What is the incidence of an adverse reaction such as seizures from 
administering acyclovir intravenous to a patient supected of having
viral encephalitis?  How dangerous are generalized tonoclonic
seizures?  How does Cerebyx effect the brain when given as the
antidote to the acyclovir?

Hello -

The PDR (Physician's Desk Reference) lists the risk of complications
of IV acyclovir (Zovirax) therapy as:
"Approximately 1% of patients receiving intravenous acyclovir have
manifested encephalopathic changes characterized by either lethargy,
obtundation, tremors, confusion, hallucinations, agitation, seizures,
or coma. ZOVIRAX should be used with caution in those patients who
have underlying neurologic abnormalities and those with serious renal,
hepatic, or electrolyte abnormalities, or significant hypoxia. "

A page which references the PDR can be found here:
http://www.hivdent.org/drugs/ACYCLOVIR.htm

Acyclovir is commonly used to treat viral encephalitis when it is
suspected that the viral cause is one of the herpes family of viruses
(simplex, zoster) and appears to greatly reduce the mortality from
this type of viral encephalitis from 60% to less than 20%.

While acyclovir isn't commonly thought to cause seizures, seizures are
a common component of viral encephalitis (particularly that caused by
the herpes viruses - simplex and zoster); in fact, abnormal EEG
activity (temporal lobe spikes) associated with seizure activity is a
common diagnostic criteria for establishing a diagnosis of herpes
encephalitis.  Incidence of seizures with viral encephalitis ranges
from 40-60% depending upon the viral cause (refs: UpToDate 'viral
encephalitis', reference #1).  The page from the Merck manual
describing viral encephalitis:
http://www.merck.com/pubs/mmanual/section14/chapter176/176c.htm

And a more approachable page:
http://www.ucdmc.ucdavis.edu/ucdhs/health/a-z/96Encephalitisviral/doc96.html

Generalized tonic-clonic seizures can be very dangerous by themselves
due to the loss of consciousness and muscle control - these dangers
are further compounded when the seizures are occuring in a patient
with underlying neuropathology.  If the seizures progress to status
epilepticus (an unremitting seizure), muscle breakdown, choking,
lactic acidosis and even neuronal death can occur.  In addtion to the
inherent dangers of the seizures, new onset seizures in a patient with
neuropathology are harbringers of brain swelling and/or brain damage.

A brief overview of seizures:
http://www.1uphealth.com/health/generalized_tonic_clonic_seizure_info.html

And a description of the dangers of status epilepticus:
http://epilepsyontario.org/faqs/seizures/status.html


Cerebyx, or fosphenytoin, is related to phenytoin (Dilantin), one of
the most commonly used anti-convulsant medications - it is used to
rapidly stop seizures.  It is not an antidote to acyclovir.  Phenytoin
(and fosphenytoin) works by blocking channels in nerve cells which
allow charged molecules (ions) to pass through the nerve cell
membranes - by blocking the flow of charged molecules, dilantin
disrupts the abnormal spread of electical activity that characterizes
a seizure.  Phenytoin is not without its side-effects, which can
include: sleepiness, balance difficulties, double-vision, slurred
speech, itching, and depressed reflexes.  Phenytoin would likely be
used to treat seizures in a patient with encepalitis.

A brief answer about the mechanism of action of phenytoin:
http://www.umu.se/pharm-neuro/inst/quiz/Phenytoin.html

A description of the side-effects of phenytoin:
http://www.rxlist.com/cgi/generic/phenyt_ad.htm



Please feel free to ask if you would like further explanation.

synarchy

The answer was composed from professional education,
Reference material found using the following Google searches:
Google: acyclovir
Google: tonic-clonic seizures
Google: cerebyx













Reference:
1) TI - Herpes simplex virus encephalitis. Diagnostic and treatment
considerations.
AU - Griffith JF; Ch'ien LT 
SO - Med Clin North Am 1983 Sep;67(5):991-1008

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Request for Answer Clarification by mystique-ga on 21 May 2003 13:34 PDT

Please explain what hypoxia means.

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Request for Answer Clarification by mystique-ga on 21 May 2003 13:38 PDT

I meant to give this 4 stars for a rating.  Please change it from two.
 The answer was very good.  The comment was weak.

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Clarification of Answer by synarchy-ga on 21 May 2003 14:54 PDT

Hello

Hypoxia refers to inadequate oxygen availability - this is usually
assessed in patients using either a pulse-oximeter (a little clip on
the finger or ear) that measures the amount of oxygen in the blood. 
Alternately, a blood sample can be drawn from an artery for a direct
measurement of the amount of oxygen.

A patient in a situation like that described could be hypoxic from a
seizure preventing breathing, from encephalitis affecting the
breathing centers of the brain, from drugs used to produce
sedation/seizure control decreasing the breathing rate, or from other
medical conditions that affect the lungs or heart.

Let me know if you need any further explanation; and thanks for the
clarification of the rating.

synarchy

This was not very meaningful.

This is the only study I have been able to find:

Arch Intern Med 1995 Jan 9;155(1):65-74 
Morbidity and toxic effects associated with ganciclovir or foscarnet
therapy in a randomized cytomegalovirus retinitis trial. Studies of
ocular complications of AIDS Research Group, in collaboration with the
AIDS Clinical Trials Group.

"Two hundred thirty-four patients with the acquired immunodeficiency
syndrome and previously untreated cytomegalovirus retinitis at 11
university centers were randomly assigned to receive intravenously
either foscarnet (n = 107) or ganciclovir (n = 127)...  The incidence
of seizures was similar in both groups (foscarnet, 12%; ganciclovir,
9%; P = .511)."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7802522&dopt=Abstract