Diazepam

Diazepam

1. Diazepam Jane Davidson MSNE 5356 Advanced Pharmacology Lamar University

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 Diazepam increasing its levels and causing possible harm.

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 seizure activity.

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 CNS than the digestive or systemic system

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