• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/123

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

123 Cards in this Set

  • Front
  • Back
Log Kill
Every dose of chemo = a fraction of cancer cells killed (first order kinetics)
Cure
In theory – every single cell must be eliminated for true cure – this is different than abx where immune system kicks in (induce remission)
�
Multiple drug therapy
Permits largest possible dose of drugs.
Uses drugs that work by different mechanisms
Uses drugs with different toxicities. (not 3 drugs with same SE)
Reduces development of resistance. 
Drugs are often used for short periods of time. With this type of therapy normal cells recover more rapidly from pulse therapy than do malignant cells and less immunosuppression occurs.
Systemic
Pharmacologic Sanctuaries
Intrathecal (BBB)-hemo into brain directly
Local
Local Chemo-used more and more at the site (put on tumor itself)
TACE: Trans arterial chemo embolization, inject chemo emboli tumor
Solid Tumor – good candidates
Universal SE for CA
Vomiting
Stomatitis mouth sores
Myelosuppression*anemia, depressed bone marrow, all cytopenia
Alopecia
Bladder toxicity
cyclophosphamide
Cardiotoxicity
doxorubicin
Pulmonary Fibrosis
bleomycin
Antimetabolites
Methotrexate
6-MP
6-TG
Fludarabine
Cladribine
5-FU
Capecitabine
Floxuridine
Cytarabine
Gemcitabine
Antimetabolites
Structurally related to compounds within cell
Interfere with purine or pyrimidine nucleotide precursor synthesis
Max cytotoxic effects are in S-phase
Cell-cycle specific
Methotrexate
Related to folic acid/antagonist
Nonproliferating cells are resistant to MTX
Genetics – process quickly or slowly based on enzyme (high or lower dose)
Monitor Kidney function & LFTs for toxicity
Take orally (can also be given IM or IV)
Hydration key – metabolite (prodrug may lead to crystalluria)
Poor CNS penetration
SE = N/V/D, Stomatitis, myleosuppression, rash, alopecia
Teratogenic & Abortifacient (used as an abortion drug)*
Antimetabolite
Uses:
ALL
Choriocarcionoma
Burkitt lymphoma
Breast CA
Head & Neck Ca
Severe Psoriasis
RA
Crohn’s Disease-rarely used
6MP
AKA Azathioprine
Maintenance & remission of ALL
Crohn’s disease-used frequently
Inhibits purine synthesis
Decrease dose by 75% if patient on allopurinol to avoid accumulation of drug
SE: anorexia, N/V/D, hepatotoxicity monitor LFTs (Text reports 1/3) less with monitoring
Prior genetic testing
Metabolite monitoring 3-6 months of first year
LFTs
6TG
Purine analog
Treats Acute non-lymphocytic leukemia
Erratic dosing/absorption
TPMT metabolites
TPMT genetics
Not for maintenance or long-term therapy for any condition due to high potential for liver toxicity
Flurdarabine
Purine nucleotide analog
CLL treatment ? Future rx of choice
Hairy cell leukemia
Indolent non-Hodgkin lymphoma
Mechanism uncertain because acts on both DNA & RNA
IV only due to degradation by intestinal bacteria
SE: N/V/D & Myleosuppression that is dose-limiting (stop drug bc severe anemia and neutropenia)
Also : fever, edema, & severe neurologic toxicity, progressive encephalopathy, blindness, & death (rare)
Cladribine
Purine Analog
Hairy Cell Leukemia, CLL, non-Hodgkin lymphoma
MS
Administered as a single, continuous infusion
Crosses BBB
Severe bone marrow suppression is a common AE + fever, give NSAIDS, tylenol
Peripheral neuropathy rare
Teratogen
5-FU
Antimetabolite
Workhorse drug
Pryimidine analog
Deprives the cell of thymidine (essential precursor for DNA)
Treats slow-growing solid tumors
Colon, breast, ovarian, pancreatic, gastric CA
Topically used in basal cell CA
IV in all other cases due to severe GI toxcity
Adjust for hepatic impairment
Levels of DPD can vary up to 6x from person-person so large dose adjustments may be needed (testing prior to start for dihydropyrimidine hehydrogenase levels) really low doses and then crank it.
N/V/D
Alopecia
Severe ulceration of the oral & GI mucosa
Rx with allopurinol mouthwash
Bone marrow depression (worse with bolus)
Anorexia
Hand-Food Syndrome
Desquamation of palms & soles
Capecitabine
Antimetabolite
Newer
Oral rx**
Fluoropyrimidine carbamate
Rx for metastatic breast cancer resistant to other rx
Colorectal CA
Similar effects in cell of 5-FU but tumor specific
Similar SE to 5-FU
Floxuridine
Antimetabolite
Analog to 5-FU
Rapid intraarterial injection for liver mets from GI cancers
Similar SE to 5-FU+ enteritis, and local erythema skin outside tumor turn red
Cytarabine
Antimetabolite
AML treatment
Pyrimidine antagonist
Give only IV or intrathecal (rare)
SE: N/V/D, Severe myelosupression, hepatic dysfunction (less common)
Rare SE with intrathecal injection (in brain spinal cord) = leukoencephalopathy or paralysis
Used for mets (breast to brain)
Gemcitabine
Antimetabolite
First line treatment of locally advanced or metastatic adenocarcinoma of the pancreas, non-small cell lung cancer & “several other tumors”
Infused IV
Excreted in urine
SE: “myleosuppression is the dose limiting toxicity”, N/V, alopecia, rash, flu-like syndrome, transient elevations of transaminases, protienuria, and hematuria.
Antibiotics in CA
Dactinomycin
Doxorubicin & danorubicin
Bleomycin
Never alone, always in combo. Dose changes in monitoring. Disrupt protein syntheses
Dactinomycin
Antibiotic
AKA actinomycin D
First abx to be used as chemo
Used in combo therapy for Wilms tumor, gestational choriocarcinoma, & some soft-tissue sarcomas
Side effects: dose-limiting toxicity is bone marrow depression, n/v/d, stomatitis, alopecia
Very high doses impair DNA synthesis
Doxorubicin & danorubicin
Anthracycline antibiotics
Same structure (one hydroxylated analog)
Doxorubicin – workhorse
Sarcomas, breast, lung, ALL, lymphomas
Daunorubicin – acute leukemias
Works through direct oxidation
IV only (deactivated in GI tract)
Extravasation = tissue necrosis
No BBB penetration
Hepatic metabolism & bile excretion
**Veins visible surrounding injection site/Red urine**
Bleomycin
Antibiotic
Works in G2 phase
Testicular cancer , SCC, and lymphomas
Can be administered SQ, IM, and into cavities
SE: Pulmonary toxicity – can progress to fatal fibrosis”bleomycin lung”, mucocutaneous reactions, alopecia, hypertrophic skin changes, hyper pigmentation of hands, fever, chills, rare anaphalaxis, rare myelosupression
Alkylating Agents
Mechlorethamine
Cyclophosphamide & ifosfamide
Nitrosoureas
Dacarbazine
Temozolomide
Mechlorethamine
Alkylating Agents
Developed as a weapon in WWI (Mustard gas)
Causes lymphocytopenia
Treat Hodgkin disease and even some solid tumors
Very unstable – must be mixed just prior to admin.
Only administer IV or will cause blistering
SE: N/V (SEVERE) , & bone marrow suppression/immunosuppression causing reactivation of old viruses common
Cyclophosphamide & Ifosfamide
Alkylating Agents
Mustard agents also
Can be taken orally
Cytochrome P450 pathway hydroxylates to activate alkylating species (not cytotoxic prior to this)
*Can be used alone or in combination
Lymphomas, breast cancer, nephrotic syndrome, RA,
SE: alopecia, N/V/D, bone marrow depression, hemorrhagic cystitis, amenorrhea, testicular atrophy, sterility, veno-occlusive disease of the liver (up to 1 in 4), and neurotoxicity
Cyclophosphamide causes sterile hemorrhagic cystitis in up to 40% of pts* - force fluids and void often
Nitrosureas
Alkylating Agents]Penetrate BBB – treat meningeal tumors/leukemias
Lipophilic
SE: delayed hematopoietic depression, renal toxicity, pulmonary fibrosis
Dacarbazine
Alkylating Agents
Treats melanoma
Alkylating agent but must undergo biotransformation to an active metabolite to be active
Given IV only
SE: N/V, later myleosupression, and with long-term treatments, hepatotoxicity and hepatic vascular occlusion can occur
Temozolomide
Alkylating Agents
Newer therapy for treatment-resistant gliomas & anaplastic astrocytomas.
Related to dacarbazine
Does not require CYP450 transformation
Crosses BBB
Excellent oral bioavailablitiy
SE: N/V, myelosuppression
Microtubule Inhibitor
Vincristine & vinblastine
Paclitaxel & docetaxel
Vincristine & vinblastine
Derived from the periwinkle flower/plant Vinca rosea
Referred to as Vinca alkaloids
Another workhorse
VX (abbreviation)
ALL in children, Wilms tumor, Ewing sarcoma, lymphomas, testicular CA, non-small cell lung CA, and many more
Cell-cycle specific/phase specific (M phase)
SE: phlebitis, cellulitis, N/V/D, alopecia, myelosuppression to different degrees, peripheral neuropathy, constipation
Paclitaxel & docetaxel
Advanced ovarian cancer, metastatic breast CA, & non-small cell lung CA
Active in the G2 and M phase of the cell cycle
Cause full cell death
No action in CNS
Do not give to neutropenic pts (ANC<1500) or give with stims like neulasta
Paclitaxel – transient bradycardia SE-on monitor
Docetaxel – fluid retention SE
Due to frequent hypersensitivity give dexamethasone, Benadryl, and H2 blockers prior to or with paclitaxel
Steroid and their antagonists
NOTE – not similar SE to other chemo **
Prednisone – discussed previously
Tamoxifen
Aromatase inhibitors
Aminoglutethimide
Anastrozole & letrozole
Exmestane
Progestins
Leuprolide & goserelin
Estrogens
Flutamide, nilutamide, & bicalutamide
Hormone responsive
Tumor regresses following treatment with a specific hormone
Hormone dependent
Removal of a hormonal stimulus causes tumor regression
Prednisone
Lymphoma
Lymphocytopenia
WBC Counts
SE already discussed
Tamoxifen
Estrogen antagonist
First line for estrogen receptor-positive breast cancer
Selective estrogen-receptor modulator (SERM)
Approved for only 5 years of use (due to possible risk of stimulating pre-malignant lesions)
In pre-menopausal women, use with leuprolide to lower estrogen levels because the drug binds the estrogen receptor
Oral administration
SE: hot flashes, N/V, rash, vaginal bleeding, vag. Discharge, hypercalcemia, bone pain, increased risk of endometrial CA, increased thrombolic risk, and vision changes.
Aminoglutheimide
Aromatase inhibitor – blocks extra adrenal synthesis of estrogen from androstenedione in liver, fat, muscle, skin, & breasts (including tumors)
Treats metastatic breast cancer in postmenopausal women
Take it with hydrocortisone because of the compensatory adrenal affects
Old drug (newer options better) may compare to this drug
Anastrozole & letrozole
>6% better than aminoglutehimide at inhibiting aromatization
No hydrocortisone supplement needed
Do not predispose to endometrial cancer
Lack androgenic SE
Second-line in US, first-line elsewhere
Hormone-dependent breast cancer in postmentopausal women
Exmestane
Steriodal , irreversible aromatase inhibitor
SE: Nausea, fatigue, hot flashes, acne, hair changes
Dose adjustments for renal failure
Progestins
Old school (this is the drug you will read about in journals as the control they compared drugs to when studied years ago)
Leuprolide & goserelin
Analog of GnRH
Desensitizes the pituitary by occupying the GnRH receptors
Inhibits release of FSH/LH
Equal to orchidectomy (taking of testicles) in prostate CA treatment
Some uses in breast CA
SE: impotence, hot flashes, tumor flare (less than old tx – estrogen) very uncommon.
Depot IM injection, SQ, or sustained release prep.
Estrogens
Old school for cancer due to more side effects
Blocked LH in androgen dependent cancers
SE: thromboemboli, MI, hypercalcemia, gynecomastia, impotence
Flutamide, nulitamide, bicalutamide
Nonsteriodal antiandrogens
Treatment of prostate cancer
Compete with natural hormones for binding to androgen receptor
Monoclonal Antibodies
Trastuzumab
Rituximab
Bevacizumab
Cetuximab
Trastuzumab
Monoclonal Antibodies
Metastatic breast cancer
Targets the HER2 (human epidermal growth factor-receptor protein 2) extracellular domain (?overproduced by cancer cells when able to target, it kills the cells.)
Decreases the number of cells in the S phase
IV admin
Does not cross BBB
Toxicity = CHF
SE: F/C, Headache, dizziness, N/V, abdominal pain, back pain
Co-treatment =$300,000/yr
Rituximab
Monoclonal Antibodies
First monoclonoal Ab approved
Chimeric – for treatment of lymphoma & CLL
IV admin
Adverse rxns have been fatal – infuse slowly!
First time – F/C common – give Benadryl, Tylenol and consider albuterol for possible bronchospasm.
Rarely tumor lysis syndrome reported in first 24 hours with ARF
Bevacizumab
Monoclonal Antibodies
First antiangiogenesis agent
First line against metastatic colorectal cancer, breast CA combo, off label -“wet” macular degeneration
How does it work?
SE: hypertension, stomatitis, diarrhea, GI bleeding, proteinuria, (rare CHF, Bowel perf [black box warning], CVA, “opening of healed wounds”)
Cetuximab
Monoclonal Antibodies
Chimeric monoclonal antibody
Treats colorectal CA
Targets epidermal growth factor on cancer surface cells (inhibiting growth)
SE: Dyspnea, hypotension with initial treatment, rash, fever, constipation, abdominal pain
Cisplatin & Carboplatin & Oxaliplatin
Workhorses
Cisplatin – most toxic requiring vigorous hydration but works with multiple solid tumors, poor CNS penetration
Carboplatin - can be used with CRF patients or ones prone to neuro- or ototoxicity
Oxaliplatin – newest
Can be given IV, intraperitoneally, or intraarterailly
SE: vomiting(SEVERE* premedicate all pts), nephrotoxicity – dose limiting, hypomagnesiumemia,
Topotecan & Irinotecan
Topotecan – metastatic ovarian CA (second line) & small cell lung CA
Irinotecan – first line with 5FU & leucovorin for color or rectal CA
S-phase specific
SE: Bone marrow suppression (neutropenia - do not use ANC <1500)N/V/D, alopecia, headache should be > 3000
Etoposide
Semisynthetic derivatives of the plant alkaloid, podophyllotoxin
Block cells in late S to G2 phase
Oat cell lung CA, Testicular CA treatment
Dose limiting myelosupression (mainly leukopenia)
Leukemia may develop? How both?
SE: alopecia, N/V, and anaphylactic rxns
Imatinib
CML during blasts or GI stromal tumor treatments
Signal transduction inhibitor
SE: fluid retention/edema, hepatotoxicity, thrombocytopenia, neutropenia, N/V
Gefitinib
Targets epidermal growth factor receptor
Non-small cell lung CA tx second line
Single oral agent
CYP450 & CYP34A & others
SE: Diarrhea, nausea, Acne “like” skin rash
Watch for: dyspnea & cough – could be the first sign of potentially fatal interstitial lung dz
Procarbazine
Hodgkin disease treatment among others
Crosses BBB readily /rapidly IV or po
Excreted via kidney
SE: Bone Marrow toxicity, N/V/D, neurotoxicity, drowsiness, hallucinations.
Works like a Monoaminaoxidase inhibitor and foods interfere including :
ETOH = antabuse rxn
Mutagenic (chromosomal abnormalities) & teratogenic (may kill it or deform)
Myelogenous leukemias have been linked
L-Asparaginase
Derived from bacteria
Treats childhood ALL
Cancer cells can’t synthesize their own asparagine (amino acid)
This drug hydrolyzes blood asparagagine
Given IV or IM (destroyed by gastric enzymes)
SE: hypersensitivity reactions, elevated LFTs, decreased clotting factors, pancreatitis, seizures, coma (hepatic encephalopathy /ammonia toxicity)
Interferons
Types : α β γ
Used: alpha 2 a or 2b 0 hairy cell leukemia, melanoma, AIDS –related Kaposi sarcoma, follicular lymphoma, MS, Hepatitis B and C
SE: Flu-like symptoms, rash, cytopenias, etc.
Hepatitis B
Peg-Interferon (produced by own body most commonly alpha) if you give interferon (like if you get a virus)mega dose (flu sx for SE) take 6 mo- 1 yr. Robaferon old. Now this, SQ 1 week. Can get depression.
Entecavir
Tenofovir
Hepatitis C
1,2,3 in US, Type 4 in Egypt. 2 and 3 eradicated with 6 mo course. Type 1 is 70% of US cases
Peg Interferon
Ribavirin 6 mo course
Boceprevir
Telaprevir
Never loose antibody, just viral load will be depleted
PCP
QD bactrim
MAC if CD4 < 50
q weekly azithromycin
Vaccines
One time Pneumovax; yearly influenza
HAV, HBV; routine adult immunizations
CD4 count
The major indicator of immune function
Most recent CD4 count is best predictor of disease progression
A key factor in decision to start ART or OI prophylaxis
Important in determining response to ART
Adequate response: CD4 increase 50-150 cells/µL per year
Check at baseline (x 2) and at least every 3-6 months
Antiretrovirals
Nucleoside reverse transcriptase inhibitors (NRTI)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors (PI)
Integrase inhibitors
Entry inhibitors
NRTI
analogs of native ribosomes that terminate DNA chain elongation
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (AZT, ZDV)
NNRTI
Delavirdine (DLV)
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine (NVP)
Rilpivirine (RPV)
Protease Inhibitor (PI)
Atazanavir (ATV)
Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)
Nelfinavir (NFV)
Ritonavir (RTV)
Saquinavir (SQV)
Tipranavir (TPV)
Integrase inhibitor
Raltegravir
Fusion Inhibitor
Enfuvirtide (ENF, T-20)
CCR5 Antagonist
Maraviroc
Initial ART treatment
3 main categories:
1 NNRTI + 2 NRTIs
1 PI + 2 NRTIs
1 II + 2 NRTIs
Combination of NNRTI, PI, or II + 2 NRTIs preferred for most patients
Alternative initial therapy dual-NRTI pairs
ABC/3TC
Once-daily dosing
Risk of hypersensitivity reaction if positive for HLA-B*5701
Possible risk of cardiovascular events; caution in patients with CV risk factors
Possible inferior efficacy if baseline HIV RNA >100,000 copies/mL
PI based initial regimens
ATV/r³ + TDF/FTC² (AI)
DRV/r (QD) + TDF/FTC�
AE with NRTI
Lactic acidosis (can be fatal), peripheral neuropathy and hepatic steatosis (highest incidence with d4T, then ddI and ZDV, lower with TDF, ABC, 3TC, and FTC)
Lipodystrophy (higher incidence with d4T)
AE with NNRTI's
Rash, including Stevens-Johnson syndrome
Hepatotoxicity (especially NVP)
Drug-drug interactions
AE with PI
Hyperlipidemia
Lipodystrophy
Hepatotoxicity
GI intolerance
Possibility of increased bleeding risk for hemophiliacs
Drug-drug interactions
AE with II
RAL
Nausea
Headache
Diarrhea
CPK elevation, myopathy, rhabdomyolysis
Rash
EVG/COBI
Decreased CrCl
Increased risk of TDF-related nephrotoxicity
Nausea, diarrhea
AE with CCR5 Antagonist
MVC
Drug-drug interactions
Rash
Abdominal pain
Upper respiratory tract infections
Cough
Hepatotoxicity
Musculoskeletal symptoms
Orthostatic hypotension, especially if severe renal disease
AE with Fusion Inhibitor
ENF
Injection-site reactions
HSR
Increased risk of bacterial pneumonia
Zidovudine
NRTI
(AZT, ZDV)
terminate DNA chain elongation
1st available tx for HIV infection
preferred in PG
oral administration
-if taken with food, peak levels may be lower but total amount of drug absorbed is not affected
-penetrates BBB
-short ½ life, BID
prophylaxis
More toxicities than TDF/FTC or ABC/3TC
DI:More toxicities than TDF/FTC or ABC/3TC
bone marrow suppression
Stavudine
NRTI
(d4T)
terminate DNA chain elongation
oral ingestion, not effected by food
penetrates BBB
Peripheral neuropathy
Lipoatrophy
Pancreatitis
Didanosine
NRTI
(ddl)
terminate DNA chain elongation
adjustment in renal insufficiency
absorption is best if taking while fasting
-penetrates CSF
use of stavudine is not recommended
second line drug
GI intolerance
Peripheral neuropathy
Possible increased risk of MI
Pancreatitis
Possible noncirrhotic portal hypertension
Tenofovir
NRTI
TDF
terminate DNA chain elongation
once daily dosing, active against HBV
renal dose adjustment
high viral efficacy
first neuclotide analogue approved
Renal impairment Decrease in bone mineral density
Headache
GI intolerance
-Potential for renal and bone toxicities
do not use with ddI, decreases atazanavir
Lamivudine
3TC
NRTI
once daily doing used with HIV combo with ATZ
renal dose adjustment
potentially fatal liver toxicities characterized by lactic acidosis and hepatomegaly with
also potential for renal and bone toxicity
-Risk of hypersensitivity reaction if positive for HLA-B*5701
-Possible inferior efficacy if baseline HIV RNA >100,000 copies/mL
- Possible risk of cardiovascular events; caution in patients with CV risk factors
Zalcitabine
NRTI
(ddC)
terminate DNA chain elongation-removed form market for toxicity
renal dose adjustment
first cytosine analog developed
potentially fatal liver toxicities characterized by lactic acidosis and hepatomegaly with steatosis
Abacavir
NRTI
ABC
terminate DNA chain elongation
renal dose adjustment
QD
potentially fatal liver toxicities characterized by lactic acidosis and hepatomegaly with steatosis
-GI disturbances, HA, dizziness
- Risk of hypersensitivity reaction if positive for HLA-B*5701
-Possible risk of cardiovascular events; caution in patients with CV risk factors- Possible increased risk of MI
Possible inferior efficacy if baseline HIV RNA >100,000 copies/mL
-HSR*
-Rash
Advantages of NNRTI
 Long half-lives
 Less metabolic toxicity (dyslipidemia, insulin resistance) than with some PIs
 PIs and II preserved for future use
Disadvantage
 Low genetic barrier to resistance – single mutation
 Cross-resistance among most NNRTIs
 Rash; hepatotoxicity
 Potential drug interactions (CYP450)
 Transmitted resistance to NNRTIs more common than resistance to PIs
Nevirapine
NNRTIs
1st generation (don't use in women with CD4 >250, men >400)
inhibit enzyme inducer ofCYP3A4 family of CYP450 enzymes
used in combo with other antiretroviral drugs for tx of HIV1 infxn in adults and children
-potential for severe hepatotoxicity so should not be used in women with CD4 T-cell counts >250 or men >400
lipophilic so enters fetus and mothers milk
-wide tissue distribution including CNS
-14 day titration period is mandatory to reduce risk of serious epidermal rxns and hepatotoxicity

Higher rate of rash
Hepatotoxicity (may be severe and life-threatening;
risk higher in patients with higher CD4 counts at the time they start NVP, and in women)
Delavirdine
NNRTI
(DLV)
1st generation
inhibitor of CYP450
NOT recommended as preferred alternate by DHHS for initial therapy
oral administration, not affected by presence of food
rash

Fluoxetine and ketoconazole increase plasma levels of this drug
-phenytoin, phenobarb and carbamazepine decrease plasma levels of the drug
Efavirenz
(EFV)
NNRTI
bind to HIV reverse site adjacent to active site to inhibit enzyme
-increases CD4 cell counts and decrease viral load
-potent inducer of CYP450 enzymes
Neuropsychiatric
Teratogenic in nonhuman primates + cases of neural tube defects in human infants after first-trimester exposure
Dyslipidemia
fluxoetine and ketoconazole increase plasma levels
2nd generation NNRTI
Etravirine (ETR)
bind to HIV reverse site adjacent to active site to inhibit enzyme
HIV strains with the common K103N resistance mutation to the 1st gen of NNRTIs are fully susceptible to this drug
oral administration
-bioavailability enhanced when taken with high-fat meal
-1/2 life of 40hrs but still indicated for twice daily dosing
AE: rash, PG category B
HIV PI Advantages
 Higher genetic barrier to resistance
 PI resistance uncommon with failure (boosted PI)
 NNRTIs and II preserved for future use
HIV PI Disadvantages
Metabolic complications (fat maldistribution, dyslipidemia, insulin resistance)
GI intolerance
Potential for drug interactions (CYP450), especially with RTV
PI AE
Hyperlipidemia
Lipodystrophy
Hepatotoxicity
GI intolerance
Possibility of increased bleeding risk
for hemophiliacs
Drug-drug interactions
Ritonovir
PI
inhibitors of HIV aspartyl
no longer used as single protease inhibitor but used as ‘booster’ of other protease inhibitors
1/2 life of 3-5hrs
take with meals, chocolate milk improves the taste
GI intolerance
Hepatitis
MOST POTENT
dosage modifications with warfarin, sildenafil and phenytoin
Rifampin and St Johns wort CI with these drugs
Saquinavir
PI
SQV
HIV aspartyl protease
given with low dose of ritonavir
1/2 life of 7-12hrs requiring twice daily dosing

GI intolerance
PR and QT prolongation

-fat redistribution- fat loss from extremities and accumulation in abdomen or buffalo hump at base of neck
LEAST potent
Indinavir
PI
IDV
inhibitors of HIV aspartyl least protein bound

acidic gastric conditions are necessary for absorption
-twice daily dosing- take 1hr before or 2hrs after food
-may take with skim milk or low fat meal
-shortest ½ life of protease inhibitors
high fat meals decrease absorption

Nephrolithiasis
GI intolerance
Diabetes/insulin resistance
Nelfinavir
(NFV)
PI
nonpeptide protease inhibitor
only protease inhibitor that cannot be boosted by ritonavir bc not extensively metabolized by CYP3A

1/2 life is 5hrs
-high fat meals can increase biovavailability
-does not require strict food or fluid conditions
Diarrhea
Fosamprenavir
PI
FPV
reversible inhibitors of HIV aspartyl protease
metabolized to amprenavir following oral absorption
-long plasma ½ life so twice daily dosing
Used with Ritonavir to decrease does to once daily
GI intolerance
Rash
Possible increased risk of MI
Lopinavir
PI
LPV
reversible inhibitors of HIV aspartyl protease
peptidomemetic alternative protease inhibitor
very poor intrinsic availability which can be enhanced by including ritonavir

GI intolerance
Diabetes/insulin resistance
Possible increased risk of MI
PR and QT prolongation
Atazanvir
PI
ATV
reversible inhibitors of HIV aspartyl protease
preferred protease inhibitor
absorbed orally and must be taken with food to increase absorption
-highly protein bound
-7hr ½ life but administered once
Hyperbilirubinemia
PR prolongation
Nephrolithiasis, cholelithiasis
unboosted it is CI with use of PPIs and administration must be spaced 10hrs apart from H2 blockers and 1hr after antacids
Tipranavir
PI
reversible inhibitors of HIV aspartyl protease

inhibits HIV protease in viruses that are resistant to other protease inhibitors
useful in ‘salvage’ regimens in pts with multidrug resistance
well absorbed when taken with food
1/2 life of 6hrs so administered twice daily with ritanovir
GI intolerance
Rash
Hyperlipidemia
Liver toxicity
Contraindicated if moderate-to-severe (BBW) hepatic insufficiency
Cases of intracranial hemorrhage
Darunavir
PI
reversible inhibitors of HIV aspartyl protease

most recently approved and preferred by DHHS guidelines
approved for both initial therapy and in naïve HIV infected pts as well as resistant HIV
must be taken with food to increase absorption
-1/2 life of 15hrs when combined with ritanovir
nausea, abdominal discomfort, HA, rash, decreased risk of hyperlipidemia
Entry Inhibitors HIV
Enfuvirtibe
Maraviroc
Enfuviride
EI
ENF
fusion inhibition of HIV and host cell
must be given SC

Injection-site reactions
HSR
Increased risk of bacterial pneumonia
VERY expensive med
-must be reconstituted prior to administration
Maraviroc
PI
MVC
Advantages: Virologic response noninferior to EFV (post- hoc analysis), Fewer adverse events than with EFV
NNRTIs, PIs, and IIs preserved for future use

Disadvantage: Requires tropism testing before use Less experience than with boosted PI- or NNRTI-based ART, Limited data with NRTIs other than ZDV/3TC, Twice-daily dosing, CYP 3A4 substrate; dosage adjustment required if concomitant inducers or inhibitors

blocks CCR5 co-receptor
second entry inhibitor
-only treats R5 virus
-must be reduced when given with protease inhibitors and increased in pts receiving NRTIs: efavirenz and etravirine
well absorbed orally- oral tablet
Drug-drug interactions
Rash
Abdominal pain
Upper respiratory tract infections
Cough
Hepatotoxicity
Musculoskeletal symptoms
Orthostatic hypotension, especially if severe renal dz
Integrase Inhibitor
Raltegravir
Advantages: Virologic response noninferior to EFV
Fewer adverse events than with EFV, RAL has fewer drug-drug interactions than with PIs or NNRTIs (not true of EVG/COBI), NNRTIs and PIs preserved for future use

Disadvantage: Twice-daily dosing
Lower genetic barrier to resistance than PIs, COBI has many drug-drug interactions, COBI may cause or worsen renal impairment, Myopathy, rhabdomyolysis, skin reactions reported with RAL (rare)


inhibits final step inintegration of strand transfer of viral DNA into host cell
-UGT1A1 mediated glucuronidation

1st of this new class of drugs
-in combo it is approved for both initial therapy of both treatment naïve pts as well as tx experienced pts with evidence of viral replication despite ongoing drug tx
1/2 life of 9hrs so dosed twice daily
Nausea, Headache, Diarrhea, CPK elevation, myopathy, rhabdomyolysis, Rash
New Integrase Inhibitor
Elvitegravir (EVG)
Currently available only in conformation with cobocistat (interferes with CYP450)
AE: Decreased CrCl, Increased risk of TDF-related nephrotoxicity, Nausea, diarrhea
NRTI Penetrates BBB
AZT/ZDV
D4T
ddl
Lipoatrophy NRTI
AZT, ZDV
d4t
ftc
Pancreatitis NRTI
d4t
ddl
ftc
increased risk MI NRTI
ddl
3TC
ABC
NRTI and HBV
3tc
ftc
tdf
Once daily dose NRTI
3tc
abc
tdf
fatal liver toxicity/lactic acidosis NRTI
3tc
ftc
ddc
abc
hypersensitivity reaction with HLA-B5701 NRTI
3TC
ABC
NNRTI not affected by food
NVP
DLV
Take on empty stomach NNRTI
EFV
Enhances CYP450 NNRTI
NVP
EFV
ETR
Take with high fat meal NNRTI
ETR