Phenytoin Flashcards
What is phenytoin?
anticonvulsant used in a wide variety of seizure types. affects ion hcannels, active transport, and general membrane stabilisation
What class of drugs does phenytoin belong to?
anticonvulsants
What are other drugs in the same class as phenytoin?
primidone gabapentin topiramate acetazolamide clobazam lotrigine levetiracetam
What is phenytoin indicated for?
tonic clonic and focal seizures
What type of seizures should phenytoin be avoided in?
absence or myoclonic seizures
What is the role of phenytoin in epileptic therapy?
used for tonic clonic seizures, focal seizures, status epilepticus, prevenion of seizures following neurosurgery, acute symptomatic seizures assoc. with head trauma or neurosurgery altho this last indication is unapproved.
What is of phenytoin given for tonic clonic or focal seizures?
Oral:
Adult - initially 3-4mg/kg or 150-300mg daily as single or in 2 divided doses. increased gradually as necessary with careful monitoring.
Usual dose 200-500mgdaily
increase dose by 30mg every 2 weeks according to clinical response and phenytoin concentration
What is the dose of phenytoin given for status epilepticus?
Give via IV either slow intraveneous injection or infusion. Monitor BP and ECG
Do not exceed 1mg/kg/minute.
Max 50mg/min
Adult: 15-20mg/kg as loading dose. Then, a maintenance dose of 100mg by mouth or IV administration should be given every 6-8 hours and adjusted according to clinical response and phenytoin concentration
What is the mechanism of action of phenytoin?
Blocks sodium channels on neuronal cell membrane to limit the spread of seizure activity and reduce seizure propagation.
Promotes sodium efflux from neurons to stabilise threshold against hyperexcitability caused by excessive stimulation/environmental changes capable of reducing membrane sodium gradient.
What are the relevant PK/PD parameters associated with phenytoin?
70-100% bioavailability 90% protein bound primarily hepatically metabolised, followed by glucuronidation and excretion into urine. Affects CYP2C19 and 2C9 half life: 22 hours
What are the relevant precautions assoc. with phenytoin use?
cross sensitivity with carbamazepine
avoid abrupt withdrawal
HLA-B* 15:02 allele in Han Chinese or Thai origin patients, as they have increased risk of steven’s johnson’s syndrome
pregnancy class D
What are the relevant contradindications with phenytoin use?
with IV: sinus bradycardia, SA block, 2nd and 3rd degree heart block
strokes adams syndrome, acute porphyria.
hepatic impairment - reduce dose
What are the relevant adverse effects with phenytoin use?
nausea, vomiting, constipation, drowsiness, insomnia, transient nervousness, tremor, paraesthesia, dizziness, headache, anorexia, gingival hypertrophy, tenderness, rash, acne, hirsutism, coarseninig of facial appearance
Hepatotoxicity is rare.
What are the relevant drug interactions with phenytoin use?
Reduces efficacy of combined OC, ECP, doxycycline, fentanyl, intraconazole, quinidine,
Marked reduction in phenytoin absortpion when given with enteral foods
benzodiazepines can increase phenytoin concentrations –> toxicity
What are the alarm bells with phenytoin use?
phenytoin follows 0 order kinetics, the half life is dependent on the elimination rate. –> monitor closely
if signs of stevens johnsons syndrome: stop immediate and seek medical help
can interact with lab tests for dexamethazone, metyrapone, folic acid, calcium, free thyroxine, protein bound iodine
monitor ECG, BP, respiratory depression, serum levels, behaviour changes incl suicidality, new or worsening depresion.
Do not take Ca containing antacids or Ca close to time of dose
