2. Case 47
A 58-year-old man presents for the evaluation of a
painful rash. He says that for 3 or 4 days he had a
sharp, burning pain radiating from his midback
around to his left side. He thought that he was
having a kidney stone.Yesterday he noticed a rash
which spread in a distribution “like a line” in the
same area in which he had the pain. He is on
glyburide for type II diabetes, simvastatin for high
cholesterol, and lisinopril for hypertension, all of
which he has been on for several years. He does have
a history of having chickenpox as a child.
3. Case 47
On examination he has a low-grade fever
and otherwise normal vital signs. His skin
examination is remarkable for a rash in a
belt-like distribution from his spine around
his left flank to the midline of the
abdomen.The rash consists of
erythematous patches with clusters of
vesicles.The remainder of his examination
is normal.You make the diagnosis of
herpes zoster and prescribe a course of
acyclovir (ACV).
4.
5. Case Summary
58-year-old man
Rash with ‘line-like distribution’
History of chickenpox as a child
Erythematous patches with vesicles
in a belt-like distribution
Diagnosed with herpes zoster virus
(HZV) and prescribed acyclovir
7. Pathogenesis
Primary replication site is
the respiratory tract
Spreads hematogenously
and lymphatically
Replicates in
Monocytes
Capillary endothelial cells
Epithelial cells
Cytotoxic lymphocytes
allow virus to enter
sensory nerves and travel
to DRG
Reactivation of
varicella zoster
(VZV)
8. Presentation
3-5 days of pain
and paresthesia
prior to rash
Unilateral
vesiculopustular
eruption
Pre-herpetic or
post-herpetic
neuralgia
9. Management
Compress rash with
normal saline solution
Administer analgesics
i.e. NSAIDs
Administer antiviral
drugs i.e. acyclovir
Gabapentin may be
prescribed for post-
herpetic neuralgia
11. Four Classes
1. DNA Polymerase Inhibitors
Acyclovir
2. ReverseTranscriptase Inhibitors
Abacavir
3. Protease Inhibitors
Ritonavir
4. Fusion Inhibitors
Enfuvirtide
All used to
treat HIV
12. Herpesviridae Agents
Acyclovir
Valacyclovir
Penciclovir
Famciclovir
Ganciclovir
Foscarnet
Trifluridine
VALACYCLOVIR
(VCV) is an analog of
acyclovir that is
rapidly converted to
acyclovir in the
body. Its advantage
is better oral
BIOAVAILABILITY!
17. Mechanism of Action
• Guanosine analog
• Converted to nucleoside
triphosphate by cellular
enzymes (phosphorylation)
• Affects only viral DNA
polymerase activity using
competitive inhibition,
terminating its growing
chain
21. Adverse Effects
Monophosphorylated by
HZV/VZV’s thymidine
kinase
NOT monophosphorylated
by uninfected cells low
risk of adverse effects
Mild side effects include
nausea and headache
31. Mechanisms of Resistance
1. A mutated viral
thymidine kinase
will be able to resist
phosphorylation
1. Mutations arising in
viral DNA
polymerase may
also affect drug
action
34. Questions 1 & 2
True or False: Acyclovir can be used to
treat cytomegalovirus (CMV) in children.
a) True
b) False
Acyclovir is an analogue of which
nucleoside?
a) Adenosine
b) Guanosine
c) Cytosine
d) Thymidine
35. Answers
B.Acyclovir has little to no effect on
cytomegalovirus. It is primarily utilized to
treat HSV1, HSV2, andVZV.
B.Acyclovir is a purine analog, specifically
guanosine.
36. Question 3
Acyclovir is a purine analog that works by
inhibiting viral DNA polymerase. Drug resistance
is a mechanism that allows a microbe to evade
drug action. Mutations in which of the following
enzymes will allow herpes zoster to evade the
drug action of acyclovir?
a) Thymidine kinase
b) Phosphodiesterase
c) DNA polymerase
d) Glycogen synthase
e) Both A & C
37. Answer
E.Acyclovir, a DNA polymerase inhibitor,
works by acting as a guanosine analog to
cease viral replication.Viruses may be able to
evade the action of acyclovir if they possess
mutations in either thymidine kinase or DNA
polymerase.
38. Question 4
A disadvantage of acyclovir is the fact that it
has a low oral bioavailability. Which of the
following agents may be substituted for
treatment of herpes zoster because of its high
bioavailability?
a) Famciclovir
b) Foscarnet
c) Valacyclovir
d) Penciclovir
39. Answer
C.Valacyclovir (VCV) is an analog of
acyclovir that acts as a prodrug. It is rapidly
converted to acyclovir in the body, resulting
in higher concentrations of acyclovir. Its
advantage is better oral bioavailability.
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