fixed-dose combo pills (e.g. tylenol, ibuprofen,
caeine). Toxicity of the non-opioid is the limiting factor to their maximum daily dose. They are adequate for mild pain
only. They have short duration of action, and have no sustained-release formulations available. Only oral options are
available.

Codeine Pro-drug of morphine that has the weakest potency of all narcotics. Notably, it requires first-pass
metabolism to convert it from codeine to morphine.

10% of Caucasians lack the hepatic enzyme that converts codeine in morphine, and will only suer its
adverse eects (e.g. N/V, constipation).

Codeine has potent anti-tussitive eects that are independent of its metabolism.

Codeine has the greatest constipating and nauseating eects. Overall, codeine has poor ecacy as an
analgesic.

Hydrocodone A useful mild opioid, limited mainly by its formulary availability as combination products only and the
ensuing ceiling dose of the non-opioid (e.g. acetaminophen, ibuprofen).

Major Opioids

Major opioids have high potency. One must be mindful that although the quantity given for a high-potency drug may seem
small, this should not minimize the perceived comfort in dosing these opioids.

These drugs are only prescribed as single agents. They usually have multiple routes available, including oral, subcutaneous,
sublingual, intravenous, intramuscular, and intrathecal.

Morphine sulfate the archetypical opioid, with a long history of use and highest documented ecacy. It is available
in multiple forms, easily titratable. Liquid morphine provides the option for the lowest dosing of any opioid.
Sustained release and instant release formulations are available. It has the lowest cost of all opioids for general use.

Oxycodone similar to morphine in most ways, with availability of lower potency oral tabs (5 mg), particularly useful for
initiating patients with moderate pain and opiate naivety (though in these patients, liquid morphine may be an even
better option). Sustained release preparations are available in a wide range of doses.

Hydromorphone pharmacologically, very similar to morphine. It is particularly useful in patients with idiosyncratic
reactions or side eects from morphine. It can be useful when very high dose treatment is needed, especially sub-
cutaneously. Unlike morphine, HM does not have vestibular action like morphine, and so patients suer fewer side
eects like motion sickness and nausea.

Fentanyl extremely high-potency, lipophilic opioid that has multiple formulations. However, it has a number of
special precautions that stem from its high potency, fast parenteral action, and transdermal and transmucosal
availability.

Fentanyl IV is most often used in anesthesia and for intensive care patients, when its rapid onset and relatively
short duration of action is advantageous. Sublingual lozenges may also be used for acute pain titration.

Fentanyl TD is appropriate only for non-naive patients with a large burden of chronic pain; never in opioid-
naive patients.

Used patches may contain enough residual drug to cause serious problems, even on surface contact
(e.g. in children, opioid-naive adults, pets). Dispose of them properly (e.g. at a pharmacy).

Transdermal patches may not be appropriate in the setting of fever, diaphoresis, cachexia, morbid
obesity, or ascites, as these conditions all significantly alter the pharmacology of fentanyl.

Non-parenterally, fentanyl has a 1218 hour delay in onset of action, with peak time reached only >20 hours.
Non-parenteral fentanyl is not an ideal analgesic for acute pain or acute exacerbations of pain. This is
because of the time it takes for a subcutaneous reservoir to build (depot eect). For the same reason, there is a
delay between discontinuation and eect of the drug.

Frequent increases in patch strength without titration by another route can produce dangerously high
peak levels on a delayed time frame.

Equianalgesia Table

Equianalgesia table using 2:1 oral:parenteral ratio used; other tables may use 3:1. All ratios are relative to oral morphine eectiveness.

When converting, always round down to the nearest formulation for the sake of convenience and
safety.

Forward conversion to fentanyl patch

This table is for forward conversion for the starting dose of a fentanyl patch only; not reverse conversion. Attempting reverse conversion using
this table can result in overdosing. Incomplete tolerance is built into this conversion table and does not need to be accounted for.

Reverse conversion from fentanyl patch

For reverse conversion (i.e. fentanyl patch to MEDD), use a 1:100 ratio.

25 mcg/h TD fentanyl = 60 mg q24h PO morphine

Pharmacokinetics

Opioids are all conjugated in the liver and excreted (9095%) by the kidney.

Plasma concentrations are achieved rapidly, with variable peak eect time.

* peak eect time varies according to how lipophilic the opioid is, as the drug must cross the lipophilic blood-brain-barrier and exert its eect centrally,
where the receptors are. Fentanyl reaches its full eect earlier than any other opioid because of its highly lipophilic nature, and may even be delivered
sublingually with 90% bioavailability.

Acute Pain Management

Opioids are a cornerstone of acute pain management in the emergency room.

Morphine sulfate, hydromorphone, and fentanyl are most commonly used.

Opioids are particularly useful because there is no set ceiling dose, only
tolerance and toxicity limit the dose.

The optimal loading and titration doses for opioids in the setting of acute pain
is yet to be determined, with little evidence-based medicine supporting any
particular regimens.

DRUG BASAL DOSE BOLUS DOSE

MORPHINE 2.55.0 mg PO 2.5 mg PO q4h PRN

0.15-0.25 mg/kg PO 0.0250.050 mg/kg PO q5min PRN

HM 0.0150.030 mg/kg IV 0.00750.015 mg/kg q515min PRN

FENTANYL 11.5 mcg/kg IV 0.250.50 mcg/kg q15min PRN

30 mcg IV q5min PRN

* MODIFIERS INCLUDE OPIATE NAIVETY, AGE, WEIGHT (<60kg vs. >60kg)

* RESPIRATORY RATE IS THE MAJOR LIMITING FACTOR OF OPIATE TITRATION
* START LOW AND GO SLOW, ESPECIALLY IN HIGH-RISK POPULATIONS (e.g. ELDERLY, CHILDREN)

Opioid Titration

In general, as with many drugs, opioid titration to analgesic eect follows the
rule start low, go slow.

BTA = breakthrough analgesics i.e. # PRNs

ATC = around-the-clock analgesics i.e. scheduled

Adjustment based on BTA

If information from an MAR is available (i.e. # of BTAs used in last 24 hours), then analgesia can be adjusted based
on this information.

1. Sum the total dose of BTAs and add to the current ATC dose (in MEDD)

2. Calculate a new ATC based on the total BTA+ATC MEDD

3. Calculate a new BTA based on the total BTA+ATC MEDD

Adjustment based on pain level

If pain is still being experienced at a current dose:

mildmoderate pain 2550% total dose increase

moderatesevere pain 50100% total dose increase

Never increase the rate of a continuous infusion without also giving a bolus dose.

It requires at least 45 half-lives of a drug to reach a new steady state. For infusions, this requires at least 1015
hours to equilibrate to a new steady state. For non-infusions, this requires about 2024 hours.

This period of time can be excruciating in the inpatient setting, but can be reduced by giving a bolus dose.

Opioid Rotation

Switching from one type of opioid to another is essential in many situations, such as changing patient tolerance, side-
eects, and issues with administration (e.g. N/V, NPO). Because dierent narcotics act on dierent opioid receptors, rotating
between dierent opioids may boost eectiveness and reduce side eects.

Whenever possible, consider stepping a patient down from parenteral to oral analgesia. This is usually appropriate if stable
pain control has been achieved (e.g. minimal BTA), and the patient has oral tolerance (i.e. no N/V, non-NPO).

Opioid rotation only refers to changes between dierent classes of narcotics, not between routes of administration.

Calculate total oral morphine equivalent daily dose (MEDD i.e. mg q24h)

Convert all opioids into their oral morphine equivalent and sum to yield the MEDD both scheduled (ATC) and PRN
(BTA) are included.

For fentanyl patches, use the reverse conversion ratio (1:100) rather than the forward conversion table.

Correct MEDD for incomplete cross-tolerance.

Between any pair of opioids, an individual may have some degree of tolerance to both drugs. To determine the eective,
equivalent dose, a correction factor is applied:

20% reduction (0.80) poorly controlled pain

25% reduction (0.75) standard reduction
40% reduction (0.60) non-nociceptive pain suspected (e.g. neuropathic, delirium)

Calculate the new scheduled i.e. around-the-clock (ATC) dose.

MS Contin, dose frequency = q12h or q8h divide corrected MEDD by 2 or 3 to determine each dose.

Methadone, dose frequency = q6h or q8h divide corrected MEDD by 4 or 3 to determine each dose.

All other opioids, dose frequency = q34h divide corrected MEDD by 8 or 6 to determine each dose.

Calculate the new PRN i.e. breakthrough analgesia (BTA) dose.

Dose quantity = corrected MEDD x 10% (0.10)

Dose frequency = q1h PRN

Precautions

There is no maximum dose for opioids, as they have no observed ceiling eect. Doses are limited only by side
eects. The only exception is codeine, which maxes out around 360600 mg q24h.

Furthermore, some opioids have toxic metabolites that can accumulate and cause opioid-induced neurotoxicity
(OIN).

The equianalgesia chart is a useful tool, but does not control for other pharmacokinetic factors half-life and
bioavailability of a drug, and pharmacodynamic factors like cross-tolerance, sex, age, and organ function

Many charts derive their data from studies conducted on opioid-naive patients. Chronic pain patients may
respond dierently to analgesia than acute pain patients.

Always manage the three Bs of opioids bowels (constipation); barfing (nausea); and breakthroughs.

A bowel routine (e.g. laxatives) and an anti-emetic (e.g. metoclopramide, ondansetron) should be standard PRN
co-orders for any scheduled opioid.

Opioid Side Eects