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VIRAL INFECTIONS

INTRODUCTION
Viruses areobligate intracellularparasites. They are
inert in the extracellular environment and depend on
the intracellular machinery of the living host cell for
replication.
Viruses are small particles of genetic material (either
DNA or RNA) that are surrounded by a protein coat.
Some viruses also have a fatty "envelope" covering.
They are incapable of reproducing on their own.
Viruses depend on the organisms they infect (hosts) for
their survival.

VIRAL INFECTION

A viral infection is a proliferation of a harmful virus


inside the body. Viruses cannot reproduce without the
assistance of a host.
Viruses infect a host by introducing their genetic
material into the cells and hijacking the cells
internal machinery to make more virus particles.
With an active viral infection, a virus makes copies of
itself and bursts the host cell (killing it) to set the
newly-formed virus particles free. In other cases, virus
particles bud off the host cell over a period of time
before killing the host cell. Either way, new virus
particles are then free to infect other cells.
Symptoms of the viral illness occur as a result of cell
damage, tissue destruction, and the associated
immune response.

VIRAL REPLICATION
5 steps: 1) attachment
2) entry and uncoating
3) biosynthesis
4) maturation
5) release

Virus Transmission
Viruses can be transmitted in a variety of ways.
Some viruses can spread through touch, saliva, or even
the air.
Other viruses can be transmitted through sexual
contact or by sharing contaminated needles.
Insects including ticks and mosquitoes can act as
"vectors," transmitting a virus from one host to another.
Contaminated food and water are other potential
sources of viral infection.

VIRAL INFECTION TYPES


1) Respiratory Viral Infections
Respiratory viral infections affect the lungs, nose,
And throat. These viruses spread by inhaling
droplets containing virus particles.
Examples include:
Rhinovirusis the virus that most often causes the common cold, but
there are more than 200 different viruses that can cause colds. Cold
symptoms like coughing, sneezing, mild headache, and sore throat
typically last for up to 2 weeks.
Seasonal influenzais an illness that affects about 5% to 20% of the
population in the US every year. Flu symptoms are more severe than
cold symptoms and often include body aches and severe fatigue. The
flu also tends to come on more suddenly than a cold.
Respiratory Syncytial Virus (RSV)is an infection that can cause
both upper respiratory infections (like colds) and lower respiratory
infections (like pneumonia and bronchiolitis). It can be very severe in
infants, small children, and elderly adults.
Frequent hand-washing, covering the nose and mouth when coughing
or sneezing, and avoiding contact with infected individuals can all

2) Viral Skin Infections


Viral skin infections can range from mild
to severe and often produce a rash.
Examples of viral skin infections include:

Molluscum contagiosumcauses small, flesh-colored bumps most often in


children ages 1 to 10 years old; however, people of any age can acquire the virus.
The bumps usually disappear without treatment, usually in 6 to 12 months.
Herpes simplex virus-1 (HSV-1)is the common virus that causes cold sores.
Its transmitted through saliva by kissing or sharing food or drink with an infected
individual. Sometimes, HSV-1 causes genital herpes. An estimated 85% of people
in the US have HSV-1 by the time they are in their 60s.
Varicella-zoster virus (VZV)causes itchy, oozing blisters, fatigue, and high
fever (characteristic of chickenpox). The chickenpox vaccine is 98% effective at
preventing infection.
The best way to avoid viral skin infections is to avoid skin-to-skin contact
(especially areas that have a rash or sores) with an infected individual. Some viral
skin infections, such as varicella-zoster virus, are also transmitted by an airborne
route. Communal showers, swimming pools, and contaminated towels can also
potentially harbor certain viruses.

3)Foodborne Viral Infections


Viruses are one of the most common
causes of food poisoning. The symptoms
of these infections vary depending on the
virus involved.

Hepatitis Ais a virus that affects the liver for a few weeks up to several
months. Symptoms may include yellow skin, nausea, diarrhea, and vomiting. Up
to 15% of infected individuals experience recurrent illness within 6 months of
infection.
Norovirushas been reported to be responsible for outbreaks of severe
gastrointestinal illness that happen on cruise ships, but it causes disease in
many situations and locations.
Rotaviruscauses severe, watery diarrhea that can lead to dehydration. Anyone
can get rotavirus, but the illness occurs most often in babies and young children.
Rotaviruses and noroviruses are responsible for many (but not all) cases of viral
gastroenteritis, which causes inflammation of the stomach and intestines. People
may use the terms stomach virus or stomach flu to refer to viral
gastroenteritis, which causes nausea, vomiting, diarrhea, and abdominal pain.
Contaminated water and fecal-oral route are potential source of infection.

4)Sexually Transmitted Viral Infections


Sexually transmitted viral infections spread
through contact with bodily fluids. Some sexually
transmitted infections can also be transmitted
via the blood (blood-borne transmission).
Human papillomavirus (HPV)is the most common sexually-transmitted infection in the
US. There are many different types of HPV. Some cause genital warts while others increase
the risk of cervical cancer.
Hepatitis Bis a virus that causes inflammation in the liver. Its transmitted through
contaminated blood and bodily fluids. Some people with the virus dont have any
symptoms while others feel like they have the flu. The hepatitis B vaccine is more than
90% effective at preventing infection.
Genital herpesis a common sexually-transmitted infection caused by herpes simplex
virus-2 (HSV-2). Herpes simplex virus-1 (HSV-1), the virus responsible for cold sores, can
also sometimes cause genital herpes. Theres no cure for genital herpes. Painful sores
often occur during outbreaks. Antiviral medications can decrease both the number and
length of outbreaks.
Human immunodeficiency virus (HIV)is a virus that affects certain types of T cells of
the immune system. Progression of the infection decreases the bodys ability to fight
disease and infection, leading to acquired immune deficiency syndrome (AIDS). HIV is
transmitted by coming into contact with blood or bodily fluids of an infected person.
People can reduce the risk of getting a sexually-transmitted viral infection by abstaining
from sex or only having sex while in a monogamous relationship with someone who does
not have a sexually-transmitted infection. Using a condom decreases, but doesnt entirely
eliminate, the risk of acquiring a sexually-transmitted infection.

5)Other Viral Infections


Viruses are abundant in the
world and cause many other
infections ranging from mild
to life-threatening.
Epstein-Barr virus (EBV)is a type of herpes virus thats
associated with fever, fatigue, swollen lymph nodes, and an
enlarged spleen. EBV is a very common virus that causes
mononucleosis (abnormally high proportion of monocytes in the blood). More
than 90% of adults have been infected with this kissing disease
that is spread primarily through saliva.
West Nile virus (WNV)is a virus thats most commonly
transmitted by infected mosquitos.Less than 1% of people with WNV
develop inflammation of the brain (encephalitis) or inflammation of
the tissue surrounding the brain and spinal cord (meningitis).
Viral meningitisis an inflammation of the lining of the brain and
spinal cord that causes headache, fever, stiff neck, and other
symptoms. Many viruses can cause viral meningitis, but a group of
viruses called enteroviruses are most often to blame.

SOME VIRAL INFECTIONS


1) COMMON COLD:
Thecommon coldis caused by many differentviruses.
Thecommon cold is transmitted by infected airborne droplets or by direct
contact with infected secretions.
The common cold is medically referred to as a viralupper respiratory tract
infection
Being in cold weather does not cause the common cold.
Symptoms of the common cold include
cough
sore throat
sneezing
runny nose
Over-the-counter medications may be used for treatment of the common cold.
Antibiotics are not necessary for the common cold.
More than 200 different types of viruses are known to cause the common cold,
with rhinovirus causing approximately 10%-40% of all adult colds.
Other commonly implicated viruses include coronavirus,adenovirus,respiratory
syncytial virus,and parainfluenza virus.

2)INFLUENZA
Influenza is a viral infection that affects mainly the
nose, throat, bronchi and occasionally lungs. Infection
usually lasts for about a week, and is characterized by
sudden onset of high fever, aching muscles, headache
and severe malaise, non-productive cough, sore throat
and rhinitis.
The virus(influenza A and B) is transmitted easily from
person to person via droplets and small particles
produced when infected people cough or sneeze.
Influenza tends to spread rapidly in seasonal epidemics.
Most infected people recover within one to two weeks
without requiring medical treatment. However, in the
very young, the elderly, and those with other serious
medical conditions, infection can lead to severe
complications of the underlying condition, pneumonia
and death.

3)CHICKEN POX

Chickenpox(varicella), a viral illness characterised


by a very itchy red rash, is one of the most common
infectious diseases of childhood. It is usually mild
inchildren,but there is a risk of serious complications,
such as bacterialpneumonia.
People who have had chickenpox almost always
develop lifetime immunity However, the virus remains
dormant in the body and it can reactivate later in life
and causeshingles.
Chickenpox is caused by theherpesvaricella-zoster
virus. It is spread by droplets from a sneeze orcough,
or by contact with the clothing, bed linens or oozing
blistersof an infected person. The onset of symptoms is
10 to 21 days after exposure.

4)MEASLES
Measles is caused by a measles virus and it is normally
passed through direct contact and through the air
(airborne disease).The virus infects the mucous
membranes, then spreads throughout the body.
Measles is a human disease and is not known to occur
in animals.
The highly contagious virus is spread by coughing and
sneezing, close personal contact or direct contact with
infected nasal or throat secretions.
The virus remains active and contagious in the air or on
infected surfaces for up to 2 hours.

5)POLIO
Poliomyelitis (polio) is a highly infectious viral disease,
which mainly affects young children. The
virus(poliovirus) is transmitted by person-to-person
spread mainly through the faecal-oral route or, less
frequently, by a common vehicle (e.g. contaminated
water or food) and multiplies in the intestine, from
where it can invade the nervous system and can cause
paralysis.
Initial symptoms of polio include fever, fatigue,
headache, vomiting, stiffness in the neck, and pain in
the limbs. In a small proportion of cases, the disease
causes paralysis, which is often permanent. There is no
cure for polio, it can only be prevented by
immunization.

6)DENGUE FEVER
Dengue is a painful, debilitating mosquito-borne
disease caused by any one of four closely related
dengue viruses. These viruses are related to the viruses
that cause West Nile infection andyellow fever.
Dengue virus is transmitted by female mosquitoes
mainly of the speciesAedes aegyptiand, to a lesser
extent,A. albopictus.
Mild dengue fever causes high fever, rash, and muscle
and joint pain. A severe form of dengue fever, also
called dengue hemorrhagic fever, can cause severe
bleeding, a sudden drop in blood pressure (shock) and
death.

7)RABIES
Rabies is an infectious viral disease that is almost
always fatal following the onset of clinical signs. In
more than 99% of human cases, the rabies virus is
transmitted by domestic dogs. Rabies affects domestic
and wild animals, and is spread to people through bites
or scratches, usually via saliva.
Therabies virus infects the central nervous system,
ultimately causing disease in the brain and death.

8)HEPATITIS

Hepatitis

is an inflammation of the liver. The condition


can be self-limiting or can progress to fibrosis
(scarring), cirrhosis or liver cancer. Hepatitis viruses are
the most common cause of hepatitis in the world but
other infections, toxic substances (e.g. alcohol, certain
drugs), and autoimmune diseases can also cause
hepatitis.

9) AIDS
AIDS is a syndrome caused by the HIV virus (RNA
ritrovirus).
AIDS occur when a persons immune system is too weak
to fight off many infections, and develops when the HIV
infection is very advanced. This is the last stage of HIV
infection where the body can no longer defend itself and
may develop various diseases, infections and if left
untreated, death.
There is currently nocure for HIV or AIDS. However, with
the right treatment and support, people can live long
and healthy lives with HIV.
HIV is a virus that gradually attacks the immune system,
which is our bodys natural defence against illness.
The virus destroys a type of white blood cell called a Thelper cell and makes copies of itself inside them. Thelper cells are also referred to as CD4 cells.

10)MUMPS
Mumps is a viral infection that primarily affects the
parotid glands one of three pairs of saliva-producing
(salivary) glands, situated below and in front of your
ears.
The hallmark symptom of mumps is swelling of the
salivary glands.
Symptoms of mumps usually appear within two weeks
of exposure to the virus. Flu-like symptoms may be the
first to appear, including:
-fatigue
-body aches
-headache
-loss of appetite
-low-grade fever

Viral Illness Prevention

Vaccines can reduce the risk of acquiring some viral


illnesses. Vaccines are available to help protect against
the flu, hepatitis A, hepatitis B, chickenpox, herpes
zoster (shingles), cancer-causing strains of human
papillomavirus (HPV), measles/mumps/rubella (MMR),
polio, rabies, rotavirus, and other viruses.
Vaccines vary in effectiveness and in the number of
doses required to confer protection. Some vaccines
require booster shots to maintain immunity.

ANTIVIRAL AGENTS
Antivirals treat viral infections by affecting viral
replication.
Because viruses lack independent metabolic activity and
can replicate only within host cells, Antiviral tend to injure
host as well as viral cells.
Although most antiviral drugs are active against either
DNA or RNA viruses, some (eg: adefovir,ribavirin)are
active against both.

Antiviral drugs have been developed to target virus specific


steps like, cell penetration,uncoating, reverse transcription, virus
assembly or maturation, etc.
-In majority of acute infections, viral replication is already at its
peak when symptoms appear. To be effective , therefore therapy
has to be started in the incubation peroid .ie, has to be prophylactic.
-> CLASSIFICATION

1) ANTI-HERPES VIRUS
2)ANTI-INFLUENZA VIRUS
3)ANTI-HEPATITIS/NONSELECTIVE ANTIVIRAL DRUGS
4)ANTI-RETROVIRUS

1) ANTI-HERPES VIRUS
a)ACYCLOVIR: synthetic acyclic analog of guanosine.
spectrum of activity: HSV-1,HSV-2,VZV,EBV(some).
Mechanism of action:
Acyclovir
Herpes virus specific thymidine kinase

Acyclovir monophosphate

Cellular kinases
Acyclovir triphosphate

Inhibits herpes virus DNA

polymerase

Gets incorporated in viral DNA and stops lengthening of DNA strand;


the terminated DNA inhibits DNA-polymerase irreversibly

-KINETICS: available in iv, oral & topical forms


well absorbed and cross BBB.
-DOSE
: GENITAL HERPES: 200mg for 5 days/ 400 mg for 5
days
chicken pox : 800 mg 5 time for 7-10 days.

Uses:

Adverse effects:

Genital Herpes simplex


(Primary disease &
Recurrent disease)

Topical: stinging and burning


sensation after each application

Mucocutaneous H. simplex

Oral: Headache, nausea, malaise


and some CNS effects

H. simplex encephalitis (type-1 virus)(iv)


H. simplex keratitis(ointment)
Herpes zoster
Chickenpox

Intravenous: Rashes, sweating,


emesis, and fall in BP(in few)
Dose dependent decrease in GFR
(in renal failure)

-Resistance : altered / deficient thymidine kinase &


DNA polymerase

traindication: hypersensitivity, glaucoma, psychiatric disease,depressi

b)CIDOFOVIR:synthetic acyclic purine nucleoside


phosphonate derivative
-approved for the treatment of CMV retinitis in AIDS
patients
-M.O.A: cidofovir
phosphorylation
cidofovir diphospahte

selective inhibition of viral DNA synthesis.


(replication process)
-available only in i.v form.(probenecid must be given
before and after each dose )
-contraindication: renal impairement , along with
nephrotoxic drugs
-ADR: ACUTR RENAL FAILURE leading to dialysis or death.
(patient must be hydrated with 1 L of normal saline before
infusing)

c)FAMCICLOVIR & PENCICLOVIR:


- Famciclovir is the prodrug of antiviral drug penciclovir.
- Penciclovir is acyclic guanosine nucleoside.
- Spectrum ofactivity : HSV-1,HSV-2,VZV
- DOSE: 500 mg every 8hr for 7 days.
- M.O.A: famiclovir
viral thymidine kinase
penciclovir monophospahte

competitive inhibition of viral DNA polymerase


and thus
inhibit synthesis of viral DNA.
- FAMICLOVIR : oral
- PENCICLOVIR: topical

d)FOSCARNET: Unlike others foscarnet is not purine or


pyrimidine analog. It is pyrophosphate derivative &
dont require activation by viral / cellular kinases.
- M.O.A: > Reversibly inhibit viral DNA nad RNA
polymerase
> Active against HIV , inhibit HIV reverse
transcriptase.
- Iv administration and crosses BBB
- Use : CMV retinitis in AIDS patients, acylovir-resistant
HSV infection.
- ADR: iv foscarnet is highly nephrotoxic.causes acute
tubular necrosis.
electrolyte abnormalities, anemia,fever
,seizures, headache etc
-given as iv infusion for 1.5-2 hrs.Do not administer as iv
bolus.

e)GANCICLOVIR: synthetic purine nucleoside analog


-

M.O.A:

ganciclovir
viral /cellular enzymes
ganciclovir monophosphate.

inhibit DNA polymerase & inhibit viral DNA synthesis.


Use: CMV retinitis in AIDS patients & for CMV prophylaxis in transplant
patients.
ADR: dose dependent neutropenia
fever , rash , GI disturbance
Ganciclovir is extremly alkaline ,avoid direct contact with skin.

f)TRIFLURIDINE & IDOXURIDINE: trifluridine is a fluorinated pyrimidine


nucleoisde analog. And structurally similar to thymidine.
- trifluridine and idoxuridine have same action.
- they convert into triphosphate and competes with thymidine and inhibit
thymidine triphospahte incorporation into viral DNA.Thus faulty DNA is
formed and destroyed.
- routes: topical , ophthalmic (iv is not used because it may cause cellualr
DNA damage)
- use: HSV-1,HSV-2,HSV keratoconjuctivitis , recurrent epithelial keratitis .

2) ANTI-INFLUENZA VIRUS
a) AMANTADINE & RIMANTADINE:

-These are adamantane derivatives.


-Rimantadine is alpha-methyl derivative of amantadine. More potent, longer
acting (t 30 hours) and better tolerated.
-amantadine is synthetic tricyclic amine. Structure similar to rimantadine .
-effective against influenza A viral infection.
-inflenza B,H5N1,H1N1,is not affected.
-M.O.A: action on early step (uncoating) as well as last step (viral assembly).
interfere with M2 protein function in virus.
(Blocks the viral membrane matrix protein, M2, which functions as a channel
for hydrogen ion
) This channel is required for the fusion of the viral membrane with the cell membrane that
ultimately forms the endosome (during internalization of the virus by endocytosis))

-USE: influenza A infection,


parkinsonism.(dopamine release and anticholinergic activity)
-ADR: ataxia,nightmare ,insomnia,depression,confusion,dizziness,
snticholinergic reaction (dry mouth ,blurred vision)
-only amantadine cross BBB
-DOSE: 10mg BD

b) OSELTAMIVIR & ZANAMIVIR :


-oseltamivir is pharmacologically similar to zanamivir but structurally
different
-M.O.A: oseltamivir undego hydrolysis and form oseltamivir
carboxylate and it will selectively inhibit influenza virus enzyme
neuraminidase.(thus virions releaseto host cell is prevented.)
-USE: active against both influenza A & B virus,
prophylaxis of influenza infection
--Oseltamivir
H5N1,H1N1 infections.
Side effects:
oseltamivir : 75mg BD 5days
Nausea and abdominal
zanamivir: 5 mg /actuation powder
pain
(gastric irritation)
inhalation

Headache, weakness,
sadness,
diarrhoea, cough, and
insomnia
Skin reactions
--zanamivir
Low oral bioavailability;
t of 25 hours

3) ANTI-HEPATIC VIRUS
FOR HEPATITIS B

FOR HEPATITIS C

*ADEFOVIR DIPIVOXIL
*LAMIVUDINE
*TENOFOVIR

*RIBAVIRIN
*INTERFERON ALPHA

->Hepatitis B virus is DNA


virus ,it will integrate into host
chromosomal DNA &cause
permanent infection.

->Hepatitis C virus is a RNA


virus , it will not integrate into
host chromosomal DNA & do
not cause non curable infection.
But may cause chronic
hepatitis.

a) ADEFOVIR DIPIVOXIL : phosphonate nucleotide analog


-M.O.A: adefovir dipivoxil undergo phosphorylation by cellular
kinase enzymes and become active disphosphate form. It will
then incorporate into viral DNA and leads to termination of
replication.
-use: HBV, Herpes virus,HIV
-dose: 10 mg / day
-ADR: nephrotoxicity,rashes,GI disturbance,acute hepatitis when

b) RIBAVIRIN:

synthetic nucleotide analog


-M.O.A: ribavirin on administration will deplete intracellular
nucleotide reserve. Thus inhibit DNA & RNA synthesis.
-use: HCV,Herpes virus,influenza A ,B
-ADR: hemolytic anemia , GI disturbance

c) INTERFERON : interferones are naturally occuring


,inducible gycoproteins that interfere with the ability of virus to
infect cells.
-synthesized by recombinent DNA technology.
- There are alpha beta & gamma interferons
- M.O.A: interferone bind to specific cell receptor & affect viral
replication at multiple steps.( viral penetration,synthesis of
mRNA,assembly ,release).ie , direct and indirect suppression of
viral multiplication.
- Interferons are not active orally . (iv,sc)
- USE: chronic hepatitis B virus infection, AIDS related kaposis
sarcoma,Herpes simple virus , H.zoster ,CMV infection.
- ADR: flu like symptoms, bone marrow suppression, weight loss,