PHARMACOLOGY

ANTIVIRAL CASE #1

F2
Paril, Marie Jennifer F.
Quilicot, Sinclair Joseph U.
Objectives:
a. To identify the diagnosis of the patient
b. To identify the basis of the diagnosis
c. To determine at least 3 differential diagnoses
d. To discuss pharmacologic and non-pharmacologic
management to the patient
e. To discuss Congenital Varicella Syndrome
f. To differentiate Varicella Immunoglobin (VZIG) and Varicella
Zoster Vaccine (VZV)
g. To discuss the reactivation of such viral infection into adult life
h. To make a prescription of the antiviral agent indicated
 5 Y/O
 vesicular lesions with
maculopapular rashes
 low to moderate
noted on the trunk and grade fever
extremities

 has poor appetite  cough

 a seatmate of his son

was absent 7 days
 fairly active ago because of
chicken pox.

Vaccination status was unremarkable.

DIAGNOSIS:
VARICELLA/
CHICKEN
POX
 Basis for Diagnosis

• - vesicular lesions with maculopapular rashes

noted on the trunk and extremities
• -a seatmate of his son was absent 7 days ago
because of chicken pox
• - low to moderate grade fever
• - poor appetite
• -5 years of age
 Basis for Diagnosis
PATIENT’S CHICKEN POX/VARICELLA’S MANIFESTATIONS
MANIFESTATIONS (Harrison’s Principles of Internal Medicine, 20th
Edition)
- vesicular lesions The skin lesions—the hallmark of the
with maculopapular infection—include maculopapules, vesicles,
rashes noted on the and scabs in various stages of evolution.
trunk and extremities These lesions, which evolve from
maculopapules to vesicles over hours to days,
appear on the trunk and face and rapidly
spread to involve other areas of the body.
a seatmate of his son The incubation period of chickenpox ranges
was absent 7 days ago from 10 to 21 days but is usually 14–17 days.
because of chicken Secondary attack rates in susceptible siblings
pox within a household are 70–90%.
 Basis for Diagnosis
PATIENT’S MANIFESTATIONS CHICKEN POX/VARICELLA’S MANIFESTATIONS
(Harrison’s Principles of Internal Medicine, 20th
Edition)
low to moderate Clinically, chickenpox presents as a
grade fever rash, low-grade fever,malaise, and
poor appetite
poor appetite

-5 years of age Historically, children 5–9 years old

were most commonly affected,
accounting for 50% of all cases.
Most other cases involved children
1–4 and 10–14 years old.
Differential
Diagnosis
 Differential Diagnoses
DIAGNOSIS VARICELLA/CHICKEN MEASLES SCARLET FEVER HERPES HERPES ZOSTER
POX SIMPLEX
Etiologic Varicella-zoster virus Measles virus/ Streptococcus Herpes Simplex reactivation of
Agent (VZV) Paramyxovirus pyogenes (Group Virus 1 latent Varicella-
A beta-haemolytic zoster virus (VZV)
streptococci or
GpA BHS)
Lesions Vesicles on Erythematous Erythematous Vesicular lesion -erythematous
erythematous base maculopapular Blanching that rapidly maculopapular
“Dew drops on a rose exanthema macules and rupture, leaving rash evolves
petal” sandpaper-like shallow ulcers on rapidly into
papules an erythematous vesicular lesions.
base -unilateral
vesicular
dermatomal
eruption
Location of Appears on the trunk Begins on the face Begins on upper Orolabial, Primarily thoracic
Rashes and face and rapidly around the trunk, then including hard (50%), remainder
spread to involve other hairline, and spreads to face palate, tongue, cranial, cervical
areas of the body. behind the ears. It and extremities and gingiva lumbar
then spreads with sparing of
downward to the the palms and
neck, trunk, arms, soles
legs, and feet.
CHICKEN POX
HERPES SIMPLEX MEASLES

HERPES ZOSTER
SCARLET FEVER
Pharmacological Management
 Pharmacological Management
ACYCLOVIR
CLASS Antiviral
Acyclic guanosine derivative
INDICATIONS Herpes Simplex Virus Infection
Varicella-Zoster Virus Infection
MOA: Antimetabolite prodrug
Pharmacodynamics
-Undergoes phosphorylation
-converted to aciclovir
monophosphate by virus-specific
thymidine kinase then further
converted to aciclovir triphosphate
by other cellular enzymes.
-Aciclovir triphosphate inhibits DNA
synthesis and viral replication by
competing w/ deoxyguanosine
triphosphate for viral DNA
polymerase and being incorporated
into viral DNA.
VALACYCLOVIR
Antiviral
L-valyl ester prodrug of acyclovir
Herpes Simplex Virus Infection
Varicella-Zoster Virus Infection
Same with Acyclovir.
Rapidly and almost completely
converted in man to aciclovir and
valine, probably by the enzyme
referred to as valaciclovir
hydrolase.
Higher bioavailability with CSF
level 50% of serum value
 Pharmacological Management
ACYCLOVIR
Pharmacokine Absorption: Poorly absorbed from the GI
tics: tract. Slight absorption after topical
application to intact skin.
Bioavailability: Approx 10-20% (oral).
Distribution: Widely distributed to body
tissues and fluids including CSF. Crosses the
placenta and distributed into breast milk.
Volume of distribution: 0.8 L/kg. Plasma
protein binding: 9-33%.
Metabolism: Converted by viral enzymes to
aciclovir monophosphate, and further
converted to diphosphate then triphosphate Excretion: Via urine (mainly as aciclovir
(active form) by cellular enzymes.
Excretion: Via urine (up to 14% as the
inactive metabolite 9-
carboxymethoxymethylguanine).
Plasma half-life: Approx 2-3 hr.
VALACYCLOVIR
Absorption: Readily absorbed from the
GI tract.
Bioavailability: Approx 54% (aciclovir).
Time to peak plasma concentration: 1-2
hr.
Distribution: Plasma protein binding:
13.5-17.9%.
Metabolism: Converted to aciclovir and
L-valine via first-pass intestinal or
hepatic metabolism.
and its metabolite 9-
carboxymethoxymethylguanine; <1% as
unchanged drug).
Plasma elimination half-life: 2.5-3.3 hr.
 Pharmacological Management
ACYCLOVIR VALACYCLOVIR
AE: Generally well tolerated. Generally well tolerated.
Infusion Related: Crystalline Nephropathy: Crystalluria Dose Related: High Doses- confusion,
Neurotoxicity (agitation, HA, confusion, sz) hallucinations, sz
DOSAGE Oral For oral dosage form (tablets):
Varicella zoster
Adult: 800 mg 4 or 5 times daily for 5-7 days. Varicella zoster
Child: >2 yr 20 mg/kg (up to max of 800 mg), 4 times Children 2 to 18 years of age—Dose is
daily for 5 days. based on body weight . The usual
dose is 20mg per kilogram (kg) of
Intravenous body weight, taken 3 times a day for 5
Varicella zoster days. However, the dose is usually not
Adult: 5 mg/kg 8 hrly. Immunocompromised patients: more than 1000 mg three times a day.
10 mg/kg 8 hrly. Dose to be given as IV infusion over
1 hr.
Child: >3 mth to 12 yr 250 mg/m2 8 hrly for 5-10
days. Immunocompromised patients: 500 mg/m2 8
hrly for 5-10 days. Dose to be given as IV infusion
over 1 hr.
 ORAL (Tablets  ORAL (Tablets/Caplets)
/Capsules/Suspension)
 TOPICAL (Ointment/Cream)
 IV (vial)
 Pharmacological Management
ACYCLOVIR
CONTRAINDICATI Hypersensitivity to aciclovir
ON and valaciclovir.
SPECIAL Patient w/ neurological
PRECAUTIONS abnormalities, significant
hypoxia or serious hepatic or
electrolyte abnormalities
(IV). Renal impairment.
Pregnancy and lactation.
DRUG Probenecid, cimetidine and
INTERACTIONS mycophenolate mofetil may
increase the plasma
concentration of aciclovir.
Increased nephrotoxic effects
w/ drugs that affect renal
physiology (e.g. ciclosporin,
tacrolimus)
COST (Available in Generic)
VALACYCLOVIR
Known hypersensitivity to valaciclovir,
aciclovir or to any of the excipients of
Valtrex
Hepatic impairment. Elderly,
haemodialysis, renal impairment; monitor
for neurological effects. Pregnancy,
lactation
Nephrotoxic drugs, incl aminoglycosides,
iodinated contrast media, methotrexate,
foscarnet, pentamidine, platinum
compounds, ciclosporin and tacrolimus.
Agents that inhibit tubular secretion.
Mycophenolate mofetil
(Unavailble in Generic)
DOC:
ACYCLOVIR
Pediatric patients mostly prefer oral
administration via suspension.

ANTIPYRETICS such as Paracetamol

can also be given to manage the
fever as well as Calamine lotion and
Antihistamine to control the itch.
Non-Pharmacologic Management
 Non-Pharmacologic Management
Lesions Fever Poor Appetite Cough
Management -Proper Hygiene -Instruct the child -Offer the child -Instruct on
/ to drink increased his/her favorite proper use of
Intervention -Instruct the child to amount of water foods if possible mask or
avoid scratching the covering of
rashes/lesions -Monitor -Small frequent mouth while
temperature feeding if coughing
-Cooling baths regularly possible
-Assist in
-Application of -Tepid Sponge proper
soothing lotions Bath if possible expectoration
of phlegm if
-Wear loose, cotton cough is
clothing productive

-Use of personal
protective
equipments such as
gloves/mask
-Proper isolation
Congenital Varicella Syndrome
 Congenital Varicella Syndrome
• an extremely rare disorder in which affected
infants have distinctive abnormalities at birth
due to the mother's infection with chickenpox
(maternal varicella zoster) early during
pregnancy.

• Affected newborns may have a low birth weight,

limb hypoplasia, cicatricial skin lesions, and
micro-cephaly at birth and abnormalities of the
skin, brain, eyes, the arms, legs, hands, and/or
feet, and/or, in rare cases, other areas of the
body.
Varicella Immunoglobin (VZIG)
and
Varicella Zoster Vaccine (VZV)
 Varicella Immunoglobin (VZIG) and Varicella
Zoster Vaccine (VZV)
VZIG
used for passive immunization
against varicella.
recommended for use in
susceptible persons who are at
high risk of developing varicella-
associated complications after
exposure to varicella or herpes
zoster (shingles).
VZV
a. Monovalent varicella
vaccine live attenuated
varicella vaccine (Oka)
B. Combination varicella
vaccine
a VZV vaccine with 18 times
the viral content of the Oka
vaccine (ZostaVax).
- combined with a measles–
mumps–rubella (MMR)
vaccine.
 Varicella Immunoglobin (VZIG) and Varicella
Zoster Vaccine (VZV)
VZIG VZV
INDICATIONS Significant exposure to a person with chicken pox or zoster A. Monovalent varicella vaccine
recommended for all children >1
Candidates (Provided They Have Significant Exposure) Include year of age (up to 12 years of age)
who have not had chickenpox and
1.Immunocompromised susceptible children without a history of for adults known to be
varicella or varicella immunization seronegative for VZV.

2. Susceptible pregnant women B. Combination varicella vaccine

Used in children ages 1 through
3. Newborn infants whose mother had onset of chickenpox 12 years of age
within 5 days before or within 48 h after delivery

4. Hospitalized premature infant (≥28 weeks of gestation) whose

mother lacks a reliable history of chickenpox or serologic
evidence of protection against varicella

5. Hospitalized premature infant (<28 weeks of gestation or

≤1000-g birth weight), regardless of maternal history of varicella
or VZV serologic status
 Varicella Immunoglobin (VZIG) and Varicella Zoster
Vaccine (VZV)
VZIG VZV

DOSAGE To be given as a single deep First dose: 12 through 15 months

inj; if the vol to be injected is Second dose: 4 through 6 years
>5 mL, dose should be
divided. VZV-seronegative persons >13 years
of age should receive two doses of
May repeat dose at 3-wk vaccine at least 1 month apart
intervals if patient is re-
exposed or continuously
exposed to varicella

This product should be given

within 96 h (preferably
within
72 h) of the exposure.
Reactivation of Viral Infection into
Adult Life
Reactivation of viral infection into
adult life
Prescription of Antiviral Agent
THANK YOU SO
MUCH!