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51 Cards in this Set
- Front
- Back
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Steps in Viral Infection and Replication
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1. Attachment and penetration
2. Uncoating Transcription of viral genome Translation of viral proteins Posttranslational modifications Assembly of virion components Release |
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Drugs Used For Herpes and Cytomegalovirus Infections
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Acyclovir
Cidofovir Fomivirsen Foscarnet Ganciclovir Valacyclovir Valganciclovir |
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HSV
Five step life cycle |
Primary mucocutaneous infection
Infection of the ganglia Establishment of latency Reactivation Recurrent infection |
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HSV
first line drugs |
Acyclovir, **Valacyclovir***(valtrex), Famciclovir
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Cytomegalovirus (CMV)
manifestations first line drugs |
Most common life-threatening viral infection in AIDS patients
Almost 45% of AIDS patients have end-organ infection Numerous manifestations of infection Retinitis, esophagitis, hepatitis, gastrointestinal involvement, pneumonitis First line treatment drugs(these are stronger drugs than for HSV) Ganciclovir, foscarnet, cidofovir |
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Acyclovir
Valacyclovir moA |
(Zovirax)(Valtrex)
Lethal synthesis required (has to be activated by host or vir to kill) Presence of viral****** nucleoside kinase to convert to monophosphate form Presence of host****** enzymes to convert monophosphate to triphosphate form Presence of virus-induced DNA polymerase that is sensitive to inhibition by triphosphate form or can incorporate the triphosphate form into the new viral DNA where it ****terminates synthesis****** (both host AND VIRAL MODIFIDE TO inhibit viral DNA synthesis) |
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Valacyclovir
indications p-kin blah |
and Acyclovir
Indications Herpes infections Pharmacokinetics Orally active – absorption can be slow and variable Elimination is by renal (filtration and secretion)(KEEP HYDRATED TO AVOID CRYSTALS) |
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Valacyclovir
adv RXs |
and Acyclovir
"well tolerated" Headache********(bigtime), nausea and vomiting -Reversible ***renal dysfunction Crystallization****** of drug in renal tubules and collecting duct -Neurological and renal toxicity with HIGH dose or intravenous infusion *****Thrombocytopenic purpura-hemolytic uremic syndrome Potentially fatal Most frequent in immunocompromised patients****WATCH IT (bruising etc.) Phlebitis and inflammation at site of infusion |
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Cidofovir
moA |
(Vistide)
Lethal synthesis to activated cidofovir diphosphate requires *****only host enzymes******* (=not as selective?) Cidofovir diphosphate incorporated into DNA slows or stops DNA polymerase*** activity Cidofovir diphosphate levels in infected and non-infected cells are similar** |
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Cidofovir
adv RXs |
****Nephrotoxicity (Black Box Warning)
Probenecid given concurrently slows uptake into proximal tubule cells reducing toxicity Anterior uveitis and neutropenia |
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Cidofovir
BBW |
Nephrotoxicity (Black Box Warning)
Probenecid given concurrently slows uptake into proximal tubule cells reducing toxicity |
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Cidofovir
indications |
*Herpes viruses
***Cytomegalovirus (pneumonia, gastroenteritis, etc.) Varicella zoster virus (chickenpox and shingles) Epstein-Barr virus (infectious mononucleosis) |
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Fomivirsen
moA |
(Vitravene)-into VITREOUS humor
Antisense to mRNA of cytomegalovirus Prevents translation** to protein and blocks viral replication** Unique mechanism of action suggests low cross-resistance to other antivirals |
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Fomivirsen
p-kin blah adv RXs |
Injected directly into vitreous humor of the eye
Degraded locally by cellular exonucleases Adverse effects (way to nephrotoxic for systemic) -Iritis Treat with topical corticosteroids Vitreitis and increased intraocular pressure Ocular inflammation when given concurrent or within two weeks of cidofovir Minimal systemic absorption |
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Foscarnet
moA |
(Foscavir)
Competitive inhibitor of viral DNA polymerase *****No lethal synthesis required***** Inhibitor of reverse transcriptase Concentration in bone prolongs slow phase of elimination |
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Foscarnet
adv rx |
Renal toxicity
Avoid concurrent use with other nephrotoxic drugs Electrolyte disturbances in acute overdosage(seen as HTN) ****Central nervous system disturbances Bone marrow depression Black Box warning Appropriate use only Renal toxicity Seizures |
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Foscarnet
BBW |
Black Box warning
Appropriate use only Renal toxicity Seizures (MONITOR bp here an early sign of acute renal failure) |
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Ganciclovir
Valganciclovir moA indications |
(Cytovene)(Valcyte)
valgang to gang in body Like acyclovir in structure, function and activation (inhibits v. DNA synth---needs lethal syn-virus only) Indicated for cytomegalovirus infections |
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Valganciclovir
adv Rxs |
Ganciclovir also
Adverse effects Acyclovir-like adverse reactions PLUS Bone marrow suppression ****Teratogenic, mutagenic and oncogenic**** potential Black Box Warning |
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Ganciclovir
Valganciclovir Black Box Warning |
Black Box Warning
Hematological toxicities(assume the TTP ass. w/acycl or BM suppress) Carcinogenic and teratogenic activity Aspermatogenesis Appropriate Oral and IV use only (ganciclovir only) |
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Treatment of Respiratory Virus Infections
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Amantadine (Symmetrel)
Rimantadine (Flumadine) Zanamivir (Relenza) Oseltamivir (Tamiflu) |
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Amantadine
Rimantadine moA |
(Symmetrel)(Flumadine)
Inhibitors of viral uncoating************* Blocks viral matrix protein M2, an ion channel, required for fusion** with cell membrane Also interferes with release** of new viral particles (early steps equals good prevention) |
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Amantadine
indications CDC warning |
Rimantadine also
Influenza A and C (mostly prevention in like nursing homes) Widespread resistance noted in the 2005-2006 flu season resulted in the recommendation that these drugs be avoided as possible during the current flu season from 10--90% R in one year |
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Amantadine
Rimantadine adv RXs |
Amphetamine-like actions
Confusion, psychosis, insomnia Avoid use in children under 15 or patients with renal or hepatic disease, epilepsy or psychosis, or during pregnancy (v-constriction) |
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Zanamivir
Oseltamivir moA indications |
(Relenza-inhaled)(Tamiflu)
Treatment of influenza A and B Started early, reduces severity and duration of influenza Potential benefit in prevention of influenza Inhibits influenza A and B virus neuraminidase (inhibits RELEASE)last step(7) Neuraminidase allow the virus to break free from the host cell to infect other cells |
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Zanamivir
adv RX |
the release inhibitor
Administered by inhalation or by nasal spray Adverse effects None distinguished from the symptoms of influenza |
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Oseltamivir
adv RX |
tamiflu
Orally active prodrug Activated by esterases in gastrointestinal tract or liver Well-tolerated? Common side effect of gastrointestinal upset Low incidence of self-injury, hallucinations and delirium reported, especially in children Under consideration for Black Box Warning by FDA |
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Oseltamivir
BBW |
tamiflu
not yet but Low incidence of self-injury, hallucinations and delirium reported, especially in children Under consideration for Black Box Warning by FDA |
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nasal zinc
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loss of sense of smell (don't use)
zinc not proven as CAM in cold influ |
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Respiratory Syncytial Virus (RSV)
causes |
Most common cause of bronchiolitis
Diagnosis is based largely on progression of symptoms Prodrome of irritability, restlessness and mild fever Cough, vomiting, diarrhea, noisy breathing and increase in respiratory rate Labored breathing with retraction of chest wall, nasal flaring and grunting Tachycardia, high respiratory rate, inspiratory rales |
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Ribavirin
moa |
(Virazole, Copegus)(route specific SEs)
Converted to monophosphate, diphosphate and triphosphate forms Monophosphate form inhibits guanosine triphosphate synthesis Triphosphate inhibits viral mRNA processing and influenza virus RNA polymerase ******Increases RNA virus mutation rate***** |
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Ribavirin
indications |
-**RSV (respiratory syncytial virus) infections of the respiratory tract using aerosol form (Virazole)
-Hepatitis C (with interferon) Hemorrhagic fevers associated with virus infections(one of the only that treats this) |
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Ribavirin-PO or IV
adverse CIs |
Hemolytic anemia – dose dependent
Increased risk when used with interferon-α Mutagenic, teratogenic and embryotoxic ***Contraindicated in pregnant women and male partners**** of pregnant women Contraindicated in patients with *****sickle cell anemia**** High risk of anemia |
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Ribavirin Aerosol
adverse |
May cause respirator malfunction as ribavirin binds and crystallized in respirator
-Systemic levels are normally low Respiratory and sometimes cardiovascular function decline with aerosol form especially in severely ill patients *********Health care workers exposed to ribavirin aerosol report headache, rash and bronchospasm |
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Ribavirin
BBW |
Not recommended for monotherapy (REsistance?)
Hemolytic anemia Teratogenic and embryocidal Use contraindicated in pregnant women, women who might be pregnant, and their male partners (in sperm) Two forms birth control recommended for up to six months following treatment |
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Treatment of Hepatic Viral Infections
agents |
Adefovir
Entecavir Interferon Lamivudine (similar to HIV drugs but AT LOWER DOSE) |
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Adefovir
moA indications |
(Hepsera)
Mechanism of Action Nucleotide adefovir incorporates into hepatitis B viral DNA, *****inhibit reverse transcriptase****** and resulting in DNA chain termination -May stimulate interferon-alpha production Indications Chronic hepatitis B |
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Adefovir
adverse -common |
Elevated creatine
Flatulence Asthenia Headache ******Exacerbation of hepatitis B following cessation of drug treatment Pregnancy Category C, safety during breastfeeding unknown (others and HBV on BBW) |
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Adefovir
BBW |
Black Box Warnings
Hepatitis B exacerbation following drug stoppage Lactic acidosis (COMMON)and severe hepatomegaly HIV resistance (DOSE PROB) Nephrotoxicity -note OBESE patients with worse-hep/ren failure |
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Adefovir
CIs |
(Hepsera)
****Impaired renal function Nephrotoxic drugs (AGs etc) Hepatoxicity drugs HIV, untreated (REs) Obesity (worse hep/ren) Hepatic transplant, and HEP tox drugs |
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Entecavir
moA indicat. |
(Baraclude)
Nucleoside entecavir converted to active triphosphate form that incorporates into hepatitis B viral DNA, *******inhibit reverse transcriptase*********** and resulting in DNA chain termination Indication Chronic hepatitis B |
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Entecavir
p-kin considerations |
(Baraclude)
Food interferes with absorption Long half-life (about 130 hours******) with slow renal excretion (filtration and secretion) |
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Entecavir
ADV RXs |
(Baraclude)
Quite similar to adefovir (hbv exac,L.ACID,hepmeg,hiv nono (ACTUALLY NOT REALLY USED FOR HIV, not much nephro) |
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Entecavir
BBW |
Black Box Warnings
Lactic acidosis and severe hepatomegaly Hepatitis B exacerbation upon cessation of therapy |
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Interferon-alfa
moA indications |
Mechanism of action
Interferes with most steps of the viral process Induction of ***host cell enzymes***** that inhibit viral RNA translation***** seems critical for action Indications Hepatitis B and C Kaposi’s sarcoma in HIV Multiple sclerosis |
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Interferon-alfa
adv. RXs |
Flu-like symptoms
High dose or chronic therapy Bone marrow suppression Psychiatric symptoms Cardiotoxicity** Black Box Warning Fatal – life threatening events |
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Interferon-alfa
BBW |
Black Box Warning
Fatal – life threatening events (when used chronically--) |
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Lamivudine
moA indications |
(Epivir HBV)=dose for HBV
Mechanism of action Lamivudine is phosphorylated to active triphosphate form that ****************inhibits both Hepatitis B and HIV reverse transcriptase*********** Negligible effects on host DNA polymerase Indications Chronic hepatitis B (Epivir HBV) |
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Lamivudine
adv RX COMMON |
(Epivir HBV)
Adverse effects – common Headache Nausea, vomiting and diarrhea Fatigue Neuropathy (more high dose scene) Musculoskeletal pain |
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Lamivudine
adv RX SERIOUS |
Adverse effects – Serious=at high dose
Fat redistribution Hepatic problems *****Lactic acidosis ****Hepatomegaly Hepatoxicity Pancreatitis Muscle wasting Anemia *****Hepatitis B exacerbation following cessation of therapy (taper) again HIV warning (see BBW) |
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Lamivudine
BBW |
(Epivir HBV)
Black box warning Lactic acidosis and severe hepatomegaly HIV testing (Hepatitis B dose is lower than HIV dosage) Hepatitis B exacerbation |
