Benzodiazepines , Barbiturates

Dd’s

 Ethanol
 Hypoglycemia
 Opiods
 Salicylates
 Sedative or hypnotic
 Seratonin
TOXIDROME Sedative/hypnotic

Benzodiazepines , Barbiturates
Central nervous system depression, ataxia,
dysarthria

Bradycardia, respiratory depression

Benzodiazepines

six major pharmacologic effects: sedative,

hypnotic, anxiolytic, amnestic,
anticonvulsant, and muscle relaxant.
isolated benzodiazepine overdose has low
mortality, and death is rare
 However, increased rates of morbidity do
result from mixed over- dose,especially in
combination with opioids.
Isolated overdose with high-potency

alprazolam, temazepam, and triazolam, is

associated with higher incidences of intensive
care unit admissions, coma, and mechanical
ventilation with toxicity compared to other
benzodiazepines, such as diazepam.
PHARMACOLOGY

 Benzodiazepines stimulate the alpha subunit of the

postsynaptic γ-aminobutyric acid (GABA ) receptor in
the CNS A

 Stimulation of this GABAA receptor leads to inhibitory

effects throughout the neuraxis, producing the typical
clinical effects of sedation, anxiolysis, anticonvulsant
activity, and striated muscle relaxation.
Benzodiazepine derivatives undergo hepatic metabolism
through different pathways depending on the agent.

 Increased and prolonged pharmacological action in

 (chronic liver disease), demographic characteristics
(advanced age), and concurrent treatment with drugs
that affect metabolism (estrogen, isoniazid, ethanol,
ketoconazole, cimetidine, and phenytoin)
 pregnancy

 The effect on fetal outcome of large doses of benzodiazepines taken

for suicide attempts by pregnant women is not clear.

 Retrospectively did not find an increased incidence of congenital

abnormalities in the offspring.

 Chronic use -withdrawal syndrome in the infant after birth such as

“floppy baby syndrome” (sedation, hypotonia, apnea, cyanosis,
hypothermia) and neonatal withdrawal (restlessness, hypertonia,
tremors).

 Brest milk entery is present for all benzodiazipines

 CLINICAL FEATURES

 The predominant manifestations of benzodiazepines are

neurologic and are characterized by somnolence, dizziness,
slurred speech, confusion, ataxia, incoordination, and general
impairment of intellectual function.

 Paradoxical reactions, including excitement, anxiety,

aggression, hostile behavior, rage, and delirium, have been
reported but are quite uncommon
 reported and that have unclear etiologies include headache,
nausea, vomiting, chest pain, joint pain, diarrhea, and
incontinence.

 Benzodiazepines may cause short-term anterograde amnesia

Propylene glycol

 a diluent in parenteral preparations of diazepam and lorazepam

 may cause severe metabolic acidosis (lactic acidosis),
nephrotoxicity, and hyperosmolar states when infused at doses >1
milligram/kg per day for an extended period of time.

 During such treatment, an osmolar gap >10 is predictive of elevated

propylene glycol concentrations.

 Treatment of propylene toxicity is generally supportive but may

require hemodialysis.
 In general, benzodiazepines have no long-term organ-system
toxicity other than that which can be ascribed to indirect
effects from neurologic or cardiorespiratory depression.
DIAGNOSIS

 Qualitative testing with urine drug screens is typically

designed to identify major metabolites of most
benzodiazepines, such as oxazepam, temazepam, or
nordiazepam, and not the parent compound.

 false-negative test can occur and is commonly seen

with midazolam and flunitrazepam.
A urine benzodiazepine screen can usually
detect a short-acting agent (e.g., lorazepam)
up to 3 days and a long-acting agent (e.g.,
diazepam) up to 30 days after ingestion.
False-positive benzodiazepine urine drug
screens have been reported with oxaprozin
and sertraline,
 treatment

 Stabilization of airway, breathing, and circulation represents

initial priorities.

 Antidote
 History
 Examination
 Toxidrome
 Diagnostic testing
 Don’t induce emesis
 Activated charcoal binds benzodiazepines effectively
 Gastric lavage, elimination enhancement by forced diuresis,
hemodialysis, or hemoperfusion is not effective
Flumazenil

 Potential clinical applications include the reversal of coma in

benzodiazepine overdose and reversal of iatrogenic
benzodiazepine- induced sedation during procedural sedation

 The dose of flumazenil is 0.2 milligram IV, which can be

repeated every minute, titrated according to response or to a
total dose of 3 milligrams.
 Anticonvulsants such as phenobarbital or
propofol are recommended for flumazenil-
induced seizures.

Flumazenil is contraindicated in patients with a

suspected elevation of intracranial pressure, such
as in severe head injury, due to its adverse effect
on cerebral hemodynamics.
DISPOSITION AND FOLLOW-UP

 Indications for observation or hospital admission include

significant alterations in mental status, respiratory depression,
and hypotension

 there is insufficient literature to recommend a specific duration

for appropriate ED observation to conclude the patient is safe
for discharge or transfer after a benzodiazepine overdose.
barbiturates

historically been associated with the highest risk of

morbidity and mortality among all sedative-
hypnotics.

still the most common class of 2nd line

antiepileptic drugs used in developing countries
pharmacology

 Barbiturates readily distribute throughout the body to most tissues,

crossing the blood–brain barrier and placenta, and are excreted in
breast milk

 In the CNS, this is accomplished by enhancing the action of the primary

inhibitory neurotransmitter γ-aminobutyric acid at its receptor. When γ-
aminobutyric acid binds to its chloride channel receptor, it causes it to
open, resulting in depolarization, which temporarily stabilizes the resting
membrane potential and inhibits the firing of new action potentials.
CLINICAL FEATURES

 Mild to moderate barbiturate intoxication closely resembles

alcohol intoxication and toxicity of other sedative-hypnotics;
drowsiness, disinhibition, ataxia, slurred speech, and mental
confusion are common features that escalate with increasing
dose

 progressive neurologic depression seen with severe barbiturate

intoxication predictably manifests as a range from stupor to
coma to complete neurologic unresponsiveness, including the
absence of a corneal reflex and deep tendon reflexes.
most common vital sign abnormalities

 respiratory depression,
 hypothermia,
 hypotension,
 GI tract motility is slowed, resulting in delayed gastric
emptying and ileus.

 Skin bullae, sometimes referred to as “barb blisters” or

“coma blisters,” are uncommon

 Death-respiratory arrest and cardiovascular collapse

diagnosis

 glucose levels,
 blood chemistries,
 CBC,
 arterial blood gas (if indicated),
 toxicology screen,
 chest radiograph,
 electrocardiogram.
 Urine drug screens most commonly use the
immunoassay methodology

 false-positive result -on the barbiturate screen has been

reported with ibuprofen and naproxen
TREATMENT

 AIRWAYASSESSMENTANDINITIALSTABILIZATION

 cardiac output and vascular tone

 Hypothermia

 ACTIVATEDCHARCOAL -stable patients who present within 1 hour of acute oral over-
dose

 consider multidose activated charcoal if a patient has ingested a life-threatening

amount of phenobarbital.23 A typical adult regimen for multidose activated
charcoal is an initial dose of 50 to 100 grams PO followed by 12.5 to 25 grams PO
every 4 hours
URINARYALKALIZATION

does enhance the clearance of phenobarbital

less effective than multidose activated charcoal
is not effective for shorter-acting barbiturates
EXTRACORPOREAL ELIMINATION

 Hemodialysis, hemoperfusion, and hemodiafiltration can

enhance elimination of phenobarbital but are reserved for
patients who are deteriorating despite aggressive supportive
care

 These modalities are not useful for poisoning from barbiturates

other than phenobarbital.

 Exchange transfusion has also been reported to be useful in

neonatal phenobarbital toxicity