A 27-year-old female patient was brought to the emergency room after consuming clonazepam, desvenlafaxine, and sertraline tablets. On examination, she was drowsy and responding to painful stimuli with decreased breathing. Benzodiazepines stimulate the alpha subunit of the GABA-A receptor in the brain, causing sedation, hypnosis, anxiolysis, amnesia, anticonvulsant, and muscle relaxing effects. They are metabolized in the liver. A benzodiazepine overdose presents with neurological impairment like somnolence and ataxia. Treatment involves ventilation, flumazenil to antagonize benzodiazepines

1. CASE PRESENTATION
BENZODIAZEPAM OVERDOSE
DR.SIVA KUMAR ER PG 2ND YR

2. • A 27yr old female patient by name Miss
soundarya was brought to ER by her
attendants with alleged to have consumption
of Desvenlafaxine 50mg+ clonazepam 0.5mg
20 tab with sertraline 50mg 20 tab on 26/7/19
at around 5:00pm near her residence.
• On arrival to ER level of consciousness of
patient is responding to painful stimuli.

3. • Airway-Patent
• Breathing-RR-18/min
BAE+
Depth inadequate
spo2 100% with hudson mask@6lit/min
• Circulation-HR-82/min iv accesses secured
BP-100/70mm hg
CRT<3sec
All peripheral pulses felt

4. • Disability-GCS-E2V1M5
CBG-126mg/dl
Pupils-2mm both eyes reactive

5. • H/O Present illness ;- Alleged consumption of
Dervenlafaxine 50mg + Clonazepam0.5mg
20tab & sertraline 50mg 20tab on 26/7/19
near her residence.
• Pt was drowsy and responding to painful
stimuli.
• One episode of vomiting
• No H/o seizures,breathlesness,chest
pain,sweatings.

6. • Past History:-H/O similar complaints 1month
back with alleged Tab.Tramadol consumption.
• No H/O any comorbidites
• Family History:-No relevant family history.
• Personal History:-Pt takes mixed diet, Bowel
and bladder habits are normal.

7. • On Examination-Patient is drowsy &
responding to painful stimuli.
• General Examination-No
pallor,cyanosis,icterus,clubbing,lymphadenop
athy & edema.

8. Systemic Examination
• Cvs-S1S2 present,no murmurs
• RS-BAE+
Decreased depth of respiration
• CNS-E2V1M5,Bil plantars flexors.
• P/A-soft , bowel sounds + , no palpable
organomegaly

9. Ph 7.40
Pco2 38
Po2 130
Hco3 24
so2 98

10. Hb 13gm/dl
Tlc 8,200
Platelets 2,73,000
Na+ 143
K+ 3.4
Urea 26
Creatinine 0.7
LFT Normal range

11. DIAGNOSIS
Alleged Drug Overdose-Clonazepam 0.5mg 20tb
Desvenlafaxine 50mg
Sertraline 50mg 20tb

12. TREATMENT
1.O2 supplementation with hudson mask @
6lit/min.
2.Iv fluids DNS @ 70ml/hr.
3.Inj.Flumazenil 0.2 mg iv + 0.2mg iv .
4.Inj.Optineuron 1amp iv
5.Inj.Pantop 40mg iv stat
6.Inj.Emset 4mg iv stat

13. BENZODIAZEPINES

14. • 1.Introduction
• 2. Pharmacology
• 3.Clinical features
• 4.Diagnosis
• 5.Treatment
• 6.Disposition And Follow-up

15. Benzodiazepines, have in common six major
pharmacologic effects
• 1.Sedation
• 2.Hypnotic
• 3.Anxiolytic
• 4.Amnestic
• 5.Anticonvulsant
• 6.Muscle relaxant

16. • So they are commonly used for the short-term
treatment of anxiety, insomnia, seizures, and
alcohol and sedative-hypnotic withdrawal.
• Midazolam,has short duration of action, is
used for procedural sedation and general
anesthesia.
• Isolated benzodiazepine overdose has low
mortality, and death is rare.

17. • Increased rates of morbidity result from mixed
over- dose, especially in combination with
opioids.
• Isolated overdose with high-potency short-
acting agents, such as alprazolam,
temazepam, and triazolam, is associated with
higher incidences of intensive care unit
admissions, coma, and mechanical ventilation.

18. PHARMACOLOGY
• Benzodiazepines stimulate the α subunit of
the postsynaptic γ-aminobutyric acid (GABAA)
receptor.
• Route of administration-Oral,IM,IV
• Diazepam can be administered per rectally.
• Midazolam can be administered intranasally
and intrbuccally.

19. STIMULATION OF ALPHA SUBUNIT OF GABAa
OPENING OF LIGAND GATED “cl“ CHANNEL
ALTERATION OF TRANSMEMBRANE RESTING POTENTIAL
DECREASED EXCITABILITY OF POST SYNOPTIC NEURONS
INHIBITORY EFFECTS THROUGH OUT NEUROAXIS

21. • BDZ’S are highly lipid soluble so they rapidly
diffuses acrosses the blood brain barrier.
• They rapidly egress from blood and brain into
inactive tissue storage sites.
• So serum half- life is not a good indicator of
the duration of action in an acute ingestion.

22. • METABOLISM: Hepatic-1.Oxidation
2.Conjugation
• It is effected by chronic liver disease,advanced
estrogen,isoniazid,ethanol,ketoconazole,
Cimetidine and phenytoin.
• Drugs that effect CYP450 mainly CYP3A4 &
CYP2C19 effects the metabolism of BZD.
• Congenital malformations associated BZD are
cleft lip and cleft palate.

23. • Chronic use of BZD are associated with withdrawl
syndrome
• FLOPPY BABY SYNDROME-Sedation
Hypotonia
Apnea
Hypothermia
Cyanosis
• NEONATAL WITHDRAWL-Restlessness,Hypertonia
and Tremors.

26. CLINICAL FEATURES
• The predominant manifestations of BZD are
neurologic & characterized by somnolence,
dizziness, slurred speech,confusion,ataxia
,incoordination & generalised impairment of
neurological function.
• Paradoxical reactions are
excitement,anxiety,agression,hostile
behaviour,rage & delirium.
• BZD cause short term anterograde amnesia which
is useful in procedural sedation.

27. • Prolonged coma is uncommon in BZD,it indicates
intoxication with other agents or non toxin
related medical condition.
• Rapid administration of large doses causes
respiratory depression & hypotention.
• Propylene glycol as a diluent in parenteral
preparations of diazepam and lorazepam may
cause severe metabolic acidosis (lactic acidosis),
neph- rotoxicity, and hyperosmolar states when
infused at doses >1 milligram/kg per day for an
extended period of time.

28. • Osmolar gap>10 indicates elevated plasma
conc of propylene glycol.
• Treatment is supportive and sometimes
require hemodialysis.

29. DIAGNOSIS
• 1.Serum benzodiazepine levels
• 2.Urine benzodiazepine screening
• 3.Immunoassays
• All these are of limited value.

30. TREATMENT
• Gastric lavage ,elimination enhancement by
forced diuresis, hemodialysis,hemoperfusion
are not effective.
• Emesis is CI benzodiazepine overdose because
of mental status depression increases the risk
for pulmonary aspiration.
• Activated charcoal binds benzodiazepines
effectively and can be used.

31. • Mechanical ventilation depending upon
neurologic and respiratory status.
BENZODIAZEPINE ANTAGONIST
• Flumazenil is selective antagonist of the
central effects of benzodiazepines.
• Potential applications include the reversal of
coma in benzodiazepine overdose and reversal
of iatrogenic benzodiazepine- induced
sedation during procedural sedation.

33. • Dose of flumazenil is 0.2 milligram IV,can be
repeated every minute, titrated according to
response or to a total dose of 3 milligrams.
• Recurrent benzodiazepine toxicity may result
once the effects of flumazenil have worn off.
• Anticonvulsants such as phenobarbital or
propofol are recommended for flumazenil-
induced seizures.

36. DISPOSITION AND FOLLOW UP
• Indications for observation or hospital admission
include significant alterations in mental status,
respiratory depression, and hypotension.
• Other causes should be ruled out if mental status
depression persists.
• 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.

37. THANK YOU