Opiates & Opioids

1. Opiates and Opioids,
Opioid Receptors & Mechanisms of Action
A. Ramasha M. Galappatthy
W. P. Rivindu H. Wickramanayake
Group no. 04a
6th Year 2nd Semester – 2020 October
Tbilisi State Medical University, Georgia

2. ● Conventionally, the term opiates refer to natural compounds usually obtained
from the poppy flower base.
● Opioids are synthesized by chemical processes.
● Opiates and opioids are among the most commonly abused substances throughout
the world.
● Addiction to opioids and opiates has become a significant health problem in the
developed world since the 2000s.
● About 21 to 29 percent of patients prescribed opioids for chronic pain misuse
them, and about 8 and 12 percent develop an opioid use disorder.
● It is estimated 4 to 6 percent who misuse prescription opioids transition to heroin.
● Opioid overdoses accounted for more than 42,000 deaths in 2016, more than any
previous year on record. About 40% of opioid overdose deaths involved a
prescription opioid.
Introduction

3. ● Opioids are derived synthetically from generally unrelated compounds.
● Opiates are derived from the liquid of the opium poppy either by direct refinement or by
relatively minor chemical modifications.
● Both opioids and opiates act on three major classes of opioid receptors: mu, kappa, delta,
and several minor classes of opioid receptors like nociceptin, and zeta.
● Simplifying significantly, the mu receptors are thought to provide analgesia, respiratory
suppression, bradycardia, physical dependence, gastrointestinal dysmotility, & euphoria.
● The kappa agonism can yield hallucinations, miosis, and dysphoria.
● The delta receptor likely has pain control and mood modulation effects, but some have
suggested that mu agonism is necessary for the delta receptor to function strongly for
analgesia.
● The nociceptin receptor modulates brain dopamine levels and has clinical effects like
analgesia and anxiolysis.
● The zeta receptor, also known as the opioid growth factor receptor, can modulate certain
types of cell proliferation, such as skin growths, and is not thought to have many functions
in the modulation of pain or emotion.
Continued;

4. ● Causes of opioid overdose can include:
• Complications of substance abuse
• Unintentional overdose
• Intentional overdose
• Therapeutic drug error
● Risk of opioid overdose increases in the following:
• Those that take escalating doses
• Return to use after cessation
• Those with severe medical and psychiatric conditions such as depression, HIV, and
lung/liver disease
• Those that combine opioids and sedative medications
• Male gender
• Younger age (20 to 40 years)
• White non-Hispanic race
● More than 1.5 million emergency department visits are related to opioid analgesics.
● Opioids are a common cause of death due to overdose.
Etiology

5. ● The 2014 United Nations Office on Drug and
Crime estimates that at least 0.4% of the
population or close to 20 million people regularly
use heroin or opium.
● The highest level of usage are in South West Asia
(1.21%), followed by Southeastern and Eastern
Europe (0.83%) and Transcaucasia and Central
Asia (0.81%).
● In Europe, the major cause of opiate deaths has
been associated with the illicit use of fentanyl and
its analogs.
● In countries where there is a heroin shortage,
fentanyl and related products have replaced
heroin as the illicit drug of use.
● Opiates:
• Buprenorphine
• Fentanyl
• Hydromorphone
• Methadone
• Morphine
• Oxycodone
● Use of codeine
decreased by 20%.
Epidemiology

6. ● Opioids work via the endogenous opioid system by acting as a potent agonist
to the mu receptor.
● This results in a complex cascade of intracellular signals resulting in dopamine
release, blockade of pain signals, and a resulting sensation of euphoria.
● Opioid receptors are located in the brain, spinal cord, and gut.
● In overdose, there is an excessive effect on the portion of the brain regulating
respiratory rate, resulting in respiratory depression and eventually death.
● The typical symptoms seen in overdose are pinpoint pupils, respiratory
depression, and a decreased level of consciousness. This is known as the
“opioid overdose triad”.
● Opioids may be agonists, partial agonists, or agonist-antagonists of opioid
receptors.
● The currently available opiates lower the perception of pain and in some case
decrease the pain stimulus.
Pathophysiology

7. ● There are several types of opiate receptors in the CNS & the PNS.
● When receptors are stimulated, it results in suppression of sensation of pain.
● However, not all opiate receptors have same analgesic potency when stimulated.
● Opioids reduce pain perception by inhibition of synaptic neurotransmission and
binding of opioid receptors in the central and peripheral nervous systems.
● Main opioid receptors that mediate effects of opioids are mu, kappa, & delta.
● Mu receptors mediate analgesia, euphoria, sedation, respiratory depression,
gastrointestinal dysmotility, and physical dependence.
● Mu receptors cause a medullary diminished response to hypercarbia and also a
decrease in the respiratory response to hypoxia, resulting in a decreased
stimulus to breathe and development of apnea.
● Kappa receptors mediate analgesia, diuresis, miosis, and dysphoria.
● Delta receptors mediate analgesia, inhibition of dopamine release, and cough
suppression.
Continued;

8. ● The role of the sigma and delta opiate receptors has not been as well studied.
● However, when the sigma receptors are stimulated the individual will develop
hallucinations, dysphoria, and psychosis, whereas the delta receptors will
produce analgesia, euphoria, and seizures.
● Sigma receptors are no longer considered opioid because naloxone does not
antagonize them.
● Tolerance occurs rapidly with opioids.
● With overdose, patients often succumb to respiratory failure.
● Tolerance to loss of the hypercarbic drive takes longer to develop than other
euphoric effects, but opioid-tolerant patients do not develop complete
tolerance to loss of hypoxic stimulus.
● This leaves them susceptible to death from overdose.
Continued;

9. ● Opiates can be administered intravenously (IV), topically, inhaled,
intramuscularly (IM), and orally.
● Following intravenous administration, the peak effects of the opiate are reached
within 5 to 10 minutes but may take up to 90 minutes when administered orally.
● Following nasal insufflation, drugs Like heroin and butorphanol can reach peak
levels within 10 to 15 minutes and about 30 to 45 minutes following
intramuscular injection.
● Fentanyl which is the only available topical analgesic agent often takes 2 to 4
hours to reach peak levels.
● When administered orally, the majority of opiate absorption occurs in the small
intestine.
● When large doses of opiates are consumed, this can lead to gastric aperistalsis
and a delay in gastric emptying and absorption of the drug.
● Once in the body, opiates are broken down by the liver to inactive compounds
that are excreted primarily by the kidneys.
Toxicokinetics

10. ● Opiates like buprenorphine and fentanyl are highly lipid soluble and tend to redistribute into
the fatty tissues and thus, have a prolonged half-life.
● Since all opiates are broken down by the liver, they tend to have a long half-life when
consumed in the presence of liver dysfunction (for example, cirrhosis).
● In these patients, opiate toxicity can occur rapidly even with small doses as the drug remains in
the body for a long time.
● The hepatic microsomal CYP2D6 enzyme is responsible for breaking down codeine into the
active metabolite, morphine.
● Some individuals carry more than 2 copies of the enzyme, and these ultrarapid metabolizers
breakdown codeine into morphine rapidly; thus, individuals who take even normal doses of
codeine may develop morphine toxicity.
● The same mechanism of ultrarapid breakdown explains why tramadol can cause opiate toxicity.
● Once broken down in the liver, the opiate metabolites are excreted in the urine.
● Individuals with renal dysfunction may develop adverse effects from the accumulated active
metabolites like normeperidine.
● Several other studies show that long-acting opiates used for non-cancer pain can increase the
risk of adverse cardiac events compared to tricyclics or anticonvulsants.
Continued;

11. ● Available in oral, IM, and IV formulations, sublingual and inhaler formulas
on the market.
● Butorphanol is available in an intranasal form and fentanyl is available both
as a topical and as an inhaler.
● The transdermal delivery of opiates like fentanyl has been widely accepted in
healthcare settings for analgesic relief.
● This route of administration is favored because the drug levels take 4 to 6
hours to peak and there is a long elimination half-life, thus making the drug
suitable for use in patients with chronic continuous pain.
● In addition, because of the relatively prolonged slow onset of action, this
route of administration is rarely known to precipitate toxicity.
● However, the topical formulation of fentanyl can contribute toward the
toxicity of parenteral or oral opiates.
Formulas of Opiates and Delivery

12. ● Dextromethorphan was once widely available in many over the counter cough
preparations, but because of diversion, it is no longer available in over the
counter products.
- Dextromethorphan may have been an over the counter preparation,
but at high doses, it is known to cause sedation and even respiratory depression.
- Further, the use of dextromethorphan by patients who have been
prescribed monoamine oxidase inhibitors can lead to the life-threatening
serotonin syndrome that can lead to adverse cardiac events.
● Tramadol (Ultram), although classified as a non-opiate analgesic, has a dual
mode of action by acting on non-opiate and opiate receptors.
- Tramadol has a comparatively long duration of action of 5 to 6
hours.
- If it is known that a patient has overdosed on tramadol, naloxone is
recommended, and most people require repeated doses or a continuous IV infusion.
Continued;

13. ● Several types of synthetic fentanyl derivatives on the street like alpha-Methylfentanyl, which
are extremely potent.
● In fact, several deaths have been reported in drug abusers with the needle still in the arm.
● One other synthetic derivative, 3-Methylfentanyl, is several thousand times more potent than
morphine and when people overdose on it, extremely high doses of intravenous naloxone
infusions are required.
● Deaths from these fentanyl derivatives often occur in clusters as the sellers go from street to
street, leading to multiple deaths along the way.
● Pentazocine is classified as a partial agonist-antagonist and is used to treat moderate to severe pain.
- It acts by stimulating the K-opiate receptors (KOR) and inhibiting the Mu-opiate receptors (MOR).
- The drug shares many of the same features of other opiates in terms of adverse effects.
- The one unique feature about pentazocine is that it also is known to cause nightmares, hallucination,
and delusions.
- The drug is also subject to a high ceiling effect, meaning once a certain dose is reached, no further
pain relief can be obtained.
- Although the pharmacological effects of pentazocine can be reversed by naloxone, extremely high
doses of naloxone (10 to 115 ng) are required.
Continued;

14. ● Propoxyphene is an opiate analgesic and was once prescribed to manage mild pain and cough.
- Naloxone can reverse the toxicity of propoxyphene but not the cardiac arrhythmias.
- The cardiac arrhythmias are due to the quinidine-like effects of propoxyphene and are unresponsive to
naloxone.
- Propoxyphene is known to cause sinus bradycardia, ear block or ventricular arrhythmia. The
treatment is to immediately administer sodium bicarbonate.
● Diphenoxylate/Atropine: This combination product is often used to treat diarrhea.
- The diphenoxylate acts like an antidiarrheal agent, and the atropine is an anticholinergic that is added
to deter deliberate overdose.
- Atropine has no antidiarrheal activity. When high doses are ingested, one may note mainly
anticholinergic side effects, respiratory depression, and constipation.
- Because of the long half-life of diphenoxylate, the adverse effects can be worrying.
- The majority of cases of diphenoxylate/atropine overdose are seen in children.
- If the child is seen in the emergency room within a few hours after ingestion, gastric decontamination
with activated charcoal may be attempted. |
- All children need to be observed for a minimum of 6 hours to ensure that they do not develop
arrhythmias.
Continued;

15. ● Body packers: Over the past 2 decades, the transport of illicit drugs in the body has
become very common.
- These individuals place drugs inside plastic bags or condoms and ingest them.
- Often the number of packages ingested vary from 1 to 3 dozen and even though well
wrapped, sometimes the packages do break open and systemic toxicity results.
- Others may develop complications like bowel obstruction or intestinal perforation.
- In some cases, when the individual is pursued by police, he or she may stuff the drugs
into the anus, vagina, or ingest them.
- These individuals are likely to suffer from adverse effects because the drugs are often not
properly packaged.
- After ingestion, systemic symptoms appear rapidly, and these individuals often require
aggressive medical therapy to prevent death, and in some cases, surgery is required to
relieve a bowel obstruction.
- Even after surgery, if the drugs have been absorbed into the systemic circulation, the risk
of death is often high.
Continued;

16. ● Since majority of patients overdosed on opiates are lethargic or comatose, the history is usually
obtained from family, friends, bystanders, and emergency medical service providers.
● On many occasions at the scene, one may find pills, empty bottles, needles, syringes and other
drug paraphernalia.
● Other features that one should try and obtain in the history are the amount of drug ingested, any
congestion, and time of ingestion.
● In the pre-hospital setting, sometimes EMS personnel may administer naloxone, which may
help make the diagnosis of opiate overdose.
 Physical Examination
● May be lethargic or have a depressed level of consciousness.
● Opiate overdose will also cause respiratory depression, generalized central nervous system
(CNS) depression, and miosis.
● However, miosis is not universally present in all patients with opiate overdose and there are
many other causes of respiratory depression.
● Other features of opiate overdose include euphoria, drowsiness, change in mental status,
fresh needle marks, seizures and conjunctival injections.
History and Physical

17.  Skin
● Examination of extremities may reveal needle track marks if IV opiates are abused.
● Morphine and heroin are also injected subcutaneously by many addicts.
● In some cases, the opium oil may be inhaled, and the individual may also have patch marks on the
body from the use of fentanyl.
● Most opiates can cause the release of histamine which can result in itching, flushed skin, and urticaria.
 Neurological
● Ability to lower the threshold for seizures, and generalized seizures can occur, especially in young
children. This is primarily due to paradoxical excitation of the brain.
● In adults with seizures, the 2 opiates most likely involved are propoxyphene or meperidine.
● In rare cases, hearing loss may be noted especially in individuals who have consumed alcohol with
heroin. However, this auditory deficit is reversible.
 Cardiovascular
● Peripheral vasodilatation, which can result in moderate to severe hypotension.
● However, this hypotension is easily reversed with changes in body position or fluid administration.
● If the hypotension is severe and is unresponsive to fluids, then one must consider other co-ingestants.
Continued;

18.  Pulmonary
● In some cases of morphine toxicity, the respiratory distress and hypoxia may, in fact, present with
pupillary dilatation.
● In addition, drugs like meperidine, morphine, propoxyphene and diphenoxylate/atropine are known to
cause midpoint pupils or frank mydriasis.
● The breathing is usually impaired in patients with a morphine overdose. One may observe shallow
breathing, hypopnea, and bradypnea.
● The respiration rate may be 4 to 6 breaths per minute and shallow.
● Since opiates can also cause bronchoconstriction, some individuals may present with dyspnea,
wheezing and frothy sputum.
 Gastrointestinal
● Both nausea and vomiting are also seen in patients with opiate toxicity;. The reason is that opiates
can cause gastric aperistalsis and slow down the intestine motility.
 Psychiatric Features
● Even though opiates are generalized CNS depressants, they can cause the following neuropsychiatric
symptoms: Anxiety, Agitation, Depression, Dysphoria, Hallucinations, Nightmares, Paranoia
Continued;

19. ● It is important to always consider opiate overdose or toxicity in a lethargic patient
with no other identifiable cause.
● Many of the individuals who abuse opiates also tend to use other illicit agents like
cocaine and prescription drugs like the antidepressants and benzodiazepines at the
same time.
● Suspicion of co-ingestants should be raised when the usual clinical signs and
symptoms of opiate toxicity differ, and the patient fails to respond to the opiate
antagonist, naloxone.
 Imaging Studies
● If any lung injury is suspected, a chest x-ray should be obtained.
● If the patient is suspected of being a body packer, then an abdominal x-ray
should be obtained.
Evaluation

20.  Electrocardiography
● An ECG is recommended in all patients with suspected opioid overdose.
Coingestants like the tricyclics have the potential to cause arrhythmias.
 Laboratory Studies
● Drug screens are readily available but often do not change initial management of
straightforward cases.
● Drug screens when performed on urine and are quite sensitive.
● In most cases, a positive opiate result will show up even 48 hours post exposure.
● In patients with opiate toxicity or overdose the following blood work is usually
performed:
• Complete blood cell count
• Comprehensive metabolic panel
• Creatine kinase level
• Arterial blood gas determinations
Continued;

21.  Management at the Scene
● The care of the patient at the scene depends on the vital signs.
● If the patient is comatosed and in respiratory distress, airway control must be obtained
before doing anything else.
● Endotracheal intubation is highly recommended for all patients who unable to protect their
airways.
● If there is suspicion of opiate overdose, then naloxone should be administered to reverse the
respiratory depression.
● Naloxone can also cause agitation and aggression when it reverses the opiate. If the individual
is a drug abuser, the lowest dose of naloxone to reverse respiratory apnea should be
administered.
● In the ambulance, the patient may become combative or violent, and use of restraints may be an
option.
● If the individual has no intravenous access, one may administer the naloxone intramuscularly,
intranasally, intraosseous or via the endotracheal tube.
● Data show that intranasal route is as effective as intramuscular route in the pre-hospital setting.
Treatment / Management

22.  Emergency Department Care
● The ABCDE protocol has to be followed.
● If there is any sign of respiratory distress or failure to protect the airways in an un-intubated
patient with a morphine overdose, one should not hesitate to intubate.
● If any suspicion of occult trauma to the cervical spine, immobilization should be a priority.
● Patients who present with an unknown cause of lethargy or loss of consciousness have their
blood glucose levels drawn.
● Initial treatment of overdose begins with supportive care. This includes assistance in
respiration, CPR if no spontaneous circulation is occurring, and removal of the opioid
agent if a patch or infusion are delivering it.
● If the physician suspects that the individual has overdosed on an opiate and has signs of
respiratory and CNS depression, no time should be wasted on laboratory studies; instead,
naloxone should be administered as soon as possible.
● Naloxone is a competitive antagonist of the opiate receptor. It can be administered by
intravenous, intramuscular, subcutaneous, or intranasal routes.
● Additionally, it can be used in an off-label manner by administering it via endotracheal tube or
in a nebulized form, though research on the efficacy of tracheal absorption has only been
Continued;

23.  Role of Activated Charcoal
● If the patient is alert at the time of admission, activated charcoal can be used to
decontaminate the gastrointestinal tract in patients with opiate overdose.
● While normally activated charcoal usually has to be administered within 1 hour of ingestion
of a drug to be effective, with opiates, there is slowing of gastric motility, and hence,
activated charcoal can be given as late as 2 to 3 hours after ingestion.
● As long as there are no contraindications, activated charcoal should be administered to all
symptomatic patients with opiate overdose.
● If the patient is not alert, then airway protection is necessary; some patients will require
endotracheal intubation prior to the administration of activated charcoal to prevent
aspiration.
● If activated charcoal enters the airways, the result can be catastrophic.
● In some patients, orogastric lavage may help.
Continued;

24.  Bowel Irrigation
● The role of whole bowel irrigation may be considered in people who have ingested drug
packets containing opiates, but there are no controlled studies to determine if this treatment has
any benefit or improves outcomes.
● However, whole body irrigation is not recommended in patients who show signs of ileus,
bowel obstruction, have obvious signs of peritonitis, hemodynamic instability or an
unprotected airway.
 Use of Buprenorphine/Naloxone
● Buprenorphine in combination with naloxone is widely available and is used to treat opiate
use disorder.
● This formula has also been used to used narcotic overdose. The big advantage of using this
combination is that it reduces the withdrawal symptoms for 24 to 36 hours. Anecdotal data
indicate that the risk of overdose is small with buprenorphine/naloxone compared to
methadone. Unfortunately, the sublingual preparation of buprenorphine and naloxone can
also be easily abused sublingually
Continued;

25. ● Clonidine toxicity
● Cyanide toxicity
● Diabetic ketoacidosis
● Ethylene glycol toxicity
● Gamma-hydroxybutyrate toxicity
● Hypercalcemia
● Hypernatremia
● Hypothermia
● Meningitis
● Neuroleptic agent toxicity
Differential Diagnosis

26.  Mortality/Morbidity
● Major cause of morbidity and mortality is due to respiratory depression.
● Rarely the individual may develop seizures, acute lung injury and adverse cardiac events.
● In individuals with prior lung pathology who overdose on opiates, the risk of respiratory
distress and death is much higher than in the normal population.
● The other reason for the opiate toxicity may be due to co-ingestants, and the eventual
toxicity depends on the type of co-ingestant.
● In one Canadian study, the risk of fatal opiate toxicity was doubled when the opiate was
ingested with gabapentin; the latter is also known to depress respiration.
● Finally, the morbidity and mortality also depend on the reason why the opiate was
ingested; some people are intent on committing suicide, and these individuals often take
several other drugs at the same time, thus, greatly increasing the risk of death.
 Prognosis
● If the patient does arrest in the setting of a pure opiate overdose, the cause in most cases is
severe hypotension, hypoxia and poor perfusion of the brain.
● The outcome for these patients is poor.
Prognosis

27. ● Narcotic Bowel Syndrome
- Characterized by frequent episodes of moderate to the severe abdominal pain that
worsens with escalating or continued doses of opiates.
- Occur in people with no prior bowel pathology and is a maladaptive response.
- The syndrome can also be associated with intermittent vomiting, abdominal
distension, and constipation.
- Eating always aggravates the symptoms, and the condition can last for days or weeks.
- Anorexia can lead to body weight loss. There is delayed gastric emptying and
intestinal transit.
- The syndrome is often confused with bowel obstruction. The key to the diagnosis is
the recognition of continued and escalating doses of opiates that worsen the abdominal
pain, instead of providing relief.
- The treatment is some psychotherapy combined with tapering or discontinuing the
opioid.
- The key to successful treatment is to develop a strong patient-physician relationship
and trust with the patient; the narcotic should be gradually withdrawn, and other non-
pharmacological treatments used to manage pain.
Complications

28. ● Withdrawal Reaction
- Withdrawal symptoms following cessation of opiates are common, but the symptoms
are often vague and not as severe as those observed with alcohol or benzodiazepines
discontinuation.
- The onset of symptoms depends on the drug ingested and usually occur within 2 to 4
days with methadone and 8 to 10 hours after meperidine.
- The autonomic symptoms may include excessive lacrimation, sweating, piloerection,
rhinorrhea, repeated yawning, myalgia, nasal congestion, diarrhea and abdominal cramps.
- The symptoms usually peak between 36 to 48 hours and gradually subside in 72 hours.
- In chronic drug addicts, the symptoms may last for 7 to 14 days.
- The treatment of withdrawal symptoms is supportive.
- The use of additional opiates to counter the symptoms of withdrawal is not
recommended.
- For severe withdrawal cases, one may use clonidine, especially when methadone may
be inappropriate or unavailable.
- After the acute treatment, the patient should be recommended to join a long-term drug
rehabilitation program to prevent relapse.
Continued;

29. ● Acute Lung Injury
- Well known to occur after a heroin overdose.
- However, acute lung injury can also occur following methadone and propoxyphene
overdose and is universally present in patients who expire from a high dose of opiate.
- As to how these opiates cause lung injury is not fully understood, but the eventual
result is hypoventilation and hypoxia.
- Clinically, heroin-induced lung injury will present with sudden onset of dyspnea,
frothy sputum, cyanosis, tachypnea, and rales- features consistent with pulmonary
edema.
- Also in children who have ingested high doses of opiates.
- Acute lung injury is very similar to ARDS in presentation, and most cases clear up
with aggressive airway management and oxygen.
- The usual drugs used to manage pulmonary edema are not used, and in fact, the use
of diuretics may exacerbate the hypotension.
Continued;

30. ● Infection
- In individuals who use intravenous opioids, complications include abscess, cellulitis,
and endocarditis.
- The most common organisms involved are the gram-positive bacteria
like Staphylococcus and Streptococci.
- If the bacteria enter the systemic circulation, the risk of epidural abscess and
vertebral osteomyelitis are other potential complications.
- These patients may present with fever and continuous back pain.
- Some IV drug abusers are known to inject the opiates directly into the neck, and this
can lead to jugular vein thrombophlebitis, Horner syndrome and even pseudoaneurysms
of the carotid artery.
- Both peripheral and pulmonary emboli have been reported in IV drug users.
- Accidental injection into the nerves has also been reported to cause permanent
neuropathy.
-
Continued;

31. - Infectious Endocarditis is a serious complication of intravenous drug abuse.
- Often these individuals use a mixture of illicit drugs and dirty needles.
- The Diagnosis is often difficult as the symptoms are vague initially.
- Although in most cases, the right-sided heart valves are affected, sometimes the
left-sided valves may also be involved.
- The most common valves involved in intravenous drug users is the tricuspid
valve.
- It often presents with fever, malaise and a new murmur.
- In some patients, recurrent septic pulmonary embolism may be the only
presenting feature.
- The most common organism involved in right-sided endocarditis is
Staphylococcus aureus,
- but left-sided endocarditis may be polymicrobial and include Streptococcus, E.
coli, Pseudomonas or Klebsiella.
- In most patients, when the left-sided valves are involved, the symptoms and signs are
usually more obvious compared to right-sided involvement.
Continued;

32. - Other manifestations of opioid abuse may be recurrent pneumonia,
- and aspiration pneumonia may also occur with the individual is unconscious.
- Rhabdomyolysis is not an uncommon complication of opiate overdose.
- It may occur even in the absence of a compartment syndrome.
- Another life-threatening complication is necrotizing fasciitis that often presents
with severe pain, fever, dark, dusky skin with crepitus.
- The individual will show signs of septic shock.
- Aggressive resuscitation and immediate surgical debridement can be life-saving.
- Seizures: Opiates are known to increase the risk of seizures, especially drugs like
propoxyphene, meperidine, pentazocine, intravenous fentanyl, and heroin.
- The individual may present with a prolonged seizure which may result as a result
of CNS hypoperfusion and hypoxia or a result intracranial injury due to a fall.
Continued;

33. References
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