week 6: cancer cytotoxic drugs and chemotherapy

Question 1

What is the primary principle behind chemotherapy?

Answer 1

Chemotherapy involves killing cells by restoring a molecular target to disrupt a pathological process.

Question 2

What are the three relationships in the pathogen–host–drug model?

Answer 2

Pathogen/host: Immune response (innate + adaptive)

Drug/host: PD/PK + side effects

Drug/pathogen: Drug targets pathogen; pathogen may resist

Question 3

What bacterial features enable selective toxicity?

Answer 3

70S ribosomes (30S + 50S subunits)

Folate synthesis

Unique peptidoglycan cell wall

Cell membrane

Non-membrane bound nucleoid

Question 3

How do PK/PD relationships influence antibiotic effectiveness?

Answer 3

Higher concentration and longer time improve effect

Drugs can be bactericidal (kill bacteria) or bacteriostatic (inhibit growth)

Question 4

What’s the difference between Gram-positive and Gram-negative bacteria?

Answer 4

Gram-positive: Thick peptidoglycan wall, stains purple

Gram-negative: Thin wall, stains pink, harder to target

Question 4

What are four major mechanisms of bacterial resistance to antibiotics?

Answer 4

Block drug entry

Produce inactivating enzymes (e.g. β-lactamase)

Alter drug target

Increase drug efflux

Question 5

What human behaviours contribute to antimicrobial resistance?

Answer 5

Over/incorrect prescription

Not completing treatment

Poor hygiene

Lack of new drug development

Question 6

What distinguishes bacteria from viruses in choosing treatment?

Answer 6

Bacteria: Unicellular, have own DNA machinery, have cell walls

Viruses: Obligate parasites, depend on host machinery

Question 7

What is the difference between the lytic and lysogenic viral cycles?

Answer 7

Lytic: Virus replicates inside host → lyses cell

Lysogenic: Viral DNA integrates into host genome, replicates with it, may enter lytic phase later

Question 8

What is the general mechanism of cytotoxic chemotherapy drugs?

Answer 8

Form covalent bonds with DNA → cross-linking → inhibit replication/transcription → apoptosis

Question 9

What are common adverse effects of cytotoxic chemotherapy?

Answer 9

Hair loss, nausea, vomiting

Question 10

What is the mechanism of action of Bleomycin?

Answer 10

Intercalates into DNA

Causes strand breaks via free radical formation

Inhibits topoisomerase

Question 10

What are common adverse effects of triazines?

Answer 10

Hair loss, nausea, renal toxicity

Question 10

What is the mechanism of action of triazine alkylating agents?

Answer 10

Cross-links DNA at guanine residues → blocks replication/transcription

Question 11

What class of drug is Bleomycin and where is it derived from?

Answer 11

Class: Intercalating agent

Source: Bacteria-derived

Question 12

What is the function of topoisomerase I vs. topoisomerase II inhibitors?

Answer 12

Topo I inhibitors: Prevent single-strand cuts

Topo II inhibitors: Prevent double-strand cuts
→ DNA remains supercoiled and cannot be replicated

Question 13

What is the mechanism of action of Mercaptopurine?

Answer 13

Prodrug → converted to nucleotides

Inhibits adenine and guanine synthesis
→ ↓ DNA replication

Question 14

What is the mechanism of action of Vinblastine?

Answer 14

Inhibits mitosis during M-phase by disrupting microtubules
→ mitotic arrest and myelosuppression

Question 14

What is the route of administration for Mercaptopurine?

Answer 14

Orally active

Question 15

What side effect is common to most cytotoxic agents, including Vinblastine?

Answer 15

Hair loss

Question 15

What is the mechanism of action of sulphonamides?

Answer 15

Sulphonamides inhibit dihydropteroate synthase, blocking the conversion of PABA into folate, thereby decreasing folate synthesis and inhibiting DNA synthesis in bacteria.

Question 16

What is a major adverse effect of sulphonamides?

Answer 16

Liver and kidney damage

Question 17

How does penicillin kill bacteria?

Answer 17

Penicillin is a β-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), especially transpeptidase, blocking peptidoglycan cross-linking, leading to cell lysis, especially in Gram-positive bacteria.

Question 18

What are adverse effects of high-dose penicillin?

Answer 18

Neurotoxicity and upset stomach

Question 19

How do protein synthesis inhibitors work?

Answer 19

50S inhibitors → block peptide transferase and translocation 30S inhibitors → competitively inhibit tRNA binding Aminoglycosides → cause irreversible misreading, inserting wrong amino acids

Question 20

What are common adverse effects of protein synthesis inhibitors, especially aminoglycosides?

Answer 20

Renal toxicity and ototoxicity (ear toxicity)

Question 21

What are the 8 stages of the viral replication cycle targeted by antiviral drugs?

Answer 21

Attachment Entry Uncoating DNA/RNA replication DNA nuclear transcription RNA translation Reassembly Release (budding or rupture)

Question 22

What are the 5 major antiviral drug classes and their targets?

Answer 22

Ion channel blockers – prevent viral entry Fusion inhibitors – prevent membrane fusion Polymerase inhibitors – block genetic replication Protease inhibitors – block protein cleavage Neuraminidase inhibitors – block virus release

Question 23

How do M2 ion channel blockers treat influenza?

Answer 23

They block acidification inside the endosome by inhibiting the M2 ion channel, preventing viral uncoating and replication.

Question 24

How do neuraminidase inhibitors treat influenza?

Answer 24

They prevent the release of new viral particles from infected cells, stopping spread of infection.

Question 25

What is the half-life and route of elimination for acyclovir?

Answer 25

t₁/₂ = 2–4 hours Excreted via kidneys, available in topical form

Question 25

What is the mechanism of action of acyclovir for herpes?

Answer 25

A guanosine analogue Activated by viral thymidine kinase into monophosphate Then converted by host enzymes to acyclovir triphosphate Inhibits viral DNA polymerase and causes chain termination Targets HSV-1 and HSV-2

Question 26

What are nucleoside reverse transcriptase inhibitors (NRTIs) and how do they work?

Answer 26

NRTIs are nucleoside analogues Phosphorylated by host enzymes into active triphosphates Incorporated into viral DNA by HIV reverse transcriptase Lack a 3’-OH group → cause chain termination

Question 27

How do non-nucleoside reverse transcriptase inhibitors (NNRTIs) differ from NRTIs?

Answer 27

Bind to allosteric site (not active site) on reverse transcriptase Do not require phosphorylation Cause conformational change in enzyme Block RNA → DNA conversion

Question 28

What is the mechanism of action of HIV protease inhibitors?

Answer 28

Bind and inhibit HIV protease enzyme Prevent cleaving of polyproteins into functional proteins Results in immature, non-infectious virions

Question 29

How does molnupiravir work against SARS-CoV-2?

Answer 29

It inhibits RNA-dependent RNA polymerase, preventing replication of viral RNA.