7.0 Chemotherapy Flashcards

Question 1

Q

Aciclovir [acyclovir]

Answer

A

Class = Purine analogue - Target = Viral DNA polymerase - Mechanism = Lacks the 3-OH group required for additional nucleotide polymerisation - Steps: 1) Taken up by cell and monophosphorylated by herpes virus thymidine kinase 2) Cellular enzymes then convert it to triphosphate 3) Aciclovir triphosphate competitively + permanently inhibits with viral DNA pol 4) Also incorporated into growing chain but cannot continue adding more nucleotides because it aciclovir lacks the 3- OH group - Info: Selective for viral infected cells because: 1) Only virally infected cells have thymidine kinase (for monophosphorylation) 2. Drug preferentially binds to virally encoded DNA pol. (30x stronger bond on viral cf. host) -Resistance: Viral thymidine kinase changes substrate sensitivity thus does not monophosphate acyclovir

Question 2

Q

Amantadine

Answer

A

Class = Antiinfluenza drug - Target = 1) M2 channel protein 2) HA processing - Mechanism = 1) Blocks function of M2 channel → prevents uncoating of virus 2) Interferes with HA processing → ↓ binding to host (HA needed to bind to sialic acid) - Steps: - Info: Used as prophylaxis or anti-influenza A Not effective against influenza B

Question 3

Q

Amoxicillin

Answer

A

Class = Antibiotic (beta-lactam) - Target = Cell wall biosynthesis - Mechanism = Inhibits Peptidoglycan transpeptidase - Steps: 1) PG transpeptidase mistakes amoxicillin for an uncrossed PG chain terminatinf in D-Ala-D-Ala 2) Active site serine attacks the beta lactam ring of the antibiotic → acyl-enzyme intermediate in which the beta-lactam ring has opened 3) This resulting covalent penicilloyl enzyme is very slow to hydrolyse → ↓↓↓ further PG synthesis 4) Causes cell lysis because of continued activity of autolysins - Info: Only proliferating cells in which autolysins are active are sensitive to beta lactam antibiotics Often combined with clavulanic acid (beta-lactamase inhibitor)

Question 4

Q

Amphotericin B

Answer

A

Class = Polyene (antifungal) - Target = Ergosterol in fungal plasma membrane - Mechanism = Binds to ergosterol → pore formation - Steps: Preferentially binds to egosterol (in fungal membranes) as opposed to cholesterol (in human plasma membrane) → selectivity Pore formation → ion + macromolecule leakage - Info: Ergosterol is also found in Leishmania (parasite)

Question 5

Q

Anastrozole

Answer

A

Class = Hormone therapy (anticancer) - Target = Aromatase - Mechanism = Inhibitor - Steps: • Aromatase = enzyme in the oestrogen biosynthetic pathway that converts androgen precursor to estradiol • Inhibition of this enzyme ⟶ ↓ oestogen - Info: Used instead of, or after, treatment with tamoxifen Also used in post-menopausal women with breast CA to prevent formation of oestrogens at peripheral sites such as muscle and fat

Question 6

Q

Artemisinin

Answer

A

Class = Antimalarial - Target = - - Mechanism = Less well known - Steps: ?Production of reactive oxygen radicals using peroxide bridge? ?Inhibition of parasite electron transport chain? ?Inhibits parasite SERCA pump? - Info: Rapid action Also inhibits development of oocytes in mosquitos

Question 7

Q

Cephalosporin

Answer

A

Class = Antibiotic (beta-lactam) - Target = Cell wall biosynthesis - Mechanism = Inhibits Peptidoglycan transpeptidase - Steps: 1) PG transpeptidase mistakes cephalosporin for an uncrossed PG chain terminatinf in D-Ala-D-Ala 2) Active site serine attacks the beta lactam ring of the antibiotic → acyl-enzyme intermediate in which the beta-lactam ring has opened 3) This resulting covalent penicilloyl enzyme is very slow to hydrolyse → ↓↓↓ further PG synthesis 4) Causes cell lysis because of continued activity of autolysins - Info: Only proliferating cells in which autolysins are active are sensitive to beta lactam antibiotics

Question 8

Q

Cetuximab

Answer

A

Class = Monoclonal antibody (anticancer) - Target = EGFR - Mechanism = Inhibition - Steps: EGFR = RTK Binding of specific ligand ⟶ conformational changes ⟶ ↑ RTK activity ⟶ ↑ cell activity such as proliferation and differentiation Abnormal EGFR expression involved in many malignancies Inhibition achieved by preventing ligand binding with anti-EGFR antibody - Info: Human-mouse chimeric monoclonal antibody Cetuximab can reverse the resistance of colorectal cancers to topoisomerase inhibitors Used in combination with irinotecan (top. inhibitor)

Question 9

Q

Chloramphenicol

Answer

A

Class = Antibiotic - Target = 50S ribosomal subunit - Mechanism = Blocks aminoacyl-tRNA interaction with P site of peptidyl transferase centre - Steps: - Info: Bacteriostatic

Question 10

Q

Chloroquine

Answer

A

Class = Antimalarial - Target = Haem polymerisation by plasmodium spp - Mechanism = Inhibits formation of hemozoin - Steps: Events during Plasmodium erythrocytic cycle: -Plasmodium in RBCs use haemoglobin as nitrogen source ⟶ accumulation of heme -Could accumulate to toxic levels (up 200-500mM) - This causes production of reactive oxygen species ⟶ harming the parasite - Parasites ∴ polymerise toxic heme ⟶ non-toxic hemozoin (in food vacuole) Mechanism of Chloroquine: Inhibits formation of hemozoin via 2 methods: 1. Inhibiting polymerase 2. Complexation of heme It also ↑ pH in food vacuole - Info: -Resistance: Parasites achieve resistance by efflux of cholorquine out of food vacuoles

Question 11

Q

Ciprofloxacin

Answer

A

Class = Antibiotic (fluoroquinolone) - Target = Topoisomerases (Type II) - Mechanism = Inhibits DNA gyrase and topo IV (both type II topoisomerases) - Steps: 1) Type II topoisomerases cleave both strands of DNA in an ATP dependent manner (DNA gyrase can supercoild DNA, Topo IV cannot) 2) Fluoroquinolones affect double strand cleavage/re-ligation cycle 3) Build up of complexes → effect on replication forks → cell death - Info: Used in UTI, osteomyelitis, gastroenteritis

Question 12

Q

Cisplatin

Answer

A

Class = Platinum compound (anticancer) - Target = N7 atoms of guanine and adenine in tumour cells - Mechanism = Covalently binds DNA ⟶ intrastrand cross-linking ⟶ prevents DNA replication - Steps: • Only active in cis form • Small size ⟶ crosslinking occurs between two neigbouring pGpG (intrastrand crosslinking) • This induces a major bend in dsDNA ⟶ changes in major groove • This (along with physical block provided by platinum adduct) ⟶ inhibition of DNA pol. ⟶ inhibition of DNA replication - Info: Used in sarcomas, some carcinomas (sc lung cancer, ovarian), lymphomas and germ cell tumours (large improvement in testicular CA treatment) IV administration (no bioavailability if oral) Inactivated by reastions with SH groups in glutathione and metallothioneins - Side effects = renal toxicity + bone marrow suppression

Question 13

Q

Clavulanate

Answer

A

-Class: Beta-lactamase inhibitor -Target: Beta-lactamase -Mechanism: forms a slowly hydrolysing acyl enzyme intermediate with Beta-lactamase to inhibit the enzyme - suicide substrate NO EFFECT ON B TYPE BETA LACTAMASE -Info: -used with amoxicillin to overcome Beta-lactamase induced resistance to Beta-lactam antibiotics. The combination of amoxicillin with clavulanate is Augmentin/co-amoxiclav

Question 14

Q

Co-trimoxazole

Answer

A

”- Class = Combination drug (sulfamethoxazole + trimethoprim) - Target = Folate synthesis (DHPS + DHFR) - Mechanism = Sulfamethoxazole → inhibits DHPS Trimethoprim → inhibits DHFR - Steps: - Info: Link with Steven Johnson syndrome<div> </div><div><img></img></div>”

Question 15

Q

Cyclophosphamide

Answer

A

Class = Nitrogen mustard (anticancer) - Target = DNA - Mechanism = Covalently binds DNA and prevents DNA replication + gene expression - Steps: Needs to be metabolised by cytochrome p450 to be activated (cyclophosphamide → phophoramide) 1) Binds to DNA + causes alkylation 2) Causes cross-linking 3) Can cause CG → AT transition 4) Basically prevents effective DNA replication and gene expression - Info: Oral admin Most commonly used alkylating agent Broad application (lymphoid/ breast/ lung/ ovary CA) Used with other drugs to reduce resistance

Question 16

Q

Daunomycin

Answer

A

Class = Antibiotic (polycyclin) - Target = DNA template - Mechanism = Non-covalent binding to DNA template - Steps: Inserts between adjacent base pairs Intercalation → affects dimensions of major and minor grooves ⟶ affects DNA/RNA pol interactions ⟶ prevention of normal replication and transcription Prevents DNA from being resealed - Info: Planar structure

Question 17

Q

D-cycloserine

Answer

A

Class = Antibiotic - Target = Cell wall biosynthesis - Mechanism = Mimics D-ala - Steps: 1) Inhibits L-alanine racemase 2) Inhibits D-ala D-ala synthase 3) Inhibits ligase (that joins to UDP-NAG) - Info: 2nd class drug anti-TB

Question 18

Q

Erlotinib

Answer

A

Class = Small molecule inhibitor (quinazoline derivative) - Target = EGFR - Mechanism = Inhibition - Steps: EGFR = RTK Inhibition → ↓ proliferation and division - Info: Orally active Potent Selective Toxicity → skin rashes + diarrhoea Good in pancreatic and advanced NSCLC

Question 19

Q

Erythromycin

Answer

A

Class = Antibiotic (Macrolide) - Target = 50s ribosomal subunit - Mechanism = Binds to polypeptide export tunnel on 50S → prevents elongation - Steps: 1) Interacts with 23S rRNA in export tunnel 2) Allows 6-8 oligopeptidyl-tRNA build up before elongation is blocked 3) Causes premature termination - Info: Bacteriostatic or bacteriocidal (depends on dose + bacterial species/density) -Resistance mechanism: -methylation of adenine in 23S rRNA of 50S subunit by N-methyltransferase to prevent binding of macrolide antibiotics.

Question 20

Q

Etoposide

Answer

A

Class = Topoisomerase II inhibitor - Target = Topoisomerase II (human) - Mechanism = Inhibition - Steps: Inhibition of type II topoisomerase in tumour cells ⟶ torsional stress on the DNA during DNA replication and transcription ⟶ genomic instability and impaired tumour cell proliferation - Info: Used in the treatment of lung cancer, testicular cancer, lymphoma

Question 21

Q

Fansidar

Answer

A

”- Class = Combination drug (sulfadoxin + Pyrimethamine) - Target = Folate synthesis (DHPS + DHFR) - Mechanism = Sulfadoxin → inhibits DHPS Pyrimethamine → inhibits DHFR - Steps: - Info:<div> </div><div><img></img></div>”

Question 22

Q

Fluconazole

Answer

A

Class = Triazole (antifungal) - Target = Enzymes involved with ergosterol synthesis - Mechanism = Inhibition - Steps: ↓ ergoesterol → alters fluidity of membrane → alters permeability + activity of membrane associated enzymes - Info: -Resistance: 1) Alterations in the amount of enzymes involved with ergosterol synthesis 2) Efflux

Question 23

Q

Fosfomycin

Answer

A

Class = Antibiotic - Target = Cell wall biosynthesis - Mechanism = Mimics phosphoenolpyruvate - Steps: 1) Inhibits pyruvryl transferase - Info:

Question 24

Q

Fusidic acid

Answer

A

Class = Antibiotic - Target = Elongation factors - Mechanism = Inhibits protein synthesis - Steps: 1) Binds to and inhibits elongation factor G - Info:

Question 25

Q

Goseraline

Answer

A

Class = Hormone therapy (anticancer) - Target = GnRH receptor - Mechanism = GnRH analogue → biochemical castration - Steps: • GnRH ⟶ ↑ LH + FSH ⟶ ↑ testosterone secretion • Testosterone can stimulate prostate cancer • Normal secretion of GnRH is pulsatile • Continuous GnRH ⟶ immediate ↑ LH + FSH ⟶ complete inhibition of their release Goseraline effectively does this (causes biochemical castration) - Info:

Question 26

Q

Imatinib

Answer

A

Class = Small molecule inhibitor (anticancer) - Target = BCR-ABl - Mechanism = Inhibition - Steps: BCR-ABl = RTK - Info: • Most chronic myeloid leukaemia patients carry the philadelphia chromosome, resulting from a reciprical exchange of the long arms of chromosomes 9 and 22 - this generates a fusion gene, leading to a BCR-ABL protein with tyrosine kinase activity. Imatinib blocks this activity to prevent excessive proliferation • Can also inhibit c-kit tyrosine kinase activity, the encoding gene of which is overexpressed in gastrointestinal stomal tumours (GISTs) Marketed as Gleevec

Question 27

Q

Isoniazid

Answer

A

Class = Antimicrobial - Target = Mycolic acid synthesis - Mechanism = Inhibition of mycolic acid synthesis - Steps: M.tuberculosis has significant intrinsic resistance to many antimicrobial compounds compared to other bacteria due to the high mycolic acid content in the lipid bilayer - Info: -first line treatment for tuberculosis against M. tuberculosis. -other bacteria, which do not feature mycolic acid, have a high intrinsic resistance to this drug

Question 28

Q

Leucovorin

Answer

A

Class = Folate source - Target = - - Mechanism = Provides a metabolic equivalent to folate - Steps: • Can be converted to reduced folic acid derivatives (e.g. tetrahydrofolate) ∴ has a vitamin activity equivalent to folic acid • ∵ does not rely on DHFR, it is unaffected by methotrexate - Info: Selectively is achieved ∵ proliferating tumour cells have much higher tetrahydrofolate requirement, thus leucovorin doesn’t help them as much as it does healthy cells

Question 29

Q

Lomustine

Answer

A

Class = Nitrosurea (anticancer) - Target = DNA - Mechanism = Not well understood - Steps: Cause alkylation and carbamoylation Can produce inter strand cross-links Bind preferentially to guanine - Info: Oral administration Lipophilic → good brain penetration → Important for brain tumours -Side effects: ↓WBC, ↓ Platelets + damage organs

Question 30

Q

Melarsoprol

Answer

A

Class = Arsenic compound (anti-parasitic) - Target = Lipoic acid dependent enzymes - Mechanism = Inhibition - Steps: Enzymes inhibited = 2-oxo-decarboxylase and pyruvate dehydrogenase Affects ATP synthesis Melarsoprol = prodrug (drug = melarsan oxide) - Info: Specific for Leishmaniasis

Question 31

Q

Methicillin

Answer

A

Class = Antibiotic (beta-lactam) - Target = Cell wall biosynthesis - Mechanism = Inhibits Peptidoglycan transpeptidase - Steps: 1) PG transpeptidase mistakes methicillin for an uncrossed PG chain terminating in D-Ala-D-Ala 2) Active site serine attacks the beta lactam ring of the antibiotic → acyl-enzyme intermediate in which the beta-lactam ring has opened 3) This resulting covalent penicilloyl enzyme is very slow to hydrolyse → ↓↓↓ further PG synthesis 4) Causes cell lysis because of continued activity of autolysins - Info: Only proliferating cells in which autolysins are active are sensitive to beta lactam antibiotics Introduced following emergence of penicillin-resistant gram positive bacteria (has a bulky 2,6-dimethoxybenzoyl substitute to reduce the susceptibility of the intermediate enzyme to hydrolysis) -Resistance mechanism: MecA gene which (encodes a beta-lactam resistance bi-functional transpeptidase/transglycosylase) Fem genes (contribute to resistance by adding a cross bridge to PG strands, which allows PG to act as a better substrate for MecA transpeptidase)

Question 32

Q

Methotrexate

Answer

A

”- Class = Folic acid antagonist - Target = DHFR (dihydrofolate reductase) - Mechanism = Inhibition - Steps: Disruption of nucleotide synthesis ⟶ disruption of DNA replication - Info: ↑↑ use of methotrexate ⟶ toxicity to normal cells (leucovorin can help with this)<div> </div><div><img></img></div>”

Question 33

Q

Miconazole

Answer

A

Class = Imidazole (antifungal) - Target = Enzymes involved with ergosterol synthesis - Mechanism = Inhibition - Steps: ↓ ergoesterol → alters fluidity of membrane → alters permeability + activity of membrane associated enzymes - Info: Also works on parasites (Leishmania)

Question 34

Q

Mitomycin C

Answer

A

Class = Antibiotic (aziridine containing antibiotic/anticancer) - Target = DNA template - Mechanism = Covalent bonding - Steps: Alkylates DNA (Preferentially at guanine bases at GC positions in complementary DNA strands) Results in the cross-linking of two guanine bases, one in each strand of the double helix ⟶ prevents strand separation during DNA replication and transcription - Info: Can also be used as an anticancer medication More reactive in low oxygen conditions

Question 35

Q

Mitoxantrone

Answer

A

Class = Anthracyclin (anti-cancer) - Target = DNA - Mechanism = Non-covalent binding - Steps: Intercalation causes unwinding of the helix → DNA + RNA pol affected → ↓ transcription and replication - Info: This is a modified version of doxorubicin - it lacks the hydroxyquinone moiety therefore does not produce the free radicals that caused all the side effects (cardiac shit) Also inhibits topoisomerase II

Question 36

Q

Nevirapine

Answer

A

Class = Reverse transcriptase inhibitor (non-nucleoside) - Target = HIV reverse transcriptase - Mechanism = Inhibition - Steps: Binds to target enzyme near catalytic site and denatures it - Info: Component of HAART Reverse transcriptase activity is early in replication cycle, therefore this drug only has effect early

Question 37

Q

Oseltamivir

Answer

A

Class = Anti-influenza drug - Target = Neuraminidase - Mechanism = Inhibitor - Steps: Inhibits NA → ↑ viral aggregation + ↓ release from host - Info: Oseltamivir is an ethyl ester pro-drug Cleaved by esterases in the plasma + gut on adsorption

Question 38

Q

Penicillin

Answer

A

Class = Antibiotic (beta-lactam) - Target = Cell wall biosynthesis - Mechanism = Inhibits Peptidoglycan transpeptidase - Steps: 1) PG transpeptidase mistakes penicillin for an uncrossed PG chain terminating in D-Ala-D-Ala 2) Active site serine attacks the beta lactam ring of the antibiotic → acyl-enzyme intermediate in which the beta-lactam ring has opened 3) This resulting covalent penicilloyl enzyme is very slow to hydrolyse → ↓↓↓ further PG synthesis 4) Causes cell lysis because of continued activity of autolysins - Info: Only proliferating cells in which autolysins are active are sensitive to beta lactam antibiotics

Question 39

Q

Prednisone

Answer

A

Class = Hormone therapy (steroid) - Target = Glucocorticoid receptor - Mechanism = Agonist - Steps: • Used in the treatment of inflammatory and autoimmune conditions • Has a lymphocytic effect and is useful against leukaemias - Info: Administered as prodrug prednisone, and is converted to active prednisolone by the liver

Question 40

Q

Pyrimethamine

Answer

A

”- Class = Antiparasitic - Target = DHFR (dihydrofolate reductase) - Mechanism = Inhibition - Steps: This inhibition traps folate co-enzyme in its useless form (dihydrofolate) Leads to rapid depletion of tetrahydrofolate - Info: Can be combined with sulfadoxin (Fansidar)<div> </div><div><img></img></div>”

Question 41

Q

Rifampin

Answer

A

Class = Antibiotic - Target = Beta subunit on DNA-dependent RNA polymerase - Mechanism = Inhibition of RNA synthesis - Steps: 1) Non-covalent binding to an allosteric site on the β subunit of the DNA-dependent RNA polymerase → blocks elongation of RNA chain 2) Directly blocks the elongating RNA chain at the di- or tri-nucleotide stage → inhibits new RNA synthesis But synthesis in progress at the time of drug exposure is not affected - Info: Derivative of Rifamycin B Binding ratio = one mole drug : one mole enzyme

Question 42

Q

Saquinavir

Answer

A

Class = HIV protease inhibitor - Target = HIV Asp protease - Mechanism = Inhibition - Steps: 1) HIV asp protease cleaves translated gag protein → mature protein 2) Lack of functioning Asp. protease means that virus is not infectious - Info: Mutation in enzymes → ↓ interaction between enzyme and inhibitor

Question 43

Q

Streptomycin

Answer

A

Class = Antibiotic (aminoglycoside) - Target = 30S subunit of ribosome - Mechanism = Prevents initiation - Steps: 1) Binds near the A site for aminoacyl-tRNA binding 2) Decreases fidelity of translation - Info: Bacteriocidal (because reduces fidelity of proteins made, therefore wrong aminoacid → leaky protein etc) -Resistance mechanism: -covalent modification of OH and NH2 residues that allow specific binding to 16S rRNA of 30S subunit. 3 types of modication: N-acetylation, O-phosphoryl trasnfer and O-adenylyl transfer. -reduced number of porins or modifications of LPS layer in Pseudomonas aeruginosa reduces uptake. Mutations in active tranporters required for uptake from periplasm -active efflux

Question 44

Q

Sulfadoxin

Answer

A

”- Class = Sulfonamide - Target = DHPS (dihydropteroate synthase) - Mechanism = Inhibition - Steps: Shuts off de-novo synthesis of folate (nneded for thymidine synthesis) causes a slow killing mechanism - Info: Can be combined with prymethamine (Fansidar) Drug analogue = sulfamethoxazole (antibiotic) P-aminobenzoate analogue<div> </div><div><img></img></div>”

Question 45

Q

Sulfamethoxazole

Answer

A

”- Class = Sulfonamide - Target = DHPS (dihydropteroate synthase) - Mechanism = Inhibition - Steps: Shuts off de-novo synthesis of folate (needed for thymidine synthesis) causes a slow killing mechanism - Info: Can be combined with trimethoprim (co-trimoxazole) P-aminobenzoate analogue<div> </div><div><img></img></div>”

Question 46

Q

Suramin

Answer

A

Class = Trypanocidal drug - Target = Glycerol-3-phosphate oxidase + NAD⁺-dependent glycerol-3-phosphate dehydrogenase - Mechanism = Inhibition - Steps: Inhibition of the above enzymes → interference with reoxidation of NADH → ↓ ATP synthesis - Info:

Question 47

Q

Tamoxifen

Answer

A

Class = Hormonal therapy (anticancer) - Target = Oestrogen receptor - Mechanism = Inhibitor - Steps: • Competitively binds to oestrogen receptor (lower affinity than oestrogen) • Once bound ⟶ complex translocates to nucleus ⟶ attenuation of oestrogen-responsive genes involved in development and growth of breast CA - Info: 70% of breast CA is +ve for oestrogen + progesterone receptor ∴ responsive to this therapy Tamoxifen can exert oestrogen agonist effect in other tissues (bone and uterus) Toremifene = tamoxifen analogue without this oestrogen agonist issue

Question 48

Q

Taxol

Answer

A

Class = Taxane - Target = Free tubular dimers - Mechanism = Prevents mitosis - Steps: • Disrupts the equilibrium between free dimers amd microtubules by shifting it in the direction of assembly rather than disassembly • Leads to the stabilization of ordinary cytoplasmic microtubules and the formation of abnormal bundles of microtubules to inhibit mitosis - Info: Used in antiproliferative drug eluting stents in coronary angioplasty for the treatment of angina and ischaemic heart disease Used in treatment of lung, ovarian, breast, head and neck cancer, and in Kaposi’s sarcoma

Question 49

Q

Tetracycline

Answer

A

Class = Antibiotic - Target = 30S subunit - Mechanism = Blocks rotation of aminoacyl-tRNA into A site - Steps: 1) Interacts with Mg²⁺ ion + nucleotides in 16S rRNA of 30S 2) Does not block initial binding of aminoacyl-tRNA, but blocks subsequent rotation into A site 3) Therefore no bond would be formed and peptide would be released prematurely - Info: Bacteriostatic Shows activity against some protozoa (Plasmodium)

Question 50

Q

Topotecan

Answer

A

Class = Topoisomerase type I inhibitor - Target = Topoisomerase type I (human) - Mechanism = Inhibition - Steps: - Info: Used in ovarian and lung CA

Question 51

Q

Trimethoprim

Answer

A

”- Class = Antibiotic - Target = DHFR (dihydrofolate reductase) - Mechanism = Inhibition - Steps: This inhibition traps folate co-enzyme in its useless form (dihydrofolate) Leads to rapid depletion of tetrahydrofolate - Info: Can be combined with sulfamethoxazole (co-trimoxazole)<div> </div><div><img></img></div>”

Question 52

Q

Valinomycin

Answer

A

Class = Antibiotic (Ionophore) - Target = Cell membrane - Mechanism = Disruption of cell membrane - Steps: Forms a circular structure that coordinates K⁺ ion Diffuses across the membrane therefore acts as a K⁺ uniporter Effect is due to dissipation of transmembrane ion gradients This disturbs ion homeostasis and energy metabolism and induce leakage of macromolecules from the bacteria - Info: Contains 3 repeating units of (L-lactate)- (L-valine)-(D-hydroxyisovalerate)-(D-valine) Lacks specificity (phospholipid bilayer not only in bacteria)

Question 53

Q

Vancomycin

Answer

A

Class = Antibiotic (glycopeptide) - Target = Cell wall biosynthesis - Mechanism = Inhibits Peptidoglycan transpeptidase action - Steps: 1) Vancomycin binds to pentapeptidyl tails in PG repeating units that end in D-Ala-D-Ala 2) this makes D-Ala-D-Ala terminus unavailable for transpeptidase enzyme Also reduces availability for the peptidoglycan transglycosylase enzyme - Info: Only proliferating cells in which autolysins are active are sensitive to this antibiotic -Resistance mechanism: -E. faecalis has acquired the Van genes, two tandemly arranged operons. One operon encodes a his-As phosphorelay that activates the second when exposed to antibiotics. The second encodes enzymes that change (D-Ala)5 to (D-lactate)5 in PG pentapeptide to prevent vanc binding.

Question 54

Q

Vinblastine

Answer

A

Class = Vinca alkaloid - Target = Free tubular dimers - Mechanism = Antimitotic - Steps: • Bind to free tubulin dimers ⟶ prevent microtubule assembly • ∴ disrupt the equilibrium between polymerisation and depolymerisation to inhibit mitosis of tumour cells - Info: Results in the disappearance of microtubules Cause granulocytopenia in animals Used in Hodgkin’s lymphoma, non small cell lung cancer, breast cancer and testicular cancer

Question 55

Q

Zanamivir

Answer

A

Class = Anti-influenza drug - Target = Neuraminidase - Mechanism = Inhibitor - Steps: Inhibits NA → ↑ viral aggregation + ↓ release from host - Info: Zanamivir is an active drug

Question 56

Q

Zidovudine (azidothymidine, AZT)

Answer

A

Class = Reverse transcriptase inhibitor (Nucleoside) - Target = Reverse transcriptase - Mechanism = Thymidine analogue → inhibits reverse transcriptase - Steps: 1) Thymidine analogue therefore acts as substrate for reverse transcriptase 2) Lack the 3’OH group therefore causes termination of elongation 3) Usually administered with hydroxyurea (this ↓ natural pyriminadine nucleotides thus enhances the effect of AZT) - Info: Must be phosphorylated by host cell before becoming active Reverse transcriptase activity is early in replication cycle, therefore this drug only has effect early - Resistance: Mutation in enzymes → ↓ interaction between enzyme and inhibitor

Question 57

Q

Define broad spectrum:

Answer

A

Effective against both Gram +ve and Gram -ve

Question 58

Q

Define narrow spectrum:

Answer

A

Effective against either Gram +ve or Gram -ve

Question 59

Q

Define limited spectrum:

Answer

A

Effective against a single organism

Question 60

Q

Define extended spectrum:

Answer

A

Chemically modifying drug to extend spectrum

Question 61

Q

Define bacteriostatic:

Answer

A

Stop bacteria from growing Elimination of bacteria is dependent on human immune system

Question 62

Q

Define bactericidal:

Answer

A

Cause cell death → ↓ cell count

Question 63

Q

Define MIC:

Answer

A

MIC = Minimum inhibitory concentration Minimum conc. that prevents bacterial growth Measure of effectiveness of bacteriostatic drugs

Question 64

Q

Define MBC:

Answer

A

MIC = Minimum bactericidal concentration Minimum conc. that kills bacterial cells Measure of effectiveness of bactericidal drugs

Answer 65

A

Infecting organism is inhibited/killed without damage to host cells

Answer 66

A

Also known as therapeutic ratio Maximum non-toxic dose / minimum effective dose

Answer 67

A

Peptidoglycan (PG)

Answer 68

A

Gram +ve - Thicker PG - Teichoic acid polymers Gram -ve - Thinner PG - Has an outer membrane

Answer 69

A

Two types of cross linking occur: 1) Glycan stands - Enzyme = transglycosylase 2) Peptide strands - Enzyme = transpeptidase Peptide cross-links → introduce covalent bonds (provides strength + is a structural barrier)

Answer 70

A

UDP + NAG → UDP-NAG → NAM-tripeptide NAM-tripeptide → NAM-pentapeptide NAM binds to bactoprenol phosphate NAG links to NAM → NAG-NAM This complex is transporter to outer surface of cell wall On outer surface - PG polymer is formed PG transglycosylase adds building unit to existing PG PG transpeptidase cross links these units

Answer 71

A

It is a serine hydrolase Attacks aminde bond between terminal D-ala₄ D-Ala₅ D-Ala₅ released as free amino acid Intermediate is covalently linked to PG Acyl transfer occurs with neighboring peptide → cross-linking

Answer 72

A

30S 50S

Answer 73

A

Formylmethionine

Answer 74

A

STAGE 1 - Initiation 1) mRNA binds to 30S - Needs IF3 2) tRNA-formylmethionine combines with mRNA-30S - Needs IF1 + IF2 + GTP 3) 50S joins this complex - GTP hydrolysed and all initiation factors are released STAGE 2 - Elongation Needs elongation factors and GTP 1) Amino acids are side by side on the 50S 2) Amino acids get linked by peptide bond (50s has transpeptidyl transferase activity) 3) tRNAs move along (P → E and A → P) 4) 30S unit moves along one codon Continues until stop codon

Answer 75

A

Generally bacteriostatic

Answer 76

A

“<div><img></img></div>”

Answer 77

A

1) Organism lacks receptor for drug 2) Concentration of drug at the target is inadequate

Answer 78

A

Due to high content of mycelia acids in a complex lipid layer outside their PG. This layer is impermeable to many drugs

Answer 79

A

1) Enzymatic inactivation of drug 2) Replacement/ amplification/ modification of drug target 3) Decreased drug uptake or increased efflux

Answer 80

A

Beta lactamase is an enzyme (serine enzyme) that hydrolyses the beta lactam ring.

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7.0 Chemotherapy Flashcards

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