CLINICAL

CASE 7
Anti Viral
 T. G., 30 y/o, male, sought consult due to
throat pain and fever.
He had throat pain and fever for 5 days and
has been self medicating with Erythromycin
and Paracetamol with no relief of symptoms.
VS: BP: 120/80mmHg, RR: 18cpm, PR:
100bpm, Temp: 39oC.
PE: hyperemic and swollen tonsils with an
overlying grayish exudate, painful ulcers
on the hard palate and tongue, tender
cervical lymphadenopathy. Tzanck smear
was positive.
 DIAGNOSIS

Acute Tonsillopharyngitis and

Gingivostomatitis secondary to
Herpes Simplex Virus
 DEFINITION OF TERMS
Tonsillopharyngitis is acute infection of the pharynx, palatine
tonsils, or both. Symptoms may include sore throat,
dysphagia, cervical lymphadenopathy, and fever.

Tonsillopharyngitis is usually viral, most often caused by the

common cold viruses (adenovirus, rhinovirus, influenza,
coronavirus, and respiratory syncytial virus), but occasionally by
Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or
HIV.

Gingivostomatitis(also known as primary herpetic

gingivostomatitis or orolabial herpes) is a combination
ofgingivitisand stomatitis, or an inflammation of theoral
mucosaandgingiva. Herpetic gingivostomatitis is often the
initial presentation during the first ("primary")herpes
simplexinfection.
 PATHOPHYSIOLOGY

Herpes Simplex Virus

Double-stranded DNA virus

Two types: HSV-1 and HSV-2
HSV-1 is usually associated with
orofacial disease
HSV-2 is usually associated with
genital disease
Tonsillopharyngitis
usually HSV-1; more common in adults than gingivostomatitis

clinical features: fever, malaise, headache, sore throat,

pharyhgeal erythema, exudates, tonsillar
enlargement/swelling, tender cervical lymphadenopathy,
vesicles

vesicles rupture to form ulcerative lesions with grayish

exudates on tonsils and posterior pharynx

may be cause by HSV-2 and associated with orogenital contact

(may occur with genital herpes)

transmission via respiratory secretions, fomites or food transmission

infection is localized in lymphatic tissue

rare significant complications of airway obstruction, decreased oral

intake and dehydration
Gingivostomatitis

manifestation of primary HSV-1; usually occurs in

children (6 mos to 5 years); adults: less severe;
associated with posterior pharyngitis

mode of transmission is infected saliva

incubation period is 3-6 days; lasts 5-7 days; symptoms

subside in 2 weeks

viral shedding may continue for 3 weeks or more

clinical features: abrupt onset, high temperature,

anorexia and listlessness, gingivitis (swollen,
erythematous, friable gums), vesicular lesions, tender
regional lymphadenopathy

perioral skin involvement

 NON-
PHARMACOLOGIC
TREATMENT
 Encouraged to drink water and other
fluids to preventdehydration.

Medicatedmouthrinse to reduce pain.

Gentledebridementof the mouth.

*In healthy individuals the lesions heal spontaneously in 714 days without
scarring.
PHARMACOLOGIC
TREATMENT
 ACYCLOVIR
Acyclovir(9-[2-hydroxy methyl]-9-H-
guanine)

Acyclic guanosine derivative against

HSV1, HSV2, and VZV

Weaker activity against EBV, CMV

and Human Herpes Virus 6 (HHV 6)
 MECHANISM OF
ACTION
REQUIRES 3 PHOSPHORYLATION STEPS:
Converted to di- and triphosphate compounds by
the hosts cellular enzymes
Converted to monophosphate derivative by virus-
specified thymidine kinase
Acyclovir triphosphate inhibits viral DNA
synthesis
Acts as a chain terminator because it lacks 3
hydroxyl group
Competitive inhibition of deoxy-GTP for viral DNA
polymerase
 RESISTANCE
HSV: absence of partial production of
viral thymidine kinase, altered
thymidine kinase substrate specificity,
and altered viral DNA polymerase

VZV: mutation in VZV thymidine

kinase and mutations in viral DNA
polymerase
 PHARMACOKINETICS
Oral bioavailability: 10-30%; decreases
with increasing dose
Clearance: GF and TS
Half-life: 3H (normal renal function); 20H
(anuria)
Distribution: body fluids (vesicular fluid,
aqueous humor, and CSF)
Concentrated in breast milk, amniotic
fluid, and placenta
Percutaneous absorption: low
 THERAPEUTIC USAGE
Acute Tonsillopharyngitis and
gingivostomatitis 2o to HSV
400mg

First and recurrent genital herpes:

200mg 5x/day X 10 days (oral)
5mg/kg per 8 hrs (IV)
Recurrent: 400mg 2x/day or
200mg 3x/day
 SIDE
EFFECTS
TOPICAL: mucosal irritation

ORAL: nausea, diarrhea, rash,

headache, renal insufficiency, and
neurotoxicity

IV: renal insufficiency, CNS SE

 VALACYCLOVIR
L- valyl ester of acyclovir
Rapidly converted to acyclovir after
oral administration
Serum levels are 3-5x > acylcovir
Primary and recurrent genital
herpes and herpes zoster infections
Prevents CMV disease in post-
transplant patients
 PHARMACOKINETICS

Oral bioavailability: 54%

CSF fluid levels: 50%

Elimination half-life: 2.5-3.3 hours

Generally well-tolerated
 FAMCICLOVIR

Diacetyl ester prodrug of 6 deoxy

penciclovir and rapidly converted to
PENCICLOVIR by FIRST-PASS metabolism

Penciclovir does not cause chain

termination

Oral form is approved for managing HSV

and VZV infections
 THERAPEUTIC USAGE
Acute Tonsillopharyngitis and gingivostomatitis 2 o
to HSV
500mg

1st episode genital herpes

250 mg TID X 5-10 days

Recurrent genital herpes

50 mg BID X 1 year

Herpes zoster (3 days)

500 mg TID x 10 days It
 SIDE EFFECTS

ORAL: headache, neutropenia,

nasopharyngitis, abdominal pain,
vomiting, dizziness, rash,
rhinorrhea, leukopenia, athralgia
 PENCICLOVIR
Penciclovir (9-[4-hydroxy-3-hydroxymethyl but-
1-yl] guanine

An acyclic guanine nucleoside

Active metabolite of famciclovir

Spectrum of activity and potency against HSV

& VZV similar to acyclovir

Inhibitory activity to HSV

 MECHANISM OF ACTION
Inhibitor of viral DNA synthesis
Initially phosphorylated by viral thymidine kinase
Penciclovir triphosphate has lower affinity in
competitive inhibition of viral DNA polymerase
thus cannot cause chain termination
100 fold less potent in inhibiting DNA
polymerase than acyclovir but present in higher
concentration and prolonged period in infected
cells
 THERAPEUTIC USAGE
Acute Tonsillopharyngitis and
gingivostomatitis 2o to HSV
0.1% cream
Mucocutaneous HSVIntravenous form-
5 mg/kg per 8-12 hrs X 7 days (IV)
Recurrent labial HS
1% penciclovir cream q2H while
awake for 4 days shortens healing
time and symptoms by about 1 day
 SIDE EFFECTS
TOPICAL: site reaction,
headache, rash, hypesthesia

Mutagenic at high concentrations

(IV form is not usually given)