Opiates/Heroin OD


The opioid toxidrome may result from exposure to any of the following:

MECHANISM/TOXICITY:

SYMPTOMS/EXAM:

DIAGNOSIS:

TESTING

TREATMENT:

COMPLICATIONS:

DISPOSITION & FOLLOW UP:

Opiate toxidrome = CNS depression, respiratory depression, and pinpoint pupils.

Naloxone is only indicated for reversal of hypoventilation and is not useful in the intubated patient.


Classification and Characteristics of Major Pharmaceutical Opioids:

  Oral Equianalgesic Dose to Morphine 10 mg SC (mg) Parenteral Equianalgesic Dose to Morphine 10 mg SC (mg) Duration of Action (hours) Elimination Half-Life (hours)
Opiate
Codeine 200 120 3-6 -
Morphine 30 10 3-6 2-3
Semisynthetic
Buprenorphine 4 SL 0.3 6-24 37
Hydrocodone 30 Not available 3-4 -
Hydromorphone 7.5 1.5 3-6 2-4
Oxycodone 20 Not available 4-6 -
Oxymorphone 6 1.5 3-6 3-4
Synthetic
Diphenoxylate 2.5 Not available -  
Fentanyl 0.125 0.100 1-2 3-4
Meperidine 300 100 1-3 3-4
Methadone 20 10 6-8 21-25
Pentazocine 150 50 SC 3-4 2-4
Propoxyphene 130 Not available 4-6 6-12
Tramadol 100 100 9 5-7

Special Considerations

Special Considerations
Buprenorphine
  • Buprenorphine is a partial agonist at μ-receptors
  • Compared with full agonists, buprenorphine possesses relatively decreased intrinsic activity at the μ-receptor, which causes its effects to plateau at higher dosages.
  • Buprenorphine has high affinity for and slow dissociation from the μ-receptor, which results in a long duration of action. Furthermore, other opioid agonists (such as heroin) cannot easily displace buprenorphine.
  • Buprenorphine has poor oral bioavailability because of extensive first-pass metabolism and is therefore administered SL or parenterally. The most frequently prescribed SL buprenorphine formulation is in combination with naloxone in a 4:1 ratio. Because naloxone has poor bioavailability from PO or SL administration, it was introduced into the preparation to discourage and limit parenteral abuse of the buprenorphine portion while not interfering with therapeutic use in the form of the SL tablet.
     
  • Buprenorphine can be associated with one of three distinct clinical scenarios:
    1. The opioid-naive patient who overdoses on buprenorphine:
      • Will experience mental status depression, nausea, vomiting, miosis, and respiratory depression (usually with a plateau).
      • Naloxone partially reversed mental and respiratory depression in two thirds of the patients to whom it was administered.
      • Because of the long duration of action of buprenorphine, readministration of naloxone and naloxone infusions are frequent, and admission to the hospital necessary in symptomatic patients.
    2. Buprenorphine exposure in the opioid-dependent patient still under the influence of the opioid agonist:
      • Will precipitate opioid withdrawal symptoms, because the partial agonist behaves like an antagonist in the presence of an agonist.
      • Buprenorphine-induced withdrawal is best managed with symptom-driven therapy, including antiemetics, nonopioid analgesics, antidiarrheals, and nonbenzodiazepine sedatives for insomnia.
    3. Buprenorphine exposure in the opioid-dependent patient undergoing withdrawal,
      • Will act as a partial agonist and alleviate the symptoms of opioid withdrawal.
      • This forms the basis for buprenorphine detoxification and maintenance therapy.
      • Thus, buprenorphine is unique in that it can both induce and treat opioid withdrawal, depending on the timing of its administration.
Methadone
  • Methadone can affect cardiac electrical conduction, producing QT-interval prolongation in acute overdose or during long-term methadone treatment. The prolonged QT interval provides the substrate for cardiac dysrhythmias, such as torsades de pointes.
  • In patients with acute methadone overdose resulting in QT-interval prolongation, serum electrolyte imbalances should be corrected and the patient should be admitted to a monitored bed until the condition resolves.
  • Patients receiving long-term methadone therapy who develop a QTc interval of >450 milliseconds but <500 milliseconds do not require a dosage adjustment, but electrolyte imbalances should be corrected, if present, and patients should be followed on an outpatient basis with frequent ECGs.
  • In patients receiving long-term methadone therapy who develop a QTc interval of >500 milliseconds, electrolyte imbalances should be corrected, methadone dosage reduction or discontinuation should be considered, and contributing factors should be sought and eliminated.
Tramadol
  • Tramadol overdoses are associated with agitation, hypertension, respiratory depression, seizures, and death, especially at doses exceeding 500 milligrams PO in adults.
  • Tramadol-induced seizures are common, and naloxone is INEFFECTIVE in reversing the seizures.
  • Treatment remains supportive.
  • Dependence during chronic therapy and withdrawal symptoms upon discontinuation have been reported with tramadol
Diphenoxylate Hydrochloride–Atropine Sulfate (Lomotil)
  • Diphenoxylate hydrochloride–atropine sulfate is a frequently prescribed antidiarrheal agent.
  • The medication is manufactured as a combination tablet containing diphenoxylate, 2.5 mg, and atropine, 0.025 mg.
  • In an overdose, initially the anticholinergic toxidrome dominates the clinical picture.
  • The second phase of intoxication is characterized by the opioid toxidrome.
  • Children <6 years of age can be symptomatic after ingestion of a single tablet.
    • In pediatric patients, absorption can be delayed up to 6 to 12 hrs in some cases because of the effect of atropine on GI motility.
    • Current recommendations are that all children <6 yrs of age be admitted to the hospital and be closely observed for 24 hrs after ingestion of a combination tablet of diphenoxylate and atropine.
    • Older children and adults should be observed in the ED for 6 hours.
    • Administration of activated charcoal:  Recommended in all cases.
Serotonin syndrome
  • The combination of meperidine, tramadol, or dextromethorphan with MAOI, SSRI, or linezolid can result in serotonin syndrome.
  • Serotonin syndrome is characterized by:
    • Disorientation
    • Hyperthermia
    • Autonomic instability
    • Hyperreflexia, and
    • Muscle rigidity, especially in the lower extremities.
  • Although uncommon, deaths have been reported.
  • Naloxone is NOT effective in treating opioid-induced serotonin syndrome.

Opioide Withdrawal

Opioide Withdrawal
  • Down-regulation of endogenous endorphins, dynorphins, and opioid receptors occurs with long-term use of opioids. Abrupt cessation of opioid use does not allow time for up-regulation of receptors and results in increased neuronal firing and the opioid withdrawal syndrome.
  • Opioid withdrawal usually starts with:
    • Feelings of anxiety, yawning, lacrimation, diaphoresis, rhinorrhea, and diffuse myalgias (Table 180-2).
    • It then progresses to piloerection, mydriasis, nausea, profuse vomiting, diarrhea, and abdominal cramping.
    • Opioid withdrawal reactions are very uncomfortable but are NOT life-threatening and rarely fatal.
  • Vomiting and aspiration of gastric contents can cause pneumonitis and dehydration.
  • Onset of withdrawal:
    • within 6 to 12 hrs of last heroin use
    • Within 30 hrs of last methadone exposure.
  • It can be precipitated by the administration of antagonists such as naloxone or naltrexone or the administration of partial agonists such as buprenorphine.
  • Opioid withdrawal symptoms usually peak on the third day of abstinence and resolve by the fifth or six day

Management:

  • Symptoms of opioid withdrawal can be rendered more tolerable by the administration of the central alpha2 agonist clonidine, antiemetics, and antidiarrheal agents.
  • Clonidine may be used at a dose of 5 mcg/kg PO if sBP >90.
  • Hydroxyzine, 50 to 100 mg PO QID for 5 days, has also been reported effective at controlling symptoms of opioid withdrawal.
  • Multidrug regimens are sometimes used in ambulatory detoxification programs to control withdrawal symptoms.
  • The management of opioid-dependent individuals hospitalized for medical or surgical reasons remains controversial.
  • Detoxification from opioids during the course of an acute medical illness is usually unsuccessful, and alleviation of withdrawal symptoms with opioid replacement should be the goal.
  • Daily administration of a verified dose of methadone PO (or half the verified dose IM if the patient cannot take oral medications) is recommended to inhibit withdrawal symptoms and reduce craving.
    • This applies only to individuals who are enrolled in a methadone treatment program and in whom the dose can be verified.
    • A habitual user who is not receiving methadone maintenance therapy can be given methadone, 20 mg PO or 10 mig IM.
    • These doses should inhibit withdrawal symptoms but not induce euphoria.
  • Buprenorphine, 0.3 to 1.2 mg IV or IM q6h, can safely be administered to a medically ill opioid-dependent patient experiencing withdrawal who will be admitted to the hospital.
  • No methadone or buprenorphine should be administered to an opioid-dependent patient until withdrawal symptoms appear
Opioid Withdrawal
Onset: within hours Onset: 12 h Onset: 24-36 h
Peak effects: 36-72 h Peak effects: 72 h Peak effects: 72h
Signs & symptoms Signs & symptoms Signs & symptoms
Anxiety Irritability Insomnia
Yawning Tremor Muscle spasms
Drug craving Piloerection Abdominal pain
Lacrimation Mydriasis Nausea, vomiting, diarrhea
Rhinorrhea  
Diaphoresis  
Myalgias