2. Diazepam
Diazepam is used to treat status epilepticus and as an adjunct in convulsive
disorders
Diazepam depresses all levels of the Central Nervous System through the
increased action of gamma-aminobutyric acid (GABA)
Diazepam is a benzodiazepine that treats unbalanced chemicals in the brain
Diazepam is generally given in the rectal form for the pediatric population in
treatment of status epilepticus
3. Epilepsy
Epilepsy, also known as seizure disorder is excessive and abnormal brain cell
activity that can occur at any age and vary in etiology
Seizures can be hereditary or congenital or acquired
There are two classifications of seizures: Partial or generalized
Partial consists of simple and complex
Generalized consists of absence, tonic-clonic, clonic, atonic, myoclonic,
and tonic seizures
Status epilepticus is another category of seizure activity that is life-threatening
and is defined as activity lasting greater than 30 minutes or two or more
consecutive seizures without recovery between them
4. Intended Drug Response
The primary goals of treating acute repetitive seizures are prompt cessation of
the seizure and prevention of recurrence
Diazepam exerts its anticonvulsant effect by interacting with receptor
molecules, the benzodiazepine receptor, to regulate the efficiency of the
inhibitory neurotransmitter GABA at the GABA (A) receptor
The GABA (A) complex is a receptor-gated chloride channel that contains the
benzodiazepine as an allosteric modulatory unit
Equilibration speed between plasma and the effect site is described by the
equilibration half-life measured by elimination of the drug from the effect
site. The determining factor for onset of action in the CNS is the equilibration
of the half-life.
Diazepam crosses the blood brain barrier to elicit its pharmacological effect
5. Potential Drug Interactions
Other CNS depressants (e.g. alcohol, barbiturates, and opioids) that may
cause increased toxicity, sedation, and respiratory depression.
Tagamet may decrease the metabolism of Diazepam resulting in an
increased half-life and a decrease in clearance of the drug.
Selective serotonin reuptake inhibitors (e.g. Prozac, Zoloft, Paxil) increase
diazepam levels and alter its clearance.
Valproic acid may also result in an increase in sedative effects of
Diazepam by displacing it from its binding sites
Strong CYP3A4 inhibitors (Doxylamine, Hydroxyzine, Fosaprepitant,
Minocycline & Olanzapine) also cause potential interactions with
6. Adverse Drug Reactions/Side Effects
Drowsiness, amnesia, vertigo, hypotension, and slowed
respiratory rate. Other possible adverse reactions noted are
tachycardia, chest pain, confusion, ataxia, slurred speech, and
headache.
Common side effects may include lightheadedness, rash,
constipation, nausea, vomiting, menstrual irregularities, and
blurred vision
Sedation is a commonly reported adverse event associated with
Diazepam in any route that is administered. This must be
monitored in comparison to the normal post-ictal sedation of
7. Pharmacokinetics
Volume distribution equals 0.8 - 1.9 L/kg
The percent bound to plasma protein equals 98 where T1/2 equals
44 - 48 hrs. Though it accumulates over time and can take longer
with prolonged use.
Oral bioavailability is greater than 90% and time to peak ranges
from 15 minutes to 2.5 hours. If fasting peak time is 1.5 hours
and with food 2.5 hours.
Metabolism of Diazepam occurs in the liver via oxidation catalysed
by cytochrome P450 (CYP) isoenzymes 3A4 and 2C19
Diazepam shows to have adverse effects that affect more of the
8. Binding Issues
Due to Diazepam being highly bound to plasma proteins,
the binding interactions with other drugs arise.
Free fatty acids are an example of a class of drugs that
displace Diazepam binding in vitro and in vivo.
Valproic acid is a drug that is a two chain fatty acid and
and displaces Diazepam with its ability to bind fatty acid
binding sites on albumin.
The inhibition of Diazepam binding by Valproic acid is
competitive due to the number of binding sites for
Diazepam.
9. Pharmacogenomics
Drug treatment of epilepsy is characterized by the unpredictably of efficacy, drug
reactions, and optimal doses in individualized patients.
The unpredictability of antiepileptics results from individual genes whose
variations exert a measurable influence on the effect of the drug given for
treatment.
Environmental and genetic factors play a role in regulation of basal expression
and function of the CYP3A4 receptors.
The current best strategy to avoid genetically dose-related adverse reactions is
used of single-dose modern day treatment of antiepileptics which are not
metabolized by the liver nor involved in idiosyncratic reactions.
10. Improving Communication
Rounding with all of the different professions (in a hospital) seems to work really well as
everyone can share their knowledge in real time
Improving communication would be face-to-face conversation or meetings consisting with the
specialist, primary care physician, charge nurse, treating nurse, nurse assistant, social
worker, dietician/nutritionist, therapists, and case manager
The treatment plan established will be a team approach and provide a solid foundation of
communication between all professions resulting in a more established means of patient
safety
In other clinical settings, the nurse or caregiver will play a vital role to ensure any medication
adjustments, frequency or intensity in seizures, seizure pattern, adverse effects, etc. are
communicated with the prescribing doctor along with the primary care physician
11. Application to Practice
Patients and caregivers must understand the different
types of seizures and understand when they should be
prompted to seek medical emergency.
Overuse and abuse must be avoided and adverse
reactions must fully be understood
Collaboration with the provider or private duty nurse,
other in-home resources, and all doctors associated
with the child’s care is imperative.
The nurse plays the most important role in this process
and must be accountable for the education provided
and assessed
