Pharmacotherapeutic Plan for Generalized Tonic-Clonic Seizures in an Elderly Patient

QUESTION

Chief Complaint

“I had a seizure a few weeks ago and banged up my head.”

HPI

Carter McNeely is a 68-year-old man whose seizures are well controlled with carbamazepine monotherapy.

The seizure from 2.5 weeks ago was the first seizure in 20 months. During the seizure, he fell to the floor and

sustained a laceration to his occipital region that required staples for closure. The description of his seizures is

vague because there have been only six seizures documented since he developed epilepsy 3 years ago.

Because Mr McNeely lives alone in an assisted living facility, only half of the documented seizures have been

witnessed by another individual who could provide a description. Two seizures were witnessed by other

residents who described him as “falling to the ground and starting to shake.” One seizure occurred in the day

room when a facility nurse was in the room, and he documented that Mr McNeely fell to the ground, developed

rhythmic extensions to both his legs, became incontinent of urine, and was sleepy and disoriented for 2 hours

after the episode.

He has only been treated with carbamazepine. This was started by his family practice physician after his

second seizure. An EEG was obtained at that time and was unremarkable. Because the seizures are so

infrequent, the dose of carbamazepine has never been adjusted.

PMH

• Tonic-clonic seizures diagnosed 3 years ago

• HTN adequately controlled with lisinopril monotherapy

• Dyslipidemia controlled with atorvastatin and low-cholesterol diet

• BPH, currently symptom-free on dutasteride

FH

Mother died at age 74 of “natural causes”; had HTN for many years. Father died at age 70 of “natural causes”;

did not have any known medical illnesses. All of his children and grandchildren are alive and well. One son and

one daughter have HTN.

2

SH

Retired factory worker; resides in an assisted living facility. He is widowed and has six children and nine

grandchildren, whom he sees frequently. He denies past or present tobacco and illicit drug use. He reports a

history of regular alcohol use but now only drinks one beer that his grandson brings to him every Saturday

evening.

Meds

• Aspirin 81 mg PO once daily

• Atorvastatin 40 mg PO once daily

• Carbamazepine XR 200 mg PO twice daily

• Dutasteride 0.5 mg PO once daily

• Lisinopril 20 mg PO once daily

• Multivitamin with minerals one tablet PO once daily

All

• NKDA

• Adverse drug effect history—none

Physical Examination

Gen

Exam reveals an elderly Caucasian man who appears his stated age in NAD

VS

BP 126/78 mm Hg, HR 72, RR 16, temperature not measured; Ht 5′10′′, Wt 72.5 kg

HEENT

Normocephalic; scalp: healing 3-cm lesion in the occipital region with corresponding mild tenderness and

bruising; PERRL

Neck/LN

No thyromegaly, lymphadenopathy, or carotid bruits

Chest/Lungs

Lungs CTA

CV

RRR, no m/r/g

3

Abd

Soft, nontender; no HSM; (+) BS

MS/Ext

Normal tone; 5/5 strength in all extremities

Neuro

Awake; A & O × 3; CN II-XII intact, reflexes 2+ and symmetric throughout

Labs

Na 127 mEq/L Hgb 13.5 g/dL Fasting Lipid Profile

K 4.7 mEq/L Hct 41% T. Chol 155 mg/dL

Cl 90 mEq/L RBC 3.9 × 106/mm3 TG 123 mg/dL

CO2 25 mEq/L WBC 5.1 × 103/mm3 HDL-C 39 mg/dL

BUN 10 mg/dL Diff WNL LDL-C 91 mg/dL

SCr 0.6 mg/dL MCV 97 μm3

Glu 100 mg/dL Carbamazepine 6 mcg/mL

EEG

Sleep-deprived EEG unremarkable. Photic stimulation failed to produce any other changes

Assessment

Sixty-eight-year-old man with fairly well-controlled seizures on carbamazepine monotherapy

ASSESSMENT AND DIAGNOSIS

1. Generalized Tonic-Clonic Seizures

PHARMACOTHERAPEUTIC PLAN

The following order(s) were transmitted to the pharmacy via e-scribe:

DRUG STRENGTH DOSAGE FORM ROUTE

Levetiracetam [Keppra] 500mg Tab PO

SIG QTY DAYS SUPPLY REFILLS

1 tab PO BID 60 30 3

DAW NOTES

N

4

DRUG STRENGTH DOSAGE FORM ROUTE

Carbamazepine XR [Tegretol] 200mg Tab PO

SIG QTY DAYS SUPPLY REFILLS

Take 1 capsule PO daily 30 30 0

DAW NOTES

N Taper down

Assignment:

1. Based on the pharmacotherapeutic plan, discuss:

a. Rationale for the choice of therapy (consider drug indications and current treatment guidelines)

b. Pharmacodynamics (drug class and mechanism of action)

c. Pertinent pharmacokinetics

2. If applicable, discuss the rationale for any medication discontinuation/taper.

3. Based on the pharmacotherapeutic plan, discuss monitoring parameters.

a. Monitoring parameters for assessing therapeutic effectiveness/ goals of therapy

b. Monitoring parameters for assessing adverse drug effects

ANSWER

Pharmacotherapeutic Plan for Generalized Tonic-Clonic Seizures in an Elderly Patient

Introduction

This essay discusses the pharmacotherapeutic plan for a 68-year-old male, Mr. Carter McNeely, who experienced generalized tonic-clonic seizures and is currently on carbamazepine monotherapy. The plan involves the addition of levetiracetam (Keppra) to optimize seizure control and manage potential side effects. This essay explores the rationale behind the choice of therapy, the pharmacodynamics of the prescribed drugs, and pertinent pharmacokinetics. Additionally, it delves into the decision to discontinue carbamazepine and the monitoring parameters for assessing therapeutic effectiveness and adverse drug effects.

Rationale for the Choice of Therapy

Levetiracetam (Keppra) Addition:
Levetiracetam, an antiepileptic drug (AED), is added to Mr. McNeely’s regimen to enhance seizure control. The rationale lies in its broad-spectrum efficacy against various seizure types, including generalized tonic-clonic seizures. The American Academy of Neurology guidelines recommend levetiracetam as a first-line option for the treatment of generalized tonic-clonic seizures due to its favorable efficacy and tolerability profile (1).

Carbamazepine Taper:
Carbamazepine monotherapy has been effective in controlling Mr. McNeely’s seizures; however, his recent seizure episode and the lack of dose adjustments due to infrequent seizures warrant reconsideration. Tapering carbamazepine is essential to prevent abrupt withdrawal and minimize the risk of seizure recurrence. The tapering process helps avoid potential rebound seizures or adverse effects associated with sudden discontinuation (2).

Pharmacodynamics

Levetiracetam:
Levetiracetam is a pyrrolidine derivative that exhibits antiepileptic activity through a unique mechanism of action. It binds to synaptic vesicle protein SV2A, which inhibits neurotransmitter release, modulates calcium channels, and stabilizes neuronal membranes. This action reduces excitatory neurotransmission and inhibits the spread of epileptic activity, thereby controlling seizures (3).

Carbamazepine:
Carbamazepine is a voltage-gated sodium channel blocker that inhibits the repetitive firing of action potentials. By stabilizing neuronal membranes, it prevents the rapid firing of neurons responsible for epileptic discharges and reduces seizure activity (4).

Pertinent Pharmacokinetics

Levetiracetam:
Levetiracetam exhibits linear pharmacokinetics with a bioavailability of nearly 100%. It has a short elimination half-life of approximately 6-8 hours and is primarily eliminated unchanged through the kidneys. Levetiracetam does not significantly interact with hepatic enzymes, reducing the risk of drug-drug interactions (5).

Carbamazepine:
Carbamazepine is well-absorbed orally, with peak plasma concentrations achieved within 4-6 hours. It undergoes extensive metabolism in the liver, primarily via CYP3A4, into active and inactive metabolites. Carbamazepine induces its metabolism and may interact with other medications metabolized by CYP3A4, necessitating careful monitoring for potential drug interactions (6).

Medication Discontinuation/Taper

The tapering of carbamazepine is essential to minimize the risk of withdrawal seizures and adverse effects associated with sudden discontinuation. Gradually reducing the dose over time allows for a smooth transition to the new therapeutic regimen while maintaining seizure control (2).

Monitoring Parameters

Therapeutic Effectiveness/Goals of Therapy:
Reduction in seizure frequency and intensity
Absence of breakthrough seizures
Improved quality of life and functional status

Adverse Drug Effects:
Levetiracetam: Monitor for potential adverse effects, such as drowsiness, irritability, and mood changes (3).
Carbamazepine: Monitor for common side effects, including dizziness, drowsiness, and gastrointestinal disturbances (4).

Conclusion

The pharmacotherapeutic plan for Mr. Carter McNeely involves adding levetiracetam to his current carbamazepine monotherapy to optimize seizure control. This choice aligns with current treatment guidelines, and the pharmacodynamics and pharmacokinetics of both drugs support their use in managing generalized tonic-clonic seizures. Tapering carbamazepine gradually is crucial to prevent adverse outcomes. The monitoring parameters for therapeutic effectiveness and adverse drug effects are essential to assess the success of the plan and ensure patient safety throughout the treatment process.