Antivirals

Question 1

Oral Viral Infections

Answer 1

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)

Question 2

Nucleoside Reverse Transcriptase Inhibitors (NRTI) - Agents to Treat AIDS

Answer 2

Zidovudine (Azidothymine, AZT) (Retrovir), Didanosine (Videx), Zalcitabine (Hivid), Stavudine (Zerit), Lamivudine (Epivir), Abacavir (Zaigen)

Question 3

DNA (dsDNA) Viruses

Answer 3

Poxvirus (smallpox), Herpes (chickenpox, herpes, shingles, CMV), Adeno (sore throat, conjunctivitis, Papilloma (warts), Hep B (dsDNA reverse transcriptase)

Question 4

RNA Viruses

Answer 4

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

Question 5

Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Adverse Effects

Answer 5

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

Question 6

Zidovudine

Answer 6

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

Question 7

Zidovudine Mechanism of Action

Answer 7

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

Question 8

Zidovudine Indication

Answer 8

Asymptomatic and symptomatic HIV infections

Question 9

Zidovudine Pharmacokinetics

Answer 9

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

Question 10

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Answer 10

Agents Used To Treat AIDS

Nevirapine (Viramune), Delavirdine (Rescriptor), Efavirenz (Sustiva)

Question 11

NNRTI Mechanism of Action

Answer 11

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

Question 12

NNRTI Indications

Answer 12

HIV infections, Used in combination with NRTI agents or protease inhibitors; Resistance develops rapidly if used alone or with only one other agent

Question 13

NNRTI Pharmacokinetics

Answer 13

Oral, Metabolized in liver (CYP450), Efavirenz has long elimination half-life of 2d - So once a day admin

Question 14

NNRTI Adverse Effects

Answer 14

Rash and various CNS disturbance particularly with efavirenz

Question 15

HIV Protease Inhibitors

Answer 15

Used to treat AIDS
Agents Saquinavir (Invirase), Ritonavir (Norvir), Indinavir (Crixivan), Nelfinavir (Viracept), Amprenavir (Agenerase)

Question 16

HIV Protease Inhibitor Mechanism of Action

Answer 16

Inhibit HIV protease essential for final step of new virus formation, Active against viral strains resistant to HIV reverse transcriptase inhibitors

Question 17

HIV Protease Inhibitor Indication

Answer 17

Used in combination with zidovudine and/other HIV reverse transcriptase 1 inhibitors to avoid resistance, Ritonavir used with saquinavir to increase retention of latter

Question 18

HIV Protease Inhibitor Pharmacokinetics

Answer 18

Oral, Metabolized in liver

Question 19

HIV Protease Inhibitor Adverse Effects

Answer 19

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

Question 20

Herpes Antivirals

Answer 20

Acyclovir (Zovirak), Valacyclovir (Valtrex), Penciclovir (Vectavir), Famciclovir (Prosurx), Ganciclovir (GanGuard)

Question 21

Herpes Antivirals Mechanism of Action

Answer 21

Converted to triphosphate w/ viral-specific thymidine kinase, Triphosphate selectivity inhibits virus DNA polymerase and thus inhibits viral DNA replication

Question 22

Herpes Antivirals Indications

Answer 22

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

Question 23

Herpes Antivirals Pharmacokinetics

Answer 23

Orally, Topically or IV, Well distributed and Excreted largely unchanged

Question 24

Herpes Antivirals Adverse Effects

Answer 24

Nausea, Vomiting, Diarrhea, Headache and Hallucinations with high dose, Leukopenia and Thrombocytopenia with Ganciclovir, Headache and Arthralgia

Question 25

Herpes Antivirals Mechanism of Resistance

Answer 25

Mutation in viral thymidine kinase

Question 26

Herpes Antivirals Avoidance

Answer 26

Acyclovir with Amphotericin B, TMP-SMX (Bactrim), Aspirin NSAID, Probenecid, Zidovudine (AZT/Retrovir), Tacrolimus (Prograf)

Question 27

Valacyclovir

Answer 27

Herpes Antiviral Acyclovir chemically bound to Valine moiety, Prodrug form of acyclovir w/greater oral bioavailability, Rapidly converted to Acyclovir after oral administration

Question 28

Valacyclovir Drug Interactions

Answer 28

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)

Question 29

Herpes Antivirals Prescription

Answer 29

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

Question 30

Foscarnet Mechanism of Action

Answer 30

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

Question 31

Foscarnet Indication

Answer 31

CMV retinitis and acyclovir-resistant mucocutaneous HSV infections in patients with AIDS

Question 32

Foscarnet Pharmacokinetics

Answer 32

IV, limited entry into CNS, may accumulate in bone, largely excreted unchanged in urine, Triphasic elimination, Longest t1/2 50hr

Question 33

Foscarnet Adverse Effects

Answer 33

Renal impairment, Headache and Seizures

Question 34

Trifluridine

Answer 34

Viroptic; Ophthalmic; Herpes Antivirals | Inhibit DNA synthesis by incorporation into viral DNA, Used to treat herpes simplex keratitis topically

Question 35

Fomivirisen

Answer 35

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

Question 36

Agents Used to Treat Viral Respiratory Infections (Influenza)

Answer 36

Amantadine | Rimantadine (Less toxic)

Question 37

Viral Respiratory Infection Mechanism of Action Amantadine Rimantadine (Less toxic)

Answer 37

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

Question 38

Viral Respiratory Infection Pharmacokinetics Amantadine Rimantadine (Less toxic)

Answer 38

Readily absorbed from GI tract, well distributed and excreted in urine

Question 39

Viral Respiratory Infection Adverse Effects Amantadine Rimantadine (Less toxic)

Answer 39

Occasional mild CNS disturbances (Nervousness, Anxiety, Agitation, Insomnia, Difficulty concentrating, Lightheadedness), Exacerbations of pre-existing seizure disorders psychiatric symptoms in PD or schizophrenia

Question 40

Viral Respiratory Infection Indication Amantadine Rimantadine (Less toxic)

Answer 40

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)

Question 41

Agents Used to Treat Viral Respiratory Infections

Answer 41

Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral

Question 42

Viral Respiratory Infections Mechanism of Action | Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral

Answer 42

Neuraminidase inhibitor, Decrease release of virus from infected cells by inhibiting breakage of bond between virus particles and host cells

Question 43

Viral Respiratory Infections Indications | Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral

Answer 43

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

Question 44

Viral Respiratory Infections Pharmacokinetics | Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral

Answer 44

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

Question 45

Viral Respiratory Infections Adverse Effects | Zanamivir (Relenza) - Powder, Oseltamivir (Tamiflu) - Oral

Answer 45

Bronchospasm, Rash, Conjunctivitis, Headache, GI Upset; Uncommon - Oral/Nasal discomfort, Bronchospasm, Delirium, Hallucinations, Other behavior

Question 46

Agents to Treat Viral Respiratory Infections

Answer 46

Ribavirin (Virazole)

Question 47

Viral Respiratory Infections Mechanism of Action | Ribavirin

Answer 47

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

Question 48

Treatment for Viral Hepatitis

Answer 48

Interferon (HBV, HCV), Lamivudine (HBV), Tenofovir (HBV), Ribavirin (HCV), Stat-C (HCV) - HCV Protease inhibitors, HCV RNA Poly inhibitors, Combinations for Hep C