Antivirals Flashcards
Oral Viral Infections
Coxsackie-Type Viruses (Picorna RNA virus) - Herpangina, Acute Lymphonodular Pharyngitis, Hands Foot and Mouth disease; Herpes type viruses (DNA virus), Human papilloma virus (DNA virus)
Nucleoside Reverse Transcriptase Inhibitors (NRTI) - Agents to Treat AIDS
Zidovudine (Azidothymine, AZT) (Retrovir), Didanosine (Videx), Zalcitabine (Hivid), Stavudine (Zerit), Lamivudine (Epivir), Abacavir (Zaigen)
DNA (dsDNA) Viruses
Poxvirus (smallpox), Herpes (chickenpox, herpes, shingles, CMV), Adeno (sore throat, conjunctivitis, Papilloma (warts), Hep B (dsDNA reverse transcriptase)
RNA Viruses
Orthomyxo - ssRNA (inluenza), Avian flu, Swine flu; Filo -ssRNA ebola, marburg; Retro +ssRNA (AIDS, Measles, Mumps), Flavi - +ssRNA (Arthropod host): West Nile, Zika, Dengue (DENV), Chikungunya, Yellow fever etc; Hep C +ssRNA; Picorna +ssRNA polio, echovirus, coxsackie
Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Adverse Effects
Agents Used to Treat AIDS Zidovudine (Azidothymine, AZT) (Retrovir) - Anemia, N. anorexia, Hepatotoxicity, Lactic acidosis, Myopathy, Peripheral neuropathy; Didanosine (Videx) - Diarrhea, Pancreatitis and Peripheral neuropathy; Zalcitabine (Hivid) - Peripheral neuropathy, Stomatitis, Pancreatitis, Rash; Stavudine (Zerit) - Lactic acidosis and peripheral neuropathy; Lamivudine (Epivir) - Headache and nausea, Pancreatitis rare; Abacavir (Zaigen) - Hypersensitivity rxn, GI, Neuro complaints;
Phosphorylated AZT accumulates in most dividing cells in body bc its activation is non-selective, Cause bone marrow suppression - Manifest as anemia and neutropenia also myopathy, Adverse effects due to inhibition of cellular polymerases by AZT triphosphate and by inhibition of cellular thymidylate kinase by AZT monophosphate
Zidovudine
Azidothymine, AZT - Retrovir
Agent used to treat AIDS - NRTI
Nucleoside analog w/alt sugar moiety similar acyclovir, Contains no 3’hydroxyl so like acyclovir it is a chain terminator, Requires phosphorylation to activate
Zidovudine Mechanism of Action
Activated by phosphorylation by host cell thymidine kinase and then by other kinases to the triphosphate, Acts as substrate for reverse transcriptase and competes with thymidine triphosphate for incorporation into DNA, Since NRTIs lack a 3’hydroxyl group, incorporation into DNA terminates chain elongation
Zidovudine Indication
Asymptomatic and symptomatic HIV infections
Zidovudine Pharmacokinetics
Oral or IV, In combination with other HIV drugs, Well distributed including CNS; Zidovudine and Didanosine are rapidly metabolized and excreted in urine; Large proportion of others excreted unchanged
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Agents Used To Treat AIDS
Nevirapine (Viramune), Delavirdine (Rescriptor), Efavirenz (Sustiva)
NNRTI Mechanism of Action
Inhibit HIV reverse transcriptase directly by binding adjacent to enzyme active site and inducing conformational changes in site, Agents do not require phosphorylation for activity
NNRTI Indications
HIV infections, Used in combination with NRTI agents or protease inhibitors; Resistance develops rapidly if used alone or with only one other agent
NNRTI Pharmacokinetics
Oral, Metabolized in liver (CYP450), Efavirenz has long elimination half-life of 2d - So once a day admin
NNRTI Adverse Effects
Rash and various CNS disturbance particularly with efavirenz
HIV Protease Inhibitors
Used to treat AIDS Agents Saquinavir (Invirase), Ritonavir (Norvir), Indinavir (Crixivan), Nelfinavir (Viracept), Amprenavir (Agenerase)
HIV Protease Inhibitor Mechanism of Action
Inhibit HIV protease essential for final step of new virus formation, Active against viral strains resistant to HIV reverse transcriptase inhibitors
HIV Protease Inhibitor Indication
Used in combination with zidovudine and/other HIV reverse transcriptase 1 inhibitors to avoid resistance, Ritonavir used with saquinavir to increase retention of latter
HIV Protease Inhibitor Pharmacokinetics
Oral, Metabolized in liver
HIV Protease Inhibitor Adverse Effects
Many and frequent; Body fat redistribution (buffalo hump), N, V, D; Hyperglycemia, Hyperlipidemia 15%, Hypercholesterolemia, 50% Paresthesias with ritonavir, Kidney stones with Indinavir (Crystalluria), Fatigue, Peripheral neuropathy
Herpes Antivirals
Acyclovir (Zovirak), Valacyclovir (Valtrex), Penciclovir (Vectavir), Famciclovir (Prosurx), Ganciclovir (GanGuard)
Herpes Antivirals Mechanism of Action
Converted to triphosphate w/ viral-specific thymidine kinase, Triphosphate selectivity inhibits virus DNA polymerase and thus inhibits viral DNA replication
Herpes Antivirals Indications
Useful in treatment of genital herpes simplex, herpes simplex labials (cold sores), herpes zoster (shingles) and varicella zoster (chicken pox), Prophylaxis against herpes viruses in immunocompromised patients, Ganciclovir useful for CMV in immunocompromised patients
Herpes Antivirals Pharmacokinetics
Orally, Topically or IV, Well distributed and Excreted largely unchanged
Herpes Antivirals Adverse Effects
Nausea, Vomiting, Diarrhea, Headache and Hallucinations with high dose, Leukopenia and Thrombocytopenia with Ganciclovir, Headache and Arthralgia
Herpes Antivirals Mechanism of Resistance
Mutation in viral thymidine kinase
Herpes Antivirals Avoidance
Acyclovir with Amphotericin B, TMP-SMX (Bactrim), Aspirin NSAID, Probenecid, Zidovudine (AZT/Retrovir), Tacrolimus (Prograf)
Valacyclovir
Herpes Antiviral
Acyclovir chemically bound to Valine moiety, Prodrug form of acyclovir w/greater oral bioavailability, Rapidly converted to Acyclovir after oral administration
Valacyclovir Drug Interactions
Better bioavailability than acyclovir, Taken less frequent, Some metabolism by alcohol and aldehyde dehydrogenase, Valacyclovir should not be prescribed with SSRI bc SSRI inhibit 2D6 enzyme needed to activate drug; Avoid using Valacyclovir w/ Cimetidine (Tagamet) or Probenecid (Benemid)
Herpes Antivirals Prescription
Acyclovir Intermitten therapy for cold sores lasting less than one week - 200mg, #25, Take one capsule five times a day for a full 5 days; Acyclovir buccal 50mg, 1, Apply buccal tablet to upper gum until sticks and let dissolve
Foscarnet Mechanism of Action
Foscavir; Herpes Antivirals; Selectively inhibits viral DNA-polymerase, RNA polymerase and HIV reverse transcriptase at pyrophosphate binding site without affecting human DNA polymerases, Inhibit replication of all known herpes viruses
Foscarnet Indication
CMV retinitis and acyclovir-resistant mucocutaneous HSV infections in patients with AIDS
Foscarnet Pharmacokinetics
IV, limited entry into CNS, may accumulate in bone, largely excreted unchanged in urine, Triphasic elimination, Longest t1/2 50hr
Foscarnet Adverse Effects
Renal impairment, Headache and Seizures
Trifluridine
Viroptic; Ophthalmic; Herpes Antivirals
Inhibit DNA synthesis by incorporation into viral DNA, Used to treat herpes simplex keratitis topically
Fomivirisen
Oligonucleotide that binds to mRNA (antisense) to inhibit human CMV protein synthesis, Indicated in CMV retinitis in patients with AIDS, Occular inflammation is most common adverse effect
Agents Used to Treat Viral Respiratory Infections (Influenza)
Amantadine
Rimantadine (Less toxic)
Viral Respiratory Infection Mechanism of Action
Amantadine
Rimantadine (Less toxic)
Inhibitor of viral uncoating, Blocks M2 proton channel in viral envelope, inhibiting acidification of virion interior, dissociation of matrix protein and uncoating, Also cause release of dopamine and NE and blocks NMDA receptor
Viral Respiratory Infection Pharmacokinetics
Amantadine
Rimantadine (Less toxic)
Readily absorbed from GI tract, well distributed and excreted in urine
Viral Respiratory Infection Adverse Effects
Amantadine
Rimantadine (Less toxic)
Occasional mild CNS disturbances (Nervousness, Anxiety, Agitation, Insomnia, Difficulty concentrating, Lightheadedness), Exacerbations of pre-existing seizure disorders psychiatric symptoms in PD or schizophrenia
Viral Respiratory Infection Indication
Amantadine
Rimantadine (Less toxic)
Prophylaxis against and possible treatment of Influenza A infection (Not Influenza B), Reduces length and severity of Influenza A infections; Amantadine used to treat Levodopa-induced dyskinesias that develop late in course of disease. Does this by blocking excitatory NMDA receptors, Due to widespread resistance, use is supplanted by Oseltamivir (Tamiflu) and Zanamivir (Relenza)
Agents Used to Treat Viral Respiratory Infections
Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral
Viral Respiratory Infections Mechanism of Action
Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral
Neuraminidase inhibitor, Decrease release of virus from infected cells by inhibiting breakage of bond between virus particles and host cells
Viral Respiratory Infections Indications
Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral
Influenza A & B to decrease intensity and duration of disease, Also complications; Used as aerosol for respiratory syncytial virus (RSV) infection in children, Oral form for hepatitis
Viral Respiratory Infections Pharmacokinetics
Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral
Some absorption into blood when used as an aerosol, Readily absorbed from GI tract, Excreted mainly as deribosylated metabolic product in urine;
Zanamivir - Poor bioavailability and administered by inhalation, Less than 20% absorbed systemically, Mostly excreted in urine;
Oseltamivir - Well absorbed orally and excreted largely unchanged in urine
Viral Respiratory Infections Adverse Effects
Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral
Bronchospasm, Rash, Conjunctivitis, Headache, GI Upset; Uncommon - Oral/Nasal discomfort, Bronchospasm, Delirium, Hallucinations, Other behavior
Agents to Treat Viral Respiratory Infections
Ribavirin (Virazole)
Viral Respiratory Infections Mechanism of Action
Ribavirin
Phosphorylated intracellularly and inhibits viral replication of both RNA and DNA viruses partly by interfering with guanosine triphosphate (GTP)_ formation and subsequent viral mRNA capping, hence viral protein synthesis; Though to increase mutagenesis - Hep C
Treatment for Viral Hepatitis
Interferon (HBV, HCV), Lamivudine (HBV), Tenofovir (HBV), Ribavirin (HCV), Stat-C (HCV) - HCV Protease inhibitors, HCV RNA Poly inhibitors, Combinations for Hep C
