Reading...
Play button
Play button
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;
56 Cards in this Set
- Front
- Back
|
HAART therapy?
|
Highly active anti-retroviral therapy (HAART)
Three to four drugs None alone or combined eradicate HIV** Decrease viral replication, improve immunological status and prolong life |
|
|
Potential Benefits of Early HIV Therapy
|
Earlier suppression of viral replication
Preservation of immune function Prolongation of disease-free survival Lower risk of resistance with complete viral suppression (Possible) decrease in the risk for viral transmission |
|
|
Seven Classes of Anti-HIV Drugs
|
NRTIs
Nucleoside reverse transcriptase inhibitors NTRTIs Nucleotide reverse transcriptase inhibitors NNRTIs Non-nucleoside reverse transcriptase inhibitors PI Protease inhibitors Fusion inhibitors CCR5 chemokine blocker Integrase strand transfer inhibitors |
|
|
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
named |
Zidovudine (AZT, Retrovir)
Stavudine (Zerit) Didanosine (Videx) Emtricitabine (Emtriva) Lamivudine (Epivir) Abacavir (Ziagen) |
|
|
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
moA |
Inhibit HIV reverse transcriptase
Inhibitor of viral life cycle following ***lethal synthesis***** to nucleotide analog Converted to active triphosphate form that competes for nucleoside triphosphates for access to reverse transcriptase Missing essential ***3’-hydroxyl group**** prevents additional nucleoside addition to DNA chain Blocks viral replication and infection of new cells |
|
|
Nucleoside Reverse Transcriptase Inhibitors (NRTIs
TOXICITIES |
Inhibition of cellular and ***mitochondrial DNA polymerases and kinases accounts for potentially lethal toxicity
Toxicity mild early in infection, more severe late in infection Primary toxicities associated with ****mitochondrial actions -****Lactic acidosis *****Severe hepatomegaly with hepatic steatosis Both potentially FATAL (Women, obese patients, alcoholics and long-term users at greatest risk) |
|
|
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
RESISTANCE |
Appearance of mutations in reverse transcriptase
Risk of resistance may increase with “interrupted” therapy “Drug holidays” to reduce toxicity(BAD IDEA) Not currently recommended for any HIV therapy ***Patient noncompliance**** |
|
|
Zidovudine
class p-kinetics |
(Retrovir)(Formerly azidothymidine (AZT))
Eliminated by biotransformation and renal systems (GOOD THUS TWO) Dosage adjustment may be necessary in patients with renal OR hepatic impairments Probenecid (blocker of tubular secretion) inhibits renal elimination -----Carefully monitor response when using any other drug that is biotransformed Ribavirin inhibits zidovudine activation Zidovudine inhibits stavudine’s activation |
|
|
Zidovudine
DRUG INTERACTIONS |
(AZT)(Retrovir)
VERY sensitive to DIs -----Carefully monitor response when using any other drug that is biotransformed ******Ribavirin(RSV,HCV,HEMORRAGIC FEVER DRUG)inhibits zidovudine activation********* Zidovudine inhibits stavudine’s(ANOTHER NRTI) activation********* |
|
|
Zidovudine
indications |
HAART
Prevention of HIV infection after needle stick exposure and possibly sexual exposure usually in combination with other drugs Maternal-neonate transmission alone or in combinations |
|
|
Zidovudine
adv. RXs |
(NRTI)
Headache, agitation, insomnia Most common *******Bone marrow effects (basically a class effect)(up to 30% of patients) Vitamin B12 deficiency Treat with supplementation Severe anemia Severe granulocytopenia Treat with transfusions, erythropoietin or colony-stimulating factors Use with caution with other drugs that suppress bone marrow function Myopathy with long-term use(hard to tell from wasting) ******Lactic acidosis ******Hepatomegaly with hepatic steatosis Fat redistribution and accumulation |
|
|
Zidovudine
BBW |
(a NRTI)
Black box warning Hematological toxicity (MONITOR) Myopathy Lactic acidosis and severe hepatomegaly( jaundice, burning tingling) |
|
|
Stavudine
class difference from prototype |
a NRTI
Noteworthy differences from zidovudine Peripheral neuropathy with high dose use Lactic acidosis incidence is highest for stavudine of all NNRTIs (? typo) Very high in pregnant women or in combination with other NNRTIs (?) Avoid use in patients with hepatic or pancreatic disease Drug interactions Avoid use with drugs that are hepatotoxic or pancreatoxic |
|
|
Stavudine
BBW |
Black box warning
Lactic acidosis and severe hepatomegaly Pancreatitis --(still of course BM suppr, myopathy) |
|
|
Zidovudine (AZT, Retrovir) & Stavudine (d4T, Zerit)
COMBO |
two NRTIs
NO Can not be given with stavudine Antagonism of effect |
|
|
Didanosine
class diff from prototype |
Noteworthy differences from zidovudine
Tablets contain phenylalanine Avoid use in phenylketonurics(pKU) Tablets are heavily buffered which may affect absorption of some drugs (ACID LABILE) Combined use with stavudine or zalcitabine associated with increased toxicity |
|
|
Didanosine
adv Rxs |
(ddi, Videx )
**********Pancreatitis (important to remember)(esp w/stavudine) Neuropathies Headache Bone marrow depression (and lactic/h-meg) |
|
|
Didanosine
BBW |
(a nrti)
Black box warning Pancreatitis Lactic acidosis with severe hepatomegaly |
|
|
Lamivudine
class dif from prototype |
(3TC, Epivir)no HBV after name
Noteworthy differences from zidovudine Generally regarded as best tolerated NRTI (still not used as much) Also active against hepatitis B virus May have hepatitis B flare up if drug stopped or hepatitis B virus becomes resistance Increased risk of pancreatitis when used in children******* Not recommended for use in combination with zalcitabine (?) Inhibit each others activation |
|
|
Lamivudine
BBW |
(3TC, Epivir)
Black box warning Lactic acidosis with severe hepatomegaly *****Non-interchangeable forms Form used for hepatitis B is not appropriate for HIV Hepatitis B exacerbations |
|
|
Abacavir
class diff from prototype |
(Ziagen) a nrti
Noteworthy differences from zidovudine Higher incidence of ********hypersensitivity 5% may be severe Repeat exposure in hypersensitive patient results in more severe hypersensitivity Avoid use in patients with hepatic disease or alcohol use |
|
|
Abacavir
BBW |
Black box warning
-****Hypersensitivity (More than two of the following) Fever Rash Nausea, vomiting, diarrhea of abdominal pain Malaise, fatigue or achiness Dyspnea, cough or pharyngitis -Lactic acidosis with severe hepatomegaly |
|
|
Emtricitabine
class dif from prototype |
(Emtriva)
a nrti no impressive changes from zidovudine Noteworthy differences Long duration of action allows for once daily dosing No interactions with biotransformation pathways Causes hyperpigmentation of soles and palms |
|
|
Emtricitabine
BBW |
Black box warning
Lactic acidosis and severe hepatomegaly No hepatitis B indication Hepatitis B exacerbation upon discontinuation of therapy |
|
|
Nucleotide Reverse Transcriptase Inhibitors (NTRTIs)
named |
Tenofovir disoproxil fumarate (Viread)
|
|
|
Tenofovir
MoA |
(NTRTIs) (Viread)
converted to tenofovir diphosphate that competes with deoxyadenosine triphosphate (dATP) for access to ****reverse transcriptase Results in chain termination*** (STill incorporates and (-)RTase Potentially useful in patients with NRTI-resistant HIV |
|
|
Tenofovir
toxicity compared to AZT avoid in... DIs |
Generally well tolerated
Once daily oral dosing Lower incidence of mitochondrial toxicity than NRTIs Avoid use in patients with renal disease Avoid concurrent use with didanosine (NRTI) and atazanavir (PI) Increases plasma levels on one or both agents |
|
|
Tenofovir
BBW |
Black box warning
Lactic acidosis and severe hepatomegaly No hepatitis B indication Hepatitis B exacerbation with discontinuation of drug |
|
|
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
named |
Efavirenz (Sustiva)
Nevirapine (Viramune) |
|
|
Nevirapine
MoA |
(NNRTIs)also Efavirenz
(more traditional ENz (-)) Inhibit reverse transcriptase by binding near the active site and inducing a conformational change that blocks enzyme activation **No activation required ***Resistance develops rapidly to this class when used alone |
|
|
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
class-wide side effects DIs |
Efavirenz (Sustiva)
Nevirapine (Viramune) All cause rash****, sometimes severe Rashes*** can vary from mild to severe, even life-threatening --All biotransformed by cytochrome P450 (Check for interactions before using with any other drug) |
|
|
Efavirenz
class indications adverse Rx DIs |
(Sustiva)a NNRTI
Indicated for HIV therapy and postexposure prophylaxis Once a day, well-tolerated Rash ****Central toxicity in about half of all patients Dizziness, headache, insomnia, euphoria, impaired cognition, nightmares, hallucinations (BAD IDEA IN PSYCH Pts) Most common in first weeks or months of therapy and fade with continued use Biotransformation interactions Inducer of CYP3A4 Inhibitor of CYP2C9 and CYP2C19 |
|
|
Nevirapine
BBW |
(Viramune)
a NNRTI (For Efavirenz also?) Black Box Warnings Rash Avoid rash by using low dose therapy initially Hepatic toxicity FDA Pregnancy Category D |
|
|
Protease Inhibitors (PI)
named |
all end in NAVIR
|
|
|
Protease Inhibitors
MoA |
Inhibits the human immunodeficiency virus ***aspartic protease** enzyme
Blocks *****posttranslational processing***** of the essential viral protein products Impairs viral replication and proliferation (Typically used with HIV reverse transcriptase inhibitors) |
|
|
Protease Inhibitors
Adverse reactions big list |
----we use these enzymes----
Adverse reactions Headache Fatigue Gastrointestinal upset (nausea and diarrhea) ********Peripheral *****neuropathies (incl Paresthesia) ****Renal and hepatic toxicity Fat redistribution and accumulation Increased bleeding in hemophiliacs ******Hyperglycemia LOTS OF Interactions at the biotransformation level All are biotransformed by and inhibit CYP3A4 (grapefruit - can incr drugs) |
|
|
Protease Inhibitors
Serious adverse reactions of class |
********Hyperglycemia
Hyperlipidemia (except atazanavir) Cholesterol and triglycerides (WATch statins for the pot. LIVER and Myopathy mixture and Rev-Tase-Is) Elevated transaminases Increase bleeding in hemophiliacs CYP3A4 biotransformation interactions Includes grapefruit interaction Paresthesias |
|
|
Saquinavir
dif BBW |
PI
(Fortovase) Well-tolerated with mild gastrointestinal effects the primary complaint Bioequivalence is Black Box Warning. (This is true for HIV Tx in general don't switch ANYthing if it is working) |
|
|
Ritonavir
BBW |
(Norvir)
Not well-tolerated at high doses ***Drug Interactions a Black Box Warning Most potent CYP3A4 inhibitor of protease inhibitors Also inhibits CYP2D6 and other CYP isoforms |
|
|
Indinavir
diff |
(Crixivan)
Renal toxicity seen in children (30%) and adults (10%) that consume less than 1.5 liters of water daily |
|
|
Nelfinavir
diff |
(Viracept)
Low incidence of serious adverse reactions make it the most often used protease inhibitor |
|
|
Atazanavir
diff |
******Can not be used with antacids, Histamine-2 acid blockers or proton pump inhibitors*******
Oral contraceptive should be low estrogen dose Use associated with gastrointestinal upset Jaundice is common side effect |
|
|
Amprenavir
diff |
PIs(Agenerase)
-High incidence of rash Oral solution contains propylene glycol (Black box warning) -Avoid in children and pregnant women Propylene glycol can produce hyperosmolality, lactic acidosis, seizures and respiratory depression Sulfonamide sensitive patients should avoid -Preparations contain high levels of vitamin E |
|
|
Fosamprenavir
Diff |
Prodrug of amprenavir
Lower toxicity than amprenavir Rash most common adverse reaction Avoid use with patients with sulfa allergy |
|
|
Darunavir
Diff |
(Prezista)
Typical protease inhibitor |
|
|
Tipranavir
Diff BBW |
(Aptivus)
Hepatotoxicity (Black box warning) Intracranial hemorrhage (Black box warning) Most common with ritonavir – tipranavir combination |
|
|
Lopinavir-Ritonavir combination
|
Ritonavir inhibition of CYP3A4 prevents inactivation of Lopinavir
|
|
|
Fusion Inhibitors
named |
Enfuvirtide (T-20, Fuzeon)
|
|
|
Enfuvirtide
moA |
(Fuzeon) ENFU a Fusion Inhibitor
Prevents the virally induced conformational change in transmembrane glycoprotein subunit (GP41) permitting viral-host cell membrane fusion (INHIBITS FUSION) Unique mechanism may add effectiveness to existing HIV therapies Received accelerated approval from the Food and Drug Administration |
|
|
Enfuvirtide
ADV rxS |
(Fuzeon)
Requires twice daily subcutaneous injections Injection site reactions are common, but rarely result in stoppage of treatment Effects of hepatic or renal disease not known Adverse effects***** Injection site reactions Hypersensitivity (eosinophilia) in up to 10% of patients |
|
|
Maraviroc
moa (KNOW IT) |
(Selzentry)
CCR5 (CC chemokine receptor 5) receptor blocker Interferes with entry of HIV-1 into host-cells by inhibiting fusion with outer membrane Only effective with HIV strains that are CCR5-tropic as this is the point of interference Resistance related to emergence of HIV that use CXCR4 receptor instead of CCR5 co-receptor for entry into cells |
|
|
CCR5 (CC chemokine receptor 5) receptor blockerS
NAMED |
Maraviroc (Selzentry)
|
|
|
Maraviroc
adv RXs |
(CCR5 blocker)(Selzentry)
Adverse reactions Hypersensitivity Cardiovascular events Myocardial infarctions, hypotension Hepatotoxicity (Black Box Warning) Suppressed immune responses (some cyp 3a4 probs)-Thioridazine (antipsychotic) increases risk of serious cardiovascular events |
|
|
Raltegravir
moA |
Mechanism of action
HIV-1 integrase strand transfer inhibitor. Prevents viral DNA from integrating******** with host genome Resistance related to mutations in integrase |
|
|
HIV-1 integrase strand transfer inhibitors
named |
Raltegravir (Isentress)
|
|
|
Raltegravir
p-kin ADV RXs |
Biotransformed by glucuronidation
Excreted in feces Adverse reactions Diarrhea, nausea and vomiting Headache ************Rhabdomyolysis*******************severe**(statin bad) dark urine |
