Chemotherapy part 2 (2) Flashcards
1
Q
HIV facts
- HIV- human immunodeficiency virus
- _____ (retrovirus) that suppresses immunity and allows opportunistic infections
- HAART (highly active antiretroviral therapy)
- there is a high rate of retroviral mutations and therefore _____ therapy essential
- combination therapy is standard for HIV
- _____ creates viral resistance to drugs
- _____ HIV treatment is very dangerous, it needs to be _____
- WHO: pandemic with total cases 54 million (2020)
A
lentivirus combination monotherapy a little all or nothing
2
Q
HIV life cycle
- _____ of virus at _____ receptor
- viral _____ and _____
- _____ makes a single DNA copy of the viral RNA and then makes another to form a _____ viral DNA
- _____ and _____ processing
- _____ enzyme cleaves polypeptides into _____ proteins
- _____ budding and maturation
A
attachment CD4 fusion uncoating reverse transcriptase double stranded transcription RNA protease functional HIV viron
3
Q
drugs for HIV
6 classes of drugs are in clinical use:
1. nucleoside and nucleotide reverse transcriptase (NTRIs) inhibitors: _____, _____
2. non-nucleoside reverse transcriptase inhibitors (NNRTIs): _____, _____
3. protease inhibitors (PIs): _____, _____
4. entry inhibitors: _____
5. integrase inhibitors: _____
6. investigational agents: _____. _____
A
zidovudine lamivudine nevirapine efafirenz ritonavir indinavir enfuvirtide raltegravir bevirimat TNX-355
4
Q
nucleoside and nucleotide analogs
- nucleoside analogs (NRTI) act as _____ or inhibitors at the substrate binding site of _____
- imitate _____, _____, _____, _____
- they incorporate into the growing DNA and inhibit _____ formation
- all NTRIs have _____ toxicity
- the first anti-HI drug approved was the NTRI known as AZT (azidothymidine) or _____
- Epivir (lamivudine), abacavir, didanosine
- ADR: _____, _____, and _____ may occur
A
chain terminators reverse transcriptase adenosine guanine thymidine cytosine chain mitochondrial Zidovudine lactic acidosis dyslipidemia insulin resistance
5
Q
non-nucleoside analogs
- non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit viral DNA replication by binding to and inhibiting _____
- three NNRTIs are currently approved for clinical use in combination therapy: _____, _____, _____
- adverse effects: GI disturbances, skin rash, stevens johnsons syndrome
- NNRTIs are metabolized by CYP 450 enzyme system and may be _____ or _____, this drug interactions
A
reverse transcriptase nevirapine delavirdine efavirenz inducers inhibitors
6
Q
protease inhibitors
- during the reproduction cycle of HIV a specific protease is needed to form mature HIV components
- if _____ is missing, _____ HIV buds are produced
- HIV protease inhibitors are specific to HIV protease because it differs significantly from _____
- saquinavir, ritonavir, indinavir
- associated with a _____ like syndrome
A
protease
noninfectious
human protease
cushing
7
Q
viral entry inhibitors
- binding of the HIV virus to the _____ receptor is the first step in viral replication
- this binding causes a conformational change to the site and allows the _____ to fuse with the _____
- _____ is a synthetic peptide which blocks entry of the virus into the cell, by preventing _____ change
- _____/not subject to hepatic enzyme degradation
- local injection sire reactions may occur
- eosinopilia and hypersensitivity reactions may occur
A
CD4 lymphocyte viral envelop cell membrane enfivirtide conformational subcutaneous injection
8
Q
integrase inhibitors and new agents
- _____ is a viral enzyme essential for HIV replication
- it promotes the integration of viral DNA strands into the _____ DNA
- _____ is a pyrimidine analog that binds integrase and prevents its action
- it is use din adult patients resistant to other agents
-investigational agents:
-new agents claim better activity, lesser side effects and convenient dosing
-virus maturation inhibitors: bevirimat
CD4 receptor inhibitor: TNX-355
A
integrase
host
raltegravir
9
Q
highly active anti retroviral therapy HAART
- 2 NTRIs with an NNRTI or a ritonavir-boosted PI or an integrase inhibitor
- in antiretroviral therapy failure, the goal of subsequent treatment is suppression of _____ to below detection levels
- ideally 3 new drugs to which the patients virus is susceptible since the virus any be dominant
- tenofovir/emticitrabine (a combination of two NRTIs) and Efavirenz (NNRTI)
- _____ should not be given to pregnant women
- _____/_____ and _____ (an integrase inhibitor) in pregnancy
A
HIV-1 RNA efavirenz tenofovir emtricitabine raltegravir
10
Q
antivirals
- acyclovir, famciclovir, ganciclovir
- acyclovir is a _____ derivative active against herpes simplex virus (HSV-1 and HSV-2)
- it is _____ and inhibits viral DNA synthesis thus preventing formation of DNA _____
- decreases duration of herpes symptoms, time for healing and duration of viral shedding
- nausea, vomiting, diarrhea, nephrotoxicity
Ganciclovir:
- inhibits viral _____
- used for CMV cytomegalovirus infections (sore throat, fever, retinal damage, intestinal symptoms and hepatitis)
- causes myelosuppression
A
guanosine
phosphorylated
chain
DNA polymerase
