HIV- AIDS DRUGS -Pharmacy Week E
What is Emtricitabine/tenofovir (Truvada)?
Comibination NRTI Pre-exposure Prophylaxis "PrEP"
What is the mechanism of action for Non-Nucleoside Reverse Transcriptase Inhibitors?
work outside the nucues to Interfere with Reverse Transcriptase; preventing RNA from making DNA
What level do the cells have to be at to make a diagnosis of AIDS?
<200 cells/mm3
What is the criteria for a HIV Positive diagnosis?
A CD4 T-cell count above 500 cells/mm3 is considered relatively high. BELOW 200 cells/mm3 indicates immunodeficiency and gives the patient a HIV diagnosis. If healthy cd4 count and deveop an opportunistic infection the patient is automatically HIV positive.
What are the HIV / AIDS TREATMENT guidelines?
ALWAYS give 3 drugs: 2 must be NRTI's 1 must be: Protease Inhibitor NNRTI Integrase Inhibitor Fusion Inhibitor or CCR5 Antagonist
What does AIDS stand for?
Acquired immunodeficiency syndrome
Zidovudine (Retrovir) is administered how?
Administered orally and IV (iv in initial phases)
What is ART?
Antiretroviral Therapy
When is the CD4 T-cell count taken?
At diagnosis and then every 3-6 months thereafter unless you get an opportunistic disease or are feeling ill
antiretroviral therapy is based on what?
CD4 counts and viral loads. How much of virus is in the person determines the drug therapy
What is the mechanism of action for Fusion Inhibitors?
Blocks HIV from Helper T cells
What is the action of CD4 Cells?
CD4 cells are essential for effective immune response. Virus invades the body Ingested by a macrophage who eats itand then antigens start to form on the macrophage. The antigens send out a call for help. CD4 comes to the resuce. It sends out a signal to the bcells. Bcells run over to the antigen and make an antibody. Without a cd4 cell this cannot occur. Low cd4 count lowers the ability of the immune system to fight and opportunistic infections occur. T-helper cell sounds the alarm to activate immune system B cell responds to produce antibodies Send out signals that activate the t cells and b cells make an antibody The cd4 cells start off the immune system nd you have to have thoses in place in order to fight an infection.
What are the Treatment Goals of HIV?
Decrease the viral load and increase the CD4 count. Maximal & durable suppression of viral load- we want to keep viral load down. Restore or preserve immune function Improve quality of life Reduce morbidity and mortality Prevent vertical HIV transmission
What does the CD4 T-cell count tell?
Degree of immunodeficiency or how well the immune system is working Damage to immune system
Other NRTI's include what?
Didanosone Tenofavir Stavudine Lamivudine
What is often Used in treating HIV infection in combination with NRTIs
Efavirenz (Sustiva)
What is both an obligate parasite & retrovirus?
HIV
What is the Post Exposure Prevention for HIV AIDS?
High risk exposures Rapid test and elisa done If negative on western blot the meds will be stopped. Initiate prophylaxis within 1-2 hrs, continue for 4 weeks 2 NRTI's Check for Antibodies against HIV (blood test) at 6 wks, 12 wks, and 6 months
What does HAART stand for?
Highly active antiretroviral therapy
What is HIV?
Human immunodeficiency virus Kills CD4 T lymphocytes which activate the immune system. High risk for opportunistic infections and certain neoplasms. Virus weakens the immune system to such a point that they cannot fight the disease.
The first class of drugs approved by the FDA to treat HIV infection and AIDS were what and what is the prototype?
Nucleoside Reverse Transcriptase Inhibitors (NRTI) Zidovudine (Retrovir) (AZT) is the prototype for NRTIs
What does the Viral load (HIV-RNA count) indicate?
Indicate magnitude of HIV replication & predict rate of CD4 T-cell destruction Disease progression- how well our body and theraoy is working.
What are the drug interactions of Efavirenz (Sustiva)?
Induces P450 St John's Wort may reduce levels of efavirenz and other NNRTI's due to accelerated metabolism secondary to induction of P450 - this is used for depression. Make sure the patient is not taking this because the medicine will no longer be effective anymore.
What is the action of Protease Inhibitors (PI)?
Inhibits HIV protease which prevents maturation of HIV. Active against both HIV-1 and HIV-2.
What are some common Protease Inhibitors (PI)?
Lopinavir/Ritonavir (Kaletra) Ritonavir (Norvir) Indinavir (Crixivan) Saquinavir (Invirase)
What are the Adult Patient Treatment Goals for HIV/AIDS?
Maximal and durable suppression of viral load Restoration or reservation of immune function Improve quality of life Reduction of HIV -related morbidity and mortality Prevent vertical HIV transmission
What are the adverse effects of the Protease Inhibitors (PI)?
Most common adverse effects: diarrhea, abdominal discomfort, nausea, and vomiting Other adverse effects include- hyperglycemia, redistribution of fat with deposition of fatty-like tissue at the base of the posterior neck and the abdominal area, hyperlipidemia, & bone loss
What is the issue with Protease Inhibitors and HIV Resistance and how can we reduce this risk?
Mutant strains of HIV are resistant to PI High likelihood of cross-resistance to other PIs PI mechanism of action is different than other antiretroviral drugs (reverse transcriptase inhibitors) cross resistance does not occur To reduce resistance risk, PIs should NEVER be used alone ALWAYS combine with at least 2 reverse transcriptase inhibitors Combinations and cocktails to reduce resistance to these medications.
Drug Interactions of Zidovudine (Retrovir)
Myelosuppressive, nephrotoxic or toxic to circulating blood cells
How does Efavirenz (Sustiva) work?
NNRTIs constrain HIV replication by binding non competitively to reverse transcriptase; blocks HIV replication by preventing RNA to DNA
What is the classification for Efavirenz (Sustiva)?
Non-Nucleoside Reverse Transcriptase Inhibitors
What is the goal for Children with HIV AIDS?
Only use drugs with approved pediatric dosages. Nursing - remember that HIV infection is accelerated in children because their cells are growing so fast.
What are some drug interactions of Protease Inhibitors?
P450 inhibitors P450 inducers P450 substrates St. John's Wort Garlic- supplements and not eating garlic
Explain the Prevention of Opportunistic Infections for those with HIV/AIDS?
PCP pneumonia - treatment of choice is trimethoprim plus sulfamethoxazole (Bactrim) is effective in 90% of patients. TB/MAC - (tuberculosis/mycobacterium avium Complex) requires polypharmacy to prevent further resistance. Four drug regimen which includes INH. Candida - frequently in the oropharynx and esophagus. Swish and swallow with nystatin suspension or sucking on a miconazole troche. Give the swish and swallow after the pills because you do not want to follow it with water for a half hour or so. This also includes not lozanges or other drin ks because we want the nystatin to stick. Troche is a throat lozenge that you can use vaginally or suck on. CMV Retinitis - leading cause of vision loss in AIDS patients. Treated with five agents including Ganciclovir. Teach about their vison and that they need to go to a eye doctor with any vision change. HSV - common. Acyclovir is the drug of choice.
Who should get Emtricitabine/tenofovir (Truvada)?
Patients that are HIV negative are the only patients who get this. If partner is positive, men having sex with men, multiple partners, and iv drug users.
What are the goals for Pregnant Patients with HIV/AIDS?
Preconception Counseling Reduce Perinatal Transmission Goal is to balance the benefits of treatment (reducing viral load which will promote the health of the mother and which will decrease the risk of vertical transmission against the risks of treatment which would be harm to the fetus). As a rule the benefits of treatment outweigh the risk Risk of causing birth defects fairly low
What represent the most effective anti-retroviral drugs known?
Protease Inhibitors (PI)
What are the adverse effects of Efavirenz (Sustiva)?
Rash CNS side effects of altered mood, sleep, anxiety Teratogenic We do not give to pregnant women
Patient teaching regarding the Treatment Regimen for HIV?
Resistance assays- matches the drug to the bug. Teach patient if they are HIV positive and have and HIV partner they must still wear protective measures because there are many HIV strains out there. Patients need to take meds on a schedule. We do not want them to skip doses and want a steady rate in their stream
Patient education for Fusion Inhibitors like enfuvirtide (Fuzeon) ?
S/S of pneumonia. Caution in smoking patients or history of lung disease, low CD4 counts, high viral loads
What is the route of administration for Fusion Inhibitor enfuvirtide (Fuzeon) ?
SQ injection- rotate sides
How is an HIV Diagnosis made and confirmed?
Screening tests: Rapid HIV testing Results in < 30 minutes ELISA (or EIA) Blood test used to screen blood supply in US Not used alone to diagnose MUST be confirmed with: Western Blot Test Blood test Best test and is very specific Only way HIV is confirmed for sure in the US Lab Tests CD4 = T-Cell Count Viral Load (HIV RNA) Count- how much virus is in the patient
What are the side effects of Emtricitabine/tenofovir (Truvada)?
Side effects are mild and usually gi like stomach upset or diarrhea.and the person gets used to it.
What is the mechanism of action for Protease Inhibitors?
Stop HIV molecule maturation
What is the mechanism of action for Integrase Inhibitors?
Stop viral DNA integration
What is the Clinical Course of HIV?
The clinical course is triphasic (3 phases) Acute/Initial Phase Massive replication- 2-4 weeks Flu-like symptoms- body is trying to combat he infection but it does not keep up. Higest likelihood of spreading HIV. Your viral load is very high at this period of time. Clinical Latency/Middle Phase Asymptomatic/chronic Can live in this phase for several decades on ART If not on ART they can last about a decade or less AIDS/Late Phase CD4 T cells drop below a critical level High vulnerability to opportunistic infections, certain neoplasms Survive 1-3 years without treatment in this phase
How does the Transmission of HIV work?
Virus present in all body fluids Spread by intimate contact with: Semen, vaginal secretions, blood Sexual contact Blood transfusions- wear gloves and eye protection. Sharing IV needles Needle sticks
What are some worries currently about taking Emtricitabine/tenofovir (Truvada)?
Worried about resistance when giving this Inapproriate populations may get this on the black market. Can give false assurance to people
What are Serious adverse effects of Zidovudine (Retrovir)?
anemia, neutropenia; may induce lactic acidosis and severe hepatomegaly
What has dramatically reduced disease progression and death among patients with HIV infection, but the optimal time to begin therapy is uncertain?
antiretroviral therapy
What is the action of Fusion Inhibitors?
blocks HIV envelope from fusing with cell membrane of CD4 - blocking viral entry & replication
What are the Laboratory Values to assess prior to therapy with Zidovudine (Retrovir)?
cbc, liver enzymes( ast, alt, and ammonia),kidney levels, and lactic acid levels.
To work best Emtricitabine/tenofovir (Truvada) must be taken how?
daily and has reduced transmission rate that is very effective. Periodically need to get tested for HIV on this medication
What is an example of a Fusion Inhibitor?
enfuvirtide (Fuzeon)
What are the enzymes needed for HIV replications?
reverse transcriptase Protease Integrase
HAART converts AIDS from what to what?
from a universally fatal disease to a more manageable "chronic" disease
Adverse effects of Fusion Inhibitors like enfuvirtide (Fuzeon) ?
injection site reactions Increases risk of pneumonia. Histomedication. ry of lung problems will avoid this
Measurement for effective therapy of HIV is determined by?
less than 50 copies/ml - this tells us if therapy is effective
What are Common adverse effects of Zidovudine (Retrovir)?
n/v/d, abdominal pain, dyspepsia, anorexia and peripheral neuropathy Anemia and neutropenia This is why we wait until cd4 cell count goes down.
Medications for HIV/AIDS are not a cure but
only keep the disease in check.
Women with HIV who take antiretroviral medication during pregnancy as recommended can do what?
reduce the risk of transmitting HIV to their babies to almost nothing
antiretroviral regimens are like what and what does this mean?
relationships—you may NOT end up settling down with your first one. You will switch antiviral regimens with this because the virus changes and the virus may or may not react any longer because it may have developed resistance. The cd4 count and viral load make it change
What do Protease Inhibitors (PI) stop?
the HIV bug from maturing
Drugs have been developed to inhibit what?
the enzymes needed for HIV replications
When used in combo with NRTI's Protease Inhibitors (PI) can?
they can reduce the viral load to a level that is undetectable with current assays.
What must retroviruses do to replicate?
transcribe their RNA into DNA
Even when plasma level is "undetectable" or below 50 the patient is still able to do what?
transmit HIV to another - although the risk is reduced (depending on the immune system functioning of the person who has contact). They are not cured even if they are low.
When do they Initiate therapy for HIV/AIDS?
when the CD4+ count is between 351-500/mm3. Normal is 500-1600, They are not technically converted to AIDS. Do not wait until CD4+ counts fall below 250 to 300 because this Increases risk of death if therapy is deferred and if we wait for count to go below 351
What is the mechanism of action for Nucleoside Reverse Transcriptase Inhibitors ?
work inside the nucles to Interfere with Reverse Transcriptase; preventing RNA from making DNA