Pain, Analgesia, and Anesthesia (PathoPharm Exam 3)

Pain

▪ Protective signal → indicates tissue

injury or threat

▪ Generated by nociceptors → CNS

processing → perception

▪ Influenced by:

▪ Biological → injury, inflammation

▪ Psychological → anxiety, past

experience

▪ Social → culture, support

▪ Key concept:

Nociception ≠ Pain

(physiologic signal ≠ experience/perception)

▪ Clinical implication:

Patient report = gold standard

Pain pathway

▪ Transduction

▪ Tissue injury → inflammatory mediators

→ nociceptor activation

▪ Transmission

▪ Signal travels → peripheral nerve →

spinal cord → brain

▪ Perception

▪ Brain interprets signal → “pain

experience”

▪ Modulation

▪ CNS ↑ or ↓ pain signal (endorphins,

descending pathways)

▪ This pathway = target of all analgesics

▪ Drugs act at different steps in this

pathway

Transduction

▪ Tissue injury → inflammatory mediators

→ nociceptor activation

Transmission

▪ Signal travels → peripheral nerve →

spinal cord → brain

Perception

▪ Brain interprets signal → “pain

experience”

Modulation

▪ CNS ↑ or ↓ pain signal (endorphins,

descending pathways)

What activates pain

▪ Mechanical → pressure, stretch, injury

▪ Thermal → extreme heat/cold

▪ Chemical → inflammation

(prostaglandins, bradykinin, ATP)

▪ What happens:

▪ Stimulus → ion channels open

→ action potential

→ signal to CNS

▪ Key concept:

▪ Inflammation = lowers pain

threshold (↑ sensitivity)

Pain mediators

▪ Pain facilitators (increase pain)

▪ Prostaglandins → sensitize nociceptors (not direct pain cause)

(KEY target of NSAIDs)

▪ Bradykinin → direct nociceptor activation

▪ Substance P → amplifies signal in spinal cord

▪ Histamine → inflammation + swelling

▪ Pain inhibitors (decrease pain)

▪ Endorphins → natural opioids

▪ Endocannabinoids → modulate pain

▪ Clinical connection:

▪ Most analgesics target these mediators or pathways

Acute pain

▪ Protective → signals injury

▪ Sympathetic activation:↑ HR, ↑ BP, ↑ RR, diaphoresis

▪ Resolves with healing

Chronic pain

▪ No longer protective

▪ CNS remodeling + persistent signaling

▪ Minimal physiologic response

▪ Psychological + functional impact

▪ Key concept: Chronic pain = disease, not just a symptom

Types of acute pain

-Nociceptive

-Neuropathic

-Inflammatory

-Central

Key Concept: Identify the pain type - guides drug choice

-Different pain types - different drug choices

Nociceptive (tissue injury)

-Somatic - sharp, localized

-Visceral - deep, diffuse

Neuropathic (nerve damage)

Burning, tingling, electric

Inflammatory

Swelling, aching, throbbing

Central (processing disorder)

No clear injury (fibromyalgia)

Where pain drugs work

Transduction - NSAIDs, corticosteroids

Transmission - local anesthetics

Perception - opioids

Modulation - antidepressants, anticonvulsants

▪ THIS is the framework for all analgesia

pharmacology

→ Drug selection depends on the type of pain + where

it acts in the pathway

NSAIDs

▪ MOA: Inhibit COX → ↓ prostaglandins

▪ Effects: ↓ pain | ↓ inflammation | ↓ fever

▪ Why they work:

▪ Prostaglandins = key pain sensitizers

▪ ADR:

▪ GI bleeding → ↓ protective prostaglandins

▪ Renal injury → ↓ renal perfusion – especially in

hypovolemia or older adults

▪ Increased BP

▪ Nursing:

▪ Monitor GI, renal function, dosing limits

Acetaminophen

▪ MOA: Acts in CNS → ↓ prostaglandins (minimal

peripheral effect)

▪ Effects: ↓ pain | ↓ fever

▪ NO anti-inflammatory effect

▪ Major ADR:

▪ Hepatotoxicity → dose dependent

▪ Max Dose:

▪ 4 g/day (healthy)

▪ ≤3 g/day (high risk)

Opioid Agonists

▪ MOA: Bind μ receptors → ↓ pain

perception + emotional response

▪ Effects: Analgesia, sedation,

euphoria

▪ Major ADR:

▪ Highest Risk: Respiratory

depression

▪ Constipation, dependence

▪ Antidote:

▪ Naloxone → reverses opioid

effects

▪ Key concept:

▪ Pain signal present → perception +

emotional response reduced

Opioid receptors

▪μ (mu) → analgesia, respiratory

depression, euphoria

▪κ (kappa) → spinal analgesia,

sedation

▪ δ (delta) → minor role

▪Clinical focus: μ receptor = most

important

Combination opioids

▪ Opioid + non-opioid (e.g., acetaminophen)

▪ Benefit: Better pain control

▪ Risk: Dose ceiling → toxicity from non-opioid

▪ Common Examples

▪ Hydrocodone/APAP (Vicodin, Norco)

▪ Oxycodone/APAP (Percocet)

▪ Codeine/APAP (Tylenol #3)

▪ What to Question (Safety Check)

▪ Is the patient taking multiple APAP-containing products?

(e.g., Percocet + OTC Tylenol, cold/flu meds)

▪ Total daily acetaminophen dose > 3–4 g/day?

▪ Liver disease, alcohol use, malnutrition?

▪ Key Danger:

▪ Acetaminophen overdose → liver failure

Assessment of pain

▪ Onset: sudden or gradual

▪ Location: where + does it radiate?

▪ Quality: sharp, dull, burning, etc.

▪ Intensity: 0–10 scale

▪ Aggravating/relieving factors

▪ Effect on function (ADLs, mobility)

▪ Influencing factors:

▪ Biological

▪ Psychological

▪ Social

Effects of ineffective pain management

1. Cardiovascular – ↑ HR, BP, cardiac workload

2. Pulmonary – Hypoventilation, atelectasis, infection

3. GI – Post-op ileus, constipation, urinary retention

4. Muscular – Weakness, fatigue

5. Psychological – Anxiety, fear, frustration

Long-Term – Chronic stress impacts heart, lungs, &

immune system

Pain management principles

▪ Pain is subjective (patient is best judge)

▪ Goal: ↓ pain → improve function (not eliminate)

▪ Multimodal: non-pharm + pharmacologic

▪ Non-pharm:

▪ Physical (heat/ice, PT, TENS)

▪ Cognitive (distraction, biofeedback)

▪ Mind–body (acupuncture, meditation, yoga)

▪ Adjuvant meds: not primary analgesics—enhance pain control

▪ Antidepressants (TCAs, SSRIs) → neuropathic pain

▪ Anticonvulsants (gabapentin, pregabalin) → neuropathic pain

▪ Corticosteroids → inflammatory pain

▪ Individualize dosing + manage ADRs

▪ Reassess pain + function

Morphine

• Class: Opioid Agonist (Narcotic

Analgesic)

• MOA: Binds to opioid receptors

(mu/kappa) in the CNS to alter pain

perception.

• Therapeutic Effects: Severe acute pain,

chronic pain, preanesthetic sedation.

• ADR: Respiratory depression, sedation,

nausea/vomiting, constipation, urinary

retention.

▪ Black box warning - Schedule II, High

risk physical/psychologic dependence.

Extended Release for opioid-tolerant

clients only, not intended for prn use

• Nursing Considerations:

▪ Monitor for sedation, respiratory

depression

▪ Monitor bowel function.

▪ Use naloxone (Narcan) for overdose.

▪ Routes: oral, IV, subcutaneous

Fentanyl

▪ Class: Opioid Agonist (IV Anesthetic)

▪ MOA: Binds to mu/kappa opioid receptors

for potent, rapid analgesia.

▪ Therapeutic Effects: Short-duration

analgesia, chronic pain management, severe

pain in controlled settings (e.g., surgery).

▪ 50-100 times more potent than morphine.

▪ Faster onset, short duration.

▪ ADR: Respiratory depression,

bradycardia, hypotension, muscle rigidity.

▪ Black Box Warning: Schedule II controlled

substance; high abuse potential, risk of misuse,

overdose, and CNS depressant interaction.

▪ Nursing Considerations:

• Ensure airway support

• Monitor for respiratory depression

• Titrate carefully, especially in opioid-naive

patients

• Routes: IV, transdermal patches, lozenges

Tramadol

▪ Class: Synthetic Opioid Analgesic

▪ MOA: binds to mu receptor, weak opioid

agonist. Inhibits

norepinephrine/serotonin reuptake,

inhibits pain transmission impulse

▪ Therapeutic Effects: Moderate pain, off-

label for neuropathic pain, restless leg

syndrome.

▪ ADR: Dizziness, N/V, lethargy, CNS

stimulation, seizures.

▪ Contraindications: History of seizures,

use in combination with SSRIs/MAOIs.

Sudden death if combined with ethanol.

▪ Nursing Considerations:

▪ Monitor for seizures

▪ Patient should avoid alcohol/CNS

depressants

▪ Assess for risk of serotonin syndrome.

▪ Schedule IV controlled substance

Anesthesia

a medically induced, reversible state of loss

of sensation—with or without loss of consciousness—used to

prevent pain during procedures.

▪ Levels of CNS Depression

▪ Sedation → calm, awake

▪ Moderate sedation → drowsy, arousable

▪ Deep sedation → difficult to arouse

▪ General anesthesia → unconscious

▪ Drugs move patients along this continuum

Types of anesthesia

-General

-Regional

-Local

-Sedation

General

•loss of sensation + loss of consciousness

•used for major surgery

▪ MOA:

▪ ↑ GABA (inhibitory) and ↓ NMDA

(excitatory)

▪ Result:

▪ Global CNS depression →

unconsciousness

▪ Risks:

▪ Respiratory depression

▪ Hypotension

Regional

•loss of sensation in a body region

•consciousness intact

•used for procedures below level (e.g.,

spinal/epidural)

Local

• loss of sensation in a small area

•consciousness intact

• used for minor procedures

▪ MOA: Block sodium channels →prevent depolarization-

stop action potentials → stops transmission

▪ Result: Pain signal never reaches CNS

▪ Examples: Lidocaine, bupivacaine

▪ Toxicity:

▪ CNS → seizures

▪ Cardiac → arrhythmias

Sedation

• reduced awareness (± mild ↓ sensation)

•consciousness variably depressed

•used for procedures requiring

relaxation/anxiolysis

Isoflurane

▪ Therapeutic Class: Inhaled general

anesthetic

▪ Pharmacologic Class: GABA ↑, NMDA ↓

▪ MOA: ↑ inhibitory (GABA) + ↓ excitatory

signaling → global CNS depression →

anesthesia

▪ Indications: Induction + maintenance of

general anesthesia

▪ ADR: Hypotension, respiratory depression,

N/V

▪ Serious: malignant hyperthermia,

arrhythmias, hepatotoxicity

▪ Contraindications: Malignant

hyperthermia, Severe hepatic disease (use

caution)

▪ Nursing Considerations:

▪ Pre-op: assess risk (MH, liver)

▪ Monitor: BP, ECG, respiratory status

▪ Post-op: respiratory depression,

hypotension, delirium

Nitrous oxide

▪ Therapeutic Class: Inhaled anesthetic

▪ Pharmacologic Class: CNS depressant

▪ MOA: NMDA receptor antagonist

→ blocks excitatory glutamate signaling→

mild anesthesia + analgesia

▪ Indications: Dental procedures, Labor

analgesia, Adjunct to general anesthesia

▪ Key Features: Rapid onset + rapid recovery;

Weak anesthetic → used with other agents

▪ ADR: Nausea, dizziness, sedation

→ Serious: diffusion hypoxia (if not given

with O₂)

▪ Contraindications: Air-filled space

conditions (pneumothorax, bowel

obstruction)

▪ Critical Safety: Must be administered with

oxygen

▪ Nursing Considerations:

▪ Monitor O₂ saturation, respiratory status

▪ Ensure oxygen delivery during and after

use

Propofol

▪ Therapeutic Class: General anesthetic

▪ Pharmacologic Class: GABA agonist

▪ MOA: Enhances GABA activity → ↑inhibitory

signaling → rapid CNS depression →

sedation/anesthesia

▪ Key Features: Rapid onset + short duration,

No analgesic effect

▪ Indications: Induction + maintenance of

anesthesia, Procedural sedation, ICU

sedation (ventilated patients)

▪ ADR: Respiratory depression, Hypotension,

Bradycardia

→ Serious: Propofol infusion syndrome

(PRIS)

▪ Contraindications: Hemodynamic

instability; Caution: egg/soy allergy

▪ Critical Safety: No analgesia → often

combined with analgesics

▪ Nursing Considerations:

▪ Ensure airway + ventilation support

▪ Monitor BP, ECG, respiratory status

▪ Watch for PRIS (metabolic acidosis,

cardiac failure)

Sedatives for anesthesia

• MOA: CNS depressants that induce relaxation and

amnesia.

• Examples: Midazolam (Versed), Diazepam (Valium).

• Indications: Used for conscious sedation during

minor procedures.

• ADR: Respiratory depression, hypotension,

drowsiness.

• Nursing Considerations:

▪ Monitor for respiratory rate and blood pressure

▪ Ensure patient safety during recovery.

Midazolam

▪ Therapeutic Class: Sedative / anxiolytic

▪ Pharmacologic Class: Benzodiazepine

(GABA agonist)

▪ MOA: Enhances GABA → ↑ inhibitory

signaling→ sedation, anxiolysis, amnesia

▪ Key Features: Rapid onset,

Causes anterograde amnesia, No analgesic

effect

▪ Indications: Procedural sedation,

Preoperative anxiolysis, ICU sedation

▪ ADR: Respiratory depression, Hypotension,

Drowsiness

→ Serious: respiratory arrest (with other CNS

depressants)

▪ Contraindications: Severe respiratory

depression, Concurrent CNS depressants

(caution)

▪ Reversal Agent: Flumazenil

▪ Critical Safety: No analgesia → combine with

analgesics if needed

▪ Nursing Considerations:

▪ Monitor respiratory status, BP, level of sedation

▪ Ensure airway support available

Neuromuscular blockers

▪ Paralysis only (no sedation, no analgesia, no

amnesia)

▪ MOA: Block ACh at nicotinic receptors (NMJ) →

↓ muscle contraction → paralysis

▪ Examples: Succinylcholine, Rocuronium

▪ Indications: Intubation, Surgical/mechanical

ventilation paralysis

▪ ADR:

▪ Respiratory paralysis

▪ Malignant hyperthermia (succinylcholine)

▪ Bradycardia, hypotension

▪ Nursing Considerations:

▪ ALWAYS give with sedation + analgesia first!

▪ Monitor airway/oxygenation continuously

▪ Have airway + reversal agents ready

▪ Monitor for malignant hyperthermia

Succinylcholine

▪ Therapeutic Class: Neuromuscular Blocker

(Depolarizing)

▪ Pharmacologic Class: Nicotinic Receptor

Agonist

▪ MOA: Persistent activation of nicotinic

receptors → sustained depolarization →

paralysis

▪ Key Concept: Initial depolarization

→ fasciculations → flaccid paralysis

▪ Indications: Rapid sequence intubation

(RSI), Short procedures requiring rapid

paralysis

▪ ADR: Hyperkalemia, Bradycardia,

Malignant hyperthermia, Respiratory arrest

▪ Contraindications: Hyperkalemia risk

(burns, crush injury, neuromuscular disease),

History of malignant hyperthermia

▪ Critical Safety: No analgesia or sedation →

must be given with sedation

Rocuronium

▪ Therapeutic Class: Neuromuscular Blocker

(Nondepolarizing)

▪ Pharmacologic Class: Nicotinic Receptor

Antagonist

▪ MOA: Competitively blocks acetylcholine at

nicotinic receptors (NMJ) → prevents

depolarization → skeletal muscle paralysis

▪ Key Concept: No depolarization → no

fasciculations → flaccid paralysis

▪ Indications: Rapid sequence intubation,

Surgical muscle relaxation, Mechanical

ventilation support

▪ ADR: Respiratory paralysis (expected),

Hypotension, Prolonged paralysis

▪ Critical Safety: No analgesia or sedation →

must be given with sedation/anesthesia

▪ Reversal Agent: Sugammadex, Neostigmine

▪ Nursing Considerations:

▪ Ensure airway + ventilation support

▪ Continuous monitoring (O₂ sat, respiratory

status)

▪ Assess neuromuscular function (train-of-

four)

Malignant hyperthermia

▪ Definition: Genetic (autosomal dominant)

→ Mutation in RYR1 receptor → ↑ Ca²⁺ release

→ Triggers→ hypermetabolic crisis

▪ Triggers: Volatile (inhaled) Anesthetics + succinylcholine

▪ Patho: ↑ Ca²⁺ → sustained muscle contraction → hypermetabolism

▪ Effects: Hyperthermia, acidosis, hyperkalemia, rhabdomyolysis

▪ Treatment:

▪ Dantrolene (antidote)

▪ Stop trigger

▪ Supportive care:

▪ Rapid cooling (ice packs, cooling blankets)

▪ 100% O₂ + ventilatory support

▪ IV fluids → prevent renal failure (rhabdomyolysis)

▪ Treat acidosis (IV bicarbonate)

▪ Manage hyperkalemia (calcium, insulin + glucose)

▪ Key Point: Get a family history before anesthesia!

Dantrolene

▪ Prototype Drug – Dantrolene (MH Antidote)

▪ Therapeutic Class: Skeletal muscle relaxant

▪ Pharmacologic Class: Ryanodine receptor

antagonist

▪ MOA: Blocks Ca²⁺ release from sarcoplasmic

reticulum → ↓ muscle contraction →

↓ hypermetabolism

▪ Indications:

▪ Malignant hyperthermia (treatment + prevention)

▪ Neuroleptic malignant syndrome (NMS)

▪ Severe muscle spasticity

▪ ADR: Muscle weakness, Drowsiness

→ Serious: hepatotoxicity

▪ Contraindications: Severe liver disease

▪ Critical Safety: Early administration is life-saving

▪ Nursing Considerations:

▪ Monitor liver function (LFTs)

▪ Assess muscle strength, respiratory status

▪ Continue supportive care (cooling, fluids,

electrolytes)

Lidocaine

▪ Therapeutic Class: Local anesthetic /

antiarrhythmic

▪ Pharmacologic Class: Amide-type sodium

channel blocker

▪ MOA: Blocks voltage-gated Na⁺ channels

→ prevents depolarization → stops nerve

conduction

▪ Key Concept: Pain signal never reaches

CNS

▪ Indications: Local / regional anesthesia

(injection, topical)

Ventricular arrhythmias (IV use)

▪ ADR:

▪ CNS: dizziness, confusion, seizures

▪ Cardiac: arrhythmias, hypotension

▪ Contraindications: Severe heart block

▪ Critical Safety: Systemic toxicity → CNS +

cardiac effects

▪ Nursing Considerations:

▪ Monitor ECG, BP, neurologic status

▪ Watch for early toxicity (tinnitus, metallic

taste, confusion)