Influenza virus has a few RNA polymerases. Which of the following is a drug target due to its cap-dependent endonuclease activity?

Which of the following DNA virus types does infect epithelial cell & establish latent infection in neurons? (Type 1 is associated with oropharyngeal lesions while type 2 infects genital mucosa)

What are the key enzymes for Herpes virus to translate viral proteins to make structural proteins, viral enzymes, and regulatory proteins?

These are deoxythymidine mimics that inhibit thymidylate synthase as they have an isosteric replacement of thymidine's methyl group

Selective toxicity of oseltamivir is due to:

Ganciclovir has more SEs compared to acyclovir. Why?

This is a guanine mimic, with a sugar with an error. This is being incorporated into the viral DNA after being triphosphorylated, causing chain termination. This is use parenterally and as an ophthalmic gel in herpetic keratitis. What is this?

Pick the DNA polymerase inhibitor

Pick the transition state inhibitor

Could agents used in influenza be effective in HIV treatment?

Treatment goals for highly active Antiretroviral therapy (HIV therapy) are

What is this class?

1. This class is a nucleoside analogue with an error sugar

2. This class is a competitive inhibitor, taken up by cells and phosphorylated by our nucleoside/tide kinases to the triphosphate form, ultimately leading to chain termination due to the absence of 3'-hydroxyl group

3. Resistance rapidly occurs to this class when used as single agents

Which of the following NRTIs is cytosine analog?

Which of the following NRTIs is guanosine analog?

Which of the following NRTIs is adenosine analog?

What is this?

1. This is a purine analogue, metabolized via alcohol dehydrogenase and glucuronidation, so less of a concern with DDIs

2. Serious hypersensitivity reactions may occur, especially in patients with HLA-B*5701 allele, which requires patient to be screened prior to initiating therapy

3. Other ADRs include lactic acidosis, coronary heart disease

Which of the classes has the following SE profiles?

1. This may have significant interactions with other drugs: All inhibit, and several induce CYP450s (eg. CYP3A family and CYP2B6)

2. Some drugs may prolong QT interval and patients may experience CNS symptoms including dizziness, insomnia, drowsiness, vivid dreams, and nightmares

3. DDIs with PPIs and other acid reducing medications

Why are NRTI combo always analogs of different bases?

Which of the following drug classes are transition state inhibitors?

Which of the following is a prodrug and requires phosphorylation by a viral-specific kinase or phosphotransferase? (Hint: UL97 kinase)

What are common SE effect profile present in all HIV Protease inhibitors?

Which of the following antivirals targets DNA processing after viral DNA replication is completed (i.e. DNA terminase complex)?

The reason that ritonavir is almost always given with other protease inhibitors

Which type of hepatitis viruses is +ssRNA virus?

Which type of hepatitis viruses is +ssRNA virus and no treatment/drugs to cure?

Which type of hepatitis viruses is DNA virus that is converted to a cccDNA in the host cell?

True/False: Severe, acute exacerbation of hep B may occur upon discontinuation of anti-hep B therapy

True/False: HBV polymerase inhibitors (ie. Reverse Transcriptase Activity Inhibitor) may cause development of HIV NRTI drug resistance in chronic Hep B patients with unrecognized or untreated HIV infection

Interferons "interfere" with viral replication by:

NS3/4A protease inhibitors are metabolized by this CYP isoform so all PIs depend in this CYP relevant metabolism

Which of the following drugs does NOT have the MOA that prevents NS5A protein from promoting RNA replication and viral assembly. (NS5A is a replication complex protein essential for RNA polymerase activity and viral assembly)

Which of the following drugs does NOT have the MOA by which inhibits NS5B polymerase in HCV, leading to inhibition of RNA synthesis and termination of replication?

Monoclonal antibodies against spike proteins (-mabs) are given IV and they block entry into cells and help kill infected cells. They are used for Tx of mild to moderate COVID-19 patients at high risk for progression to serious disease and death.

T/F: They are NOT effective in patients who are already hospitalized with severe COVID-19

What is the advantage of antiviral drugs over other approaches to treat COVID-19?

This drug was developed for Ebola virus, but it was found ineffective, and it was shown to be useful in SARS and MERS instead. This is a phosphoramidate prodrug that inhibits RNA-dependent RNA polymerase, leading to competing with ATP and delaying a chain termination. What is this?

Name this drug:

1. This drug was developed for influenza virus, but abandoned due to adverse effect, and developed later for SARS CoV2.

2. This drug is an ester prodrug of N⁴-hydroxycytidine (ie. nucleoside analog) that is phosphorylated to triphosphate nucleotide, gets incorporated into RNA, which results in inhibition of replication and lethal mutations.

3. Some concerns for emergence of dangerous variants and possible mutations to human genome are raised and this drug may harm the fetus.

Name this drug:

1. This drug is tripeptide and mimics one of the viral endogenous substrate peptides. When activated, nitrile group forms covalent bond with 3CL protease.

2. This drug is used in combo with ritanovir (PK booster) for high-risk patients to prevent progression to severe COVID-19, including hospitalization or death.

3. This drug must be given immediately or within five days of diagnosis.

Which of the following species is known most lethal that it infects all stages of erythrocytes and creates greatest parasite load?

Which of the following species is known to be able to maintain hepatocyte infection as a dormant form known as the hypnozoite?

What are the potential ways to control malaria?

Which of the following antimalarials is NOT drugs that target parasites residing in erythrocytes (ie. blood schizonticides) so not effective for the RBC stage?

Quinoline drugs have SAR of

Quinoline drugs are (_) charged inside food vacuole, which trap them inside after entering through pores of the vacuole.

Due to development of resistance that pumps out a drug targeting, chloroquine is ineffective against most strains of this species.

What are the SEs of Chloroquine?

Which of the following is NOT the SE of Quinine?

Which of the following quinoline drugs has BBW for history of depression, generalized anxiety disorder, psychosis, or schizophrenia?

Which of the following CYP isoforms mainly metabolizes quinoline drugs: Quinine, Chloroquine, Mefloquine, etc.?

This drug inhibits Plasmodium mitochondrial electron transport chain indicated for prophylaxis and treatment of chloroquine-resistant malaria

This is a tissue schizonticide that eliminate developing or dormant liver forms relevant to P. vivax and P. ovale only; thus, the drug is not effective for the RBC stage. The MOA is still unclear but it is believed its metabolites create oxygen species which interfere with Plasmodium ETC.

This causes drug-induced anemia in patients with glucose-6-phosphate dehydrogenase deficiency that results in decreased NADPH and GSH synthesis making the cell more sensitive to oxidative agents leading to hemolysis.

Chloroquine only eliminates parasites in RBCs, not liver.

 Mr. G is 36 y.o. Married software engineer who was born and raised in India. He comes to the US and is completely well for 6 months. He then begins to experience episodes of fever, headache, and body aches. One week later, he goes to his physician, who examines a smear of Mr.G’s blood, diagnoses malaria, and prescribes chloroquine for treatment. Therapy with chloroquine resolves his symptoms completely. However, Mr.G notes recurrence of fevers and other symptoms 3 months later and returns to his doctor’s office. What is likely explanation for the return of Mr.G’s fever?

 Mr. G is 36 y.o. Married software engineer who was born and raised in India. He comes to the US and is completely well for 6 months. He then begins to experience episodes of fever, headache, and body aches. One week later, he goes to his physician, who examines a smear of Mr.G’s blood, diagnoses malaria, and prescribes chloroquine for treatment. Therapy with chloroquine resolves his symptoms completely. However, Mr.G notes recurrence of fevers and other symptoms 3 months later and returns to his doctor’s office. And it is more likely due to infection with either P. vivax or P. ovale. How can Mr. G's treatment be modified so that his illness will not return?

Which of the following statements is NOT correct for Chagas Disease?

Which of the following drugs are used for drug treatment in Chagas disease by the MOA that they are activated to nitro radical anions leading to formation of oxygen radicals that damage parasites?

Which agent is trapped inside the parasite organelle?

Trypanosoma cruzi is particularly sensitive to drugs (Benznidazole and Nifurtimox) due to inefficient detoxification capabilities while mammalian cells poorly activate drug and detoxify oxygen radicals

Benznidazole and Nifurtimox are safe in pregnant women

Patients on Benznidazole and Nifurtimox should avoid alcohol use as disulfiram effects

Which of the following adverse effects is NOT in SE profile of Sulfadiazine?

What is this drug?

This drug has a nitro group that serves as an electron acceptor, forming reduced cytotoxic compounds that damage DNA, resulting in death of the protozoal trophozoites (anaerobic pyruvate metabolism)

Metronidazole and Tinidazole acquire a selectivity for killing parasites not human cells as the parasites activates the drugs while humans do not

Which of the following statements is NOT correct for metronidazole and tinidazole?

Mebendazole and Albendazole have the SAR two structures that perform the following MOAs:

1. Prevents cell division in worms by interfering with microtubule assembly

2. Irreversibly blocks glucose uptake, thereby depleting glycogen stored in the parasite but do not affect glucose metabolism or bind to mammalian tubulin in the host (ie. selectivity to worms not human cells)

Which of the following ADRs does belong to a SE profile of mebendazole and albendazole?

Name the drug:

This drug is a depolarizing neurotransmitter blocking agent that causes spastic paralysis in worms and released from the intestinal tract.

Additionally, AChE inhibition of the drug adds to its neuromuscular blocking activity, and it exerts a local action in the GTI as poorly absorbed

Name the drug:

This drug is a depolarizing neurotransmitter blocking agent that causes spastic paralysis in worms and released from the intestinal tract.

Additionally, AChE inhibition of the drug adds to its neuromuscular blocking activity, and it exerts a local action in the GTI as poorly absorbed

Name the drug:

This drug is used for infections caused by schistosomes. The drug increases cell membrane permeability resulting in the influx of extracellular calcium, which causes massive contractions and ultimate paralysis, followed by detachment from blood vessel walls and phagocytosis. Rapidly metabolized by CYP3A4.

Name the drug:

This drug is used for onchocerciasis (river blindness) and used in strongyloidiasis (thread worm disease). The drug only kills microfilariae not adult worms. The drug is a strong allosteric modulator of the glutamate-gated chloride ion channels, which are important in invertebrate nerve and muscle cells (not expressed in humans). Hyperpolarization follows due to an increase in chloride ion permeability, leading to muscle paralysis and eventually cell death of the worms

Which of the following agents show selective toxicity due to attacking a unique target to worms?

Which of the following is the example of Intrinsic Resistance to antimicrobial agents?

Name this process of acquiring resistance:

Bacteria can take up DNA released from lysed bacterial cells. It is then integrated into a homologous region on the recipient genome. In other words, homologous region is required

Name this process of acquiring resistance:

Chromosomal fragment of DNA that can be translocated from one bacterial cell to another even in absence of homologous sequence (ie. hopping gene)

Name this process of acquiring resistance:

R-plasmid is transferred from one bacteria to another via an appendage known as pilus (R+ to R-; Mating). The plasmid may contain multiple antibiotic-resistant genes, and particularly common in Gram (+) bacteria

Name this process of acquiring resistance:

Transfer of genes via bacteriophages that invade bacterial cells, integrate their own DNA into the bacterial chromosome, and replicate forming new phages. During its release from the chromosome, it may pick up a resistant gene and transfer it to other cells that it invades

Name this process of acquiring resistance:

Regulators of several resistant genes on the bacterial chromosomes are only activated by the presence of antibiotics. Eg. the efflux system along with reduced permeability of several antimicromial agents is activated by the presence of only one of these agents, leading to MDR species

Primary mechanism of Antibiotic Resistance are

Which of the following statements is NOT TRUE for gram negative bacteria?

These bacteria grow in both aerobic and anaerobic, but GREATER growth in presence of O₂ (e.g., E.coli)

Agents with a broad spectrum may be appropriate for empiric therapy of life-threatening infections, whereas narrow spectrum is preferred for definitive therapy (know the pathogen causing disease)

Which of the following types of hypersensitivity can be life-threatening, has an immediate onset, IgE-mediated, lasting hours with symptoms of hives, edema, and anaphylaxis?

This type of hypersensitivity is complement-mediated that cause immune complex disease, "serum sickness", vasculitis, and nephritis

Which of the following types of hypersensitivity can be life-threatening, has an immediate onset, IgE-mediated, lasting hours with symptoms of hives, edema, and anaphylaxis?

This type of hypersensitivity is RBC-mediated that cause hemolytic anemia, thrombocytopenia, and antibody-dependent cell killing lasting days (delayed onset).

This type of hypersensitivity is Delayed T cell-mediated that maculopapular rashes, SJS, and nephritis

Which of the following statements is NOT TRUE for effects on antibiotic on normal bacterial flora?

Antibiotic-associated colitis/diarrhea is often caused by infection with C. difficile. Name the two exotoxins that cause diarrhea and inflammation resulting in damage to the colon.

Antibiotic-associated colitis/diarrhea is often caused by infection with C. difficile. Which of the following antibiotics are most associated with C. difficile infections?

This gram positive coccus is (1) part of the normal microflora of the female genital tract and perineum and (2) 2nd most common cause of UTIs in sexually active young women (honeymoon cystitis)

This gram positive coccus is (1) found on the skin and in the nose of healthy people, (2) typically resistant to penicillins, and (3) cause many common bacterial infections in humans like skin and soft tissue infections

This gram positive coccus is (1) part of the normal skin microflora, (2) has an ability to form biofilms on plastic devices (major virulence factor), and (3) is a common cause of infection that appears in patients with indwelling catheters and prosthetic devices

This gram positive coccus is normal microflora in the mouth and associated with dental infections and cavities. This species cause diseases such as Endocarditis (heart valve infection) following dental procedures or infection when displaced into the bloodstream.

This gram positive coccus has "cell wall antigen" (M protein) that prevents complement activation and inhibits phagocytosis by immune cells. Also, this species cause diseases, such as strep throat, skin infections, scarlet fever & toxic shock caused by pyrogenic exotoxin, and rheumatic heart disease.

This gram positive coccus is normal microflora in the GIT and cause diseases (of childbirth) such as infection in vagina (mom) can lead to meningitis, pneumonia, sepsis in the newborn. For adults, it can cause serious invasive infections in older poeple.

This gram positive coccus colonizes the upper respiratory tract and its polysaccharide capsule prevents bacteria from being phagocytized. This species can cause diseases such as Meningitis, Pneumonia, Middle ear infection in children, etc.

This bacterial species is typically resistant to Penicillins:

1. Most produce Penicillinase (beta-lactamase that destroys Penicillin and Amoxicillin)

2. Use penicillinase-resistant penicillin or add beta-lactamase inhibitor or use cephalosporin (natural penicillinase-resistant)

3. May be resistant to ALL beta-lactams due to acquisition of altered transpeptidase (penicillin binding protein, PBP2a); eg. MRSA or MRSE

This bacterial species are susceptible to Penicillin G and V except this pneumoniae that expresses low affinity penicillin binding proteins making penicillins less effective

This bacterial species are inherently resistant to most beta-lactams, especially cephalosporins and have acquired resistance to Vancomycin (VRE)

This bacterial species is associated with food poisoning and can invade macrophages, endothelial cells and proliferate, eventually entering bloodstream and through placenta of pregnant women. Also, it is inherently resistant to cephalosporins whereas Ampicillin is effective due to higher affinity for target enzyme.

This is an anaerobic gram negative, spiral shaped, microaerophilic species that have 2-7 flagella that increase its motility through viscous mucus layer of stomach. This species produce urease which hydrolyzes gastric urea to form ammonia and CO₂. NH₃ neutralizes gastric acid and forms a protective "neutral pH cloud" around the organism and infects the protective tissue that lines the stomach and duodenum causing inflammation that result in peptic ulcer disease. Also, this species increases risk for gastric cancer and gastric mucosa-associated tissue lymphoma (MALT lymphoma)

This is an anaerobic gram negative species that leads cause local injury allowed by oxygen tolerance and a polysaccharide capsule when displaced beyond mucosal barriers. The local injury includes formation of intra-abdominal abscesses and entering the bloodstream may result in abscess formation in other organs. This species isolates almost always produce beta-lactamse, which not only inactivates penicillins but other beta-lactams, such as many cephalosporins.

This is an anaerobic gram negative species with rod shaped and facultative anaerobe that is part of normal GI flora. Some species are important etiologic agents of diarrhea and E. coli, Proteus mirabilis, Klebsiella pneumoniae are EPK pathogen that most commonly cause UTI. Klebsiella species are responsible for many hospital-acquired infections and many of this species produce beta-lactamases that destroy all beta-lactam drugs

This is an aerobic gram negative diplococci that is a major cause of meningitis and bacteremia

This is an aerobic gram negative diplococci that is the cause of gonorrhea and has acquired drug resistance to Sulfonamides, Penicillin (beta-lactamase), fluoroquinolones due to mutation of target. 3rd generation cephalosporins are only effective treatment.

This is an aerobic gram negative and human pathogen of respiratory tract. This causes many childhood infections, including meningitis, bacteremia, pneumonia, cellulitis, otitis media, conjunctivitis, sinusitis, and acute epiglottis. Type b of this species causes the worst disease, especially in children bacteremia and meningitis which can be protected by vaccination. Other strains can cause invasive infections in children and may cause up to half of serious infections in adults, and often express beta-lactamases that inactivate Amoxicillin.

This is an aerobic gram negative species that cause 10-20% of all nosocomial (hospital associated) disease. This species is ubiquitous in environment, forming biofilms and causes infections when immune defenses are disrupted: burn wound infections, IV or urinary catheters, and neutropenia. This can persist in the lungs of cystic fibrosis patients, and is a leading cause of ventilator-associated pneumonia (VAP). Multidrug resistance has become a major issue in management of hospital-acquired infections with this species due to (1) acquisition of beta-lactamases, (2) porin channel mutations, and (3) efflux pumps.

This atypical bacteria lack peptidoglycan and causes community-acquired pneumonia especially in younger patients, and is the cause of atypical or walking pneumonia.

This atypical bacteria is gram negative but have very little peptidoglycan in cell wall. It is an obligate intracellular pathogens that cause STI or community-acquired pneumonia that mirrors the other species in its person-to-person transmission, clinical features, and treatment is less common

This atypical bacterial pathogen is a gram negative aerobic bacillus that has a very thin peptidoglycan layer, and is not easily stained using the gram staining method. It causes outbreaks due to poorly maintained artificial water systems. It can replicate inside human cells within membrane bound vesicles. Beta-lactams and aminoglycosides are not effective in treating diseases caused by this pathogen.