Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
antiviralls
UVa med pharm block 4
| Question | Answer |
|---|---|
| What are common ways for resistance to form against Acyclovir? | Alteration, or deficiency of HSV Thymidine Kinase (thus, the virus does not activate the drug. Alteration of HSV DNA polymerase (the target for Acyclovir) |
| How is Zidovudine administered? What is its half life? | Orally only. Half life of only 1 hour, thus taken every 4 hours. |
| How is Acyclovir used for treatment of Varicella-Zoster? | Reserved only for severe disease (i.e. immunocompromised host) when the infection involves the eye. If Acyclovir is given early in Varicella infection, it can reduce time course of disease. |
| Which compounds are additive in nephrotoxicity with Foscarnet? | Amphotericin B Aminoglycosides Pentamidine |
| What are some Drug Interactions with Ritonavir? | Powerful P450 inducer (CI with many anti-arrhythmics, sedative/hypnotics, Terfenadine, Astemizole, and Cisapride) - Can still use many drugs metabolized by P450 but with caution Severe reaction when taken with Disulfiram or Metranidazole |
| What are some advantages to Tenofovir? | Dosed once per day, can be taken with meals, does not require further phosphorylation for anti-RT activity. |
| What is a side effect of LONG TERM Zidovudine use? | Muscle wasting (myopathy) |
| Which drugs interfere with Zidovudine hepatic gluconuridation? | Acetaminophen Aspirin (and "aspirin like drugs") TMP/SMZ |
| Which cocktail has achieved "undetectable" levels of HIV? | Indinavir (PI) + Lamivudine (NRTI). Also Indinavir + Lamivudine + Zidovudine has done the same. |
| Why might someone on HIV Therapy look cachexic, but not actually be cachexic? | Many HIV drugs can cause Lipodystrophy, moving fat from the face and extremities to the belly, making them look cachexic. |
| How can you reduce the nephrotoxicity of Cidofovir? | Pre-hydrate patient with normal saline, and treat with Probenecid (reduces tubular secretion of Cidofovir). |
| What is the recommended use for Zidovudine? | HIV-1, and ONLY IN COMBINATION with another Reverse Transcriptase inhibitor or a PI. |
| What are general adverse effects of HIV therapy? | -Lactic acidosis -> hepatic steatosis -Lipodystrophy -> elevated blood lipids, insulin resistance, buffalo hump -Peripheral neuropathy (treat with gapapentin) |
| How does Zidovudine affect transplacental HIV transmission during pregnancy? | Give it to mother during pregnancy, and to baby during first 6 weeks of life: Reduces transmission from 30% to 8%. |
| Which HIV drug can cause Nephrolithiasis? | Indinavir |
| What HIV drug (there are many, but only one on need to know) is associated with Peripheral Neuropathy (neuropathic pain)? What is used to treat this type of pain? How effective is it? | Indinavir (Protease Inhibitor) Treat with Gabapentin. Only mildly effective. |
| What is the mechanism of action of Acyclovir? What parts of the mechanism makes its action specific Herpesvirus? | prodrug needs to be phosphorylated to be active. The triphosphate analog of Acyclovir selectively inhibits HSV DNA Polymerase (competitively). It can only be activated by HSV! It is triphosphorylated by HSV-specific Thymidine Kinase. |
| Besides treating resistant CMV/HSV infections, what else is Foscarnet sodium approved for? | CMV Retinitis |
| What HIV drug is approved for chronic treatment of Hepatitis B? | Lamivudine |
| What drugs are used to treat Herpesvirus infections? What is the prototype drug? | Acyclovir (Prototype) Ganciclovir Cidofovir Foscarnet sodium |
| Which HIV drug is associated with Fanconi Syndrome? | Tenofovir |
| What are untoward effects of Indinavir? | Nephrolithiasis (precipitates in renal collecting system --> blockage --> renal colic): Can be avoided with proper hydration. GE Reflux Mild-moderate bilirubin elevation. |
| How does Ganciclovir differ from Acyclovir in its mechanism? How does this affect resistance? | Ganciclovir is more susceptible to phosphorylation by host cell enzymes, and therefore not as dependent on HSV Thymidine Kinase to be activated. This makes it less susceptible to resistance. |
| What are some major differences between Antivirals and Antibacterials, in general? | Antivirals are usually: - Less efficacious - More toxic - Only suppressive (They do not eradicate) |
| How do you treat the anemia caused by Zidovudine? | Transfusions or EPO |
| What drug reduces renal clearance of Acyclovir? What drug's clearance rate is reduced by Acyclovir? | Probenecid reduces Acyclovir clearance (remember, it also reduces Penicillin clearance) Acyclovir reduces renal clearance of Methotrexate (competes for binding in tubules) |
| What subclasses of Herpesvirus is Acyclovir most active against? | HSV-1 HSV-2 |
| What are untoward effects of Ritonavir? | Mild-moderate GI distress Headaches, fatigue, taste-disturbances Circumoral Paresthesia Elevated Liver Transaminases, CK, Triglycerides They are dose-dependent |
| What are the drugs used for Hepatitis B virus? | Lamivudine (Also used for HIV) Telbivudine |
| What is the resistance to Telbivudine like? | 21% of patients had rebound in HBV DNA levels after 2yrs. High level of cross resistence between Telbivudine and Lamivudine (not good, seeing as they are the two main drugs for Hep. B. Adefovir/Entecavir is too new to know.) |
| What are adverse effects of Cidofovir? | 25% have to withdraw drug due to one of the following: Nephrotoxicity Ocular Hypotony Neutropenia Metabolic Acidosis |
| Why must patients be monitored hematologically when taking Zidovudine? | 50% of patients get Granulocytopenia and Anemia. |
| What are two serious adverse effects are caused by Ganciclovir? | Bone marrow suppression --> Neutropenia & Thrombocytopenia (up to 33% of patients) CNS toxicity: Headache, psychosis, seizures, coma (5-15% of patients). |
| Why are Zidovudine and Lamivudine such a good combination for cocktail? | The combination can actually reverse the resistance to Zidovudine. They also synergize their anti-HIV effects --> Decreased HIV load. |
| What is Ganciclovir used to treat? What types of patients do you use it in? | It is only approved to treat CMV. Usually AIDS or transplant patients (transplant patients sometimes use Ganciclovir prophylactically). |
| What is the mechanism of Telbivudine? | HBV Polymerase Inhibitor |
| Besides Indinavir, what other drugs from the pharm course can cause Peripheral Neuropathy? | Metronidazole Dapsone Isoniazid Ethambutol Vincristine |
| Which drug decreases renal excretion of Zidovudine? | Probenecid |
| Which antiviral causes hypocalcemia? | Foscarnet |
| What is a very specific nephrotoxicity that is related to Tenofovir? | Fanconi's Syndrome (Proximal Tubule impairment --> Lack of absorption of Glucose, AA's, Uric Acid, Phosphate, Bicarbonate). Fanconi's Syndrome can lead to Renal Tubular Acidosis (due to lack of bicarbonate reabsorption) |
| What is the most common combination of drug classes in an HIV "cocktail"? | At least one Protease Inhibitor and two Reverse Transcriptase Inhibitors. |
| Which classes of virus can be targeted by antiviral therapy? | HIV Herpesviruses Influenza viruses |
| Which HIV drug is specifically notorious for causing Lactic Acidosis? What other condition can this lead to? What are general symptoms of Lactic Acidosis? | Zidovudine. Lactic acidosis --> Hepatic Steatosis --> Hepatomegaly. Symptoms: Severe nausea, vomiting, peresistent abdominal pain, dyspnea (Kussmaul respirations). |
| Besides HIV, what other infection is Lamivudine approved for? | Chronic Hepatitis B |
| How does Indinavir affect P450? How does this affect therapy recommendations? | It is metabolized by P450, AND it induces its metabolism (not as badly as Ritonavir). No drugs are absolutely CI, but many should be avoided. |
| What is the mechanism of Foscarnet sodium? | Inhibits viral DNA polymerases and Reverse Transcriptases by interacting with pyrophosphate binding sites. |
| If Acyclovir is given at high levels by IV, what is a possible dangerous side effect? | Encephalopathy (1% risk) Would see: - Lethargy - Confusion - Delirium - Seizures - Coma |
| What are positives to using Enfuviritide? Negatives? | Positives: Increases efficacy of any active antiretroviral regimen. Negatives: Twice daily SC injections, expensive, 98% local reaction, limited supply. |
| What drug specifically interferes with Indinavir metabolism? | Ketoconazole |
| How does alpha-interferon interact with Zidovudine? | It enhances HIV activity, and also dramatically increases risk of Neutropenia and Hepatotoxicity. |
| What is the mechanism for Protease Inhibitors? | They block processing of Viral proteins. |
| What are adverse effects of Foscarnet Sodium? What are some compounds to avoid co-administration with Foscarnet? | Nephrotoxicity, Hypocalcemia, Anemia, CNS toxicity. Avoid other nephrotoxic compounds (Amphotericin-B, Aminoglycosides, Pentamidine). Pentamidine & Foscarnet are notorious for --> Hypocalcemia. |
| What HIV drug is incompatible with Lamivudine as a cocktail? Why? | Emtricitabine, because there is no synergism and complete cross-resistance. |
| How is Acyclovir used in prophylactic treatment? | In HSV-seropositive individuals who are being immunosuppressed, Acyclovir can help prevent mucocutaneous infection. |
| What is the exact mechanism of Zidovudine? | Zidovudine triphosphate binds to reverse transcriptase and inhibits enzyme competitively (100:1 to normal substrate), and is incorporated into the growing DNA poly chain --> Terminates growth. |
| Why might Indinavir have problems with drug compliance? | It must be taken every 8 hours (not just 3 times a day), and be taken during a fasting state. That is not always easy to do. |
| If Ritonavir has so many side effects/drug interactions, why use it? | Despite all of that, it markedly slows progression of HIV, and most importantly REDUCES MORTALITY. |
| How is Acyclovir administered? How is Ganciclovir administered? | Acyclovir: IV, oral, or topical Ganciclovir: Only IV (although there is an oral version, Valganciclovir) *Valganciclovir is not on need to know list. |
| Bone marrow toxicity is enhanced when taking ______ with Zidovudine. | Amphotericin B |
| How is Acyclovir used to treat CMV? | Only prophylactically for immunosuppressed individuals. It does NOT affect active CMV infections! |
| Does Acyclovir cure Genital Herpes (HSV-2)? | No. It only suppresses it (and usually only the initial episode). |
| What is the HIV Fusion Inhibitor drug? | Enfuviritide |
| Why are HIV drugs always given in "cocktails"? | Monotherapy has shown very rapid resistance to any single agent. |
| What is the mechanism of Cidofovir? How does its difference from Acyclovir/Ganciclovir changes its resistance? | Its mechanism is similar to Acyclovir, and needs to be phosphorylated into active form. However, it is phosphorylated strictly by CELLULAR, and NOT VIRAL enzymes. This makes it much less susceptible to viral resistance. |
| What is the mechanism for Non-nucleoside Reverse Transcriptase Inhibitors? | Unlike NRTIs, NNRTIs are NOT pro-drugs. They inhibit Reverse Transcriptase directly. |
| How is Foscarnet sodium administered? | IV (in large volumes due to poor aqueous solubility) |
| What is the therapeutic use for Oseltamivir? How effective is it? | Acute, uncomplicated influenza viruses (reduces duration of illness). Also works prophylactically. Works in about 2/3 of patients. |
| What are the need to know HIV drugs? | Zidovudine Lamivudine Emtricitabine Abacavir Tenofovir Efavirenz Ritonavir Indinavir Enfuviritide |
| What is the main dose-limiting toxicity of Acyclovir? | Renal insufficiency. |
| What is the mechanism of Enfuviritide? | It is a Fusion Inhibitor. It blocks conformation change to viral coat protein necessary for viral entry into the host cell. |
| How does resistance occur to RT and Protease inhibitors? | Mutation of Viral RT and Protease genes. |
| What class of drug is Ritonavir? | Protease Inhibitor |
| What is the mechanism of Oseltamivir? | It inhibits Neuraminidase (Neuraminidase is on surface of virus, and allows injection of viral material into cell) |
Created by:
sam.mrosenfeld
Popular Pharmacology sets