Pharmacology for Nursing

Drugs Affecting the Central Nervous System

(CNS)

Analgesic Agents

Dr. Hanan Al-Shamaly

 Outlines
• Definition of Pain
• Pain Threshold
• Pain Tolerance
• Classification of Pain by Origin
• Pain Transmission
• Controlling pain
• Opioids and non-opioid analgesics
• Indications and adverse reactions of opioid analgesics.
• Physiologic dependence, psychologic dependence, and drug toxicity.
• Implications for the administration of opioid analgesics.
• Opioid Analgesics pharmacologic profile.
• Pharmacological profile of commonly used opioids
 Intended Learning Outcomes
• At the end of this lecture, students will be able to:
• Define Pain
• Recognize the pain threshold.
• Explain the state of pain tolerance.
• Classify pain by origin.
• Explain the etiology of pain transmission.
• Identify important terms related to pain control.
• Compare between opioids and non-opioid analgesics.
• Describe indications and adverse reactions of opioid analgesics.
• Define physiologic dependence, psychologic dependence, and drug toxicity.
• Discuss nursing implications for the administration of opioid analgesics.
• Analyze the pharmacologic profile of opioid analgesics.
• Compare between Pethidine and Morphine.
 Pain
▪ An unpleasant sensory and emotional experience
associated with actual or potential tissue damage.

▪ A personal and individual experience.

▪ Whatever the patient says it is.

▪ Exists when the patient says it exists.

 Pain Threshold

• Level of stimulus needed to produce the perception of pain.

• A measure of the physiologic response of the nervous

system.
 Pain Tolerance
• The amount of pain a person can endure without
interfering with normal function.

• Varies from person to person.

• Subjective response to pain, not

a physiologic function.

• Varies by attitude, environment, culture & ethnicity.

Classification of Pain by Origin

• Somatic • Referred
• Visceral • Neuropathic
• Superficial • Phantom
• Deep • Cancer
• Vascular • Central
Nociception (cont’d)
 Pain Transmission

Gate Theory
• Most common and well-described.

• Uses the analogy [similarity] of a gate to describe how

impulses from damaged tissues are sensed in the brain.

• Many current pain management strategies are aimed at

altering this system.
 Pain Transmission
 Tissue injury causes the release of :
➢ Bradykinin
➢ Histamine
➢ Potassium
➢ Prostaglandins
➢ Serotonin

 These substances stimulate nerve endings,

starting the pain process.
 Pain Transmission (cont’d)
 Two types of nerves stimulated:

➢ “A” fibers

➢ “C” fibers

 Types of pain related to the proportion of “A” to “C”

fibers in damaged areas.
 “A” vs “C” fibers
▪ A-delta fibers are lightly myelinated axons and conduct action
potential rapidly. In other words, it carries ‘fast’ type of pain.
e.g.; a sudden, sharp, prick on the body sends a high-speed pain
message to the brain to avoid it. These nerve fibers have medium
to large-diameter cell bodies.

▪ On the other hand, C-fibers mediate ‘lingering' type of pain such

as burning or aching. The C-fibers have unmyelinated axons, and
small-diameter cell bodies and conduct slow action potential.

▪ More than 70% of the nociceptive fibers are C-fibers. Some

subset of A-delta fibers responds to low-threshold stimuli such as
touching or brushing. Likewise, some of the C-fibers sense
warmth or cold.
 Pain Transmission (cont’d)

 These pain fibers enter the spinal cord and travel up to the

brain.

 The point of spinal cord entry or the “gate” is the dorsal horn.

 This gate regulates the flow of sensory impulses to the brain.

 Pain Transmission - Gate Theory

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p=desktop&v=oQLFfvGM7nI

Please see
https://www.youtube.com/watch?app=desktop&v=oQLFfvGM7nI
 Pain Transmission (cont’d)
 Closing the gate stops the impulses.
 If no impulses are transmitted to higher centers in the brain, there is NO pain
perception.

 Activation of large-diameter “A” fibers closes the gate.

 Inhibits transmission to the brain.
➢ Limits perception of pain by carrying pain impulses that modulate the pain
sensation.
 Activation of small-diameter “C” fibers opens the gate.
 Allows impulse transmission to the brain.
➢ Pain perception.

 Gate innervated by nerve fibers from brain, allowing the brain some control
over gate.
 Allows brain to:
➢ Evaluate, identify, and localize pain.
➢ Control the gate before it is open. [through impulses modulating the pain]
 Pain Transmission (cont’d)
 The body has endogenous neurotransmitters.

➢ Enkephalins.

➢ Endorphins [endogenous morphine].

 Produced by the body to fight pain.

 Bind to opioid receptors.

 Inhibit transmission of pain by closing the gate.

 These substances close the spinal cord gates, in

a manner similar to that of opioid analgesic drugs.

 Pain Transmission (cont’d)
▪ Rubbing a painful area with massage stimulates large
sensory fibers

▪ Results with:

➢ Closes gate.

➢ Reduces pain sensation.

 Controlling Pain - Important terms
 Analgesics: Are the drugs which selectively relieves pain by acting in
the CNS or on peripheral pain mechanisms, without significantly
altering the consciousness such as “Painkillers”– Opioids and Non-
steroidal anti-inflammatory drugs (NSAIDs).
[NSAIDs : are medicines that are widely used to relieve pain, reduce inflammation,
and bring down a high temperature].
 Opioids: Any drug which binds to the opioid receptors
(Pharmacologically related) in the CNS and antagonized by Naloxone.
They may be – Natural, Synthetic and semi-synthetic.
 Opiates: Drugs derived from opium – Natural or semi-synthetic.

 Narcotics: Drugs derived from opium or opium like compounds, with

potent analgesic effects associated with significant alteration of mood
and behavior, and with the potential for dependence and tolerance
following repeated administration.
 Analgesic Agents
OPIOID ANALGESICS
 Pain relievers that contain opium, derived from the

opium poppy or chemically related to opium.

 Very strong pain relievers.

 Opioids - Classification

1. Natural Opium Alkaloids: Morphine and Codeine.

2. Semi-synthetic: Diacetylmorphine (Heroin).

3. Synthetic Opioids:

➢ Pethidine (Meperidine).
➢ Fentanyl.
 Opioid Analgesics (cont’d)

• Codeine sulfate [ weak pain]

• Meperidine HCl (Demerol)

• Morphine sulfate

• Hydromorphone [ moderate to severe pain ]

• Fentanyl

• Others
Opioid Analgesics: Mechanism of Action

 Three classifications based on their actions:

1. Agonist

2. Partial agonist

3. Antagonist
 Agonists
 Bind to an opioid pain receptor in the brain.
 Cause an analgesic response (reduction of pain sensation).
 Antagonists

 Reverse the effects of these drugs on pain receptors.

 Bind to a pain receptor and exert no response.

 Also known as competitive antagonists.

 Agonists-Antagonists

 Bind to a pain receptor.

 Cause a weaker neurologic response than a full agonist.

 Also called partial agonist or mixed agonist.

 Opioid Receptors
Five types of opioid receptors:

1. Mu*

2. Kappa*

3. Delta*

4. Sigma

5. Epsilon

* Primary receptors
 Opioid Analgesics: Indications
 Main use: to alleviate moderate to severe pain.
 Often given with adjuvant analgesic drugs to assist primary

drugs with pain relief.

Opioids are also used for:
➢ Cough center suppression (codeine, hydrocodone).
➢ Treatment of diarrhea “anticholinergic” (Lomotil).
➢ Fentanyl is used in combination with anesthetics during
surgery “Balanced Anesthesia”.
➢ Known drug allergy.

➢ Severe asthma.
 Opioid Analgesics:
Use with extreme caution if:
1. Respiratory insufficiency.
2. Elevated intracranial pressure.
3. Morbid obesity.
4. Sleep apnea.
5. Paralytic ileus.
Opioid Analgesics: Adverse Effects
1. Euphoria.
2. CNS depression.
3. Leads to respiratory depression (The most serious adverse
effect)
4. Release of Histamine.
5. Nausea and vomiting.
6. Urinary retention.
7. Diaphoresis and flushing.
8. Pupil constriction (Miosis).
9. Constipation.
10. Itching.
 Opioid Analgesics: Adverse Reactions
“By Systems”
 CNS: Sedation, increased intracranial pressure.
 Respiratory: Depressed breathing [rate/depth- death

usually occur].
 GI: Constipation, anorexia, biliary tract spasms.

 Cardiovascular: Tachycardia, bradycardia,

peripheral circulatory collapse.

 Genitourinary: Urinary retention/hesitancy.

 Allergic reactions: Pruritus, rash, urticaria.

 Other reactions: Sweating, pain at the injection site,

local tissue irritation.

 Opioids: Opioid Tolerance
 A common physiologic result of chronic opioid treatment.

 Result: larger dose is required to maintain the same level of

analgesia.
 Opioids: Physiologic Dependence
• Physiologic adaptation of the body to the presence
of an opioid.

• Opioid tolerance and physical dependence are

expected with long-term opioid treatment and
should not be confused with psychologic
dependence (addiction).
 Opioids: Psychologic Dependence

 A pattern of compulsive drug use characterized by

a continued craving [desire] for an opioid and the

need to use the opioid for effects other than pain

relief.
 Opioids
• (Tolerance & Dependence): Misunderstanding of
these terms leads to ineffective pain management
and contributes to the problem of under treatment.
• Physical dependence is seen when the opioid is
abruptly discontinued or when an opioid antagonist
is administered.
• Opioid withdrawal/opioid abstinence syndrome.
 Toxicity and Management of Overdose

• Naloxone (Narcan).

• Naltrexone (Revia).

o These drugs bind to opiate receptors and prevent a response.

o Used for complete or partial reversal of opioid-induced

respiratory depression.

• Regardless of withdrawal symptoms, when a patient

experiences severe respiratory depression, an opioid
antagonist should be given.
Toxicity and Management of Overdose (cont’d)
• Opioid withdrawal/opioid abstinence syndrome.
• Mild, moderate or severe [according to clinical scale:
withdrawal scale].
• Taking opioids mimic the effects of naturally occurring
opioids].
• [opioids change the way that nerve work in the brain].
• Manifested as:
⁃ Anxiety, irritability, chills and hot flashes, joint pain,
lacrimation, rhinorrhea, diaphoresis, nausea, vomiting,
abdominal cramps, diarrhea, confusion.
 Opioid Analgesics: Interactions
1. Alcohol; Antihistamines; Antidepressants; Sedatives:
Increased risk for CNS depression.
2. Opioid agonist-antagonist: Opioid withdrawal symptoms.

3. Barbiturates (sedative-hypnotic): Respiratory depression,

hypotension, and/or sedation [e.g.; methohexital before
operation], can be used to treat insomnia and anxiety.

4. Herbal Alert: Passion flower: Large doses may cause

CNS depression.
Passion Flower
Opioid Analgesics: Implications for Administration
 Before beginning therapy, perform a thorough history
regarding allergies and use of other medications, including
alcohol, health history, and medical history [slower disposal
rate and may account for possible toxicity].
 Obtain baseline vital signs and Intake & Output.
 Assess for potential contraindications and drug interactions.
• Perform a thorough pain assessment, including pain
intensity and character, onset, location, description,
precipitating and relieving factors, type, remedies, and other
pain treatments.
• Assessment of pain is now being considered a “fifth vital
sign”.
• Rate pain on a 0 to 10 scale.
Opioid Analgesics: Implications for Administration
 Be sure to medicate patients before the pain becomes severe so
as to provide adequate analgesia and pain control.
 Pain management includes pharmacologic and
nonpharmacologic approaches; be sure to include other
interventions as indicated.
 Instruct patients to notify physician for signs of allergic reaction
or adverse effects.
 Oral forms should be taken with food to minimize gastric upset
[this may minimize stomach irritation].
 Ensure safety measures, such as keeping side rails up, to prevent
injury.
 Withhold dose and contact physician if there is a decline in the
patient’s condition or if vital signs are abnormal, especially if
respiratory rate is less than 10 to 12 breaths/min.
Opioid Analgesics: Implications for Administration
Check dosages carefully
• Follow proper administration guidelines for IM injections,
including site rotation.

• Follow proper guidelines for IV administration, including

dilution, rate of administration.

Relieving Chronic Severe Pain

• Morphine sulfate: Should be scheduled around the clock.

• Controlled-released forms: Indicated for the management

of pain when a continuous analgesic is needed for an
extended time.
Opioid Analgesics: Implications for Administration

 Constipation is a common adverse effect and

may be prevented with adequate fluid and fiber intake.

 Instruct patients to follow directions for administration

carefully and to keep a record of their pain experience
and response to treatments.

 Patients should be instructed to change positions slowly

to prevent possible orthostatic hypotension.
 Monitor for Adverse Effects
• Contact a physician immediately if vital signs change, the
patient’s condition declines, or the pain continues.
• Report a significant increase or decrease in the pulse rate
or a change in the pulse quality.
• Report a significant decrease in blood pressure (systolic
or diastolic) or a systolic pressure below 100 mm Hg.
• Respiratory depression may be manifested by a respiratory
rate of less than 10 breaths/min, dyspnea, diminished
breath sounds, or shallow breathing.
 Monitor for Therapeutic Effects
 Decreased complaints of pain.

 Decreased severity of pain.

 Increased periods of comfort.

 Improved activities of daily living, appetite, and sense of

well-being.
Opioid Analgesics Pharmacologic Profile
General Use
 Management of moderate to severe pain. Fentanyl is also
used as a general anesthetic adjunct.

General Action and Information

 Opioids bind to opiate receptors in the CNS, where they act

as agonists of endogenously occurring opioid peptides

(Eukephalins and Endorphins). The result is alteration to the
perception of and response to pain.
 Opioids – other uses
 Antidiarrhoeal agents: Diphenoxylate and Loperamide.

 Antitussives: Codeine, Dextromethorphan, Noscapine,

Pholcodeine, Levopropoxyphene.

 Loosing the secretion , anti-congestion and facilitate

breathing.
 Contraindications
• Hypersensitivity to individual agents.
• Precautions
1. Use cautiously in patients with undiagnosed abdominal
pain, head trauma, liver disease, or history of addiction to
opioids.
2. Use smaller doses initially in the elderly and those with
respiratory diseases.
3. Prolonged use may result in tolerance and the need for
larger doses to relieve pain.
4. Psychological or physical dependence may occur.
Interactions
 Increases the CNS depressant properties of other drugs,
including alcohol, antihistamines, antidepressants,
sedatives/hypnotics, phenothiazines, and
Monoamine Oxidase Inhibitors (MAO) inhibitors.

- MAO usually prescribed to treat depression and

Parkinson’s disease; they inhibit the activity of
the Monoamine Oxidase enzyme.
Assessment
 Assess the type, location, and intensity of pain prior to and at a peak
following administration.
 When titrating opioid doses, increases of 25–50% should be
administered until there is either a 50% reduction in the patient’s pain
rating on a numerical or visual analog scale or the patient reports
satisfactory pain relief.
 A repeated dose can be safely administered at the time of the peak if
the previous dose is ineffective and side effects are minimal.
 Patients requiring higher doses of opioid agonist-antagonists if it
should be converted to opioid agonists.
 Opioid agonist-antagonists are not recommended for prolonged use or
as first-line therapy for acute or cancer pain.
 Assess blood pressure, pulse, and respirations before and periodically
during administration. If the respiratory rate is10/min, assess the level of
sedation. Physical stimulation may be sufficient to prevent significant
hypoventilation.
 The dose may need to be decreased by 25–50%. Initial drowsiness
will diminish with continued use.
 Assess prior analgesic history. Antagonistic properties of agonist-
antagonists may induce withdrawal symptoms (vomiting, restlessness,
abdominal cramps, and increased blood pressure and temperature) in
patients physically dependent on opioids.
 Prolonged use may lead to physical and psychological dependence
and tolerance. This should not prevent patients from receiving
adequate analgesia.
 Most patients who receive opioid analgesics for pain do not develop
psychological dependence.
 Progressively higher doses may be required to relieve pain with
chronic therapy.
 Assess bowel function routinely. Prevention of constipation should be
instituted with increased intake of fluids and bulk, stool softeners, and
laxatives to minimize constipating effects.
• Stimulant laxatives should be administered routinely if
opioid use exceeds 2–3 days unless contraindicated. [some
laxatives cause damage to the colon].
• Monitor intake and output ratios. If significant discrepancies
occur, assess for urinary retention and inform the physician.
• Toxicity and Overdose:
• If an opioid antagonist is required to reverse respiratory
depression or coma, Naloxone (Narcan) is the antidote.
• Dilute the 0.4 mg ampule of Naloxone in 10 mL of 0.9%
NaCl and administer 0.5 mL (0.02 mg) by direct IV push
every 2 min.
• Titrate dose to avoid withdrawal, seizures, and severe pain.
 Potential Nursing Diagnoses
● Acute pain (Indications).

● Disturbed sensory perception (auditory, visual) (Side Effects).

● Risk for injury (Side Effects).

● Deficient knowledge, related to disease process and

medication regimen (Patient/Family Teaching).

Implementation
● Do not confuse morphine with hydromorphone (potent Morphine) or
meperidine (Pethidine);(narcotic analgesics); errors have resulted in
fatalities.
● Explain the therapeutic value of medication before administration to
enhance the analgesic effect.
● Regularly administered doses may be more effective than PRN
administration. Analgesic is more effective if given before pain
becomes severe.
● Co-administration with nonopioid analgesics (e.g.; Acetaminophen,
NSAIDs) may have additive analgesic effects and may permit lower
doses.
● Medication should be discontinued gradually after long-term use to
prevent withdrawal symptoms.
 Patient/Family Teaching
● Instruct patient on how and when to ask for pain medication.
● Medication may cause drowsiness or dizziness. Caution patient to call
for assistance when ambulating or smoking and to avoid driving or
other activities requiring alertness until response to medication is
known.
● Advise patient to make position changes slowly to minimize
orthostatic hypotension.
● Caution patient to avoid concurrent use of alcohol or other CNS
depressants with this medication.
● Encourage the patient to turn, cough, and breathe deeply every 2 hrs.
to prevent atelectasis (complete or partial collapse of the lungs).
 Evaluation/Desired Outcomes

 Decreased severity of pain without a significant alteration

in level of consciousness or respiratory status.

 Tramadol
 Centrally acting analgesic.
 Very low action on opioid receptors.
 Other mechanisms involved in analgesic action – [(5-
hydroxytryptamine [5-HT] and NA reuptake inhibition [blocking
the action of the norepinephrine/noradrenaline transporter] – spinal
inhibition of pain.
 Effective both orally and IV (100mg = 10 mg Morphine)
 Side effects are similar to Morphine but less prominent.

 Well tolerated and has low abuse potential.

 Only Partially reversed by Naloxone.

 Used in chronic neuropathic pain and short diagnostic procedures.

 Dose: 50-100 mg IM/IV/Oral.

 Pethidine
• Morphine VS Pethidine:
• Pethidine is 1/10th as potent as Morphine.
• Similar abuse potential.
• Pethidine: Less spasmodic action in smooth muscles – less
miosis, constipation, and urinary retention.
• Pethidine: Rapid but short duration of action (2-3 Hrs.).
• Pethidine: Vagolytic effect – Tachycardia.
• Pethidine: Devoid of antitussive action, less histamine release –
safer in asthmatics.
• Morphine: Better oral absorption.
✓ Pethidine is no more recommended as before because of safety
issues.
References
- Lilley, L.L., Collins, S. R, Snyder, J. S. (2020). Pharmacology and the
nursing process. 9th Edition.

- Michelle J. Willihnganz, Samuel L. Gurevitz, Bruce D. Clayton.

Clayton’s Basic Pharmacology for Nurses (2013), (18th edition).
Philadelphia, Elsevier Mosby.

- Paul Barber and Deborah Robertson (2020,) Essential of

pharmacology for nurses, (4th edition).