71 terms

Clinical Science II Exam III

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Side Effect
any effect beyond that which is intended
Adverse Drug Reaction
an unintended, undesired and possibly unknown reaction to a medicine given at the correct that can harm the patient
Pharmacology
how drugs and biologics act on the human body
Kinetics
how the drug is absorbed, distributed, metabolized, and eliminated
Dynamics
how the drug binds to cause an action
Cytochrome P450 Enzymes
exist in mostly all organisms, important intracellular acts, very important in drug metabolism
Two Types of Antifungals
polyenes and azoles
Two Types of Polyenes
amphotericin and nystatin
Five Types of Azoles
ketonconazole, fluconazole, itraconazole, posaconazole, voriconazole
Amphotericin
IV for severe systemic fungal infections, may last months (6-8 weeks common), fungistatic or fungicidal
Nystatin
only used for candidiasis, oral and topical formulations, no systemic absorption
Ketonconazole
often used to treat fungal infections in HIV, weak base, needs gastric acid for dissolution and absorption
Fluconazole
new anti-fungal agent, for vaginal candidiasis
Itraconazole
interferes with P450 activity, decreasing ergosterol synthesis and inhibiting cell membrane formation
Virus-Cell Interactions
viruses attach to cell structure, penetrates the plasma cell membrane, capsid uncoats so the virus can replicate, viral subunits assemble into a mature virus, host cell realeases virus particles from nuclear or plasma cell membrane budding
Capsid
protein coat on a virus that contains nucleic acid and is composed of capsomeres. Can be helical or icosahedral
Capsomeres
nearly identical repeating protein subunits
Helical Shape
a coil of protein subunits along the helical spiral of the viral nucleid
Icosahedral Shape
20 sided nearly spherical shape
DNA Viruses
all are double-stranded, icosahedral. Establish lifelong, persistent infections
Herpes Simplex Viruses
cause wide spectrum of diseases, biological and external stimuli can trigger reactivations, can transform cells in vitro
HSV-1 Infections
primary infection is in the form of a localized lesion transmitted by contact, type 1 occurs in the mouth, most adults have antibodies to this virus, after primary exposure, it enters the ganglion cells and becomes latent. Can cause keratoconjunctivitis and encephalitis
HSV-2 Infections
associated with the genitals, can be transmitted from mother to fetus during birth causing a severe and often fatal neonatal infection, a drug with the suffix "ovir" would be used as and antiviral.
HSV-2 Rx
acyclovir
Varicella-Zoster Virus
establishes lifelong ganglia latent infection. Causes chicken pox (primary infection) and shingles (reactivation of latent virus)
VZV Infections
highly contagious and spread by direct contact with lesions or aerosols. Vesicular lesions begin on head or trunk. The latent infection develops with age and in the immunocompromised; will not affect whole body, just one area.
VZV Rx (latent infection)
acyclovir
VZV Prevention
primary virus vaccine in children and latent virus vaccine for age > 60
Cytomegalovirus
hallmark of infection is perinuclear cytoplasmic inclusions. Produces a lifelong infection in monocytes and neutrophils. It's a transforming agent. Virus is shed in urine, saliva, semen, breast milk, the cervix, and carried in WBCs.
CMV Infection
transferred transplancentally, by transfusion, transplant, or close person-to-person contact. Most infections are subclinical. Congenital infection is associated with developmental defects and mental retardation. Typical infections in older people occur as hepatitis or mononucleosis. Immunocompromised can develop severe disseminated disease.
CMV Rx
gangcyclovir
Key Difference Between Viral and Bacterial
with bacterial, only WBC count is elevated
Epstein-Barr Virus
can only be grown in vitro in lymphocytes. Transforms the host cell, and these transformed B-cell clones persist for life. Can reactivate intermittently with viral shedding usually clinical unapparent
EBV Infection
transmitted via infected saliva, not easily communicable. Usually occurs in college-aged patients as mono. Comes along with an itchy rash upon exposure to penicillin. Associated with Burkitt's lymphoma in African children.
EBV Rx
oral acyclovir
Hepatitis B
DNA nucleocapsid; has three important antigens: surface, core and E antigen
Surface Antigen
allows virus to infect host, antibody confers immunity
Core Antigen
these antibodies indicate an acute infection rather than chronic
E Antigen
when found in blood, indicates that blood is infectious
Hep B Infections
liver is damages as immune system attacks infected liver cells. 2-10% become chronically infected, asymptomatic with infectious virus in blood. 40% of these patients die from cirrhosis of the liver or liver cancer. Can be spread from sharing needles, tattoo equipment, ear piercing, shared toothbrushes, razors, towels. When spread from mother to baby, baby becomes long term carrier and is chronically infected.
STORCH
acronym for all diseases passed through the birth canal: syphilis, toxoplasmosis, other viruses (hep B, AIDS, chlamydia), rubella, CMV, and herpes simplex
Hep B Prevention and Treatment
genetically engineered vaccine could eliminate the disease. Exposed ppl can be given an immune globulin with higher titer of antibody (passive immunity)
Papillomaviruses
DNA, no envelope. Can be transmitted sexually and present as genital warts on penis, anus, vagina, or cervix. Infants can acquire virus from mother and develop warts on respiratory tract.
Verrucae
common warts. Spontaneous healing occurs within 1-2 years. Many folk remedies can help. Can be contracted from wrestling mats, towels and shower floors.
HPV Treatment and Prevention
cryosurgery with liquid nitrogen for common warts, genital warts. Also lasers. Pap smear to detect cervical dysplasia, cervical cancer.
Adenovirus
41 types, frequently caused by the common cold. DNA, no envelope; attachment fibers project from virus. Transmitted via respiratory droplets, fomites, fecal-oral. Adenoids are lymphatic tissue.
Adenovirus infection
Pharyngoconjunctivitis: cough, fever, sore throat, conjunctivitis (outbreaks in summer camps)
Acute Respiratory disease: pharyngitis, fever, cough (young military recruits). Passes very easily.
Eye: swimming pool conjunctivitis
GI: infantile gastroenteritis (types 40 & 41)
RNA viruses
12 families of RNA viruses. Classification is based on envelope, capsid, and genome.
Influenza viruses
Frequent antigenic changes occur in H & N.
Drift= minor antigenic changes
Shift= drastic antigenic changes; new virus subtype (responsible for pandemics of influenza)
Most shift and drift comes from avian virus. Human virus and duck virus infect the same cell in a pig and then it creates a whole new virus.
Orthomyxovirus (Influenza A & B)
RNA, envelope w/ hemmaglutinin [H] and neurominidase [N], spikes.
Peak incidence=winter (thrives in cold weather)
Influenza A is subject to antigenic drift and shift: continually mutates; constant genetic change in the glycoprotein envelope.
Influenza A is the most tenacious and harbors in the respiratory tract
Orthomyxovirus clinical findings
Uncomplicated influenza: abrupt onset, fever, chills, headache, dry cough, muscle aches
Pneumonia: may result from influenza or secondary bacterial infections (S. aureus, H. influenza).
People mostly die of a secondary infection not the flu...people with COPD, emphysema, or cardio pulmonary disease are at high risk for secondary infection.
Reyes Syndrome (influenza viruses)
Encephalopathy, fatty degeneration brain, liver, kidneys. Related to aspirin used to treat flu symptoms (children 2-19 y/o). Children under 19 should not take aspirin when they have the flu, it elevates their risk for Reyes syndrome (multi-organ degeneration).
Guillain-Barre Syndrome (influenza viruses)
Watch for this if people are not recovering from the flu. Neurological autoimmune: weakness and sensory loss. Treatment is supportive.
Orthomyxovirus Rx/vaccine
Rx: Amantadine (easy to overdose) and rimantadine (for influenza A), relenza and tamiflu. These can also be used as prophylaxis in exposed individuals.
Vaccine: Recommended for high risk groups and caregivers (herd protection). Takes about a year to prepare the vaccine.
Flu vaccine
4 kinds of flu vaccines.
1. Traditional trivalent vaccine; contains attenuated viral particles from 3 dif. kinds of flu virus.
2. Intradermal vaccine. 13-62 y/o; needle is small.
3. Nasal spray. For young children and adults
4. Quadrivalent vaccine: covers 4 viral species.
Parainfluenza Viruses (types 1-4 paramyxovirus family)
RNA, envelope
Via: close contact by large respiratory droplets.
Types 1 & 2= fall/winter epidemics
Type 3= spring epidemics

Parainfluenza, mumps, measles
Croup
(Laryngotracheobronchitis)
respiratory obstruction due to laryngeal swelling, barking cough, usually in children. Epiglottis is closed and when it opens, air comes rushing out. Causes bronchiolitis/pneumonia if it spreads to lower trachea/bronchi... (types 1 & 2).
Bronchiolitis/pneumonia
organism spreads to lower trachea/bronchi (type 3).
Enteroviruses (Picomavirus family)
Coxsackievirus A & B, Echoviruses, Polioviruses...
RNA, no envelope, stable at acid pH.
Transient inhabitants of the GI tract.
VIA: fecal-oral routes
Polioviruses, types 1-3 (enteroviruses)
Present year-round; 99% of infections asymptomatic.
Abortive Poliomyelitis: fever, headaches, sore throat, complete recovery (most common form)
Non-Paralytic Polio: aseptic meningitis
Paralytic Polio: virus infects motor neurons in spinal cord/brain; flaccid paralysis. May reoccur w/ muscle wasting YEARS later.
Coxsackieviruses
Group A- 23 types, group B- 6 types.
Recovered more frequently in summer/fall.
Aseptic meningitis w/ mild muscle weakness.
Herpangina: severe, febrile, pharyngitis; pharynx has vesicles (not tonsils) - group A viruses.
Hand-foot-and mouth disease: oral/pharyngeal ulceration, vesicular rash (palms/soles). Most likely to occur in young children. Looks like rubella.
Pleurodynia: fever, stabbing chest pain (group B). Pain from infection of intercostal muscles.
Myocarditis: acute inflammation of the heart. Group B.
Echoviruses
32 types. Infections more common in summer/fall.
Aseptic meningitis
Rash (maculopapular)
Infantile diarrhea
Hepatitis A
From fecal contamination of water, raw shellfish, other food.
Often EPIDEMIC in nature; acute viral infection.
Most cases mild, self-limiting, some require many weeks of rest.
20-80% of NY city residents have HAV antibody.
Vaccine now available.
NOT related to hep B or C; does not turn into chronic infection like those two but does also infect the liver.
Hepatitis C
Post-transfusion hepatitis, NOT sexually transmitted...they had to be exposed to blood products.
Antibody does not show up for months, difficult to screen blood donors.
High percentage of infected people become chronic carriers, develop cirrhosis.
Liver inflammation can lead to reduced liver function, liver failure, or liver cancer.
Most people infected have no symptoms until liver damage becomes apparent (may take decades).
Treatment with interferon and antivirals.
Hep C treatment
FDA recently approved 4 drug products to treat chronic HCV infection:
1. Olysio
2. Sovaldi
3. Harvoni
4. Viekira Pak
Enteroviruses: treatment/prevention
Vaccine for polioviruses: live attenuated oral vaccine (Sabine vaccine)
Killed virus vaccine (Salk vaccine) much more effective, injectable.
Passive immunity for exposed to hep A (gamma globulin), new vaccine also for active immunity.
Human Immunodeficiency Virus
Retrovirus Family
RNA, enveloped
Reverse transcriptase makes DNA from RNA, DNA incorporates into host cell genome
Transmission: sexual intercourse, transfer of blood or blood products
When you get HIV, you have it for life because it gets into your genome and there is no way to get rid of it. It targets the very cells we would need to combat it in our body, T cells and CD-4 cells. Multiplies in macrophages and particularly targets CD-4 cells; this is why we look at CD-4 count. Eventually compromises entire immune system.
HIV transmission/risk factors
Mother to child
Risk factors: homosexual/bisexual males, IV drug abuse, blood transfusion/organ transplant, newborn.
Age > 55 now high-risk
Most widespread in Africa
1/5 in D.C. is HIV positive
small percentage of people have natural immunity to HIV. Mutuated co-receptor, CCR-5 receptor.
HIV pathogenisis
Enters body - replicates in macrophages, dissemination to lymphoid organs (CD-4 cells) - asymptomatic infection - clinical disease is AIDS.
Long incubation period. Varies from individual to individual.
Within first 2 weeks: acute, flu-like syndrome. General, non-specific symptoms.
Around 1 month: antibody starts to appear
2-3 years for symptoms to occur.
If left untreated, patients develop AIDS. Opportunistic infections cause most deaths. AIDS associated cancers (kaposis sarcoma), wasting syndrome, AIDS dementia
HIV diagnosis
Serology: measure antibodies to virus (s;ensitive screening test + confirm positives)
Culture: available only in research labs
Viral Load testing: monitors disease progression, response to treatment.
Measure CD-4 count; once it drops to 350, we see signs and symptoms
50-100 means pretty much immunocompromised = AIDS
HIV treatment/prevention
Multiple Rx (zidovudine, protease inhibitors)
Rx to prevent opportunistic infections
Eliminte high risk activities
No vaccine (its mutating constantly, thats why HIV is so successful).