YZ , a 20 year old female medical student intentionally took 10 tablets of Diazepam 10

mg/ tab after discovering her boyfriend was having an affair with her best friend. She was
brought to the FUMC ER due to dizziness and confusion by her best friend,

Vital Signs were as follows at the ER

BP 100/60

CR 50 bpm

RR 12 cpm

1. What is the MOA of Benzodiazepines and discuss briefly the symptoms of overdose

What is benzodiazepine?
Benzodiazepine are sedative-hypnotic drugs that act as a central nervous
depressant used in the treatment of anxiety, sleep disorders, alcohol withdrawal as well
as seizure disorders. These medications are tightly regulated and are only available
with a prescription. They have a wide variety of usage including anxiolytic effects or to
relieve anxiety, anticonvulsants, hypnotic for insomnia and to treat withdrawal
symptoms (alcohol withdrawal).

Classification
There are three types of benzodiazepines:
 Short acting (3-8 hours)
o Have a stronger withdrawal or come down effects and can be more
addictive than long-acting ones
o Half-life: < 24 hours
o Ex: Midazolam, Brotizolam, Triazolam, Oxazepram
 Intermediate acting (10-20 hours)
o Half-life: > 24 hours
o Ex: Nitrazepam, Estazolam
 Long acting (1-3 days)
o Half-life: > 48 hours
o Ex: Diazepam, Flurazepam

DIAZEPAM

 Long-acting benzodiazepine
 Onset of action
 o Oral: 30 min – 1 hour
o IM: 15 – 30 min
o IV: <15 min
 Peak plasma levels:
o Oral: 30-60 min
o IM: 30-90 min
o IV: 15 min
 Bioavailability
o > 90%
o Taken rapidly to brain
o Absorption after IM dose is slow and erratic except when given into the
deltoid
 Plasma half-life
o 14-60 hours

Uses

Food and Drug Administration (FDA)Trusted Source have approved benziodiazepine for the
treatment of:

 insomnia
 generalized anxiety disorder
 social anxiety disorder
 seizure disorders, such as epilepsy
 panic disorder

Pharmacokinetics
 Readily and completely absorbed from GIT
 Cross the placental barrier during pregnancy
 Protein binding
o 98% bound
 Metabolized in the liver
 Excretion:
o Eliminated in the kidneys
o Excreted in the urine as oxidized and glucuronide-conjugated metabolites

Mechanism of action
 Neurons

communicate with each other through neurotransmitters. When one neuron is

stimulated, it will release excitatory neurotransmitters like glutamate which bind to
receptors on the next neuron. This causes the next neuron to depolarize and release its
own excitatory neurotransmitters, propagating the signal throughout the brain. Now, we
also have inhibitory neurons that will shut down this chain of events. These neurons
release the main inhibitory neurotransmitter which is the GABA (gamma glutamyl butyric
acid) which binds to GABA receptors on other neurons. These receptors form ligand-
gated ion channels that open up to let chloride ions into the cell.

Benzodiazepine act by potentiating the activity of GABA in the CNS. When

benzodiazepine bind or attach to the GABA receptor, it binds at a location separate from
where GABA itself binds, and exert an influence over GABA binding. This type of action
is called an allosteric effect. Benzodiazepine increases the effect that GABA has which
is reducing neuronal excitability when it binds to the receptor. That effect is to open an
ion channel and allow the passage of negatively charged chloride ions into the neuron.
This influx of negatively charged chloride ions pushes the membrane potential by
hyperpolarizing it and makes it less likely to fire an action potential and inhibit cellular
excitation. This type of neural inhibition is the basis for the effects of benzodiazepines,
by inhibiting the activity of neurons involved with anxiety and arousal, thus this drug is
able to produce calming effects.

Pharmacodynamics
ADVERSE EFFECT
 Cardiovascular: Bradycardia/Tachycardia, Hypotension
 CNS: Amnesia, anxiety, drowsiness, depression
 Dermatologic: rash
 GIT: Constipation/Diarrhea, nausea, vomiting
 Local: Pain with injection
 Respiratory: Apnea, decrease respiratory rate, laryngospasm

Contraindication
Benzodiazepines are not recommended for use during pregnancy or breastfeeding
as they are associated with pre-term delivery, low birth weight and potential birth
defects. They may also be dangerous for people with:
 Acute asthma, emphysema or sleep apnea
 Advanced liver or kidney disease
 History of substance use disorders, as their use can lead to dependence
 Elderly people can increase their risk of falls and injury

DISCUSS THE SYMPTOMS OF OVERDOSE

 Mixing benzos and alcohol significantly increases the risk of an overdose. Combining
benzos with opioid painkillers, cough medicines and other central nervous system depressants
can lead to profound sedation, breathing trouble and death.
In addition, individuals suffering from and overdose may display symptoms opposite of the
drug’s typical effects. For example, a person may get excited, agitated, or talkative rather than
sluggish, fatigued and calm. This reaction is referred to as “paradoxical reaction” and occurs in
less than 1% of patients.

 Slow breathing
o Benzodiazepine can depress the central respiratory drive, chemoreceptor
responsiveness to hypercapnia, inspiratory and expiratory muscle strength
resulting to reduced respiration.
o In addition, benzodiazepine can cause upper airway obstruction via relaxation of
the tongue and neck (apnea)
NOTES:
Benzodiazepines decrease the ventilatory response to carbon dioxide, but this
effect is not usually significant if they are administered alone. More severe respiratory
depression can occur when benzodiazepines are administered together with opioids.
Another problem affecting ventilation is airway obstruction induced by the hypnotic
effects of benzodiazepines. (Katzung)

 Clammy skin
 Low blood pressure
o When action potential is inhibited, the activity of vascular smooth muscle is also
inhibited, so the vascular smooth muscle relaxes leading to vasodilation and
decrease blood pressure
 Enlarged pupils
o Overuse of benzodiazepine can cause pupils to dilate because it stimulate GABA
which has a muscle-relaxing effect
 Sluggish reflexes
o Inhibits the contractility of smooth muscles in the periphery
 Weak or rapid pulse
 Bluish lips
 Coma
 Death
2. What ancillary procedures should be requested in your patient?
 Blood glucose
o To rule out and address hypoglycemia as the cause of altered mental status
 Hypoglycemia must be rule out in every patient with altered mental status
even benzodiazepine poisoning is suspected
o In a study, overuse of benzodiazepine is associated with low blood sugar
 ECG
o ECG should be ordered to rule out ingestion of drugs that may widen the QRS or
QTc intervals and may precipitate arrythmia
 Acetaminophen and aspirin levels
o Along with ethanol levels should be ordered to evaluate for possible coingestions
 ABG
o to know if respiratory depression is present
o To quantify the degree of hypoxia (lactic acidosis)
o Patients with benzodiazepine overdose are at risk of developing Type 2
respiratory failure due to respiratory depression
 why we need to measure liver function test in diazepam poisoning why we need to
measure liver function test in diazepam poisoningUrinalysis
o A positive urine benzodiazepine drug screen only indicates recent exposure but it
does not confirm, causality for acute symptoms, toxicity or overdose
o NOTES
 In general, benzodiazepine can be detected as early as 3 hours after
ingestion and remain detectable for up to 2 weeks

Whereas short acting drugs are used for the treatment of depression, anxiety, muscle sickness
and sleeping disorder and long acting drugs are using for the treatment of physical relaxation,
nausea and drowsiness etc.