chemotherapy part 2 Flashcards
_______
- new class of antifungal agents that inhibit fungal ______ synthesis
- fungi cell wall: _____, ________
- _______ are carbhohydrate polymers that are cross linked w other fungal cell wall components
- inhibition of Beta 1-3 Glycan of the fungal cell:
- __________(Cancidas) for treatment of Candida and Aspergillus
- _________: esophogeal, oropharyngeal and invasive candidiasis
- used in hematopoietic stem cell transplantation patients
- adverse effects include headache, fever, phlebitis at injection site, abnormal LFTs
echinocandins cell wall chitin, Beta-D glucan beta glucans caspofungin micafungin
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
HIV-1 RNA efavirenz tenofovir emtricitabine raltegravir
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
reverse transcriptase nevirapine delavirdine efavirenz inducers, inhibitors
Potential Adverse Effects of fluconazole antifungals
- common adverse effects include GI disturbances, headache, and dizziness
- _________ areata and ________
- increased levels of _______, _______, _______
- decreased ________ levels: carbamazepine and isoniazid
- mild elevation in _____ enzymes may occur, which usually returns to pretreatment levels after drug therapy is over:
- patient should avoid alcohol
alopecia, stevens johnson
amitrytline, phenytoin, warfarin
fluconazole
liver enzymes
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)
lentivirus combination monotherapy a little all or nothing
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
integrase
host
raltegravir
clinician responsibilities
- adminsiter before infusion of other ____, to decrease adverse effects and to identify effects
- administer a 1 mg test before full dose
- keep patient well _______
- monitor electrolytes, CBC, and renal and hepatic function throughout therapy
- educate patients of the likelihood of transfusion reaction and other adverse effects
- ________ amphotericin B: a newer drug delivery system which uses a _____ vesicle to carry Amphotericin to target _____ in the body and then preferentially bind to _________
drugs hydrated liposomal lipid organs ergosterol
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
protease
noninfectious
human protease
cushing
Azoles: Flucaonazole (Diflucan)
- inhibits enzyme lanosterol 14-ademythlase
- this enzyme converts lanosterol to _________
- depletion of ergosterol in fungal membrane disrupts the structre and functions of fungal membrane
- greater affinity for ergosterol than ___________
- esophageal, oropharyngeal, vulvovaginal
- ______ fungal infections: _________, and aspergillosis
- used in __________
- _____/____
ergosterol cholesterol systemic histoplasmosis HIV-AIDs oral, IV
Other Antifungal agents:
1) . ___________
- deposited in _____ precursor cells of skin, hair, and nails, where it disrupts ________ function and inhibits _______ growth
- induces CYP450 to reduce _______ and ________ concentration
- absorption enhanced w fatty foods
2) ____________
- a synthetic Allylamine used for _________
- _______ because it interferes with ergosterol synthesis
- used for ________ and ________
Grisofulvin keratin microtubule dermatophyte warfarin, oral contraceptives Terbinafine oncyomycosis fungicidal tinea corporis, tinea cruris
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 cell membrane
- _____ 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
CD4 lymphocyte viral envelop enfivirtide conformational subcutaneous injection
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
attachment CD4 fusion uncoating reverse transcriptase double stranded transcription RNA protease functional HIV viron
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: _____. _____
zidovudine lamivudine nevirapine efafirenz ritonavir indinavir enfuvirtide raltegravir bevirimat TNX-355
Azole antifungals
-classification: 2 classes
1) _________: ketoconazole, clotrimazole, miconazole
- oral and _____
- GI absorption of these does not occur in _________ or when a patient is receiving ____ or ____
2) _______ - itraconazole, fluconazole, voriconazole
- oral and _______
- ________: prodrug, convered in acidic environment into hydroxyitraconazole which inhibits 14 alpha sterol demethylase
- achieves high levels in the meninges/ significance???
imadazoles topical achlorhydria H2 blockers, PPIs Triazoles IV itraconazole
crosses BBB
Fungal Infections -fungal infections are divided into 3 main groups: 1 2 3
superficial mycoses
subcutaneous mycoses
systemic mycoses
Fungi
- Fungi: Yeasts, Molds: _____
- Surgical, ICU, Prostheses, IV catheters, HIV
- __________, cancer, and transplant pts
- _______ infections
- traditional diagnostics: culture
- NEW: PCR, Western blot, antigen detection
mycoses
immunosuppressat
oppurtunistic
antivirals
- acyclovir, famciclovir, ganciclovir
- acyclovir is a _____ derivative active against herpes simplex virus (HSV-1 and HSV-2)
- it is phosphorylated and inhibits viral DNA _____ 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
guanosine
synthesis
chain
DNA polymerase
Amphotericin B
- ______ antifungal that works by binding to membrane. sterols (______) in fungal cell membranes, resulting in increased cell permeability, cell leakage,and death
- May cause damage to host cells as well (______)
- ______ spectrum ________
- used only for treating progressive and potentially fatal _______ infections because of its severe adverse. effects
- _________ patients with fungal pneumona, cryptococcal meningitis and histoplasmosis
polyene ergosterol cholesterol broad fungicidal systemic immunocompromised
Potential Adverse Effects of Amphotericin B
2 types of Adverse reactions
1) ___________-related reactions - chills, fever, headache, nausea, vomiting. Premedication advised with _________. drugs, steroids and antipyretics. slow the infusion rate.
2) cumulative _________ - __________ is severe (20% of pataients), _____ occurs which is irreversible. there may also be anemia, leucopenia, and severe ______ and magnesium loss
infusion anti-inflammatory toxicity nephrotoxicity ATN potassium
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 Zidovudine
- Epivir (lamivudine), abacavir, didanosine
- ADR: _____, _____, and _____ may occur
chain terminators reverse transcriptase adenosine guanine thymidine cytosine chain mitochondrial lactic acidosis dyslipidemia insulin resistance
________
- related to Amphotericin B
- used only as ______ therapy
- not used _______ because of its toxicity
- used to treat topical ______ and oral ______ infections (Candida infections)
- oral suspension of Nystatin should be ______ through the mouth and then spit out, as directed by prescriber
- currently available as ointments, crams, mouthwash and suppositories
- oropharyngeal thrush, vaginal candidiasis
Nystatin topical systemically vaginal fungal swished
