Download Viral Infections

Immunity and Infection:
Viruses, Retroviruses
&
Medications for Immunity
The Immune System
Physiology
• The immune system includes tissue and cells in the
lymph system, spleen, liver, lungs, GI tract, and brain.
• An integrated immune system response provides the
body’s response to invasion.
• Anything foreign to the body is an “antigen”:
• Antigens are identified as “non-self” by the body thus
are in need of attack by the immune system.
• Immunizations (vaccinations) utilize live, dead or
synthetic viruses to “trick” the immune system into
establishing an antigen response.
Pathophysiology
Four abnormal conditions can weaken the immune
system and stimulate the immune response:
– Neoplasms (result from the growth of mutant cells,
called cancers)
– Viral invasion
– Autoimmune diseases
– Organ transplant rejection
Pathophysiology
• Viral invasion of a cell changes the cell’s membrane and
antigenic action.
• In autoimmune diseases, the body responds to specific
self-antigens by producing antibodies against the self
(autoantibodies).
Examples:
– Rheumatoid arthritis
– Lupus erythematosis
• Organ transplantation weakens the immune system as
the body reacts to the introduction of foreign cells.
Cytokines
• Cytokines are chemical mediators released by WBCs in
response to antigenic invasion of the blood or tissues.
• Cytokines serve to enhance and accelerate the
inflammatory and specific responses that will destroy
the invading antigen.
• Cytokines are generally pro-inflammatory, but many
also have antiviral, anti-proliferative, and antineoplastic
properties.
Prototype drug: interferon alpha-2b (Intron)
Produced by recombinant DNA technology using
Escherichia coli bacteria.
Interferon: Core Drug Knowledge
• Pharmacotherapeutics
– Some types of cancer and chronic hepatitis
• Pharmacodynamics
– Inhibits the growth of tumor cells, prevents these cells from
multiplying
– Stimulates the immune system
• Side/Adverse effects
– Dizziness, confusion, lethargy, flu-like symptoms, anorexia,
nausea, and changes in taste
• Minimizing adverse effects
– Pre-medicate patients with drugs such as acetaminophen or
diphenhydramine to reduce the flu-like adverse effects.
Pathophysiology: Rheumatoid Arthritis
• A systemic, inflammatory disease.
• Effects are not limited to joint destruction.
• Affects all age groups.
– May onset as early as age 2 years
• Believed to be an autoimmune.
• Primary characteristics are symmetrical, severe
polyarticular inflammation.
• Can cause inflammation of glands, the linings of the
heart, the lungs, and the vascular system.
• RA has a substantial effect on quality of life because of
the associated pain, fatigue, and depression, and the
increased risk of heart disease.
Disease-Modifying Anti-rheumatic
Drugs
• Disease-modifying anti-rheumatic drugs
(DMARDs) are used in conjunction with
salicylates and NSAIDs, or as monotherapy.
• They are so named because they are capable of
arresting the progression of RA and can induce
remission in some patients.
Prototype drug: methotrexate (Rheumatrex)
Methotrexate: Core Drug Knowledge
• Pharmacotherapeutics
– Used in treating various malignancies (cancers) and
rheumatoid arthritis
• Pharmacokinetics
– Administered: orally or parenterally. Metabolized in
the liver, excreted in the kidneys
• Pharmacodynamics
– Exerts immunosuppressive effects by inhibiting the
replication and function of T lymphocytes that
stimulate the production of cytokines
Methotrexate: Core Drug Knowledge
• Contraindications and precautions
–
–
–
–
Immunosuppression,
Blood disorders
Pregnancy Category X
Lactation
• Side effects
– Rash, headache, nausea and vomiting, diarrhea, stomach
inflammation, alopecia (hair loss)
• Adverse effects
– Bone Marrow suppression
– White blood cell suppression
Methotrexate: Planning and
Interventions
• Maximizing therapeutic effects
– Administer medication as ordered.
– Drink plenty of water to prevent nephrotoxicity.
• Minimizing adverse effects
– Folic acid will interfere with effectiveness of drug.
– Can cause photosensitivity
– Monitor CBC for bone marrow suppression (anemia)
– Monitor for opportunistic infections (WBC
suppression)
What is a
Virus?
What is a Virus? How does it replicate?
http://www.youtube.com/watch?v=L8oHs7G_syI
Physiology of Viral Reproduction
The reproduction of viruses in humans requires
five steps:
Adsorption – Attachment to human cells
Penetration – Entering human cells
Un-coating – Virus sheds its protein coat
Replication – Viral RNA converts to DNA by
“hijacking” the human DNA
Transcription – New viruses are synthesized
After this, the cell lyses (splits) and the new
viruses are released
Viral Reproduction
Pathophysiology of Selected Viral
Infections
Hepatitis
– Five types: HAV, HBV, HCV, HDV, and HEV
– Most common in the United States: Hepatitis A, B,
and C
– HAV: spread via oral–fecal route (“food poisoning”)
– HBV and HCV: spread via blood or body fluids
Symptoms of Hepatitis include jaundice, fatigue,
abdominal pain, nausea, and anorexia.
Pathophysiology of Selected Viral
Infections
Herpes simplex (HSV)
– Two types: HSV-1 and HSV-2
– Characterized by the formation of painful
vesicles:
• HSV-1 on or near the mouth
• HSV-2 in the genital region
HSV Type 1
HSV Type 2
Pathophysiology of Selected Viral
Infections
Herpes zoster (Chickenpox, Shingles)
– Acute segmental inflammation of the peripheral
nervous system’s dorsal root ganglia caused by
infection with the herpes virus varicella zoster
(chickenpox)
– Follows along dermatomes of trunk and occasionally
on arms and legs
• A dermatome is an area of skin in which sensory nerves
derive from a single spinal nerve root
– Post-herpetic neuralgia (nerve pain) is a common
complication.
Dermatomes of the Head, Face
and Neck
Herpes Zoster Virus:
Shingles (left) and Chicken Pox (right)
Purine Nucleoside Analogue Drugs
• The largest group of antiviral drugs are the
purine nucleoside analogue drugs.
• They have relatively selective toxicity to viruses
because viral DNA polymerases are more
sensitive than human polymerases to inhibition
by these drugs.
Prototype drug: acyclovir (Zovirax)
Acyclovir: Core Drug Knowledge
• Pharmacotherapeutics
– Suppress outbreaks of herpes viruses
• Pharmacokinetics
– Administered: topical, oral, or IV
• Pharmacodynamics
– In an infected cell, acyclovir is converted by
viral enzymes and incorporated into the virus.
Once inside, it terminates viral DNA synthesis.
Acyclovir: Core Drug Knowledge
• Side effects
– Light-headedness, anorexia, nausea, vomiting,
abdominal pain, and headache
• Adverse effects
– Risk for confusion, seizures or nephrotoxicity
(oral or IV)
• Minimizing adverse effects
– Advise the patient to drink at least 8-oz glasses of
water a day.
– Administer IV acyclovir over 60 minutes.
Acyclovir: Core Drug Knowledge
• Patient and family education
– Emphasize that acyclovir does not prevent the
transmission of infection to another person and does
not cure the infection.
• Ongoing assessment and evaluation
– Monitor for the effectiveness of therapy
– Document new lesions
– Assess for possible secondary bacterial infections.
Pathophysiology of Selected Viral
Infections
Influenza
– Attacks both the upper
and the lower respiratory
tracts
– A and B are the only
types affected by current
antiviral medications
Drugs Used for Influenza
• Influenza can be a debilitating virus though it
generally subsides without pharmacotherapy.
• Certain populations require treatment due to
possible life-threatening symptoms.
– Elderly
– Infants and children
– Immunocompromised persons
Prototype Drug : oseltamivir (Tamiflu)
Oseltamivir: Core Drug Knowledge
• Pharmacotherapeutics
– Used to manage influenza A or B virus; drug of
choice for H5N1 and H1N1
• Pharmacodynamics
– Appears to inhibit the release of viruses from
infected cells, reducing spread to adjacent cells
• Maximizing therapeutic effects
– Works best when started within 48 hrs of onset of
symptoms
Oseltamivir: Core Drug Knowledge
• Side effects
– Nausea and vomiting, bronchitis, insomnia, vertigo
• Maximizing therapeutic effects
– Works best when started within 48 hrs. of onset of
symptoms
• Minimizing adverse effects
– Reduce nausea and vomiting by administrating the
drug with milk, a snack, or a meal.
Pathophysiology of Selected Viral
Infections
Respiratory syncytial virus (RSV)
– Highest rates of RSV illness occur in infants 2-6
months of age
– Symptoms include hacking cough and
wheezing on exhalation.
Examples: Infant RSV
http://www.youtube.com/watch?v=lIE_UElOk3c
Retroviruses:
Drugs
Treating HIV
Infection and
AIDS
Physiology of the Immune System Cells
• CD4 cells are receptors on T-cells, a type of
white blood cell.
• The CD4 site recognizes foreign antigens and
infected cells and helps activate the antibodyproducing B lymphocytes.
• B lymphocytes then produce natural
antibodies that help T-cells to induce
immunity.
• T-cells are necessary for normal immune
function.
CD4 T-Cell Function
Human immunodeficiency virus
– HIV is like all other viruses in physical
structure.
– HIV has an affinity for CD4 cells. By hijacking
CD4 cells, it reduces the development of Tcells and reduces human immunity.
– The HIV virus is called a retrovirus.
The difference between a virus and a
retrovirus is in the genetic material (RNA)
Pathophysiology
• HIV infection begins when the virus binds to cells
that have a CD4 protein receptor site.
• Once the virus is bound to the cell, the viral
envelope and the plasma membrane fuse
(adsorption)
• Inside the cell, viral RNA is transcribed into a
single strand of viral DNA that then is able to be
inserted into the healthy human DNA strand by
enzymes such as integrase and protease.
• Many anti-HIV drugs act to prevent the enzymes.
Diagnosis of HIV and AIDS
Diagnosis of HIV infection is usually made by a
salivary screening test followed by a confirmatory
serum (blood) assay.
• Viral load. This test measures the amount of
virus in your blood. Studies have shown that
people with higher viral loads generally fare
more poorly than do those with a lower viral
load.
• CD4 count. HIV infection progresses to AIDS
when your CD4 count dips below 200.
The Difficulty in Treating HIV
• HIV viruses take over human T-cells and insert
themselves into the human DNA
• When you attack the HIV, you also attack the
host cell
• Thus, killing HIV also kills human T-cells.
• Drugs work by trying to prevent the HIV from
hijacking the host cell’s DNA strand through
affecting different enzymes that help the
RNA/DNA insertion of the virus.
Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors
• These are the first class of drugs approved to
treat HIV infection and AIDS.
• These drugs inhibit reverse transcriptase, an
enzyme critical to HIV replication.
Prototype drug: zidovudine (Retrovir)
Zidovudine: Core Drug Knowledge
• Pharmacotherapeutics
– Epstein-Barr virus, hepatitis B virus, and HIV
infection
• Side effects
– GI symptoms, headache, and sleepiness
• Adverse effects
– Seizures and hematologic toxicities
In-class Quiz #8:
The Immune System and Viruses
• Complete the proctored, 20 point quiz in class.
• You will repeat this quiz in class on 4/13
• 10 participation points will be awarded on 4/8
for completing the quiz.
• 10 participation points will be awarded on
4/13 for completing the quiz.
• Overall learning of material will be evaluated
in the ATI Exam #4.