Opioids and Opiates

Slide 1 · Opioids and Opiates

Environmental and nutritional pathology

Toxicologic injury • organ pathology • clinicopathologic interpretation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish naturally occurring opiates from the broader opioid group.

Explain how potency, adulteration and loss of tolerance increase overdose risk.

Connect heroin exposure with pulmonary, infectious, cutaneous and renal pathology.

Interpret representative multisystem clinicopathologic scenarios.

Slide 3 · Drug injury has more than one mechanism

Pharmacologic action

Direct CNS and respiratory drug effects

Adulterants / contaminants

Particulate and toxic admixture reactions

Hypersensitivity

Reaction to the drug or its additives

Contaminated needles

Infections arising from injection exposure

Slide 4 · Opiates and opioids: Terminology

Opiates

Naturally occurring chemicals derived from poppy plants

Morphine is the naturally occurring example

Opioids

Broader group including derivatives and synthetic variants

Includes agents used medically and outside therapeutic settings

Slide 5 · Opioid agents and their exposure contexts

Agent

Context in the chapter

Morphine

Example of a naturally occurring opiate

Heroin

Poppy-derived street drug related to morphine

Oxycodone / hydrocodone

Prescription opioids also used nontherapeutically

Tramadol / methadone

Prescription opioids also used nontherapeutically

Fentanyl

Highly potent synthetic opioid; also a therapeutic analgesic

Slide 6 · The μ-opioid receptor is a molecular target

Opioid

Narcotic

μ-opioid receptor

Agonism

Central nervous

System effects

Respiratory

Suppression risk

Central effects include somnolence and sedation; Profound respiratory suppression is the major acute danger.

Schematic

Slide 7 · Therapeutic efficacy does not imply safety in misuse

Medical use

Fentanyl is an effective sedative and analgesic when appropriately used

Supervised administration provides clinical oversight

Nontherapeutic use

Unknown drug composition and tolerance status

Potentially fatal respiratory suppression

Slide 8 · Global exposure: Historical figures

31.5 million

Opiate users

60.4 million

Opioid users

Global estimates for 2021 (UNODC 2023). Groups may overlap and should not be added together.

Slide 9 · Opioid overdose: Historical public-health context

Illicit synthetic opioids, particularly fentanyl, increased the burden of drug overdose.

The text reports more than 80,000 U.S. Opioid-related deaths in 2023.

Mixing or substitution with fentanyl can make the actual exposure unpredictable.

The figure describes 2023; It is not a present-day surveillance count.

Slide 10 · Four broad routes to heroin-associated harm

Direct drug effect

Central nervous system and respiratory depression

Cutting agents

Foreign-body and other toxic reactions

Hypersensitivity

Reactions to heroin or its adulterants

Contaminated needles

Infection at local and distant sites

Slide 11 · Fentanyl amplifies drug-composition uncertainty

Fentanyl is highly potent and inexpensive to produce illicitly.

It may be mixed with, or substituted for, another drug.

The person taking the drug may not know fentanyl is present.

Unexpected potency magnifies overdose risk, especially without opioid tolerance.

Slide 12 · Concealed fentanyl exposure: Causal sequence

Drug sold as

Another substance

Fentanyl present

Without knowledge

Dose exceeds

Tolerance

Profound respiratory

Suppression

Schematic: The absence of knowledge and tolerance can convert exposure into an acute lethal event.

Schematic

Slide 13 · Tolerance modifies overdose risk

Tolerance present

Repeated exposure may establish tolerance

No guarantee of protection from a very potent or variable illicit supply

Tolerance absent or lost

Unfamiliar users may be particularly vulnerable

Risk also rises when former tolerance has waned

Slide 14 · Neurobehavioral effects described for heroin

Euphoria is one recognized central nervous system effect.

Hallucinations may occur.

Somnolence and sedation reflect prominent CNS suppression.

The clinical effects vary; No single behavioral finding proves exposure.

Slide 15 · Fatal opioid toxicity centers on breathing

Opioid

Exposure

Respiratory

Suppression

Failure of

Ventilation

Potential

Fatal outcome

Respiratory depression is the usual mechanism of death described in the chapter.

Schematic

Slide 16 · Naloxone reverses opioid effects when timely

Naloxone is an opioid antagonist.

It can rapidly reverse opioid-induced respiratory suppression.

The opportunity for reversal is time-sensitive.

Antagonist reversal addresses pharmacologic toxicity, not injection-associated infections.

Slide 17 · Why unsuspected users face disproportionate danger

Content

An unrecognized potent synthetic opioid

Potency

Profound effect from unexpected exposure

Tolerance

Little or no prior opioid adaptation

Outcome

Rapid respiratory suppression

Slide 18 · Heroin: Origin and clinical setting

Heroin is a poppy-derived street drug closely related to morphine.

The sold product is generally diluted with one or more cutting agents.

The amount of active drug is often unknown to the purchaser.

Intravenous and subcutaneous exposure create additional route-associated injury.

Slide 19 · Administration routes shape tissue injury

Intravenous injection

Immediate entry into blood circulation

Exposure to contaminated equipment

Vein injury with repeated injection

Subcutaneous injection

Local deposition in skin/subcutis

Cellulitis, abscess or ulceration

Repeated local damage and scarring

Slide 20 · Cutting agents are a second toxic exposure

The heroin supply may contain talc or quinine.

Talc is linked with foreign-body granulomatous lesions.

Quinine itself has neurologic, renal and auditory toxicity.

Reactions may arise from the admixture rather than heroin alone.

Slide 21 · Variable street purity limits dose prediction

2%–90%

Purity range described in chapter

Unknown

Active dose to purchaser

The reported range is a source-era observation, not a universal or current purity distribution.

Slide 22 · Independent sources of dose uncertainty

Variable purity

Active heroin proportion differs between illicit preparations

Unknown dose

Purchased quantity does not establish opioid amount

Fentanyl admixture

A more potent opioid may be added without knowledge

Tolerability

Tolerance does not reliably match unknown drug potency

Slide 23 · Immediate death has several mechanisms

Potential terminal event

Reported pathology / effect

Respiratory depression

Profound suppression of breathing

Arrhythmia

Potential lethal disturbance of cardiac rhythm

Cardiac arrest

Final cessation of cardiac function

Severe pulmonary edema

Acute lung fluid accumulation

Slide 24 · Loss of tolerance explains deaths after abstinence

Repeated prior

Heroin exposure

Period without

Exposure

Tolerance

Declines

Return to prior

Use → danger

Loss of tolerance during a period without drug exposure can make a return to use dangerous.

Schematic

Slide 25 · Respiratory depression is the primary toxic target

Respiratory suppression is a predictable pharmacologic effect of opioids.

In profound toxicity, it is the usual cause of death.

Potent synthetic opioids can rapidly intensify this effect.

Reversibility with naloxone demonstrates the importance of recognizing the mechanism.

Slide 26 · Cardiac events may also be terminal

Arrhythmia can contribute to sudden opioid-associated death.

Cardiac arrest is another reported terminal event.

An arrhythmia may culminate in cardiac arrest.

Neither an arrhythmia nor cardiac arrest identifies a unique myocardial lesion.

Slide 27 · Severe pulmonary edema in sudden death

Pulmonary edema is explicitly linked to sudden heroin-associated death.

The amount of fluid accumulation may be clinically severe.

It belongs in the acute toxicologic differential rather than being assumed infectious.

Pulmonary edema and infectious lung injury are different etiologic categories.

Slide 28 · Pulmonary disease is heterogeneous

Acute toxic injury

Pulmonary edema

Vascular infection

Septic pulmonary embolism from endocarditis

Parenchymal infection

Lung abscess / opportunistic infection

Particle reaction

Foreign-body granulomas from adulterants

Slide 29 · Edema versus septic disease: Different pathways

Pulmonary edema

Associated with acute toxicity and sudden death

Fluid accumulation is the essential lesion

Septic embolic disease

Associated with infective endocarditis

Infected material can reach lung circulation

Slide 30 · Right-sided endocarditis can injure the lung

Injection-

Associated infection

Right-sided valve

Endocarditis

Septic emboli

To lung

Pulmonary

Injury

The vascular relationship helps explain why the tricuspid valve and lungs are linked clinically.

Schematic

Slide 31 · Lung abscess belongs to the infectious spectrum

Lung abscess is listed among heroin-associated pulmonary complications.

It must be distinguished conceptually from sterile pulmonary edema.

Septic embolization is another infectious pulmonary mechanism.

An abscess cannot be attributed to a particular pathogen from opioid exposure alone.

Slide 32 · Opportunistic pulmonary infections

Opportunistic infections form part of the reported pulmonary spectrum.

They represent an infectious, not purely pharmacologic, injury category.

Associated HIV infection is another recognized hazard in people sharing injection equipment.

The infecting organism must be established by case-specific evidence.

Slide 33 · Injected adulterants may trigger granulomas

Talc or other

Adulterant

Foreign material

In tissues

Granulomatous

Reaction

Pulmonary and

Other organ lesions

Schematic of particle-associated foreign-body inflammation; Not a photomicrograph.

Schematic

Slide 34 · Foreign-body giant cells are a morphologic clue

Talc crystals may be trapped within foreign-body granulomas.

Some crystals are enclosed by multinucleated foreign-body giant cells.

This finding favors a tissue reaction to exogenous particulate material.

It does not identify the active opioid or establish a drug concentration.

Slide 35 · Polarization can reveal retained talc

Routine tissue assessment

Recognize a foreign-body granulomatous pattern

Look for embedded particulate material

Polarized light

May highlight retained talc crystals

Can improve detection of material within giant cells

Slide 36 · Granulomas are not restricted to the lungs

Pulmonary tissue is the principal site emphasized in the text.

Other described sites include spleen and liver.

Upper-extremity–draining lymph nodes may also contain foreign-body granulomas.

Distribution is consistent with systemic exposure to injected particulate adulterants.

Slide 37 · Four pulmonary lesions require distinct explanations

Lesion

Dominant causal category

Discriminating idea

Edema

Acute toxic response

Fluid in lung

Septic emboli

Valve-related infection

Infected embolic material

Abscess / opportunistic infection

Infectious complication

Pulmonary infection

Talc granuloma

Foreign-body reaction

Particles and giant cells

Slide 38 · Injection-associated infection is multisite

Skin / subcutis

Cellulitis, abscess and ulceration

Heart valves

Often right-sided, especially tricuspid

Liver

Viral hepatitis associated with needle sharing

Lungs

Septic emboli, abscess and other infections

Slide 39 · Local injection sites can seed infection

Skin or venous

Puncture

Contaminated needle

Or inoculum

Local soft-tissue

Infection

Potential distant

Complications

The diagram distinguishes entry site pathology from infection of valves or lung.

Schematic

Slide 40 · Tricuspid valve endocarditis is characteristic

Endocarditis is a recognized complication of injection-associated drug use.

Right-sided heart valves are often involved.

The tricuspid valve is highlighted as a particularly typical site.

In one hospitalized series, more than 10% had endocarditis; This is not a population prevalence.

Slide 41 · Staphylococcus aureus is frequently implicated

Staphylococcus aureus causes most cases of the endocarditis described in this setting.

Fungi are also implicated.

Many other organisms can cause the complication.

Organism identification requires patient-specific clinical microbiology, not source-level inference.

Slide 42 · Valve and lung findings may be causally linked

Valve

Infection

Vegetative

Infective material

Pulmonary

Septic emboli

Secondary lung

Disease

Anatomic schematic: Material from right-heart valves travels toward pulmonary vessels.

Schematic

Slide 43 · Sharing needles permits viral hepatitis transmission

Viral hepatitis is described as the most common infection in the addicted population under discussion.

Needle sharing is the identified exposure route.

A diagnosis of viral hepatitis does not by itself establish the infecting viral subtype.

Bloodborne viral infection is distinct from direct opioid pharmacologic toxicity.

Slide 44 · HIV is another needle-associated infection

Shared injection equipment is linked to HIV transmission.

HIV infection has historically been a major complication in U.S. Injection-drug users.

This is an infection-related complication, not a direct opioid receptor effect.

Exposure through shared equipment is the relevant causal link.

Slide 45 · A shared injection pathway reaches distant organs

Shared /

Contaminated needles

Bloodborne

Pathogen exposure

Systemic

Infection

Valves, liver,

Lung and beyond

Different pathogens and anatomic pathways produce different lesions; The pathway is illustrative, not a universal sequence.

Schematic

Slide 46 · Acute injection-site pathology

Cutaneous lesion

Clinicopathologic significance

Abscess

Localized suppurative infection

Cellulitis

Inflammatory infection of skin / soft tissue

Ulceration

Breakdown at subcutaneous injection sites

Slide 47 · Chronic cutaneous findings preserve exposure history

Repeated injection can leave scarring at puncture sites.

Hyperpigmentation may occur over commonly used veins.

Thrombosed veins are another described sequela.

Together these form a pattern of repetitive local injury.

Slide 48 · Venous lesions differ from active infection

Active tissue lesions

Abscesses, cellulitis and ulceration

Require evaluation for infection and tissue damage

Chronic track lesions

Scarring, venous pigmentation, thrombosed veins

Indicate repeated local injury in the appropriate setting

Slide 49 · Two renal patterns dominate the discussion

Amyloidosis

Associated generally with recurrent skin infections

Can present with significant proteinuria

Focal and segmental glomerulosclerosis

Another recognized pattern in heroin-associated renal disease

Also causes proteinuria / nephrotic syndrome

Slide 50 · Skin infection can be upstream of amyloidosis

Recurrent skin

Infections

Secondary

Amyloidosis

Renal

Involvement

Proteinuria /

Nephrotic syndrome

This is the causal association the textbook specifically makes for heroin-associated amyloid disease.

Schematic

Slide 51 · FSGS is a second glomerular injury pattern

Focal and segmental glomerulosclerosis is a recognized renal lesion in heroin users.

The designation refers to sclerosis involving portions of some glomeruli.

The renal manifestation may include marked proteinuria.

FSGS must be distinguished from secondary amyloidosis despite a shared syndrome.

Slide 52 · Different renal lesions converge on protein loss

Renal amyloidosis

Proteinuria

Nephrotic syndrome

Focal / segmental glomerulosclerosis

Proteinuria

Nephrotic syndrome

Parallel injury pathways with a shared clinical phenotype; Amyloidosis does not cause FSGS in this figure.

Schematic: Independent renal pathways

Slide 53 · Renal differential: Same syndrome, distinct lesions

Feature

Amyloidosis

FSGS

Textbook association

Often follows skin infections

Recognized separate heroin-associated lesion

Lesion category

Amyloid deposition

Focal segmental sclerosis

Potential phenotype

Proteinuria / nephrotic syndrome

Proteinuria / nephrotic syndrome

Relationship to skin infections

Generally secondary to recurrent infections

No such cause is specified here

Slide 54 · Integrated organ map: One exposure, several paths

Brain / respiration

Direct opioid pharmacology

Lung

Edema, infection and foreign-body reaction

Heart / blood

Right-sided endocarditis; Arrhythmia

Skin / kidney

Injection injury; Infection-linked amyloid or FSGS

Slide 55 · Exposure mechanism predicts type of pathology

Dominant exposure pathway

Expected category of injury

Opioid receptor agonism

CNS effects; respiratory suppression

Variable concentration / fentanyl

Unexpected overdose

Foreign particulate adulterants

Granulomatous reaction

Contaminated injection equipment

Skin infection, endocarditis, bloodborne viral infection

Chronic skin infection

Secondary renal amyloid disease

Slide 56 · Case: Unexpected fentanyl exposure

CLINICAL STEM

A person without known opioid tolerance uses a drug believed to contain no fentanyl and becomes profoundly somnolent with severely suppressed breathing.

Which exposure uncertainty explains the rapid deterioration?

Unrecognized fentanyl content plus absent tolerance; The most immediate lethal mechanism is respiratory suppression.

Illustrative case — not patient data

Slide 57 · Case: Injection use and pulmonary septic injury

CLINICAL STEM

A patient who injects heroin develops a valvular infection involving the right heart and then signs of pulmonary infection.

What valve-to-lung mechanism best links these findings?

Tricuspid/right-sided infective endocarditis with septic embolization to the lungs.

Illustrative case — not patient data

Slide 58 · Case: Particulate-associated pulmonary lesion

CLINICAL STEM

Tissue from the lung contains foreign-body granulomas with particles highlighted by polarized light, sometimes within giant cells.

What exposure is suggested by this pattern?

Particulate cutting agents such as talc; This is a tissue reaction, not proof of an opioid concentration.

Illustrative case — not patient data

Slide 59 · Case: Repeated skin infections and proteinuria

CLINICAL STEM

A person with longstanding subcutaneous injection-associated skin infections subsequently develops proteinuria and a nephrotic presentation.

Which renal lesion is specifically linked to the recurrent infection history?

Secondary amyloidosis. FSGS remains another heroin-associated renal pattern but is not stated to arise from those infections.

Illustrative case — not patient data

Slide 60 · Clinicopathologic inference requires a causal category

Identify

Organ lesion

Ask: Direct drug,

Particle, immune, infection?

Relate to exposure

And route

Avoid claiming

Unproven cause

Opioid-related disease is not reducible to a single toxicologic mechanism.

Schematic

Slide 61 · Acute hazards to retain

Unexpected fentanyl exposure can be fatal in a person without tolerance.

Profound respiratory suppression is the usual acute mechanism of death.

Arrhythmia, cardiac arrest and severe pulmonary edema are other reported fatal mechanisms.

Timely naloxone can reverse opioid-mediated respiratory suppression.

Slide 62 · Long-term pathology to retain

Injection-associated infections involve skin, right-sided valves, liver and lungs.

Particulate adulterants may produce pulmonary or systemic foreign-body granulomas.

Acute and chronic skin lesions reflect repeated injection-associated injury.

Renal amyloidosis and FSGS can each produce proteinuria and nephrotic syndrome.

Slide 63 · Source and scope

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 9, “Opioids and Opiates,” pp. 387–388.

Parent section: “Injury by Nontherapeutic Agents (Drug Use Disorder),” p. 386, including Table 9.6.

Historical surveillance numbers are preserved as reported in the textbook. No independent epidemiologic update or original chapter-PDF verification was performed.

Figures in this lecture are original editable explanatory schematics; no diagnostic photographs are represented as authentic source images.