Opioid Analgesics Lecture Slides

1. Opioid Analgesics
Shivankan Kakkar, MD

2. Learning Objectives
On completion of this lecture, the students will be
able to:
• Explain how pain intensity is used to determine
treatment using opioids and nonopioid
analgesics.
• Discuss the uses, general drug actions, general
adverse reactions, contraindications, precautions,
and interactions of the opioid analgesics.
• Discuss the important points about the use of
opioid analgesics.

3. Key Terms
• adjuvant therapy used in addition to the
primary treatment
• agonist a drug that binds with a receptor and
stimulates the receptor to produce a
therapeutic response
• agonist-antagonist drug with both agonist
and antagonist properties
• miosis constriction of the pupil of the eye

4. Key Terms
• opioid drug having opiate properties but not
necessarily derived from opium; used to
relieve moderate to severe pain
• opioid naive no previous use or infrequent
use of opioid medications
• partial agonist agent that binds to a receptor
but produces a limited response
• tolerance the body’s physical adaptation to a
drug

5. Introduction
In this lecture, the opioid
drugs used for severe pain are
discussed as well as how the
intensity of pain determines
the use of these drugs. The
World Health Organization
(WHO) developed a three-
step analgesic protocol based
on intensity as a guideline for
treating pain. This “pain
ladder” directs the use of
both opioid and nonopioids in
the treatment of pain using
three steps (Fig.1).
FIGURE.1 World Health Organization
pain relief ladder.

6. Introduction
For mild pain, a health care
provider uses Step 1, which
stipulates prescribing a nonopioid
analgesic, such as an NSAID or
acetaminophen.
If pain persists or worsens even
with appropriate dosage
increases, a provider moves to
Step 2 or Step 3, changing or
adding to an analgesic as
indicated.
Step 2 and Step 3 analgesics
typically contain opioid
substances. Most patients with
severe pain require treatment at a
Step 2 or Step 3 level.
FIGURE.1 World Health Organization
pain relief ladder.

7. OPIOID ANALGESICS
• Opioid is the general term used for the opium-derived or
synthetic analgesics used to treat moderate to severe
pain. The opioid analgesics are controlled substances.
The analgesic properties of opium have been known for
hundreds of years. These drugs do not change the tissues
where the pain sensation originates; instead, they change
how the patient perceives the pain in the brain.
• The opiates are natural substances and include morphine
sulfate, codeine, opium alkaloids, and tincture of
opium.
• Synthetic opioids are those manufactured analgesics
with properties and actions similar to the natural opioids.
Examples of synthetic opioid analgesics are methadone,
fentanyl and meperidine.

8. OPIOID ANALGESICS
• Morphine sulfate, when extracted from raw opium and treated
chemically, yields the semisynthetic opioids hydromorphone,
oxymorphone, oxycodone, and heroin. Hydrocodone is a
semisynthetic drug made from codeine.
• Narcotic is a term referring to the properties of a drug to produce
numbness or a stupor-like state.
• Although the terms opioid and narcotic were once interchangeable,
law enforcement agencies have generalized the term narcotic to
mean a drug that is addictive and abused or used illegally.
• Health care providers use the term opioid to describe drugs
used in pain relief.
• Additional analgesics and antagonists are listed in the classification
drug table given in the next slide.

9. Classification Drug Table

10. Preparations
Opioid Analgesics
1. Morphine: 10–50 mg oral, 10–15 mg i.m. or s.c., 2–6 mg i.v.; 2–3 mg epidural/intrathecal; children 0.1–0.2 mg/
kg i.m. or s.c. MORPHINE SULPHATE 10 mg/ml inj; MORCONTIN 10, 30, 60, 100 mg continuous release tabs;
30–100 mg BD; RILIMORF 10, 20 mg tabs, 60 mg SR tab.
2. Codeine: 30–60 mg oral; CODEINE 15 mg tab, 15 mg/5 ml syr.
3. Pethidine: 50–100 mg oral/i.m./s.c., 10–15 mg i.v. (rarely); PETHIDINE 50, 100 mg tabs, 100 mg/2 ml inj.
4. Fentanyl: 2–4 µg/kg i.v.; 12.5–100 µg/hr transdermal; TROFENTYL, FENT 50 µg/ml in 2 ml amp and 10 ml vial, DUROGESIC transdermal
patch delivering 12.5 µg/hr, 25 µg/hr, 50 µg/hr, 75 µg/hr and 100 µg per hour; the patch is changed every 3 days.
5. Methadone: As analgesic 2.5–10 mg oral/i.m. (not s.c.); for methadone maintenance therapy 5-40 mg per day; METHADONE 5 mg/ml and
10 mg/ml syr; 5, 10, 20, 40 mg tabs.
6. Dextropropoxyphene: 60–120 mg oral; PARVODEX 60 mg cap; PARVON, PROXYVON, WALAGESIC:
dextropropoxyphene 65 mg + paracetamol 400 mg cap; WYGESIC, SUDHINOL 65 mg + paracetamol 650 mg cap.
7. Tramadol: 50–100 mg oral/i.m./slow i.v. infusion (children 1–2 mg/kg) 4–6 hourly. CONTRAMAL, DOMADOL, TRAMAZAC 50 mg cap, 100
mg SR tab; 50 mg/ml inj in 1 and 2 ml amps.
Opioid Agonist-Antagonists and Pure Antagonists
1. Pentazocine: 50–100 mg, oral, 30–60 mg i.m., s.c., FORTWIN 25 mg tab., 30 mg/ml inj., FORTSTAR, SUSEVIN
30 mg/ml inj; FORTAGESIC pentazocine 15 mg + paracetamol 500 mg tab.
2. Butorphanol: 1–4 mg i.m./i.v.; BUTRUM 1 mg/ml and 2 mg/ml inj.
3. Buprenorphine: 0.3–0.6 mg i.m., s.c. or slow i.v., also sublingual 0.2–0.4 mg 6–8 hourly; NORPHIN, TIDIGESIC
0.3 mg/ml inj. 1 and 2 ml amps. 0.2 mg sublingual tab; BUPRIGESIC, PENTOREL 0.3 mg/ml inj in 1, 2 ml amp.
4. Naloxone: Adults 0.4–0.8 mg i.v. every 2–3 min (max 10 mg); neonates 10 µg/kg in the umbilical cord; NAR- COTAN 0.4 mg in 1 ml (adult)
and 0.04 mg in 2 ml (infant) amps; NALOX, NEX 0.4 mg inj.
5. Naltrexone: 50 mg/day oral; NALTIMA, NALTROX 50 mg tab.

11. ACTIONS
• Cells in the central nervous system (CNS) have receptor sites
called opiate receptors. Although opiates are attracted to many
different receptor sites, the mu (μ) and kappa (κ) receptors produce
the analgesic, sedative, and euphoric effects associated with
analgesic drugs.
• Drugs that bind well to a receptor are called agonist agents.
An opioid analgesic may be classified as an agonist, partial
agonist, or mixed agonist- antagonist. The agonist binds to a
receptor and causes a response. A partial agonist binds to a
receptor, but the response is limited (i.e., is not as great as with
the agonist). An agonist-antagonist has properties of both the
agonist and antagonist. These drugs have some agonist activity and
some antagonist activity at the receptor sites. Antagonists bind to a
receptor and cause no response. An antagonist can reverse the
effects of the agonist. This reversal is possible because the
antagonist competes with the agonist for a receptor site.

12. ACTIONS
• In addition to the pain-
relieving effects, other
nonintended responses
occur when the opiate
receptor sites are
stimulated. These include
respiratory depression,
decreased gastrointestinal
(GI) motility, and miosis
(pinpoint pupils).
• Table.1 identifies the
responses in the body
associated with three of the
opiate receptors.
TABLE.1 Bodily Responses Associated
with Opioid Receptor Sites

13. ACTIONS
• The actions of the opioid analgesics on
the various organs and structures of the
body (also called secondary pharmacologic
effects) are shown in Box.1. (See next slides)
• With long-term use, the patient’s body
adapts to these secondary effects. The only
bodily system that does not adapt and
compensate is the GI system. Slow GI
motility and the resulting constipation are
always a problem in opioid therapy.

14. BOX .1 Secondary
Pharmacologic Effects of the
Opioid Analgesics
• Cardiovascular—peripheral vasodilation, decreased peripheral resistance,
inhibition of baroreceptors (pressure receptors located in the aortic arch
and carotid sinus that regulate blood pressure), orthostatic hypotension,
and fainting
• Central nervous system—euphoria, drowsiness, apathy, mental confusion,
alterations in mood, reduction in body temperature, feelings of relaxation,
dysphoria (depression accompanied by anxiety); nausea and vomiting are
caused by direct stimulation of the emetic chemoreceptors located in the
medulla. The degree to which these occur usually depends on the drug
and the dose.
• Dermatologic—histamine release, pruritus, flushing, and red eyes

15. BOX .1 Secondary
Pharmacologic Effects of the
Opioid Analgesics
• Gastrointestinal—decrease in gastric motility (prolonged emptying time);
decrease in biliary, pancreatic, and intestinal secretions; delay in digestion
of food in the small intestine; increase in resting tone, with the potential
for spasms, epigastric distress, or biliary colic (caused by constriction of
the sphincter of Oddi). These drugs can cause constipation and anorexia.
• Genitourinary—urinary urgency and difficulty with urination, caused by
spasms of the ureter. Urinary urgency also may occur because of the
action of the drugs on the detrusor muscle of the bladder. Some patients
may experience difficulty voiding because of contraction of the bladder
sphincter.

16. BOX .1 Secondary
Pharmacologic Effects of the
Opioid Analgesics
• Respiratory—depressant effects on respiratory rate (caused by a reduced
sensitivity of the respiratory center to carbon dioxide).
• Cough—suppression of the cough reflex (antitussive effect) by exerting a
direct effect on the cough center in the medulla. Codeine has the most
noticeable effect on the cough reflex.
• Medulla—Nausea and vomiting can occur when the chemoreceptor
trigger zone located in the medulla is stimulated. To a varying degree,
opioid analgesics also depress the chemoreceptor trigger zone. Therefore,
nausea and vomiting may or may not occur when these drugs are given.

17. ACTIONS
• The most widely used opioid, morphine sulfate, is an effective drug for
moderately severe to severe pain. Morphine sulfate is considered the prototype
(model) opioid. Morphine sulfate is also considered the gold standard in pain
management—morphine sulfate’s actions, uses, and ability to relieve pain are the
standards against which other opioid analgesics are often compared.
• Charts called equal-analgesic conversions compare other opioid doses with the
doses of morphine sulfate that would be used for the same level of pain control.
This conversion process is helpful when drugs are changed because of lessening or
increasing pain and if adverse effects worsen to the point they are unmanageable
for the patient. These conversions are particularly helpful when drugs change
form, such as IV infusion to oral doses.
• Other opioids, such as meperidine are effective for the treatment of moderate
to severe pain. For moderate pain, the primary health care provider may order an
opioid such as codeine, or pentazocine.

18. USES
• The opioid analgesics are used primarily for the treatment of
moderate to severe acute and chronic pain and in the
treatment and management of opiate dependence. Morphine
sulfate is one of the primary drugs. In addition, the opioid
analgesics may be used for the following reasons:-
• To decrease anxiety and sedate the patient before surgery. Patients
who are relaxed and sedated when an anesthetic agent is
given are easier to anesthetize (requiring a smaller dose of an
induction anesthetic), as well as easier to maintain under
anesthesia
• To support anesthesia (i.e., as an adjunct during anesthesia)
• To promote obstetric analgesia
• To relieve anxiety in patients with dyspnea (breathing difficulty)
associated with pulmonary edema

19. USES
• Administered intrathecally (a single injection into spinal cord
space) or epidurally (catheter placed into spinal cord space for
multiple injections), to control pain for extended periods without
apparent loss of motor, sensory, or sympathetic nerve function
• To relieve pain associated with a myocardial infarction (morphine
sulfate is the agent of choice)
• To manage opiate dependence
• To induce conscious sedation before a diagnostic or therapeutic
procedure in the hospital setting
• •To treat severe diarrhea and intestinal cramping (camphorated
tincture of opium may be used)
• To relieve severe, persistent cough (codeine may be helpful,
although the drug’s use has declined)

20. ADVERSE REACTIONS
Central Nervous System Reactions
• Euphoria, weakness, headache
• Lightheadedness, dizziness, sedation
• Miosis, insomnia, agitation, tremor
• Increased intracranial pressure, impairment of mental and physical tasks
Respiratory System Reactions
• Depression of rate and depth of breathing
Gastrointestinal System Reactions
• Nausea, vomiting
• Dry mouth, biliary tract spasms
• Constipation, anorexia

21. ADVERSE REACTIONS
Cardiovascular System Reactions
• Facial flushing
• Tachycardia, bradycardia, palpitations
• Peripheral circulatory collapse
Genitourinary System Reactions
• Urinary retention or hesitancy
• Spasms of the ureters and bladder sphincter
Allergic and Other Reactions
• Pruritus, rash, and urticaria
• Sweating, pain at injection site, and local tissue irritation

22. Concept Mastery Alert
• Although the respiratory system will adapt to
secondary effects of opioids, the GI system
does not.
• Adverse effects such as constipation and slow
GI motility do not dissipate.

23. CONTRAINDICATIONS
• All opioid analgesics are contraindicated in patients with
known hypersensitivity to the drugs. These drugs are
contraindicated in patients with acute bronchial asthma,
emphysema, or upper airway obstruction and in
patients with head injury or increased intracranial
pressure. The drugs are also contraindicated in patients
with convulsive disorders, severe renal or hepatic
dysfunction, and acute ulcerative colitis.
• The opioid analgesics are not recommended for use
during pregnancy or labor because they may prolong
labor or cause respiratory depression in the neonate. The
use of opioid analgesics is recommended during pregnancy
only if the benefit to the mother outweighs the potential
harm to the fetus.

24. PRECAUTIONS
• Opioid analgesics should be used cautiously in older
adults and in patients considered opioid naive, that is,
who have not been medicated with opioid drugs before
and who are consequently at greatest risk for respiratory
depression. The drugs should be administered cautiously in
patients undergoing biliary surgery (because of the risk for
spasm of the sphincter of Oddi, between the bile duct and
small intestine; in these patients, meperidine is the drug of
choice).
• Patients who are lactating should wait at least 4 to 6 hours
after taking the drug to breastfeed the infant. Additional
precautions apply to patients with undiagnosed abdominal
pain, hypoxia, supraventricular tachycardia, prostatic
hypertrophy, and renal or hepatic impairment.

25. INTERACTIONS
The following interactions may occur when an opioid analgesic is
administered with another agent:-

26. Tolerance Versus Dependence
• Over time, the patient taking an opioid analgesic develops a
tolerance to the drug.
• This is different from physical dependence, where the body
experiences adverse effects if the medicine is stopped.
• With tolerance, the body physically adapts to the drug, and
greater amounts are needed to achieve the same effects.
The rate at which tolerance develops varies according to
the dosage, the route of administration, and the individual.
• Patients taking oral medications develop tolerance more
slowly than those taking the drugs parenterally. Some
patients develop tolerance quickly and need larger doses
every few weeks, whereas others are maintained on the
same dosage schedule throughout the course of the illness.

27. KEY POINTS
• Opioid is a term used for drugs that change the pain
sensation by attaching to receptor sites in the brain
producing an analgesic, sedative, and euphoric effect. Most
of these are derived from opium or a synthetic substance
like opium.
• These drugs are used to treat moderate to severe pain.
• Narcotic is a term referring to the properties of a drug to
produce numbness or a stupor-like state. Although the
terms opioid and narcotic were once interchangeable,
law enforcement agencies have generalized the term
narcotic to mean a drug that is addictive and abused or
used illegally. Health care providers use the term opioid to
describe drugs used in pain relief.

28. KEY POINTS
• Morphine sulfate is a drug used through multiple
routes for relief of chronic and acute pain.
• Other opioids are compared to this drug (the gold
standard) when attempting to determine dosing
or conversion between drug types.
• The more common non–pain relief effects
(known as secondary effects) of these drugs
include respiratory depression, decreased GI
motility, and miosis.
• Constipation is the one side effect to which the
body does not build a tolerance.