Term
| If we have a drug that we know attacks early in the viruses life cycle, what does that mean for its administration? |
|
Definition
| We must administer the drug early in the infection |
|
|
Term
| How do drugs that inhibit viral nucleic acid synthesis work? |
|
Definition
| They act as ANTIMETABOLITES because they are structurally similar to purine and pyrimidine bases |
|
|
Term
| When are acyclovir and ganciclovir first phosphorylated? |
|
Definition
| They are first phosphorylated by viral kinases |
|
|
Term
| When are AZT and other nucleoside analogs phosphorylated? |
|
Definition
| First by host cell kinases |
|
|
Term
| How do drugs that inhibit viral nucleic acid synthesis actually do their job? |
|
Definition
| Phosphorylation converts nucleosides to nucleotide analogs that may inhibit viral DNA polymerases OR act as substrates for viral enzymes- they get INCORPORATED into viral nucleic acids |
|
|
Term
| In order to do their job, Ganciclovir and Acyclovir require what enzyme? Are they selectively toxic? |
|
Definition
They require VIRAL kinases
This makes them VERY selectively toxic |
|
|
Term
| What enzyme phosphorylates acyclovir? |
|
Definition
|
|
Term
| What enzyme phosphorylates ganciclovir? |
|
Definition
|
|
Term
| What is acyclovir used to treat and why is it more selectively toxic? |
|
Definition
Herpes
Acyclovir's initial phosphorylation is by VIRAL TK, which is absent in uninfected cells |
|
|
Term
| What is the spectrum of activity of acyclovir? |
|
Definition
Herpes Simplex
Epstein-Barr
Varicella Zoster |
|
|
Term
| How does resistance to acyclovir develop? |
|
Definition
In HSV or VZV, via alteration in either:
a) Viral Thymidine Kinase (TK)
or
b) Viral Polymerase |
|
|
Term
| What ester of acyclovir is a longer acting agent? How does it work? |
|
Definition
Valacyclovir
Converted to acyclovir when ingested orally- serum levels 3-5 times higher than oral acyclovir |
|
|
Term
| What is valacylcovir used to treat? |
|
Definition
| Recurrent genital herpes or zoster infections |
|
|
Term
| What are the occasional side effects of valacyclovir? |
|
Definition
| Nausea, diarrhea, and headache |
|
|
Term
| What is famciclovir used to treat? |
|
Definition
| Acute herpes zoster and for the suppression of recurrent genital herpes |
|
|
Term
| What drug undergoes first pass metabolism to pencivlovir (PCV) after oral administration? |
|
Definition
|
|
Term
| Where does famciclovir get converted to pencivlovir? |
|
Definition
| Metabolic steps in intestinal wall and liver |
|
|
Term
| What are the symptoms of herpes encephalitis? |
|
Definition
| ANY AGE- acute onset of fever, headache, decreased consciousness, and seizures |
|
|
Term
| Which herpes virus is more common in adults and which is more common in infants? |
|
Definition
Adults- HSV-1
Infants- HSV-2 |
|
|
Term
| What is the most rapid test for HSV encephalitis (only available in some places)? |
|
Definition
|
|
Term
| According to Caldwell, what do we see in a CSF sample of Herpes Encephalitis? |
|
Definition
| WBC's, elevated protein (this contradicts some other courses) |
|
|
Term
What do we give to treat CMV?
WHAT DO WE GIVE TO TREAT CMV? |
|
Definition
|
|
Term
|
Definition
| A guanosine analog to treat CMV |
|
|
Term
| How does ganciclovir work? |
|
Definition
| Acts as an antimetabolite which is phosphorylated first by viral kinase to from a nucleotide that inhibits CMV DNA polymerase |
|
|
Term
| Why is ganciclovir selective? |
|
Definition
| It is phosphorylated FIRST by viral kinase (monophosphorylation) |
|
|
Term
| What drug is used to treat CMV retinitis in AIDS patients? What is it? |
|
Definition
Cidofovir
A cytosine analog |
|
|
Term
| Cidofovir has broad spectrum in vitro activity against what viruses? |
|
Definition
| CMV, HSV 1 and 2, VZV, EBV, HHV-6, adenovirus, and HPV |
|
|
Term
| What drug is given topically for mucocutaneous herpes infections? |
|
Definition
|
|
Term
| How is Cidofovir cleared, and what does this mean? |
|
Definition
Cleared by the kidney
Nephrotoxicity is the major dose-limiting adverse effect with IV use |
|
|
Term
| How can we limit the nephrotoxicity of cidofovir? |
|
Definition
| Give probenacid along with it |
|
|
Term
| What are the potential side effects of IV cidofovir? |
|
Definition
| Nephrotoxicity, neutropenia, and peripheral neuropathy |
|
|
Term
| What drug causes dose dependent proximal tubular cell toxicity (kidney) and what can be done to minimize this? |
|
Definition
| Cidofovir- coadminister with probenacid |
|
|
Term
| How is cidofovir activated? |
|
Definition
| By intracellular enzymes to form an inhibitor of DNA polymerases |
|
|
Term
| What drug is 1000-fold more effective against DNA polymerases of viruses such as herpes than it is against the DNA polymerase of the host cell? |
|
Definition
| Cidofovir- thus it is very selectively toxic |
|
|
Term
| What is foscarnet, and what is it used to treat? |
|
Definition
Inorganic pyrophosphate compound
BROAD SPECTRUM- used to treat HSV, VZV, CMV, EBV, HHV-6, HBV, HIV |
|
|
Term
| What is the mechanism of action of foscarnet? |
|
Definition
| It inhibits viral DNA polymerase, RNA polymerase, or HIV reverse transcriptase directly WITHOUT REQUIRING PHOSPHORYLATION |
|
|
Term
| What broad-spectrum antiviral does NOT require activation by phosphorylation? |
|
Definition
|
|
Term
| What two antivirals are preferentially phosphorylated by viral-encoded enyzmes? |
|
Definition
| Ganciclovir and Acyclovir |
|
|
Term
| What is the role of hemagglutin in influenza infection? |
|
Definition
| It binds virus to sialic acid residues on host cells allowing internalization and fusion |
|
|
Term
| What is the role of neuraminidase in influenza infection? |
|
Definition
| It releases newly synthesized virus by cleaving sialic acid from host cell glycoproteins when budding |
|
|
Term
| What releases newly synthesized influenza virus by cleaving sialic acid? |
|
Definition
|
|
Term
| What binds to sialic acid allowing internalization and fusion of influenza? |
|
Definition
|
|
Term
| What is the mechanism of action of adamantanes? |
|
Definition
| Inhibit uncoating of influenza virus |
|
|
Term
| What drugs inhibit uncoating of influenza virus? |
|
Definition
|
|
Term
| What are the symptoms of CNS toxicity of amantidine and rimantadine? |
|
Definition
Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness
Avoid activities requiring mental alertness |
|
|
Term
| What are the symptoms of GI toxicity of amantadine and rimantadine? |
|
Definition
| Nausea, vomiting, anorexia |
|
|
Term
| What are the symptoms of amantadine or rimantadine overdose? |
|
Definition
| Mental depression, psychosis, seizures |
|
|
Term
| When should amantadine be avoided? |
|
Definition
Untreated angle closure glaucoma
Anticholinergic Effects |
|
|
Term
| What drugs should NEVER be given to patients with untreated angle closure glaucoma? |
|
Definition
|
|
Term
What is the mechanism of action of neuraminidase inhibitors?
Can you name 2 of these drugs? |
|
Definition
Inhibit viral cleavage of sialic acid
Inhibit the release of newly formed virus
Zanamivir and Oseltamivir |
|
|
Term
| What class of drugs inhibits viral cleavage of sialic acid? |
|
Definition
Neuraminidase inhibitors
-Zanamivir and Oseltamivir |
|
|
Term
| What are neuraminidase inhibitors used for? |
|
Definition
| Reduce duration of uncomplicated influenza A and B infection symptoms by 1 day if started within 2 days of onset of symptoms |
|
|
Term
| What drugs can be given to prevent up to 84% of influenza infections? |
|
Definition
|
|
Term
| What drugs are currently available to treat RSV (respiratory syncytial virus)? |
|
Definition
RSV Immune Globulin
Palivizumab
Ribavirin |
|
|
Term
| What is the mechanism of action of RSV IgG? |
|
Definition
| Neutralizing and protective IgG antibodies against RSV |
|
|
Term
| What is the mechanism of action of palivizumab, and what is it used to treat? |
|
Definition
Treats RSV
Binds to fusion protein of RSV
Prevents infection of host cell, reduces replication of RSV and spread to other cells |
|
|
Term
| Describe the dosing, kinetics, and onset of palivizumab: |
|
Definition
Given IM monthly- up to 5x during RSV season, 1st dose just before RSV season
Half life- 13-27 days
Onset: within 48 hours |
|
|
Term
| What is ribavarin used to treat, and what is the mechanism of action? |
|
Definition
Treat RSV
Synthetic nucleoside analog (guanosine)
Inhibits viral nucleic acid synthesis and decreases nucleotide pool |
|
|
Term
| What are the pulmonary toxicities of ribavarin? |
|
Definition
Deaths due to mechanical ventilator dysfunction- caused by precipitation of ribavarin
Worsening of respiratory status |
|
|
Term
| What are the cardiovascular toxicities of ribavarin? |
|
Definition
| Cardiac arrest, hypotension, bradycardia, tachycardia (if heart disease) |
|
|
Term
| What is the hematological effect of ribavarin? |
|
Definition
| Anemia- reversible upon discontinuation |
|
|
Term
| What are the adverse effects of ribavarin on health care personal, and why do they happen? |
|
Definition
Ribavarin disperses in immediate bedside area
Headache, conjunctivitis, rhinitis, nausea, rash, dizziness, lacrimation, pharyngitis |
|
|
Term
| Who should never be around ribavarin? |
|
Definition
| Pregnant women or women planning to get pregnant |
|
|
Term
| What drug is teratogenic and pregnant women should never be exposed to it? |
|
Definition
|
|
Term
| FROM NOTES: Name 3 indications for acyclovir: |
|
Definition
Mucocutaneous herpetic lesions
Genital herpes lesions
Prophylaxis in AIDS and other immunocompromised patients |
|
|
Term
| FROM NOTES: name 2 blood related toxicities of ganciclovir: |
|
Definition
LEUKOPENIA- low leukocytes
THROMBOCYTOPENIA- low platelets |
|
|
Term
| FROM NOTES: what can be monitored to determine duration of action of foscarnet? |
|
Definition
Clearance is directly proportionate to CREATININE CLEARANCE
-daily creatinine and BUN |
|
|
Term
| FROM NOTES: What is the major toxicity of Zanamivir and what population should never receive it? |
|
Definition
BRONCHOSPASM
Never give to patients with COPD or asthma |
|
|
