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Antiviral drugs ยาต้านเชื้อไวรัส, Concurrent use of drugs metabolized by…
Antiviral drugs ยาต้านเชื้อไวรัส
Antiviral Drugs for
Herpesvirus Infection
Herpesvirus infection
Herpes simplex virus (HSV)
Disease
Herpes orolabialis
Herpes genitalis
Cause
Herpes simplex virus (HSV)
incubation period 7-14 days
Type
HSV-1
mouth
face
skin
esophagus
brain
HSV-2
genitals
rectum
skin
hands
meninges
Sign & symptom
urinary retention
Flu-like symptoms
Multiple painful pustular or
ulcerative lesions
paresthesias
Varicella-zoster virus (VZV)
Disease
Chickenpox
herpes zoster
Cause
Varicella-zoster virus
(VZV)
Sign & symptom
Chickenpox
fever
headache
stomachache
loss of appetite
Herpes zoster
painful rash
develops on one
side of face or body
blisters (scab
over in 7-10 days)
Drugs
Acyclovir (Zovirax®),
Valacyclovir (Valtrex®)
Group
Inhibition of viral genome replication
Mechanism
viral kinases
inhibit viral DNA-polymerase
Clinical uses
HSV
VZV
ADR
Encephalopathic changes
dizziness
agitation
Dosage form
Oral (F 15-20%, 3-5 times/day)
IV, Topical (5% cream, 5 times/day)
Penciclovir (Denavir®),
Famciclovir (Famvir®)
Group
Inhibition of viral genome replication
Mechanism
viral kinases
inhibit viral DNA-polymerase
Clinical uses
HSV-1
HSV-2
VZV
ADR
Erythema multiforme
Dosage form
Topical (1% cream, q2hr)
Antiviral Drugs for
Cytomegalovirus (CMV) Infection
Cytomegalovirus (CMV)
a common virus in the same family as herpesvirus
spread by direct contact of body fluids
infections occur in the setting of HIV
patient, CD4 <50 cells/mm3
Disease
Common
CMV retinitis
Others
hepatitis
colitis
pneumonia
encephalitis
Drugs
Ganciclovir (Cytovene®),
Valganciclovir (Valcyte®)
Group
Inhibition of viral
genome replication
Mechanism
viral kinases
viral kinases
polymerase
Clinical uses
CMV retinitis
ADR
Neutropenia
thrombocytopenia
anemia
Fever
phlebitis
Dosage form
IV
Antiviral Drugs for
Influenza Virus Infection
Influenza virus
Type
Influenza A viruses (H3N2 & H1N1)
Seasonal epidemics of the flu
Regular
Influenza B viruses
Sporadic outbreaks
Primary route of
transmission
Inhalation
Symptoms
Factor
Age
immunocompetence
smoking
comorbidities
etc.
Classical sign
Fever
myalgia
headache
malaise
nonproductive cough
sore throat
rhinitis
Incubation period
1-7 days
Diagnosis
viral culture
Prevention
vaccination
Drugs
Amantadine (Symmetrel®),
Rimantadine (Flumadine®
Mechanism
Inhibitors of viral uncoating
Clinical uses
Influenza A
PK
Oral F >90% -> Oral form
ADR
Neuroleptic malignant syndrome (NMS)
Exacerbation of mental disorders
confusion
insomnia
hallucination
Orthostatic hypotension
peripheral edema
Amantadine
200 mg/day in 1-2 doses until symptom
resolution
Rimantadine
200 mg/day in 1-2 doses × 7 days
Zanamivir (Relenza®),
Oseltamivir (Tamiflu®)
Mechanism
Inhibition of viral release
Clinical uses
Influenza A & B
PK
Zanamivir (oral F 5%)
Nasal inhaler
Oseltamivir (oral F 80%)
Oral form
ADR
Bronchospasm
respiratory depression
GI disturbance
Dose
Zanamivir
2 inhalations twice daily × 5 days
Oseltamivir
75-mg capsule twice daily x 5 days
Antiretroviral therapy (ART)
Human immunodeficiency
virus (HIV) infection
Goal of Treatment
Decrease morbidity and mortality
Improve quality of life
Restore and preserve immune function
Prevent further transmission through
maximum suppression of HIV replication
Main classes of
antiretroviral agents (ART)
NNRTIs
viral genome
replication
Agent
Efavirenz
(EFV)
CNS effects
psychiatric symp
depression
suicidal ideation
Nevirapine
(NVP)
Rash
Serious hepatotoxicity
hepatitis
Rilpivirine
(RPV
Insomnia
depression
↑ liver enzymes
NRTIs
viral genome
replication
Agent
Abacavir (ABC)
Hypersensitivity
reaction** (fatal)
Didanosine (ddI)
Peripheral neuropathy
retinal changes
Pancreatitis
hyperuricemia
MI (possible)
ZDV or AZT
hyperlipidemia
neutropenia
Macrocytic anemia
DM
myopathy
Lamivudine
(3TC)
Headache
Stavudine
(d4T)
Peripheral neuropathy
Lipodystrophy
Tenofovir
(TDF)
hepatotoxicity
Renal toxicity
osteomalacia
PIs
viral maturation
Atazanavir
(ATV)
Peripheral
neuropathy
Indirect
hyperbilirubinemia
Prolonged PR
or QTc interval
Lopinavir/ritonavir
(LPV/r)
GI intolerance
Hypertriglyceridemia
↑ liver enzymes
Nelfinavir
(NFV)
diarrhea
Ritonavir
(RTV)
Paresthesias
Entry inhibitors
viral attachment
& entry
Maraviroc (Selzentry®)
Mechanism
Block chemokine
receptor (CCR5)
Inhibit viral attachment
and entry
Clinical uses
HIV
Dose: 150 mg bid
Metab: CYP3A4
ADR
Hepatitis
Myocardial infarction
orthostatic hypotension
Consideration
combination with other anti-HIV drugs
Enfuvirtide (Fuzeon®)
Mechanism
Inhibit gp41-mediated fusion of
HIV envelope with host plasma membrane
Inhibit viral attachment and entry
Clinical uses
HIV
ADR
Renal insufficiency
Thrombocytopenia
neutropenia
eosinophilia
Peripheral neuropathy
conjunctivitis
Consideration
Enfuvirtide is a peptide
administer parenteral
twice-daily
combination with other anti-HIV drugs
INSTIs
viral genome replication
Raltegravir
(RAL)
Metab: UGT1A1
glucoronidation
Suicidal risk
insomnia
headache
dizziness
Muscle aches
↑ liver enzymes
↑ creatine kinase
rhabdomyolysis
Renal failure
Dolutegravir
(DTG)
Metab: UGT1A1
glucoronidation
↑ liver enzymes
หลักการใช้ยาต้านไวรัสเอดส์
ไม่ให้ยาเดียว
เพราะอาจจะมีการดื้อยาได้ง่าย
ต้องให้ยาอย่างน้อย 3 ชนิด
Highly Active Antiretroviral
Therapy (HAART)
NNRTIs 1 ชนิด + NRTIs 2 ชนิด
NRTIs 2 ชนิด + PIs 1 ชนิด
ให้ ART ในผู้ติดเชื้อทุกรายในทุกจำนวน CD4 ที่มีความพร้อมของการกินยาระยะยาว
การรับประทานยา
รับประทานทุก 12 ชั่วโมง ตรงเวลา
ลืมเพียงแค่ 3 มือต่อเดือน ทำให้เชื้อดื้อต่อยาได้
Concurrent use of drugs
metabolized by CYP3A4 is
contraindicated for all NNRTIs
Metab: 2B6, 3A4
Metab: 3A4
Metab: CYP3A4
นางสาวธนัชชา คงคำวรณ์ 045