Phenytoin Flashcards
Dr. Lugo Exam 2
Indication of Phenytoin (Dilantin)
-tonic clonic seizures
-complex partial seizures
-prevention of seizures after head trauma
Dosage forms of Phenytoin
Salts (sodium): 92% phenytoin
-IV
-capsule
-XR
Acids: 100% Phenytoin
-suspension
-chewable tablets
What is the therapeutic plasma concentration of Phenytoin?
10-20 mg/L
GOAL free concentration concentration of phenytoin: 1-2 mg/L
What is the maximum IV infusion rate?
50 mg/min
-the excipient propylene glycol may cause hypotension when infused to rapidly
slow to 20g/min when ADR
1-3 mg/kg/min for children
-0.22 micron needle filter should be used for IV administration
What is the function of Propylene glycol in Phenytoin?
-to make Phenytoin more water-soluble
Phenytoin is lipophilic
What to look out for in the Phenytoin formulation?
-it may precipitate out -> use a 0.22 micron needle filter
bc Phenytoin is not very water-soluble
Rate to infuse for patients with CV disease
20 mg/min
Rate of infusion for children
1-3 mg/kg/h
What happens if Phenytoin IV is administered too rapidly?
-Hypotension
-cardiac arrhythmias
What would be the loading dose in a patient with status ellipticus (actively seizing)?
15-20 mg/kg
when given orally: administer in divided doses bc there is a rate-limited GI absorption
-> max 400 mg per dose
-> f.e for a loading dose of 1200 mg: 400mg every 2h x3 doses
What is the maintenance dose for Phenytoin?
5-6 mg/kg/day or 300 mg per day (adults)
OR
-300mg in 3 divided doses
-1-2 doses if extended-released
Adverse effects of Phenytoin
-GI: N/V (especially with high doses)
-CNS: dizziness, confusion, drowsiness, ataxia (loss of coordination) -> at high doses, with frequent use
-often given at bedtime, so the patient sleeps, and they are not affected by the side effects
-anti-epileptic hypersensitivity syndrome (AES): rash within the first 5 weeks as a symptom triad
Which side effects are referred to as the symptom triad when taking Phenytoin
rash, pruritus (itching), and fever
-it may progress to life-threatening Steven-Johnsons-syndrome (SJS) or toxic epidermal necrolysis
Other side effects
Hirsutism: hair growth in unusual areas
Osteomalacia: soft, weak bones
Teratogenicity: defects in the fetus
Megaloblastic anemia
Arrhythmia
Inhibits insulin release
Lymphadenopathy (swelling of the lymph nodes)
Gum hypertrophy (gingival hyperplasia)
Ataxia (loss of coordination, at high doses)
Nystagmus (repetitive uncontrolled eye movements)
Diplopia (double vision)
K: Vitamin K deficiency
remember: Hotmail G and K
Other side effects II
ADR: hepatoxicity, hyperglycemia, thickening of facial features, peripheral neuropathy (numbness and pain of hands and feet)Sig
Signs of acute toxicity (Phenytoin)
-Intention tremor
>20 mg/L: nystagmus and diplopia
>30 mg/L: ataxia and GI
>40 mg/l: lethargy, confusion, combative, slurred speech
<50 mg/L: choreoathetois (involuntary twitching)
Signs of chronic toxicity (Phenytoin)
-Confusion (delirium)
-Cerebellar dysfunction (dysarthria (difficulty speaking, ataxia, muscular hypotonia)
-peripheral neuropathy
What type of enzyme kinetics applies to Phenytoin?
Michaelis Menten kinetics
-when changing from one formulation to the other (salt (92%) to acid (100%)) -> small changes in bioavailability can have a significant effect
What is the Volume of distribution of Phenytoin?
adults and children: 0.6 - 0.7 L/kg
infants and neonates: 1.2 L/kg
obese: adjusted Vd for obese patients (higher than the normal)
0.65 L/kg * [IBW + 1.33 (TBW - IBW)]
What is the percentage of free concentration of phenytoin?
-10% free concentration
-90% bound to albumin
Which portion of phenytoin is reported on lab reports?
Bound + Unbound = total phenytoin
the free fraction of phenytoin is 0.1
in patients with normal albumin and achieved goal of 10-20 mg/L
-> the free concentration (active drug) is 1-2 mg/L
What affects the free concentration of phenytoin?
-diseases and meds affecting albumin levels
-diseases and meds affecting phenytoins binding affinity (Ka) to albumin
-hypoalbuminemia -> the total phenytoin appears normal, but the free concentration is higher bc less albumin to bind to
-end-stage-renal disease (ESRD): accumulation of toxic substances affecting the affinity of phenytoin to albumin
A patient with hypoalbuminemia has a total concentration of 17 mg/L and a free concentration of 3.5 mg/L
Is the patient therapeutic?
What is the unbound fraction?
No, possible toxicity bc his free concentration is over the recommended free concentration of 1-2 mg/L
-could be due to low albumin or meds affecting the affinity of phenytoin
unbound fraction: 20.58%
How to account for low albumin
Equation for Albumin Correction to phenytoin
Corrected Phenytoin = Phenytoin observed / (Albumin x 0.2) + 0.1
