A 54 Year Old Man With Epilepsy And Ischemic Heart Disease Presents With Complains Of Lethargy

A 54-year-old man with a history of epilepsy and ischaemic heart disease is seen in clinic with a 3 month history of lethargy.
Blood tests are as follows:
Hb 9.6 g/dl
MCV 123 fl
Plt 164 * 109/l
WCC 4.6 *109/l

Which one of his medications is most likely to be responsible?

A. Clopidogrel
B. Atorvastatin
C. Carbamazepine
D. Atenolol
E. Phenytoin

Answer:
E. Phenytoin

Discussion: Phenytoin may cause a megaloblastic anaemia by altering folate metabolism 

Phenytoin is used to in the management of seizures. 

Mechanism of action 

 sodium channel blocker, decreasing the sodium influx into neurons which in turn decreases excitability 

Adverse Effects: Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic.

Acute

 initially: dizziness, diplopia, nystagmus, slurred speech, ataxia 

 later: confusion, seizures 

Chronic 

 common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness 

 megaloblastic anaemia (secondary to altered folate metabolism) 

 peripheral neuropathy 

 enhanced vitamin D metabolism causing osteomalacia 

 lymphadenopathy 

 dyskinesia Idiosyncratic 

 fever 

 rashes, including severe reactions such as toxic epidermal necrolysis 

 hepatitis 

 Dupuytren's contracture

 aplastic anaemia 

 drug-induced lupus 

Teratogenic 

 associated with cleft palate and congenital heart disease