Final Flashcards
Virus Main Features
Protein Coat:
- Capsid
- Provides structure and keeps the genetic material inside the cell
Protein Spikes:
- Help attach to the host cell
Membrane Envelope:
- Not always Present
- Can serve as protection
- Helps recognize the host
- Useful during fusion and budding
Nucleic Acid (DNA or RNA):
- Contains the genetic material
Virus
Type of pathogen that can only replicate within a host organism
- Either DNA or RNA (CANNOT HAVE BOTH at same time**)
- Can remain in a latent, non-replicating state for long periods without causing disease
- Activation of latent virus may produce symptoms of primary disease (Eg. genital herpes) or cause different symptomology (Eg. shingles instead of chicken pox)
Virion
Mature infective virus particle
Replication of Viruses
1) Virus invades the host cell
2) Virus injects its genetic material into the host cell
3) Virus’s genetic material reprograms the host’s DNA and starts to replicate itself
4) When the host cell is filled w/ virus copies, it bursts and releases then into the bloodstream to repeat the process
Stages of Viral Infection
1) Attachment to host cell
2) Penetration of genes and enzymes (Injection)
3) Synthesis of nucleic acid and proteins (once viral DNA integrates into host chromosome = Provirus
4) Assembly & packaging
5) Release of virions (lysis)
Types of Viruses
Oncogenic:
- Cause CA
- HPV cause cutaneous and genital warts (linked to cervical CA)
Other:
- rhinoviruses
- corona
6 Types of herpes viruses:
- HSV type 1 (Eyes, mouth, lips, genitals)
- HSV type 2 (Genital infection)
- Cytomegalovirus (CMV) = immunocompromised pts
- Varicella-zoster virus (VZV) = shingles (zoster) & Chicken pox (varicella)
- Epstein-Barr virus (EBV) = Mononucleosis, Burkett’s lymphoma
(Don’t need to memorize all types, just know what herpes is/does)
Acyclovir (Zovirax)
Therapeutic Effects and Uses:
- Herpes viruses (*Most effective against HSV-1 & HSV-2)
- Effective only at high doses against CMV and varicella-zoster as well
MOA:
- Triphosphate form competes w/ guanosine for incorporation into DNA
- Triphosphate form inhibits DNA polymerase
Adverse Effects:
- Few adverse effects when given PO or Topically**
- Nausea, vomiting, anorexia
- Elevated liver enzymes
- Skin irritation/rash/localized pruritis
Serious Adverse Effects:
- Neurotoxicity (high doses)
- Nephrotoxicity (IV delivery)
Disease Caused by Viruses
SARS-CoV-2
Measles
Rhinoviruses
SARS-CoV-2
- Covid
- Coronaviruses have single-stranded RNA as their genetic material which allows them to mutate and evolve over time
- Features large spike proteins on their outer envelope that allow the virus to bind to the ACE2 receptor in the lungs, heart, kidneys and intestines
- Ability to suppress the host’s interferon response (a key part of the antiviral immune response) in early stages of infection, allowing virus to replicate more freely in the early phase of infection
Measles
-Caused by measles virus
Highly contagious through air droplets from coughing or sneezing
Symptoms:
- 10-14 days after exposure to the virus and can range from mild to severe
- Fever, cough, conjunctivitis, skin rash (distinctive red, blotchy
- *Koplik Spots = small, white spots w/ bluish-white centre that appear on the inside of the cheeks
- (Rash will appear about 3-5 days after the fever begins, starts on the face and behind the ears, then spreads down to rest of body)
- *NO TREATMENT** = Management primarily focuses on relieving symptoms and supporting immune system
Rhinoviruses
AKA Common Colds
- More common in fall and spring
- Primarily infect the nasal and throat epithelial cells
- Replicate upper respiratory tract causing the typical cold systems (sneezing, runny nose, cough, sore throat, fatigue)
- Commonly transmitted through respiratory droplets when an infected person coughs or sneezes but can also spread through indirect contact w/ contaminated surfaces
NO VACCINE = large # of different strains and it’s ability to rapidly mutate
- Mild and self-limiting w/ symptoms generally lasting 7-10 days
Complications = otitis media, sinusitis, chronic bronchitis, exacerbations fo asthma
Influenza
3 Types: A, B, C
- Type A = most common, most severe symptoms, multiple subtypes and cause serious pandemics
- Type B & C = less common, milder symptoms, no major subtypes
Structure:
- Single-stranded RNA viruses w/ 2 key surface proteins = Hemagglutinin & Neuraminidase
Drugs for Influenza
Amantadine and neuraminidase inhibitors are effective but VACCINES MORE EFFECTIVE
AMANTADINE (SYMMETREL):
Indications:
- Prevent infection and manage active flu infections
- Also used for Parkinson’s disease
MOA:
- Prevents uncoating of virus once it enters host cell by blocking M2 proteins
Adverse Effects:
- Insomnia
- Loss of concentration
- Dizziness
- Mental confusion
- Nervousness
**use w/ caution in pts w/ RENAL PROBLEMS
NEURAMINIDASE INHIBITORS (OSELTAMIVIR)
Indications:
- Manage active influenza infections
MOA:
- Prevents release of virus from infected host cell
Adverse Effects:
- Nausea, vomiting, abdominal pain
Hepatitis
Liver Inflammation (many causes including hepatitis viruses = DNA)
5 Types:
1) Hep A = Vaccine Available (usually resolves on its own)
2) Hep B = Vaccine Available (treated w/ antivirals, interferons)
3-5) Hep C, D, E = NO vaccine (less common than A & B)
Hepatitis Stages of Progression
1) Healthy Liver
(Reversible)
2) Acute Inflammation
(Reversible)
3) Chronic Inflammation
(Permanent damage)
4) Cirrhosis = life expectancy shortened
(Permanent Damage)
5) End Stage = disease is terminal
Hep B Symptoms
Fever
Jaundice
Dark Urine
Nausea & vomiting
Pain in right side of abdomen
Headache
Hives
Joint pain
Weakness, fatigue
Loss of appetite
Hepatitis Drugs
ADEFOVIR (VIREAD)
Indications:
- Chronic Hep B infection
- Combined infection w/ HIV
MOA:
- Analog to adenosine that inhibits viral DNA synthesis by inhibiting DNA polymerase or reverse transcriptase in HIV
Adverse Effects:
- Nausea, Vomiting, diarrhea, abdominal pain
- Headaches, weakness, fever
INTERFERONS (IFNs):
- Also used to treat active hep infections
- IFN alfa-2b = Chronic HBV infection
- IFN alfacon-1 = Chronic HCV infections
- PEG IFN alfa-2a & PEG IFN alfa-2b = Chronic HBV and HCV infections w/ evidence that virus is replicating
- Addition of polyethylene glycol (PEG) extends action of interferons
Don’t need to know specifics, just that interferons are used
HIV/AIDS
Retroviruses (Eg. HIV):
- Initially have RNA as their genetic material they carry an enzyme called “reverse transcriptase” that converts RNA into DNA after infection (This viral DNA is integrated into the host cell’s genome where it exists in latent state)
HIV attacks and destroys the infection-fighting CD4 cells (CD4 T lymphocyte)
- Loss of CD4 cells makes it difficult for body to fight off infections, illnesses, and certain cancers
- Causes AIDS
AIDS (acquired immunodeficiency syndrome)
- Final Stage* of HIV infection
- Immune system becomes severely weakened
- Body becomes vulnerable to opportunistic infections and certain cancers
- CD4 count is less than 200 cells/mm3
HIV Life Cycle
1) Attachment
- HIV binds CD4 receptor and CCR5 on surface of T4
2) Fusion
- CCR5 necessary for HIV entry into Cell
3) Viral Reverse Transcriptase (RT)
- Viral RT converts vRNA into vDNA
4) Integration
- Viral integrase enzymes incorporates vDNA into host DNA
- Latent, asymptomatic phase for pt
- Transcription begins leading to next phase
5) Replication
- T4 cell machinery used to produce long chains of viral proteins and viral RNA
6) Assembly
- New viral proteins and vRNA move to surface of cell to form immature, non-infectious HIV
7) Budding
- Immature HIV leave T4
- Viral protease cleaves long proteins into shorter active proteins
- Shorter active proteins form mature, infectious HIV
Pathogenesis of HIV Infection
Acute Retroviral Syndrome:
- Sore throat, fever, rash, malaise, weight loss lasting several weeks
- Often mistaken for symptoms of common cold or flu
Progression to AIDS involves gradual destruction of immune system
Principles of HIV Pharmacotherapy
- Be cautious w/ antiretroviral therapy = expensive, little effect in some cases, promote resistance
Initiation of antiretroviral therapy:
- history of AIDS-defining illness
- Low CD4 count, high viral load
- Pregnant women
- HIV-assoc, nephropathy
- Co-infections w/ hep B virus
Effectiveness of antiretroviral therapy is measured using 2 Lab Tests
1) CD4 Lymphocyte count
2) HIV RNA in the blood (viral load) = therapy initiated if count above
Treatment Failure = Adverse effects, lack of adherence, HIV strain is not responsive to drug
Many drug interactions via P450 cytochrome enzymes and absorption w/ food
HAART
Highly Active Antiretroviral Therapy
-Aggressive therapy w/ multiple drugs
- Simultaneous use of drugs from several classes reduces probability of drug resistance
Drugs that Interrupt Phases of HIV Life Cycle
- Entry inhibitors (fusion inhibitors, CCR5 antagonists)
- Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs)
- NNRTIs
- Integrase inhibitors
- Protease Inhibitors (PIs)
Zidovudine
Therapeutic Effects and Uses:
- Symptomatic and asymptomatic HIV-infected pts
- Post-exposure prophylaxis in HIV-infected exposed healthcare workers
- To reduce transmission rate of HIV from and HIV+ mother to her fetus
MOA:
- Mimics thymidine
- Inhibits RT leading to defective strands of vDNA
Adverse Effects:
- Nausea, vomiting, diarrhea
- Anemia, neutropenia
- Fatigue, myalgia, generalized weakness
- Headache
Serious Adverse Effects:
- Bone Marrow depression
- CNS toxicity - peripheral neuropathy
- Acidosis
PREP
Pre-exposure Prophylaxis
- Help HIV pts to still live a normal life
- Prevents partners from getting HIV
Nivirapine
Therapeutic Effects:
- Initial therapy of HIV infection
- Usually used in combination w/ other anti-retrovirals
MOA (NNRTI):
- Binds directly to reverse transcriptase, preventing production of vDNA
Adverse Effects:
- Nausea, vomiting, diarrhea
- Rash
- Headache, fatigue, muscle weakness
Serious Adverse Effects:
- Fever, chills, flu symptoms
- Dark urine
- Signs of jaundice
- Stevens-Johnson syndrome
Prophylaxis of HIV Infections
HIV replicates quickly and regularly makes errors leading to mutation
Vaccines are in development but nothing is approved
Post-exposure prophylaxis:
- Most effective if initiated within 36hrs of infection**
- Treatment consists of cocktail of different classes of antiretroviral drugs
Pregnancy
- Antiretroviral therapy is recommended regardless of viral load
*Therapy before and immediately after delivery can reduce transmission from mom to fetus by 70%
Post-partum:
- Therapy must begin on neonate within 48hrs to be effective
Considerations for Antiretroviral Agents
- **Obtain baseline lab values for liver and renal function, blood glucose, CBC, HIV RNA or CD4 counts
- Monitor viral load
- Monitor temp and WBC as measures of possible infection
- Rash = Steven-Johnson
Fungal Infections (Mycoses)
- Move around by spreading spores into the air or physical environment
SYSTEMIC Infections:
- Affect internal organs & multiple systems (lungs, brain and digestive organs)
- Originates in lungs, through inhalation of fungal spores
- Fatal for immuno…
- Culture & Sensitivity help in diagnosis
- Aggressive oral or parental medications, for many months to ensure it’s eliminated
SUPERFICIAL Infection:
- Skin, hair and nails
- Usually skin, mucosal membranes, mouth and vagina
Dermatomycoses:
- Tinea corporis = ring worm
- Tinea cruris = jock itch
- Tinea pedis = athlete foot
- Tinea captis = infection of head, eyebrows or eyelashes
Athlete’s Foot
Flaky white or red rash between toes caused by a group of fungi called “dermatophytes”
Anti-Fungal Medications: Amphotericin B (fungizone)
Amphotericin B (fungizone):
- FOR SEVERE SYSTEMIC MYCOSES**
MOA:
- Binds to ergosterol in fungal cell membranes, causing cell to become more permeable
Adverse Effects:
- Acute fever, chills
- Nausea, vomiting, anorexia
- Headache
- Phlebitis, fluid retention, electrolyte imbalances (Low K & Mg)
Serious Adverse Effects:
- Cardiac arrest
- Blood abnormalities
- Dysrhythmias
- Ototoxicity
- NEPHROTOXICITY**
- HEPATOTOXICITY**
Considerations:
-Monitor for extravasation as drug can be irritating to veins
Anti-Fungal Medications:
Azole
Broad Spectrum - largest and most versatile group of anti-fungals
Route:
- Systemic (PO or IV) or topically (Eg, Clotrimazole)
- Similar to Amph B but less toxic*
FlucoNAZOLE:
- Used in infections by Candida albacans, cryptococcal meningitis, & mycoses that are resistant to other anti-fungals
MOA: Interferes w/ synthesis of ergosterol
Adverse Effects:
- Nausea, vomiting, diarrhea, **STEVENS-JOHNSON Syndrome (fever, blistering skin, rash, flu-like symptoms)
Anti-Fungal Medications:
Nystatin
Used in Candida infections of vagina, mouth, skin and throat
Route: PO or topically**
DOES NOT TREAT SYSTEMIC INFECTION**
Adverse Effects:
PO = nausea, vomiting, diarrhea
Topical = minor skin irritation & burning, contact dermatitis
**AVOID OCCLUSIVE DRESSINGS as they increase moisture
Protozoa
Single-celled parasitic organisms found in water, soil and animal hosts
Spread through Vectors - organisms that carry parasite from one host to another
Eg) Mosquito - malaria
Tsetse fly - Sleeping sickness
Pathogenesis Of Malaria
Transmitted by female mosquitos carrying sporozoites which is injected into humans with a bite
- Parasite travels and incubates in the liver cells then invade RBCs and multiply
Symptoms:
- fever
- sweats
- chills
- headaches
- vomiting
- diarrhea
Treatment of Malaria
Chemoprophylaxis (Prevention > cure)
Treatment of acute attacks
CHLOROQUINE:
- Anti-malaria drug used in prophylaxis & treatment
MOA:
- Prevents breakdown of heme in RBCs (heme is required by parasite to produce its own proteins for energy)
- Also inhibits activity of histamine, serotonin, and prostaglandins reducing inflammation
Adverse Effects (Normal Doses):
- Nausea, diarrhea
Serious Adverse Effects (High Doses):
- CNS toxicity = confusion, delirium, reduced reflexes, convulsions
- Renal toxicity
- Cardiovascular toxicity (hypOtension, dysrhythmias)
Non-Malarial Protozoan Infections
AMEBIASIS:
Spread by drinking contaminated water, food, or surfaces containing cysts
- Asymptomatic in 90% of pts
- Causes colon ulcerations, abdominal pain, distention, cramping, bloody diarrhea, fever
- Obtain stool samples, culture of infected area to determine need for therapy
METRONIDAZOLE (Flagyl):
Therapeutic Effects (PO, IV, Top):
- Amebiasis, Trichomoniasis (STI), Crohn’s, colitis, C. diff
MOA:
- Disrupts DNA helical structure, preventing DNA synthesis, causing cell death in protozoans and anaerobic bacteria
Inhibits CYP450 enzymes = slow down metabolism of other meds Eg. warfarin)
Adverse Effects:
- Nausea, vomiting, diarrhea, abdominal pain, poor-appetite-anorexia, dizziness, headache, dry mouth, DARK & RUSTY URINE
Serious Adverse Effects:
- CNS toxicity = seizures, peripheral neuropathy
- **AVOID ALCOHOL (causes a disulfiram-like response
Parasitic Worms
ASCARIASIS (Round worm):
- Transmission when person ingests eggs
ENTEROBIASIS (Pinworm):
- mostly affects kids, experienced as itching, insomnia, enuresis
HOOKWORMS:
- “Ground itch” at site of infection
TAPEWORMS:
- Transmitted through contaminated meat
- Loose stool, nausea, abdominal pain, hunger pains, weight loss
Parasitic Worm Treatment
MEBENDAZOLE (Vermox)
MOA:
- Prevents formation of microtubules which inhibits glucose uptake by parasites leading to cell death
Adverse Effects:
- Diarrhea
- Abdominal pain
- Elevated liver enzymes
- Fever
Serious Adverse Effects:
- Seizures
- Angioedema
- Agranulocytosis
- Leukopenia
- Thrombocytopenia
