IDT Exam 2

A small infectious agent made of a nucleic acid core plus a protein coat. It can multiply only inside living host cells because it relies on host metabolic machinery.

Either DNA or RNA, but not both. The genome may be single-stranded or double-stranded depending on the virus.

The protective protein coat around the viral genome. It is built from repeating protein units called capsomeres.

The viral nucleic acid genome plus its protective capsid.

A lipoprotein bilayer surrounding some viruses. Enveloped viruses often have surface spikes used for attachment or release.

Icosahedral/cubic, helical, and mixed/combined symmetry.

Genome type, virion morphology, envelope presence, replication strategy, and serologic relationships/serotypes.

Attachment → entry → uncoating → transcription → translationeplication → assembly → release/maturation.

A viral attachment protein, often a spike glycoprotein, binds a specific host-cell receptor.

The capsid is completely or partially removed so the viral genome becomes exposed inside the host cell.

Viruses use host-cell machinery, so fewer virus-specific targets exist. Good antivirals exploit viral enzymes or steps that differ from human processes.

HBV, HCV, and HDV can cause chronic infection. HAV and HEV generally do not cause chronic hepatitis.

Fecal-oral transmission, often through contaminated food or water.

Bloodody-fluid exposure, percutaneous or permucosal exposure, sexual transmission, contaminated needles, and for HBV, mother-to-child transmission at birth.

Influenza is a segmented, single-stranded RNA virus. Influenza A has 8 viral genes.

Influenza A, B, and C.

HA helps attachment and penetration. NA helps release of new influenza virions from host cells.

Minor mutations in HA and/or NA that occur frequently and gradually change influenza antigenicity.

A major change in influenza surface antigens due to genetic reassortment, producing a new subtype with little population immunity. It can cause pandemics.

Influenza A.

High fever, prominent headache, severe body aches, early extreme exhaustion, and cough/chest discomfort that can become severe.

Neuraminidase inhibitors active against influenza A and B.

Within 24–48 hours after symptom onset.

Oseltamivir is an oral prodrug that is hydrolyzed in the liver to the active carboxylic acid.

Peramivir is given IV as a single dose and may be used for severe or hospitalized influenza patients.

Inhaled via a Diskhaler.

They inhibit neuraminidase, reducing release of new virions from infected host cells.

HSV has a double-stranded DNA genome inside an icosahedral nucleocapsid, surrounded by tegument and an envelope with glycoprotein spikes.

HSV-1 is classically oral herpes; HSV-2 is classically genital herpes.

No. They can shorten outbreaks and help prevent outbreaks while the medication is being taken, but they do not eradicate latent HSV.

Acyclovir, valacyclovir, famciclovir, and penciclovir.

A valine ester prodrug of acyclovir with better GI absorption than acyclovir. It is converted to acyclovir in the intestinal wall or liver.

Viral thymidine kinase converts acyclovir to acyclovir monophosphate.

It is a poor substrate for human thymidine kinase but is activated by viral thymidine kinase, so activation is concentrated in virus-infected cells.

Acyclovir triphosphate is incorporated into viral DNA during synthesis and terminates chain elongation, reducing viral DNA synthesis.

A prodrug converted to penciclovir by esterase and aldehyde oxidase.

It is activated to a triphosphate form and inhibits viral DNA polymerase.

Ganciclovir IV and valganciclovir oral prodrug.

Ganciclovir triphosphate inhibits viral DNA polymerase. CMV-infected cells phosphorylate it efficiently using a virally encoded kinase.

CMV retinitis in immunocompromised patients.

A partially double-stranded and partially single-stranded DNA genome within an enveloped virion.

Hepatitis B surface antigen, a glycoprotein envelope antigen produced in excess and found in blood during infection.

Entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, lamivudine, and adefovir.

A guanosine nucleoside analog that is phosphorylated to an active triphosphate form.

Post-treatment severe acute exacerbation of hepatitis B, lactic acidosis, and severe hepatomegaly with steatosis.

It is an acyclic phosphonate analog of AMP that inhibits reverse transcriptase and terminates viral DNA after incorporation.

It delivers tenofovir more efficiently to the liver, allowing lower doses and improved bone and kidney safety compared with older tenofovir formulations.

A positive-sense enveloped RNA flavivirus that can cause chronic hepatitis, cirrhosis, and hepatic failure.

NS3/4A protease, NS5B polymerase, and NS5A phosphoprotein.

Glecaprevir is an NS3/4A protease inhibitor.

Pibrentasvir is an NS5A phosphoprotein inhibitor.

Ledipasvir is an NS5A inhibitor.

Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor.

Velpatasvir is an NS5A inhibitor.

Fatigue, headache, nausea, and possible hepatitis B reactivation.

In oral combinations for about 8–24 weeks, with very high cure rates in modern regimens.

A complex enveloped RNA virus with two copies of single-stranded RNA and viral proteins including reverse transcriptase, protease, and integrase.

gp120 and gp41.

The core or capsid antigen that forms the cone-shaped nucleocapsid.

CD4 on T helper cells.

CCR5 and CXCR4.

Primary infection, clinically asymptomatic stage, symptomatic HIV infection, and progression from HIV to AIDS.

NRTIs, NNRTIs, integrase inhibitors, protease inhibitors, fusion inhibitors, CCR5 antagonists, attachment inhibitors, post-attachment inhibitors, and capsid inhibitors.

They are nucleoside or nucleotide-like agents converted to triphosphates and incorporated by HIV reverse transcriptase into proviral DNA, causing chain termination.

Zidovudine, lamivudine, emtricitabine, abacavir, and tenofovir.

Bone marrow toxicity, including macrocytic anemia, neutropenia, and granulocytopenia; also lactic acidosis and hepatomegaly with steatosis.

It is sensitive to heat and light because of its azide group, so it should be stored in a colored bottle at 15–25°C.

Peripheral neuropathy, lactic acidosis with severe hepatomegaly and steatosis, and post-treatment exacerbation of hepatitis B.

It is similar to lamivudine but requires only once-daily dosing.

Risk of hypersensitivity reactions; also lactic acidosis, severe hepatomegaly, blood disorders, and post-treatment HBV exacerbation.

They block HIV protease, preventing cleavage of gag-pol polyproteins into mature structural proteins, so immature noninfectious virions are produced.

Ritonavir, atazanavir, tipranavir, darunavir, and fosamprenavir.

It is used mainly as a pharmacokinetic booster by inhibiting CYP3A4 and increasing plasma concentrations of the companion protease inhibitor.

High drug-interaction potential, including large increases in fluticasone exposure and interaction with trazodone; kava may increase hepatotoxicity risk.

Jaundice and hyperbilirubinemia.

Treatment-experienced patients with viral replication and resistance to multiple protease inhibitors, often with ritonavir.

It is highly effective and has a high genetic barrier to resistance; it is boosted with ritonavir or cobicistat.

Jaundice, severe rash including Stevens-Johnson syndrome, allergic reactions, and hyperglycemia.

High CYP3A4 interaction potential, dyslipidemia, jaundice, and hyperglycemia.

Penicillins, cephalosporins, monobactams, carbapenems, and beta-lactamase inhibitors all contain beta-lactam-related chemistry.

They inhibit bacterial cell-wall biosynthesis.

The transpeptidation or crosslinking step of peptidoglycan synthesis.

Penicillin-binding proteins, including transpeptidases that form peptidoglycan crosslinks.

The D-Ala-D-Ala end of the peptidoglycan pentapeptide substrate.

The active-site serine of the PBP attacks the beta-lactam, forming a stable acyl-enzyme complex that hydrolyzes slowly.

They prevent peptidoglycan crosslinking, weakening the cell wall so bacteria can lyse under osmotic pressure.

Alternating N-acetylglucosamine and N-acetylmuramic acid strands with pentapeptide side chains.

Crosslinks between pentapeptide side chains make the polymer rigid and insoluble.

Acquisition of beta-lactamase enzymes that hydrolyze the beta-lactam ring.

Serine beta-lactamases and metallo-beta-lactamases.

Classes A, C, and D.

Class B.

Both form acyl-enzyme intermediates, but beta-lactamases hydrolyze the intermediate rapidly, destroying the drug instead of staying inhibited.

They are secreted or located along the exterior cytoplasmic membrane, often in large amounts.

In the periplasmic space or bound to the exterior of the cytoplasmic membrane.

Ring strain helps beta-lactams react with PBPs, but also contributes to enzymatic deactivation and acid instability.

They can be unstable in acidic media, especially at pH less than 5, leading to degradation in the stomach.

6-aminopenicillanic acid.

A free carboxyl on the thiazolidine ring and a substituted amide at position 6.

Reactivity, solubility, beta-lactamase protection, spectrum of activity, oral bioavailability, and protein binding.

Adding an electron-withdrawing group near the side-chain carbonyl decreases acid hydrolysis and improves oral bioavailability.

Adding bulky groups near the side-chain carbonyl blocks beta-lactamase access to the beta-lactam ring.

They also reduce access to PBPs, so beta-lactamase-resistant penicillins are less potent than natural penicillins.

They help the drug pass through Gram-negative porin channels.

Natural penicillins, aminopenicillins, beta-lactamase-resistant penicillins, and extended-spectrum or antipseudomonal penicillins.

Penicillin G and Penicillin V.

Oral availability.

They are readily hydrolyzed by beta-lactamases and mainly cover susceptible Gram-positive organisms.

Ampicillin and amoxicillin.

An amine on the carbon adjacent to the amide carbonyl.

Expanded activity against many Gram-negative organisms compared with natural penicillins.

No. They are easily cleaved by beta-lactamases.

Amoxicillin is about twice as well absorbed as ampicillin and usually causes less GI upset.

Clavulanate inhibits many beta-lactamases, extending amoxicillin’s useful spectrum.

They avoid destruction by many staphylococcal beta-lactamases, but they do not inhibit the enzyme.

Methicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin.

Methicillin.

Nafcillin.

Cloxacillin and dicloxacillin.

Antipseudomonal penicillins.

Carbenicillin, ticarcillin, and piperacillin.

Tazobactam, forming piperacillin/tazobactam.

Hypersensitivity, ranging from rash to anaphylaxis.

Penicillin or degradation products can covalently modify host proteins, forming antigenic complexes.

Ampicillin.

7-aminocephalosporanic acid.

A free carboxyl at C-4, although it can be derivatized as an ester prodrug.

Spectrum of activity and acid stability.

Reactivity and acid stability.

Aromatic alkoximino groups on the side chain and replacing H-7 with OCH3 to form a cephamycin skeleton.

The syn alkoximino isomer.

By generations, based on time of discovery and spectrum of activity.

Good Gram-positive activity except MRSA and MRSE; relatively modest Gram-negative activity.

Cefazolin, cephalexin, and cefadroxil.

Parenteral prophylaxis before surgery.

Oral first-generation cephalosporin; good for UTIs; mostly excreted unchanged in urine.

Usually covers first-generation susceptible organisms plus most strains of Haemophilus influenzae; more Gram-negative activity than first generation.

Cefprozil, cefuroxime, and cefoxitin.

A cephamycin grouped with second-generation cephalosporins; has anaerobe and Gram-negative bacilli activity and good beta-lactamase resistance from C-7 OCH3.

It has a syn oxime ether for beta-lactamase resistance; the axetil ester prodrug improves oral absorption.

Less Gram-positive activity than first generation but broader Gram-negative activity; some agents cover Pseudomonas.

Cefdinir, ceftriaxone, and ceftazidime.

A widely used injectable cephalosporin with a very long half-life allowing once-daily dosing; used for pneumonia, meningitis, and gonorrhea.

Ceftazidime.

Most is excreted unchanged by kidneys, and half-life is prolonged in renal impairment.

Broad spectrum; Gram-positive activity similar to first generation, Gram-negative activity similar to third generation including Pseudomonas, and broad beta-lactamase resistance.

Cefepime.

A quaternary amine helps access Gram-negative bacteria, and it has broad beta-lactamase resistance.

Nosocomial infections and bacterial meningitis due to good CSF access and high concentrations.

Broad spectrum with Gram-positive activity similar to first generation, less Gram-negative activity than fourth generation against Pseudomonas, and MRSA activity.

Ceftaroline fosamil, a prodrug of ceftaroline.

Community-acquired bacterial pneumonia and acute bacterial skin infections.

A beta-lactam that is not fused to another ring.

Aztreonam.

Narrow spectrum against many aerobic Gram-negative bacteria, with no activity against anaerobes or Gram-positive organisms.

Inhaled therapy for Pseudomonas aeruginosa in cystic fibrosis patients.

Avoidance: alter the antibiotic so it is not a substrate. Neutralization: give a beta-lactamase inhibitor with a beta-lactam antibiotic.

A prototype Class I beta-lactamase inhibitor with weak antibacterial action that inhibits many beta-lactamases.

Amoxicillin/clavulanate.

It extends amoxicillin’s life by inhibiting beta-lactamases so amoxicillin can reach PBPs.

Synthetic Class I beta-lactamase inhibitors with weak antibiotic activity that potentiate beta-lactam antibiotics.

Ampicillin/sulbactam, parenteral.

Piperacillin/tazobactam, parenteral.

Tazobactam; sulbactam is not good against Pseudomonas beta-lactamases.

Broad-spectrum beta-lactam antibiotics, not mainly as beta-lactamase inhibitors.

Imipenem, meropenem, and ertapenem.

Extremely broad spectrum; stable to most serine beta-lactamases and inhibits many Gram-negative beta-lactamases.

Cilastatin inhibits renal dehydropeptidase-1, preventing imipenem breakdown and extending its half-life.

A reversible competitive inhibitor of renal DHP-1; it is not an antibiotic.

Seizures in about 2% of patients in the lecture.

Very broad spectrum, greater in vitro antipseudomonal activity, fewer seizure reports, and does not require cilastatin.

Metallo-beta-lactamases and carbapenemases.

No.

Meropenem plus vaborbactam, a non-beta-lactam beta-lactamase inhibitor.

It is not active against Pseudomonas aeruginosa or Acinetobacter species.

Once-daily 1 g dosing due to long half-life and high protein binding.

When the treatment target is Pseudomonas aeruginosa.