Street Drugs Part 4: Prescription for Trouble Robert S. Cole

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Street Drugs Part 4Prescription for Trouble

• Robert S. Cole
• Paramedic, CCEMT-P

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Overview

• We will review some common principles of caring
  for the Pharmacologically gifted
• We will focus on some of the particular problems
  with prescription and OTC drugs
• We will discuss 4 CLASSES of the drugs that every
  paramedic should know.
• There is no way we can be all inclusive in an
  hour so bear with me.

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Drugs we will cover

• Triclyclic Anti-depressants
• SRI anti-depressants
• Benzodiazepines
• MOAIs
• OTC Drugs

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TRICYCLIC ANTIDEPRESSANT

• Leading cause of death in intentional overdoses
• Began to be used in the 50s
• Approx 1 million cases of TCA overdose per year -
  400 fatalities.

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BACKGROUND

• Tricyclic drugs enhance the concentrations of
  norepinephrine and serotonin.
• These neurotransmitters, known as monoamines,
  once been secreted, must then be inactivated by a
  variety of mechanisms including reuptake into the
  secreting cells.
• Tricyclics impede this reuptake process so that
  the monoamines remain active longer after
  secretion,
• Some Tricyclic side effects have similar effects
  on other neurotransmitters in the CNS, notably
  histamine and acetylcholine.

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NAMES OF TRICYCLIC ANTIDEPRESSANTS

• Amitriptyline (Elavil)
• Amoxapine (Asendin)
• Clomipramine (Anafranil)
• Desipramine (Norpramin)
• Doxepin (SinequanAdapin)
• Imipramine (Tofranil)
• Nortryptyline (Aventyl Pamelor)
• Protriptyline (Triptil, Vivactil)
• Trimipramine (Surmontil)

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Level of Sedation

• Sedative
• Dothiepin Prothiaden
• Amitriptyline
• Clomipramine Anafranil
• Maprotiline
• Mianserin
• Less-sedating
• Desipramine
• Imipramine
• Lofepramine Gamanil
• Nortriptyline

• Stimulant
• Protriptyline

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SIGNS AND SYMPTOMS OF TRYCYCLIC OVERDOSE

• Primarily concerned over Cardiac and Neurologic
  problems
• Cardiovascular QRS widening, conduction
  abnormalities, Tachycardia, ectopy, dysrhythmias,
  hypotension
• Neurologic Rapid mental status
  deterioration,confusion, hallucinations
  (uncommon), coma, seizures (lowers SZ
  threshold), dilated pupils
• Other Renal failure, ARDS, s/s histamine and
  anticholinergic stimulation
• Acidosis may complicate severe overdose
• Onset Toxicity generally develops within 4-6
  hours (may be sooner for large amounts)

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Basic Treatment

• Detailed scene search, Hx taking
• Good aggressive airway management
• Aspiration precautions
• Seizure precautions
• V.O.M.I.T.
• R/O other causes. (BG, Hx of events, etc.)
• Beware of poly-pharm ODs
• Consider either oral or NG/OG charcoal.

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Focused Treatment

• Hypotension Fluid challenges
• Poly-Pharmacy OD?
• Narcan 0.4-2 mg SIVP
• Romazacon is contraindicated
• Cardiac toxicity
• Bicarb 50-100 meq IV, 100 meq/1000 cc NACL,
  titrate for decrease in s/s.
• Lidocaine, Bretylium per ACLS,
• Procainamide and Amioroderone are
  contraindicated. As are other drugs that widen
  the QRS.
• Seizures Benzos
• Transport to a tertiary care facility regardless
  of perceived stability is recommended.

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Long Term effects

• Renal Failure
• Liver problems?
• Prolonged QT interval
• CHF
• Hyponatremia

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Interactions

• Anticholinergic and sympathomimetic meds may be
  additive to the toxic effects of a TCA.
• Histamine blockers may raise TCA levels
• Thyroid supplements may increase severity of
  cardiovascular side effects
• TCAs potentiates the sedative effect of alcohol
  and benzos on the CNS on the CNS.

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Take Home Information

• Beware of Poly-Phar ODs
• Bicarb and benzos as needed
• Avoid Amiodarone and Procainamide

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Selective Serotonin Re-uptake Inhibitors (SSRIs)
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SSRI anti-depressants
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BACKGROUND

• Replaced TCAs as the most common pre-scribed
  anti-depressant
• Focuses on serotonin (5HT) re-uptake and has no
  effect on nor-epinephrine
• Much safer profile than TCAs
• Are still taken by the depressed during ODs
  because of availability
• Prozac (an SSRI) has a relative risk 6.6 times
  higher for deliberate self-harm (DSH) than the
  tricyclic antidepressant Amitriptyline and 3.5
  time higher than the average of tricyclic
  antidepressants examined in one study.

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NAMES

• Citalopram (Cipramil)
• Fluoxetine (Prozac)
• Fluvoxamine (Faverin)
• Paroxetine (Seroxat)
• Sertraline (Lustral).

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Morbidity

• SSRI antidepressants are rarely fatal in
  overdose when taken alone. During the 10 years
  that SSRI antidepressants have been marketed,
  there have been remarkably few fatal overdoses
  reported in the literature or to the AAPCC or FDA
  involving ingestion only of an SSRI.
• SSRI overdoses in combination with alcohol or
  other drugs are associated with increased
  toxicity, and almost all fatalities involving
  SSRIs have involved co-ingestion of other
  substances.
• SSRI safety in overdose by Barbey JT, Roose SP
  Division of Clinical Pharmacology, Georgetown
  University Medical Center, Washington, DC, USA.
  J Clin Psychiatry 1998 59 Suppl 1542-8

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S/S OF AN OVERDOSE

• Minor to moderate overdoses (up to 30 times the
  common daily dose) are associated with minor or
  no symptoms
• Major overdoses (30-60 times daily dose)
• Nausea vomiting
• lethargy
• sedation
• At very high doses (gt 75 times the common daily
  dose), more serious adverse events, including
  seizures, electrocardiogram (ECG) changes, and
  decreased consciousness may occur.
• No evidence that seizures occur following
  overdose of the SSRI agents.

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Serotonin Syndrome

• Patients concomitantly ingesting
  dextromethoraphan, monoamine oxidase inhibitors,
  MDMA/PMA Ecstasy and other serotonergic agents
  may develop a "serotonin syndrome."
• Characterized by agitation, hyperthermia,
  sympathetic hyperactivity, severe hypertension,
  altered muscle tone and seizures.
• Occurs within 2 hours of ingestion of offending
  agent and resolves 6 -24 hours after
  discontinuing the agent.

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BASIC TREATMENT

• Supportive
• Standard ALS
• Observe of cardiac toxicity in case of
  poly-pharmacy overdoses.
• Transport

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FOCUSED TREATMENT

• Serotonin syndrome
• Benzodiazepines, hydration and cooling are the
  mainstays of therapy.
• Neuromuscular blockade (with EEG monitoring) may
  be necessary for refractory hyperthermia and
  increased muscle activity.

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Long Term effects

• SEROTONIN SYNDROME OUTCOME
• mortality rate 11
• ICU admission 40
• intubated 25
• cause of death
• cardiovascular collapse
• rhabdomyolysis
• DIC
• ARDS

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Interactions

• Opioids, Lithium, TCAs, MDMA all increase
  available CNS serotonin and may precipitate
  serotonin syndrome or simply increase sedation
  depending on levels

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Detox, Dependence and Withdrawal

• Abrupt discontinuation may cause serious
  withdrawal reactions that include crashing into
  depression with possible suicidal and/or violent
  behavior.
• It is highly recommended to gradually taper off
  SSRI
• Also includes dizziness, trouble with balance or
  coordination, headaches, nausea, fatigue or
  lethargy, tingling, electric shock-like
  sensations, insomnia, and vivid dreams. Less
  common reactions are gastrointestinal discomfort
  and flu-like symptoms.

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Take Home Information

• SSRIs are less cardio toxic than TCAs
• Most side effects are easily manageable
• Serotonin Syndrome , while rarely seen, can be
  life threatening
• Serotonin withdrawal will be more commonly found.

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BACKGROUND

• Benzodiazepines (BZDs) are sedative-hypnotic
  agents that were first introduced in 1960.
• Because of their widespread popularity, these
  drugs commonly are abused. In addition, BZDs
  frequently are used in overdose, either alone or
  in association with other substances
• In addition they are used in illicit activities
  such as date rape.

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Background

• Most of BZDs effects come from its stimulation
  of the Gamma-aminobutyric acid (GABA) sites.
• Benzodiazepines generally are thought to be safe
  and death is rare. It usually occurs in
  conjunction with concomitant alcohol ingestion or
  use of other sedative-hypnotics..
• Intravenous administration is associated with
  greater degrees of hypotension than other routes
  of administration and occasional cardiac and
  respiratory arrest.

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S/S OF AN OVERDOSE

• Dizziness
• Confusion
• Drowsiness
• Blurred vision
• Unresponsiveness
• Nystagmus
• Hallucinations
• Slurred speech
• Ataxia
• Coma

• Weakness
• Altered mental status, impairment of cognition
• Amnesia
• Paradoxical agitation
• Respiratory depression
• Hypotension

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BASIC TREATMENT

• Supportive
• Airway management
• EKG, IV, Etc
• Activated charcoal -- Most useful if
  administered within 4 h of ingestion. Repeat
  doses may be used, especially with ingestion of
  sustained release agents. Limited outcome studies
  exist, especially when administration is more
  than 1 h of ingestion.

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FOCUSED TREATMENT

• Romazicon if BZD is the only confirmed agent that
  works similarly on the GAPA sites as Narcan does
  on the Opiate sites.
• Dose
• 0.2 mg IVP
• Repeat 0.3 Mg
• Max 0.5 mg to 1 mg.
• Caution with mixed drug overdose toxic effects
  due to other drugs taken in overdose (eg, cyclic
  antidepressants) may occur with reversal of
  benzodiazepine effects (I.e. SZ suppression)
• Beware of use in the chronic BZD pt (greater than
  4 weeks)

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Interactions

• Any drug that has sedative effects may expect to
  be potentiated by a BZD.
• BZD may suppress the SZ activity in a TCA
  overdose, masking the TCA.

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Detox, Dependence, and Withdrawal

• Benzodiazepine withdrawal syndrome is believed to
  be caused by a dampening of the action of GABA as
  neuroadaptivity causes GABA to become dependent
  on stimulation from the benzodiazepine to
  initiate its primary action.
• Most s/s are the reverse of the desired effect of
  a benzo.
• Worst case scenario onset of seizures

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TAKE HOME INFORMATION

• Supportive care is best
• Be familiar with BZD withdrawal syndrome
• Indiscriminate use of Romazicon is bad.