Exam III Antivirals and Antiretroviral Medications Flashcards
What are the mechanisms of antivirals?
- *1) Alter uncaring of virus
- to begin replication
- these drugs prohibit this phase so can’t penetrate the host, and therefore can’t replicate
**2) Polymerase inhibitors
**3) Inhibit viral protein synthesis
What are the indications and mechanism for amantadine (Symmetril) and rimantidine (Flumadine)
**Indication= Influenza A
mechanism= blocks uncaring of virus, prevents pretension into host
-rimantidine is significantly MORE active than arantadine
What are the side effects for amantadine (Symmetril) and rimantidine (Flumadine)
1) CNS stimulation
- enhanced by antihistamines
2) Insomnia
3) Grand Mal Seizures
What are the indications for oseltamivir (Tamiflu)?
Indication= Influenza A and B
- used for tx and prophylaxis
- classic PRODRUG= hydrolyzed to active form
What does the drug oseltamivir (Tamiflu) inhibit ?
**Neuraminidase inhibitor: drug is an enzyme inhibitor that cleaves the budding viral progeny form its cellular envelope attachment point just prior to release
What are the indications and mechanism for ribavirin (Rebetol, Virazole)?
**indications= tx of respiratory syncytial virus
- *Mechanisms= prevents synthesis of virus proteins encoded by viral mRNA
- Inhibits virus RNA polymerase
- disrupts transcription, translation or promotes digression of viral RNA
What are the side effects for ribavirin (Rebetol, Virazole)?
1) mutagenic
2) teratogenic
3) carcinogenic
What are the indications for trifluridine (Viroptic) ?
Indications: herpes simplex keratitis (in eye); keratoconjunctivitis
What is the mechanism for trifluridine (Viroptic) ?
interferes w/ viral replication by incorporating into viral DNA in place of thymidine, causing formation of defective proteins
What is the mechanism for acyclovir (Zovirax) ?
-inhibits viral DNA polymerase preferentially (cycle specific)
What are the indications for acyclovir (Zovirax
- **IV drug of choice for HSV encephalitis
- *PRIMARY and RECURRECT HERPES in IMMUNOCOMPROMISED PATIENTS
- Herpes zoster
- Genital HSV infection
- USED every 3 hrs which is consistent with cycle phases of viruses
What is the indication/mechanism for ganciclovir (Cytovene) ?
Indication: **Human cytomegalovirus (CMV)
**Used in tx for CMV retinitis
mechanism: inhibits viral DNA synthesis
Describe famciclovir and valacyclovir
- recurrent genital herpes
- *CLASSIC PRODRUGS: converted to penciclovir and acyclovir respectively as they pass thru intestine
- has not been studies for use in herpes labials
what are interferons?
- Family of naturally occurring inducible glycoproteins that interfere with the ability of viruses to infect cells
- Antivirals, cytotoxic, immunomodulatory actions
Interferons:
Synthesized by ____________
3 types of interferes: ______, _____, ____
Administered ______, ______, ______.
Antiviral mechanism is __________understood
Induction of host cell enzymes that ______ viral RNA ______, ultimelty leading to the __________ of viral _______ and ______
- recombinant DNA technology
- alpha, beta, gamma
- intralesionally, subcutaneously, or IV
- incompletely
- *inhibit
- *translation
- *degradation
- *mRNA
- *tRNA
What are 7 known mechanisms for interferon?
1) Induce gene transcription
2) Inhibit cellular growth
3) alter sate of cell differentiation
4) Interfere with oncogene expression
5) Alter cell surface antigen expression
6) increase phagocytic activity of macrophages
7) Augment cytotoxicity of lymphocytes
The most common indication for interferons are ?
1) **Hepatitis B and C
2) **Multiple sclerosis
- Also used for some cancers
What are some adverse effects of interferons?
1) **Flu-like symptoms -fever,chills, myalgias, arthralgia, GI disorder (nausea, vomit, diarrhea)
2) Rash
3) **Bone marrow suppression -granulocytopenia
4) ** Neurotoxicity - somnolence, behavioral disturbances
5) **CNS Effects -headaches, depression
6) **Severe fatigue
7) **Severe weight loss
8) **Autoimmune disorders - thyroiditis
9) **Cardiovascular - CHF
10) ** Oral -taste changes, reactivation of herpes labials, excessive salivation
What are the drugs for Hep C?
1) Ledipasvir + sofosbuvir (Harvoni)
- 100k for 12 wks
- 40% of pts take for 8 wks
2) simeprevir (Olysio)
3) sofosbuvir (Sovaldi)
4) boceprevir (Victrelis)
5) telaprevir (Incivek)
What are the challenges with Antiretrovirals?
-to kill the virus, host cells, are often harmed
***Anticirals that alter viral replication
processes are often TOXIC to host cells
Viral disease:
All circuses must infect cell to __________
***infection begins when virus _________to _________.
Attachment is mediated by viral proteins that bind to _________ on host cell membrane.
Once enter is gained into host cell, virus is available for ______.
**Viral DAN or RNA itself is ______
replicate attaches host cell specific receptors replication replicated
What are the mechanism for Antiretrovirals ?
- Inhibiting viral attachment and entry (limits spread)
- Alter genome replication = polymerase inhibitors
- Immunization = provides **antibodies against viral envelope proteins
- -blocks viral attachment/penetration
- -virucidal= antibodies destroy or inactive virus before it interacts w/ receptor on target cells
What drug is the first antiviral HIV agent that inhibits viral enter into host cells ?
enfuvirtide (Fuzeon)
-Fusion protein inhibitor
What is a retrovirus?
Any virus in the family Retroviridae that has RNA as it n.a
- Uses enzyme** reverse transcriptase
- *Essential for HIV replication
- Virus penetrate lymphocyte by releasing RNA into cytoplasm
- Reverse transcriptase is a DNA polymerase
- -Copies RNA retrovirus into DS DNA
- **TARGER OF ANTIRETROVIRALS: REVERSE TRANSCRIPTASE
Retrovirus:
The DNA segment is presently incorporated int to the cell’s DNA within the nucleus, process is called ____________.
The integrated DNA segment = ?
The new RNA synthesizes viral proteins which are eventually incorporated into new _______ which after release from cell to another ______ ***may represent an ____________ ____
integration provirus virus cell (macrophage) infectious virion
What are the Subtypes (3 primary classes) of antiretroviral drugs for HIV?
1) Nucleoside reverse transcriptase inhibitors
2) Protease inhibitors
3) Nonnucleoside reverse transcriptase inhibitors
- integrase inhibitor
What is an example of a fusion protein inhibitor?
enfuvirtide (Fuzeon)
__________ inhibitors were the very first class of HIV inhibitors to be used a s drugs
Reverse transcriptase inhibitors
What are the drug concepts for HIV?
-Drug tragets structural and functional differences btwn viral and human proteins
-Tx of HIV infection requires combo therapy = HAART
(Highly active antiretroviral therapy)
-“Cocktails” (used to improve effect)
-
What does a typical cocktail consist of?
ex?
nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor and a protease inhibitor
Ex: lamivudine, nevirapine, and sawuinavir
TX w/ antiretrovirals:
Started for most HIV infected pts when immunosuppression becomes _________. CD4
pronounced 500 -2 nuceloside reverse transcriptase inhibitors w/ a protease inhibitor -resistant -alternative drug -opportunist infections
What are the side effect of antiretrovirals?
1) Anemia
- toxic to bone marrow and blood cells (transfusions)
2) Leukopenia and granulocytopenia
- predispose pt to infections, fatigue, muscle pain, rashes, nausea, diarrhea, headaches.
3) Hepatotoxicity
4) Peripheral neuropathy
5) Pancreatitis
What is the goal of antiretrovirals is to what?
- Prevent opportunistic infections
- Vaccines and other drugs are used for immunoprophylaxis for many infections
Pt taking anti-infective agents for what 6 conditions?
1) Pneumonia
2) infleunza
3) TB
4) Hep B
5) Herpetic infections
6) Candidiasis
What is the tx for opportunistic infection in HIV/AIDS, **Pneumocystis carinii?
oral trimethoprimsulfamethoxazole (Bactrim) **SULFA DRUG
What is the tx for opportunistic infection in HIV/AIDS, **viral infections?
gancilovir, foscarnet, acyclovir
What is the tx for opportunistic infection in HIV/AIDS, **candidiasis?
fluconazole, ketoconazole
What is the tx for opportunistic infection in HIV/AIDS, **cryptococcus, histoplasma?
(yeast-like fungi= fluconazole, ketoconazole, amphotericin B
What is the tx for opportunistic infection in HIV/AIDS, **tuberculosis?
isoniazid (INH), rifampin, ethambutol, streptomycin
What is the tx for opportunistic infection in HIV/AIDS, **CMV?
ganciclovir
What is the tx for opportunistic infection in HIV/AIDS, **EBV?
acyclovir, ganciclovir
What are nucleoside reverse transcriptase inhibits?
- drugs are chemically nucleosides
- **Must be biotransformed/bioactivated to work
- drug integrated into DNA polymerase so DNA terminated
**INHIBTING VIRLA ENUME REVERSE TRANSCRIPTASE
-without reverse transcriptase viral RNA can’t be made into DNA segment and integration doesn’t occur.
Nucleoside reverse transcriptase inhibitors:
Reverse transcriptase of HIV is _______ times more susceptible to _____ than normal human cells.
Drugs have _______ on cells already ________
1100 X
inhibition
no effect
containing HIV
What are examples of Nucleoside reverse transcriptase inhibitors?
1) abacavir (Ziagen)
2) **didanosine (Videx)
3) emtricitabine (Emtriva)
4) lamivudine (Epivir)
5) stavudine (Zerit)
6) zalcitabine (Hivid)
7) **zidovudine (Retrovir) = “AZT”
Zidovudine (Retrovir) = AZT: inhibits HIV \_\_\_\_\_reduces \_\_\_\_\_ from AIDS and AIDS related complex. Very \_\_\_\_\_\_ = bone marrow depression -patient often require \_\_\_\_\_\_\_ Side effects? \_\_\_\_\_\_, \_\_\_\_, \_\_\_\_\_, \_\_\_\_\_
synthesis morbidity/mortality toxic transfusions -CNS, -**nausea (FREQUENT), -ORAL EFFECT (taste, tongue edema, bleeding gingiva, mouth ulcers) -drug interactions inhibit metabolism of drug = potentiates toxicity of both agents
What are the drug interactions of Zidovudine (Retrovir) = AZT?
- acetaminophen
- aspirin
- indomethacin (NSAID)
Nonnucleoside reverse transcriptase inhibitors:
Also block reverse ____________
Drugs inhibit the ______ reaction of reverse transcriptase that is ________ of nucleotide binding.
**DO NOT REQUIRE _________
transcriptase
catalytic
independent
***BIOACTIVATION
Resistance of Nonnucleoside reverse transcriptase inhibitors develops if used alone (4) list them
1) delavirdine (Rescriptor)
2) efavirenz (Sustiva)
3) etravirine (Intelence)
4) nevirapine (Viramune)
What are protease inhibitors?
-suppress viral replication by inhibiting protease, responsible for cleaving viral precursor peptides into infective virions
***preventing maturation of HIV-infected cells
***PRIMARY DIFFERENCE OF THESE DRUGS = INTERFERENCE W/ ACTION OF HIV INFECTED CELLS
List 8 protease inhibitors
1) atazanavir (Reyataz)
2) darunavir (Prezista)
3) fosamprenavir (Lexiva)
4) **indinavir (Crixivan)
5) **nelfinavir (Viracept)
6) ritonavir (Norvit)
7) **sawuinavir (Invirase)
8) tipranavir (Aptivus)
Nucleotide Reverse Transcriptase Inhibitors :
interfere with HIV viral RNA ________ DNA _________ resulting in ______ of viral replication
Ex: ___________
dependent
polymerase
inhibition
tenofovir (Viread)
Integrase inhibitors:
Inhibits _________, the enzyme that helps to insert viral _______strand into __________
-prevents ______ of proviral gene into human DNA.
Examples: __________ , ___________
integrase
cDNA
human genome
integration
- raltegravir (Isentress)
- dolutegravir (Tivicay)
What is the NEW HIV medication approved?
Use?
- *Complera
- COMBO drug used for initial tx of HIV
Use: tx of HIV-1 (complete regiment) with HIV-1 RNA
What are the 3 medication from different classes in **Complera ?
1) emtricitabine
2) rilpivirine
3) tenofovir disoproxil fumarate
What are the adverse events from **Complera ?
lactic acidosis/severe hepatomegaly w/ steatosis; post tx acute exacerbation of hep B
What are 3 oral complications seen in the gums with Complera ?
- linear gingival erythema
- NUP
- Periodontitis
