β Correct β B: 6-APA = penam nucleus β 4-membered Ξ²-lactam + 5-membered thiazolidine ring sharing N-C bond. Commercial semi-synthetic penicillins made by (1) fermenting 6-APA from Penicillium chrysogenum culture (penicillin-G acylase cleaves benzyl group), OR (2) chemical enzymatic acylation with appropriate acid chloride. Mechanism: Ξ²-lactam ring mimics D-Ala-D-Ala of peptidoglycan, irreversibly acylates Transpeptidase (PBP = Penicillin-Binding Protein) β blocks peptidoglycan cross-linking β bacterial cell wall weakening β osmotic lysis β bactericidal.
β A wrong: Cephem = cephalosporin nucleus (7-ACA with 6-membered dihydrothiazine).
β C wrong: Macrolides.
β D wrong: Purine = nucleosides.
2
Penicillin is inactivated in stomach because: GPAT 2019
ADenatured by pepsin
BOxidised
CΞ²-lactam ring is acid-labile
DNot inactivated
π Explanation
β Correct β C: Penicillin G (benzylpenicillin) β acid-labile because electron-donating aromatic CHβ side chain increases rate of proton-mediated Ξ²-lactam opening. Semi-synthetic acid-stable penicillins: penicillin V (phenoxymethyl, -OCHβ- EWG); ampicillin (Ξ±-aminobenzyl); amoxicillin (Ξ±-amino-4-hydroxybenzyl); dicloxacillin (isoxazolyl). Ξ²-Lactamase-stable (anti-staphylococcal): methicillin (2,6-dimethoxybenzyl), oxacillin, cloxacillin, nafcillin β bulky R group sterically hinders Ξ²-lactamase. Extended-spectrum: ampicillin + amoxicillin (Gβ» coverage); piperacillin, ticarcillin (Pseudomonas).
β A/B wrong: Mechanism incorrect.
β D wrong: Acid inactivation is real.
3
Ξ²-Lactamase inhibitors include: Most Probable
AClavulanic acid
BAminoglycosides
CQuinolones
DMacrolides
π Explanation
β Correct β A: Old Ξ²-lactam-based inhibitors (irreversible "suicide" inhibitors): clavulanic acid (from Streptomyces clavuligerus) + amoxicillin (Augmentin) or ticarcillin (Timentin); sulbactam + ampicillin (Unasyn), sulbactam + cefoperazone; tazobactam + piperacillin (Zosyn/Tazact). New non-Ξ²-lactam inhibitors β DBO class: avibactam (+ ceftazidime = Avycaz, + aztreonam = Zaviam, + ceftaroline); boronic-acid class: vaborbactam (+ meropenem = Vabomere); relebactam (+ imipenem/cilastatin = Recarbrio). Enmetazobactam, xeruborbactam, taniborbactam β investigational. Cover Ambler classes A, C, some D, NOT class B metallo-Ξ²-lactamases (MBLs).
β B/C/D wrong: Different classes.
4
Cephalosporin nucleus: GPAT 2018
A6-APA
B7-Aminocephalosporanic
CMacrolactone
DErythronolide
π Explanation
β Correct β B: 7-ACA from cephalosporin-C (produced by Acremonium chrysogenum/Cephalosporium). Historical generations β each with wider Gβ» coverage: 1st gen (cefazolin, cefalexin) β broad GβΊ, limited Gβ»; 2nd gen (cefuroxime, cefoxitin) β more Gβ» + anaerobes (cefoxitin is cephamycin); 3rd gen (ceftriaxone, cefotaxime, ceftazidime, cefoperazone) β extended Gβ» incl. Pseudomonas (ceftazidime); 4th gen (cefepime) β broad; 5th gen (ceftaroline, ceftobiprole) β active against MRSA (binds PBP2a). Siderophore cephalosporin: cefiderocol β uses iron transport to enter CRE.
β A wrong: 6-APA = penicillin.
β C wrong: Macrolides.
β D wrong: Erythromycin nucleus.
5
Carbapenem general structure: Most Probable
AΞ²-lactam fused with thiazolidine
BΞ²-lactam alone without fused ring
CΞ²-lactam fused with 5-membered pyrroline
DΞ²-lactam fused with 6-membered ring like cephalosporin
π Explanation
β Correct β C: Carbapenems: imipenem (+ cilastatin to inhibit DHP-I renal deactivation), meropenem, ertapenem, doripenem, faropenem, tebipenem (orally bioavailable prodrug). Broadest-spectrum Ξ²-lactams β cover GβΊ, Gβ» including Pseudomonas (except ertapenem), anaerobes, ESBL-producers, some AmpC. NOT active against MRSA, Enterococcus faecium, Stenotrophomonas, MBL-producing CRE (NDM, VIM, IMP). Adverse: seizures (imipenem > meropenem; avoid in epilepsy + high dose). Reserved for serious/resistant infections β use carefully to avoid selection for CRE.
β A wrong: Penam.
β B wrong: Monobactam.
β D wrong: Cephem.
6
Aztreonam (monobactam) is active against: Most Probable
AGram-positive
BAnaerobes
CFungi
DAerobic Gram-negative
π Explanation
β Correct β D: Aztreonam = only clinically used monobactam; monocyclic Ξ²-lactam (no fused ring). Spectrum = narrow Gβ» including Pseudomonas aeruginosa, Enterobacteriaceae, H. influenzae, Neisseria. No GβΊ or anaerobic activity. Key use: patients with severe penicillin allergy needing Gβ» coverage β structural differences with penicillins mean rare cross-reactivity (except ceftazidime, because of same aminothiazolyl side chain). Resistant to most penicillinases but susceptible to ESBLs; combined with avibactam (aztreonam-avibactam) = active against MBL + KPC producing CRE.
β B wrong: Penicillium = penicillins, griseofulvin.
β C wrong: E. coli is target.
β D wrong: Natural product.
8
Amikacin is resistant to most aminoglycoside-modifying enzymes due to: GPAT 2020
AIts amino groups
BL-Ξ±-hydroxyaminobutyric acid
CLack of OH groups
DLipid solubility
π Explanation
β Correct β B: Amikacin = semi-synthetic from kanamycin A; L-HABA at N1 confers resistance to major aminoglycoside-modifying enzymes (acetyltransferases AAC, phosphotransferases APH, adenyltransferases ANT) by steric hindrance. Arbekacin similar mechanism. Plazomicin (approved 2018) β next-gen AG against CRE, KPC, ESBL producers. All AGs share same ribosomal target; resistance via enzymatic modification (AAC, APH, ANT), efflux, target methylation (16S rRNA methyltransferase β ArmA, RmtB β pan-resistance). Therapeutic drug monitoring (TDM): peak & trough concentrations; once-daily dosing preferred for concentration-dependent killing + reduced toxicity.
β A/C/D wrong: Not the mechanism.
9
Tetracycline basic ring system: GPAT 2019
A3 linear rings
B5 linear rings
COctahydronaphthacene
D6 rings
π Explanation
β Correct β C: Tetra-cycline = 4 rings. First discovered: chlortetracycline (Aureomycin, 1948, Streptomyces aureofaciens); oxytetracycline (Terramycin, 1950, S. rimosus); tetracycline (semi-synthetic, 1953); demeclocycline (natural, S. aureofaciens mutant); methacycline; doxycycline & minocycline (semi-synthetic 2nd gen); tigecycline (glycylcycline, 3rd gen, 2005); eravacycline (2018). Mechanism: bacteriostatic; binds 30S ribosomal subunit at A site β blocks aminoacyl-tRNA entry. Chelate divalent/trivalent cations (CaΒ²βΊ, MgΒ²βΊ, AlΒ³βΊ, FeΒ²βΊ) β reduced absorption with dairy/antacid; deposit in growing bone/teeth β CI children < 8 yrs & pregnancy.
β A/B/D wrong: Wrong ring count.
10
Doxycycline differs from tetracycline in: GPAT 2019
AHigher lipid solubility
BLower potency
COnly injectable
DNo effect on bone
π Explanation
β Correct β A: Doxycycline = Ξ±-6-deoxytetracycline; 2nd-gen with superior PK. Dose 100 mg BD (or 200 mg OD). Uses: atypical pneumonia (Mycoplasma, Chlamydia, Legionella), Rocky Mountain spotted fever & other Rickettsia, Lyme disease (Borrelia burgdorferi), cholera, brucellosis, acne (anti-inflammatory sub-antibacterial dose), malaria prophylaxis (chloroquine-resistant Plasmodium falciparum), periodontitis (sub-antimicrobial for MMP inhibition). Minocycline = methylamino analogue β best BBB penetration (used in neurological infections; pigmentation ADR); also for acne, Mycobacterium leprae, Nocardia.
β B wrong: Similar potency.
β C wrong: Oral mainstay.
β D wrong: Still deposits in bone/teeth (less).
11
Fleming discovered penicillin in: GPAT 2019
A1920
B1928
C1942
D1910
π Explanation
β Correct β B: Fleming (St. Mary's Hospital, London) β serendipitous observation. Ushered "antibiotic era." Production issues (low yield from P. notatum) solved at Oxford (Florey, Chain, Heatley) β P. chrysogenum (higher-yielding) + deep-tank fermentation + corn-steep liquor medium β industrial-scale by WWII. First human patient: Albert Alexander (1941, near-death from septicaemia β recovered then died when supply ran out). Fleming, Florey, Chain = Nobel 1945.
β A/C/D wrong: Wrong years.
12
Chloramphenicol structural features: GPAT 2018
AMacrolactone
BTetracyclic
CNitrobenzene
DAminoglycoside
π Explanation
β Correct β C: Chloramphenicol (from Streptomyces venezuelae 1947; now fully synthetic). Mechanism: binds 50S ribosomal subunit at peptidyl transferase site β blocks peptide bond formation β bacteriostatic. Broad-spectrum. Uses (narrow now because of ADR): typhoid (ceftriaxone preferred now), meningitis (alternative), anaerobic, rickettsial. ADR: reversible bone marrow suppression (dose-dependent); idiosyncratic aplastic anaemia (1 in 25,000-40,000; fatal; unpredictable) β limits use; "Gray baby syndrome" in neonates (β UGT conjugation β accumulation β vasomotor collapse). Thiamphenicol (less aplastic anaemia); chloramphenicol succinate (IV prodrug); palmitate (oral suspension).
β A/B/D wrong: Different classes.
13
Vancomycin mechanism: Most Probable
AGlycopeptide
BInhibits topoisomerase
CBlocks 30S ribosome
DInhibits dihydrofolate reductase
π Explanation
β Correct β A: Vancomycin (Amycolatopsis orientalis, 1955 β old drug, still front-line for MRSA) binds by 5 H-bonds to D-Ala-D-Ala. Resistance mechanism in VRE/VRSA: alter terminus to D-Ala-D-Lactate (vanA, vanB β inducible) or D-Ala-D-Ser (vanC β intrinsic in E. gallinarum/casseliflavus) β β affinity 1000Γ. IV for systemic (not oral-absorbed); oral for C. difficile colitis (acts locally). ADR: "red man syndrome" (histamine release on rapid IV); nephrotoxicity (AUC > 600 mgΒ·h/L); ototoxicity. Target AUC/MIC > 400. Related: teicoplanin, dalbavancin, oritavancin, telavancin (lipoglycopeptides β bactericidal + membrane disruption).
β B wrong: Quinolones.
β C wrong: Aminoglycosides/tetracyclines.
β D wrong: Trimethoprim/sulphonamides.
14
Penicillin-G is typically administered: GPAT 2019
AOrally
BTopically
CRectally
DIM or IV
π Explanation
β Correct β D: Penicillin G (crystalline Na/K salt) β IV; short tΒ½ (30 min). Procaine penicillin G β IM suspension; 12-24 h duration. Benzathine penicillin G β IM; very prolonged (2-4 weeks) β single-shot treatment of syphilis (all stages except neurosyphilis which requires IV aq penicillin); secondary prophylaxis for rheumatic fever. Oral Pen V (phenoxymethyl) β acid-stable; used for strep pharyngitis, step 1 in rheumatic fever prevention. Uses: meningococcus, streptococci (all), Treponema pallidum, Listeria (with gentamicin), Actinomyces. Resistance common in Staphylococcus (95%+ produce Ξ²-lactamase) and increasingly Pneumococcus (via altered PBP2x).
β A/B/C wrong: Not main routes.
15
Methicillin is unique among penicillins because: GPAT 2019
AAcid stable
BΞ²-Lactamase-resistant
CBroad spectrum
DActive against Pseudomonas
π Explanation
β Correct β B: "Anti-staphylococcal penicillins" or "isoxazolyl penicillins" (cloxacillin, oxacillin, flucloxacillin, dicloxacillin) β bulky side chains. MRSA mechanism: mecA gene encodes PBP2a (=PBP2'), a low-affinity PBP β all Ξ²-lactams lose activity except newer 5th-gen cephalosporins (ceftaroline, ceftobiprole which bind PBP2a). Also, MRSA isolates are resistant to ALL standard Ξ²-lactams. Treatment: vancomycin / linezolid / daptomycin / ceftaroline / tigecycline (AUC/MIC pharmacodynamics important).
β A/C/D wrong: Not the distinguishing feature.
16
Ampicillin differs from penicillin-G in: GPAT 2019
AMore active against MRSA
BΞ²-lactamase stability
CBroader Gram-negative spectrum
DBetter CNS penetration
π Explanation
β Correct β C: Ampicillin = aminobenzylpenicillin. Amoxicillin = Ξ±-amino-4-hydroxybenzylpenicillin; better oral (~ 90 %), same spectrum as ampicillin. Amoxicillin-clavulanate = popular combination. Ampicillin ADR: rash (esp. with EBV β Mono rash), diarrhoea (β normal flora disruption vs amoxicillin). Still Ξ²-lactamase susceptible β not effective against Ξ²-lactamase-producing strains without inhibitor. Ampicillin-sulbactam = IV combo.
β A wrong: Not active against MRSA.
β B wrong: Ξ²-lactamase-labile.
β D wrong: Similar CNS penetration.
17
Ceftriaxone is a 3rd-gen cephalosporin with: GPAT 2018
ALong tΒ½
BShort tΒ½
COnly IV
DOnly topical
π Explanation
β Correct β A: Ceftriaxone β IV/IM once daily. Does not require renal adjustment. CI: biliary sludging β avoid in neonates + calcium-containing IV solutions (fatal precipitates). DOC: community-acquired meningitis, gonorrhoea (single IM 500 mg), typhoid (ceftriaxone vs ciprofloxacin β widespread resistance now), CAP, endocarditis (with vancomycin), chancroid, severe otitis. Cefotaxime = similar spectrum, shorter tΒ½, no biliary sludging. Ceftazidime = anti-pseudomonal 3rd-gen (loses anti-Gram-positive coverage compared to ceftriaxone).
β B/C/D wrong: Not accurate.
18
Imipenem is administered with cilastatin because: Most Probable
AAdjuvant activity
BCilastatin is a dehydropeptidase-I
CCilastatin is antibiotic
DSynergistic against Pseudomonas
π Explanation
β Correct β B: Imipenem (first carbapenem, 1985) is hydrolysed by renal DHP-I β nephrotoxic. Cilastatin is specific DHP-I inhibitor (not antibacterial) β co-administered 1:1 as Primaxin/Tienam. Newer carbapenems β meropenem, ertapenem, doripenem β have 1Ξ²-methyl substituent that makes them DHP-I-stable β no cilastatin needed. Meropenem now preferred (fewer seizures, broader Gβ»). Carbapenems reserved for serious MDR infections; CRE (via KPC, OXA-48, NDM, VIM, IMP) is growing problem globally β need new agents (ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, plazomicin etc.).
β A/C/D wrong: Incorrect.
19
Tigecycline is classified as: Most Probable
AMacrolide
BAminoglycoside
CFluoroquinolone
DGlycylcycline
π Explanation
β Correct β D: Tigecycline approved 2005 (Tygacil). Steric bulk at C9 overcomes tet(M) & tet(B) efflux/ribosomal protection β active against tetracycline-resistant strains. FDA black-box: β mortality vs comparators in trials (attributed to wider use in MDR septicaemia). Not effective in bloodstream infection alone. Eravacycline (Xerava, 2018) β similar class, IV+oral prodrug. Omadacycline (Nuzyra, 2018) β aminomethylcycline, oral + IV. Sarecycline β narrow-spectrum for acne only.
β Correct β B: Sulbactam β ("suicide" inhibitor) binds serine at Ξ²-lactamase active site β irreversible covalent inhibition. Unique: has intrinsic anti-Acinetobacter baumannii activity (binds PBP2/3), often exploited for MDR Acinetobacter. Tazobactam (similar mechanism, piperacillin-tazobactam = Zosyn/Tazact β broad spectrum IV). Durlobactam β new DBO inhibitor + sulbactam (Xacduro 2023) for carbapenem-resistant Acinetobacter baumannii. Clavulanic acid (Amoxiclav, Augmentin) β oldest. All inhibit Ambler class A & some class D, NOT class C (AmpC) or B (metallo).
β Correct β B: Imidazoles (topical mainly β clotrimazole, miconazole, econazole, ketoconazole β also PO historically but hepatotoxicity + adrenal). Triazoles (systemic): fluconazole (Candida except krusei/glabrata; oral, IV; BBB +), itraconazole (Aspergillus, endemic mycoses; oral capsule/solution), voriconazole (Aspergillus DOC; QT, visual disturbances, hepatotoxicity, SCC risk), posaconazole (broad incl. Mucor), isavuconazole (broad, tolerable, QT-shortener unlike others). Drug-drug interactions plentiful β all are CYP3A4 inhibitors (voriconazole + fluconazole also 2C9, 2C19). Resistance: ERG11 mutations, efflux (CDR, MDR pumps). Ketoconazole SYSTEMIC β also inhibits steroid synthesis (CYP17, CYP11) β used off-label for Cushing's.
β A/C/D wrong: Wrong targets.
35
Echinocandins (caspofungin, micafungin, anidulafungin, rezafungin): Most Probable
AInhibit Ξ²- -D-glucan
BBind ergosterol
CInhibit CYP51
DInhibit DNA synthesis
π Explanation
β Correct β A: Echinocandins = semi-synthetic cyclic lipopeptides. Unique fungal target (humans lack Ξ²-1,3-glucan synthase) = selective toxicity. Rezafungin (2023) β once-weekly dosing due to long tΒ½. Ibrexafungerp β first oral glucan synthase inhibitor (approved 2021 for vulvovaginal candidiasis). Resistance: fks1/fks2 hot spot mutations. No cross-resistance with azoles or AmB. DOC for candidaemia/invasive candidiasis (except CNS where fluconazole/AmB preferred due to CSF penetration).
β B wrong: Polyene mechanism.
β C wrong: Azole mechanism.
β D wrong: Flucytosine mechanism.
36
Griseofulvin mechanism: GPAT 2020
AErgosterol binder
BGlucan synthase inhibitor
CBinds fungal microtubule β inhibits
DInhibits squalene epoxidase
π Explanation
β Correct β C: Griseofulvin (Penicillium griseofulvum 1939). Oral; absorbed best with fatty meal. Narrow spectrum β dermatophytes only (Trichophyton, Microsporum, Epidermophyton). Long duration: scalp ringworm (tinea capitis) 6-8 wks, onychomycosis 6-12 months. Largely replaced by: terbinafine (squalene epoxidase inhibitor β squalene accumulates toxic; fungicidal; short duration 6 wks nails; oral/topical; hepatotoxic), itraconazole (pulse dosing for nails 400 mg/day 1 week/month Γ 2-3 cycles). Topical: clotrimazole, ketoconazole, terbinafine, naftifine, butenafine, amorolfine, ciclopirox for superficial fungal.
β A/B/D wrong: Other targets.
37
Flucytosine (5-FC) mechanism: Most Probable
APolyene
BAzole
CEchinocandin
DFluorinated
π Explanation
β Correct β D: 5-FC β narrow-spectrum: Cryptococcus neoformans (cryptococcal meningitis in HIV β AmB + 5-FC induction phase), Candida. ADR: bone marrow suppression (from small amount of 5-FU formed in enterocytes by gut flora deaminase), hepatotoxicity, colitis. Dose-adjusted by TDM (peak < 100 Β΅g/mL). Oral bioavailability good. Monotherapy rapidly selects for resistance. Combined with fluconazole for cryptococcal meningitis in resource-limited settings where AmB unavailable.
β A/B/C wrong: Different classes.
38
Metronidazole is activated by: GPAT 2018
AOxidative environment
BReduction by anaerobic
CΞ²-lactamase
DCYP3A4
π Explanation
β Correct β B: Metronidazole β 5-nitroimidazole. Active against anaerobes (B. fragilis, Clostridia) + protozoa (Entamoeba, Giardia, Trichomonas). Uses: PID, intra-abdominal, pseudo-membranous colitis (oral for C. difficile β now vancomycin or fidaxomicin preferred), H. pylori (triple therapy), BV. ADR: metallic taste, nausea, disulfiram-like reaction (avoid alcohol 24 h), peripheral neuropathy (long use), rare neurotoxicity. CYP2C9 substrate, CYP3A4 inhibitor. Pregnancy category B (avoid 1st trimester). Tinidazole = longer tΒ½, similar spectrum. Nitazoxanide = broad anti-protozoal/anti-helminthic; active in Cryptosporidium, Giardia, H. pylori adjunct.
β A/C/D wrong: Not activation pathway.
39
Clindamycin mechanism: Most Probable
ABinds 50S ribosomal
BΞ²-lactam
CAminoglycoside
DDNA gyrase
π Explanation
β Correct β A: Clindamycin = lincosamide (chlorinated 7-deoxy derivative of lincomycin, Streptomyces lincolnensis). Excellent for aspiration pneumonia, lung abscess, necrotising fasciitis, MRSA soft-tissue (CA-MRSA often retains clinda sensitivity). Also inhibits toxin production in S. aureus/S. pyogenes (TSS β adjunct with antitoxin/IVIG). Uses: anaerobes, streptococci, staph (test D-zone for inducible clindamycin resistance = iMLSB phenotype), CA-MRSA, toxoplasmosis (with pyrimethamine), malaria (falciparum adjunct). Topical for acne. Resistance: erm methyltransferase (= MLSB, cross-resistance with macrolides + B streptogramin).
β B/C/D wrong: Different classes.
40
Voriconazole major ADR: GPAT 2020
ANephrotoxicity
BOtotoxicity
CVisual disturbances
DBone marrow suppression
π Explanation
β Correct β C: Voriconazole β 2nd-gen triazole; DOC for invasive aspergillosis. CYP2C19 genetic polymorphism important β poor metabolisers need lower dose (TDM recommended; target trough 1-5.5 Β΅g/mL). Many drug interactions (CYP3A4 substrate + inhibitor). Visual symptoms typically transient. Long-term use in immunocompromised β skin SCC (avoid sun, regular dermatological screening). Isavuconazole = newer, tolerable, QT-shortening (not prolonging β unlike other azoles), broad-spectrum including Mucor.
β A/B/D wrong: Not signature.
41
Ethambutol ADR: GPAT 2019
AHyperuricaemia
BDose-dependent retrobulbar
COrange urine
DPeripheral neuropathy
π Explanation
β Correct β B: ATT ADR summary: Isoniazid β peripheral neuropathy (add pyridoxine), hepatotoxicity; Rifampicin β hepatotoxicity, orange body fluids, flu-like, CYP inducer; Pyrazinamide β hepatotoxicity, hyperuricaemia (avoid in gout), arthralgia; Ethambutol β optic neuritis, acidosis; Streptomycin β ototoxicity (vestibular), nephrotoxicity. Drug-induced hepatitis (DIH): if AST > 3Γ ULN with symptoms, or > 5Γ asymptomatic β stop & re-challenge after recovery. Renal impairment: reduce Z + E doses; rifampicin + isoniazid safe.
β A wrong: Pyrazinamide.
β C wrong: Rifampicin.
β D wrong: Isoniazid.
42
Nitrofurantoin is used for: Most Probable
AUncomplicated lower UTI
BTB
CMeningitis
DPneumonia
π Explanation
β Correct β A: Nitrofurantoin β activated intracellularly by bacterial nitroreductase β reactive intermediates damage DNA, ribosomes, cell wall. Concentrates in urine > 20Γ serum β effective cystitis agent. Dose: 100 mg BD Γ 5 days. Preferred first-line due to minimal resistance & low collateral damage. ADR: acute pulmonary reactions (pneumonitis), chronic pulmonary fibrosis (long-term), peripheral neuropathy, hepatotoxicity, haemolysis in G6PD deficiency. CI: renal impairment (CrCl < 30 β inadequate urine levels + more toxicity), 3rd trimester (fetal haemolysis), neonates. Fosfomycin single 3 g dose β alternative for cystitis.
β B/C/D wrong: Not UTI indications.
43
Trimethoprim-sulphamethoxazole (cotrimoxazole) first choice for: GPAT 2020
ATB
BMeningococcus
CCholera
DPneumocystis
π Explanation
β Correct β D: PCP in HIV: cotrimoxazole TMP 15-20 mg/kg/day IV/PO for 21 days; prophylaxis at CD4 < 200. ARDS-like presentation in advanced immunosuppression β add steroids if PaOβ < 70 mmHg. Pentamidine, atovaquone, primaquine-clindamycin = alternatives. Stenotrophomonas maltophilia β intrinsically resistant to carbapenems; cotrimoxazole is DOC. Whipple disease, brucella, listeria (alternative) also treated. Toxoplasmosis in immunocompromised: pyrimethamine + sulphadiazine + folinic acid (cotrimoxazole if SMX preferred). ADR: hyperkalaemia, rash, SJS, haemolysis in G6PD, renal impairment exaggerated creatinine.
β A/B/C wrong: Not DOC.
44
Terbinafine's mechanism: Practice Question
ACYP51 inhibitor
BAllylamine inhibitor of fungal
CΞ²-glucan synthase inhibitor
DPolyene
π Explanation
β Correct β B: Terbinafine (Lamisil) = allylamine. 250 mg OD Γ 6 wks for fingernail, 12 wks for toenail onychomycosis. Topical 1 % cream for tinea corporis/cruris/pedis. ADR: hepatotoxicity (rare but idiosyncratic, check LFTs), taste disturbance, neutropenia, SJS/TEN, lupus flare, depression. CYP2D6 inhibitor β care with antidepressants, Ξ²-blockers. Naftifine, butenafine β related topicals. Tolnaftate (OTC topical) β similar mechanism.
β Correct β D: Neuraminidase = viral surface enzyme that cleaves sialic acid from host cells β releases new virion. Inhibitors: oseltamivir (Tamiflu, oral prodrug β oseltamivir carboxylate), zanamivir (Relenza, inhaled), peramivir (IV), laninamivir (inhaled, Japan). M2 inhibitors (amantadine, rimantadine) β withdrawn for influenza due to resistance (now used in Parkinson's). Baloxavir marboxil (Xofluza, 2018) β first-in-class PA endonuclease inhibitor for influenza; single-dose oral. Oseltamivir: rationale in epidemics/pandemics (swine flu H1N1 2009, COVID-flu coinfections); modest benefit in uncomplicated flu but reduces complications in high-risk.
β A wrong: Amantadine class (withdrawn).
β B/C wrong: HIV classes.
48
Remdesivir mechanism: Most Probable
AProtease inhibitor
BAdenosine nucleotide
CNeuraminidase inhibitor
DM2 blocker
π Explanation
β Correct β B: Remdesivir (Veklury) β broad-spectrum RdRp inhibitor originally developed for Ebola; approved for SARS-CoV-2 (2020). IV only, 5 days (or 10 for ventilated). Evidence: shortens time to recovery (ACTT-1 trial), mixed mortality benefit (Solidarity showed no mortality β). Works best early + high-risk outpatients. Other COVID drugs: nirmatrelvir/ritonavir (Paxlovid β SARS-CoV-2 main protease inhibitor, oral 5 days early; many drug interactions via CYP3A4); molnupiravir (oral mutagenic ribonucleoside β error catastrophe; teratogenic CI pregnancy); ensitrelvir (Xocova, Japan). Monoclonal antibodies mostly obsolete due to variants.
β A/C/D wrong: Different antiviral classes.
49
Chloroquine resistance mechanism in Plasmodium falciparum: GPAT 2020
AΞ²-lactamase
BEfflux of chloroquine from parasite food vacuole β encoded by pfcrt gene mutation (K76T primary marker) + pfmdr1
CEfflux via pfcrt gene mutation
DTarget amplification
π Explanation
β Correct β C: Chloroquine accumulates in parasite food vacuole (acidic pH) by ion trapping β binds ferriprotoporphyrin IX (haem β toxic by-product of haemoglobin digestion) β prevents haemozoin (hemozoin) polymerisation β parasite toxicity. Resistance (PfCRT K76T mutation) β accelerated efflux of protonated chloroquine out of vacuole. CQ now obsolete for P. falciparum in almost all endemic regions (widespread resistance since 1990s). Still effective for P. vivax (some resistance emerging) + P. ovale + P. malariae. Hydroxychloroquine β similar to CQ; also used in SLE, RA (autoimmune).
β A/D wrong: Other mechanisms.
50
Primaquine is used for: GPAT 2020
ARadical cure of vivax malaria
BOnly erythrocytic stage
CFungal infections
DTB
π Explanation
β Correct β A: Primaquine β 8-aminoquinoline. After blood stages cleared by chloroquine/artemisinin β primaquine 0.25-0.5 mg/kg/day Γ 14 days for radical cure (prevents relapse from liver hypnozoites in P. vivax/ovale). Tafenoquine (Krintafel) β single-dose 300 mg alternative for radical cure, approved 2018, but same G6PD concern. Severe haemolysis in G6PD-deficient patients (5-10% in many endemic areas) β routinely test. Methaemoglobinaemia. CI in pregnancy + infancy (fetal G6PD status unknown). Gametocyte-killing reduces transmission β public health benefit.
β B wrong: Schizonticides (chloroquine, artemisinin).
β C wrong: Antifungals.
β D wrong: Anti-TB.
51
Artemisinin-based combination therapy (ACT) β first-line for P. falciparum malaria: GPAT 2020
AChloroquine alone
BExamples
CMefloquine alone
DPrimaquine alone
π Explanation
β Correct β B: Artemisinins β rapid parasite clearance but short half-life β must combine with longer-acting partner to prevent resistance. WHO recommends 5 ACTs for uncomplicated malaria. Severe falciparum malaria: IV/IM artesunate Γ 24 h (minimum 3 doses), then complete with oral ACT. Monotherapy with artemisinins is prohibited by WHO. India NVBDCP first-line: AL (artemether-lumefantrine) in North-East, AS+SP elsewhere. Resistance to artemisinins emerged in Greater Mekong (Cambodia, Thailand, Myanmar) β kelch13 (K13) propeller mutations; now spreading to Africa (Rwanda, Uganda). Triple-ACT (e.g., DHA-PPQ + mefloquine) under study.
β A/C/D wrong: Monotherapies not recommended for falciparum.
52
Metronidazole is DOC for: GPAT 2018
AMalaria
BLeishmaniasis
CTrypanosomiasis
DIntestinal & hepatic
π Explanation
β Correct β D: Amoebiasis therapy: (1) Metronidazole 800 mg TDS Γ 5-10 days for invasive disease (intestinal + hepatic); (2) follow with a LUMINAL agent (paromomycin, iodoquinol, diloxanide furoate) to eradicate intraluminal cysts (metronidazole does not reach the colonic lumen well). Tinidazole = longer tΒ½ (14 h), once daily dosing alternative. Nitazoxanide β for Cryptosporidium, also Giardia. ADR metronidazole: metallic taste, disulfiram-like (avoid alcohol), peripheral neuropathy (prolonged use), neurotoxicity. Category B pregnancy (avoid 1st trimester).
β A/B/C wrong: Not primary indications.
53
Sofosbuvir mechanism: Most Probable
ANS5B polymerase inhibitor
BProtease inhibitor
CIntegrase inhibitor
DCCR5 antagonist
π Explanation
β Correct β A: DAA era revolutionised HCV β cure rates > 95 % with 8-12 week oral regimens (no interferon/ribavirin). Classes: NS3/4A protease inhibitors (-previr suffix β glecaprevir, voxilaprevir, grazoprevir); NS5A inhibitors (-asvir β ledipasvir, velpatasvir, elbasvir, pibrentasvir); NS5B polymerase inhibitors (-buvir β sofosbuvir nucleotide, dasabuvir non-nucleoside). Pan-genotypic regimens: sofosbuvir/velpatasvir (Epclusa), glecaprevir/pibrentasvir (Mavyret). WHO 2030 goal: HCV elimination β India has generic DAA production enabling cost < $100 per course.
β B/C/D wrong: HIV drug classes.
54
Liposomal amphotericin B is DOC for: GPAT 2020
AHIV
BVisceral leishmaniasis
CMalaria
DTB
π Explanation
β Correct β B: Kala-azar (Leishmania donovani in Indian subcontinent). Previous first-line: sodium stibogluconate (pentavalent antimony β now obsolete in India due to resistance in Bihar > 60 %). Current first-line: single-dose liposomal AmB 10 mg/kg (99 % cure; WHO-recommended); alternative miltefosine (first oral anti-leishmanial, 100 mg Γ 28 days, teratogenic); paromomycin injection 15 mg/kg Γ 21 days; combinations for XDR / PKDL. HIV-VL coinfection requires combination + ART. India's Kala-azar Elimination Programme targets < 1 case/10,000 at sub-district level.
β A/C/D wrong: Different diseases.
55
Miltefosine mechanism: Most Probable
AInhibits DNA
BKills by osmotic disruption
CAlkylphosphocholine that disrupts
DFolate antagonist
π Explanation
β Correct β C: Miltefosine (hexadecylphosphocholine) β originally developed as anticancer agent; approved 2002 for VL. Active against cutaneous leishmaniasis (L. braziliensis), mucocutaneous, visceral, free-living amoeba (Acanthamoeba, Naegleria, Balamuthia β last-resort in PAM). ADR: GI (common), hepatotoxic, nephrotoxic, teratogenic. Long tΒ½ (~ 150 h) means contraception for 3 months after. Resistance: alterations in P-type ATPase, CDR1 efflux.
β A/B/D wrong: Not the mechanism.
56
Pentamidine is used for: Most Probable
AAfrican trypanosomiasis
BTB
CHIV
DInfluenza
π Explanation
β Correct β A: Pentamidine β aromatic diamidine; intracellular binding to DNA (kinetoplast), inhibits multiple parasite enzymes. IM / IV / inhaled (for PCP prophylaxis). Severe ADR: severe hypotension (IV infusion), hypoglycaemia + ketoacidosis + insulin-dependent diabetes, pancreatitis, nephrotoxicity, QT prolongation, arrhythmias. For T. brucei gambiense stage 2 (CNS) β eflornithine (DFMO) or nifurtimox-eflornithine combination therapy (NECT). T. brucei rhodesiense (East African) β suramin (stage 1), melarsoprol (stage 2; very toxic with post-treatment reactive encephalopathy 5-10 %). Fexinidazole (2018) β first oral drug for both stages.
β B/C/D wrong: Not the indications.
57
Nifurtimox + benznidazole used for: Most Probable
AMalaria
BKala-azar
CGiardiasis
DAmerican trypanosomiasis
π Explanation
β Correct β D: Chagas disease β Trypanosoma cruzi, transmitted by reduviid bug ("kissing bug") in Latin America. Acute phase β myocarditis, meningoencephalitis. Chronic β "megasyndromes" (megacolon, megaoesophagus, cardiomyopathy β heart failure). Benznidazole (first-line, 60 days) + nifurtimox (alternative). Both are nitro-heterocycles activated by parasite nitroreductase. ADR: GI, peripheral neuropathy, rash, bone marrow suppression. WHO Chagas elimination effort. Fexinidazole (approved 2018) also for Chagas in some regulatory approvals.
β A/B/C wrong: Other diseases.
58
Mefloquine is used for: GPAT 2020
AAmoebiasis
BMalaria chemoprophylaxis
CLeishmaniasis
DTrypanosomiasis
π Explanation
β Correct β B: Mefloquine (Lariam) β arylaminoalcohol; long tΒ½ (3 weeks); weekly dosing for prophylaxis + 3-dose treatment. ADR: neuropsychiatric (vivid dreams, anxiety, depression, psychosis β FDA black box 2013); cardiotoxicity (QT). CI: history of seizures, depression, psychosis; 1st-trimester pregnancy (2nd-3rd OK). Atovaquone-proguanil (Malarone) = daily alternative with better tolerability but shorter duration. Doxycycline β cheaper daily option with photosensitivity. Tafenoquine (ArakodaΓ) β weekly prophylaxis like primaquine but single-dose.
β A/C/D wrong: Different indications.
59
Oseltamivir dose for adult influenza treatment (5 days): Most Probable
A75 mg BD oral Γ 5 days
B500 mg single dose
C10 mg IV
D1 g TID
π Explanation
β Correct β A: Oseltamivir β prodrug oseltamivir phosphate β oseltamivir carboxylate (active). Adult 75 mg BD Γ 5 days treatment; 75 mg OD Γ 7-10 days prophylaxis. Paediatric dose by weight. Severe influenza may need dose increase + duration extension. Renal dose adjustment if CrCl < 30. ADR: nausea & vomiting (take with food), transient neuropsychiatric events in children (Japan reports). Rising resistance β H275Y mutation in H1N1pdm09 β oseltamivir-resistant. Baloxavir 40-80 mg single dose alternative.
β B/C/D wrong: Wrong dose/route.
60
Pyrimethamine is used for toxoplasmosis β always given with: Most Probable
AVitamin B12
BLeucovorin
CPyridoxine
DVitamin C
π Explanation
β Correct β B: Pyrimethamine β 2,4-diaminopyrimidine; DHFR inhibitor selective for parasite DHFR (~ 1000Γ selectivity). Uses: toxoplasmosis (with sulphadiazine, "Toxo regimen"); P. falciparum malaria (with sulphadoxine as Fansidar; now obsolete for prophylaxis due to resistance; IPT-p for pregnant women in Africa); Pneumocystis (alternative to cotrimoxazole). Folinic acid bypasses DHFR block in host (parasite cannot use folic acid from outside β selective). Price controversy β Turing Pharmaceuticals raised US price from $13.50 to $750/pill (2015, Martin Shkreli).
β A/C/D wrong: Other vitamins.
61
Praziquantel is antihelmintic β active against: Most Probable
AMalaria
BAmoebiasis
CSchistosomiasis
DOnly nematodes
π Explanation
β Correct β C: Praziquantel β drug of choice for all forms of schistosomiasis (S. mansoni, haematobium, japonicum, intercalatum, mekongi), taeniasis (T. saginata, solium), hymenolepiasis, diphyllobothriasis. Also used in CNS cysticercosis (with dexamethasone + albendazole β 15 mg/kg Γ 8-30 days). Liver flukes (Opisthorchis, Clonorchis) responsive. Dose 20-25 mg/kg q 4 h Γ 3 doses. ADR: abdominal cramps, dizziness, urticaria (dying parasite reaction). Larval cestode infestations (hydatid disease β Echinococcus) β albendazole primary.
β A/B/D wrong: Not the spectrum.
62
Ivermectin is used for: Practice Question
AOnchocerciasis
BMalaria
CHIV
DCancer
π Explanation
β Correct β A: Ivermectin (Mectizan) β macrocyclic lactone from Streptomyces avermitilis (Campbell & Εmura Nobel 2015). Binds parasite Glu-Cl channels β hyperpolarisation/paralysis (mammals lack these; GABA-A less affected below clinical doses). P-gp protects mammalian BBB from entry β hence safety. Mass drug administration programmes for river blindness (Onchocerciasis) in Africa & Americas (donated by Merck since 1987 = "Mectizan Donation Program"); elephantiasis (lymphatic filariasis) under WHO GPELF. COVID-19 controversy β no proven benefit in RCTs (WHO, FDA, EMA discouraged use).
β Correct β B: Albendazole (Zentel) β single 400 mg for Ascaris, hookworm, Enterobius (pinworm β repeat 2 weeks); multiple doses for strongyloidiasis, cutaneous larva migrans, trichinellosis, echinococcosis (hydatid cyst 10-15 mg/kg Γ 1-6 months). Also covers Taenia, Giardia, microsporidia, neurocysticercosis (with praziquantel + steroids). Metabolised to active albendazole sulphoxide. Food (fatty) β absorption. Mebendazole = older benzimidazole, similar spectrum. ADR: hepatotoxic with long-term use, marrow suppression. Teratogenic (avoid 1st trimester).
β A/C/D wrong: Wrong mechanisms.
64
Diethylcarbamazine (DEC) is used for: Most Probable
ALymphatic filariasis
BMalaria
CAmoebiasis
DTB
π Explanation
β Correct β A: DEC = piperazine derivative; microfilaricidal + partially adulticidal. India's "National Filaria Elimination Programme" β annual MDA with DEC + albendazole in endemic districts. Dose: 6 mg/kg Γ 12 days for individual, or 400 mg single dose in MDA. CI: onchocerciasis (causes Mazzotti-like severe reaction) + co-infection with Loa loa (risk of encephalopathy). Triple therapy IDA (ivermectin + DEC + albendazole) β new WHO-endorsed MDA strategy for accelerated elimination.
β B/C/D wrong: Other diseases.
65
Pyrantel pamoate mechanism: Most Probable
AΞ²-tubulin binder
BFolate antagonist
CDepolarising neuromuscular blocker
DDNA polymerase inhibitor
π Explanation
β Correct β C: Pyrantel β OTC in many countries; single dose 10-11 mg/kg. Covers Ascaris lumbricoides, Enterobius vermicularis (pinworm), hookworms. Not effective against whipworm (Trichuris). Safe profile. Levamisole (another nAChR agonist; historically for Ascaris, now rarely β immunomodulator in cocaine adulteration). Pyrantel contrast: piperazine β GABA agonist β flaccid paralysis (obsolete due to toxicity). Tapeworms respond to niclosamide (oxidative phosphorylation uncoupler β tapeworm-specific) or praziquantel.
β A/B/D wrong: Different mechanisms.
66
First-line anti-leprosy regimen (WHO MDT, multi-drug therapy): Most Probable
AMultibacillary leprosy
BIsoniazid alone
CStreptomycin monotherapy
DPenicillin
π Explanation
β Correct β A: India's National Leprosy Eradication Programme (NLEP) provides MDT blister packs free. Dapsone = DHPS inhibitor (similar to sulphonamides); ADR = haemolysis in G6PD, methaemoglobinaemia, sulphone syndrome, agranulocytosis. Clofazimine = red-orange pigmentation (reversible), GI, crystal deposits in liver/lymph nodes. Rifampicin same as anti-TB. 2018 WHO recommended single-dose rifampicin + moxifloxacin + minocycline as post-exposure prophylaxis. Second-line drugs: minocycline, clarithromycin, ofloxacin, moxifloxacin.
β B/C/D wrong: Monotherapies not used.
67
Dapsone (4,4'-diaminodiphenylsulphone) mechanism: Most Probable
ACell wall
BInhibits
CDNA gyrase
DRibosomal 50S
π Explanation
β Correct β B: Dapsone β sulphone; same site as sulphonamides. Uses: leprosy, PCP prophylaxis, dermatitis herpetiformis (anti-inflammatory action), acne, vasculitis. Also used for insect-bite reactions with toxic necrosis (brown recluse spider β though evidence weak). ADR: haemolytic anaemia (especially in G6PD deficiency β test first!), methaemoglobinaemia (treat with methylene blue), agranulocytosis, dapsone hypersensitivity syndrome (DRESS), motor neuropathy (long-term high dose), skin pigmentation. NAT2 polymorphism β slow acetylators accumulate more β β ADR.
β A/C/D wrong: Wrong targets.
68
Clofazimine's unique ADR: Most Probable
AOtotoxicity
BNephrotoxicity
CNeuropathy
DReddish-brown to black
π Explanation
β Correct β D: Clofazimine β riminophenazine; binds mycobacterial DNA + generates reactive oxygen species. Highly lipophilic β accumulates in adipose & skin & macrophages β pigmentation. Phase II trial showed QT prolongation in MDR-TB. Also has anti-inflammatory properties β useful in ENL (Erythema Nodosum Leprosum) type 2 lepra reaction. Alternative leprosy drugs: ofloxacin, minocycline, clarithromycin. For ENL reactions: thalidomide (WHO recommended β CI pregnancy), prednisolone, pentoxifylline.
β A/B/C wrong: Not the characteristic ADR.
69
Methenamine is a urinary antiseptic that releases: Most Probable
AChlorine
BIodine
CFormaldehyde
DMercury
π Explanation
β Correct β C: Methenamine (hexamine) β hexamethylenetetramine; in acidic urine decomposes to formaldehyde + NH4. Used for long-term UTI prophylaxis (not treatment). Must co-administer acidifier (mandelic acid = methenamine mandelate; hippuric acid = methenamine hippurate). Limited efficacy against urease-producing organisms (Proteus, Providencia) that alkalinise urine. Alternatives for UTI prophylaxis: low-dose nitrofurantoin, trimethoprim, cranberry products (modest evidence), D-mannose, vaccine (Uro-Vaxom), topical vaginal estrogen (postmenopausal).
β A/B/D wrong: Wrong chemistry.
70
Nalidixic acid (1st gen quinolone) primary use: GPAT 2019
AUncomplicated UTI
BMeningitis
CEndocarditis
DTB
π Explanation
β Correct β A: Nalidixic acid (1962) = founder of quinolone class; narrow Gβ» (E. coli, Proteus, etc.); used for UTI & bacillary dysentery historically. Modern era: fluoroquinolones (ciprofloxacin, levofloxacin) have superseded nalidixic acid; nalidixic acid sensitivity used in labs as surrogate for emerging fluoroquinolone non-susceptibility in Salmonella. Pipemidic acid, pefloxacin = 2nd gen; cinoxacin intermediate. SAR of quinolone: C3 COOH + C4 ketone essential; C6 F β gyrase binding; C7 piperazine/pyrrolidine β spectrum; C8 methoxy β phototoxicity.
β B/C/D wrong: Not adequate for these.
71
Fosfomycin mechanism & use: Most Probable
AΞ²-lactam
BRibosomal 30S binder
CFolate antagonist
DPhosphoenolpyruvate analogue
π Explanation
β Correct β D: Fosfomycin (Streptomyces fradiae 1969) β small MW, broad spectrum including some ESBL/CRE strains. Oral trometamol salt concentrates in urine; single dose for uncomplicated cystitis. IV disodium salt for severe infection. Bactericidal. Resistance: MurA mutation, uhpT/glpT transporter loss (β uptake), fosA/fosB enzymes (glutathione/cysteine transferases β inactivate). Safety: safe in pregnancy. Synergistic with Ξ²-lactams, carbapenems β used in combinations for MDR UTI.
β A/B/C wrong: Wrong mechanisms.
72
Thalidomide in leprosy: Practice Question
AFirst-line anti-leprotic
BDrug of choice for ENL
CAntimycobacterial
DSteroid replacement
π Explanation
β Correct β B: Thalidomide (1950s β sedative/antiemetic for pregnancy β phocomelia disaster β withdrawn 1961). Rediscovered for ENL (1965), then multiple myeloma + MGUS, cutaneous lupus, Crohn's fistulae, Kaposi sarcoma. Mechanism: binds cereblon (CRBN β part of CRL4 E3 ubiquitin ligase); degrades IKZF1/3 transcription factors β immunomodulation; inhibits TNF-Ξ±, angiogenesis (VEGF, FGF). Derivatives: lenalidomide (Revlimid), pomalidomide (Pomalyst) β more potent, less teratogenic. STEPS/REMS programme mandatory: pregnancy test every 4 weeks, 2 contraception methods, physician + pharmacy certification.
β Correct β C: Rituximab (MabThera, Rituxan) β first approved mAb for cancer (1997). Chimeric (mouse-human). ADR: infusion reactions (slow first infusion + premedication), reactivation of Hepatitis B (screen before), PML (JC virus), late neutropenia. CAR-T cell therapy also targets CD19 (tisagenlecleucel, axicabtagene β for relapsed/refractory ALL, DLBCL). Obinutuzumab = glycoengineered anti-CD20 (CLL). Ofatumumab = fully human anti-CD20.
β A/B/D wrong: Other targets.
82
Immune checkpoint inhibitors (ICIs): Most Probable
β Correct β B: Tamoxifen β 5-10 years adjuvant; chemoprevention in high-risk women. Raloxifene = SERM used in osteoporosis + breast cancer prevention (no endometrial risk, but can cause VTE). Fulvestrant = pure ER antagonist (no agonist activity anywhere; monthly IM in metastatic ER+ breast). Aromatase inhibitors (AIs) β for postmenopausal: anastrozole, letrozole (non-steroidal competitive); exemestane (steroidal irreversible). More effective than tamoxifen in postmenopausal but cause osteoporosis + joint pain (no endometrial Ca risk). Combined with CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) β standard for ER+/HER2- metastatic. GnRH agonists (leuprolide, goserelin) β ovarian suppression in premenopausal.
β A/C/D wrong: Different classes.
84
Etoposide mechanism: GPAT 2020
ATopoisomerase II inhibitor
BMicrotubule inhibitor
CAntimetabolite
DAlkylator
π Explanation
β Correct β A: Etoposide (VP-16), teniposide (VM-26) = Topo II inhibitors. Similar actions to anthracyclines at the topo II level but without DNA intercalation. ADR: myelosuppression, hypotension during infusion (rapid administration), alopecia, secondary MLL-rearranged AML (t(11q23) translocation β ~ 1 %). Topo I inhibitors (also plant-derived, from Camptotheca acuminata): topotecan (ovarian, SCLC), irinotecan (colorectal β FOLFIRI; CPT-11 β active SN-38; UGT1A1*28 pharmacogenetics); severe diarrhoea (cholinergic acute, SN-38-induced delayed).
β B/C/D wrong: Wrong classes.
85
Bleomycin signature ADR: Most Probable
ACardiotoxicity
BOtotoxicity
CPulmonary fibrosis
DHaemorrhagic cystitis
π Explanation
β Correct β C: Bleomycin = glycopeptide antitumour antibiotic (Streptomyces verticillus); binds DNA + Fe(II) β oxygen radicals β DNA strand breaks. Uses: Hodgkin (ABVD), testicular (BEP), Kaposi sarcoma, squamous cell carcinomas. Pulmonary fibrosis β progressive, frequently fatal. Minimal myelosuppression (unique β used in combinations). Monitor baseline + periodic lung function. Limit cumulative dose. Caution: supplemental O2 during anaesthesia + surgery can precipitate fatal ARDS years after treatment.
β A wrong: Anthracyclines.
β B wrong: Cisplatin.
β D wrong: Cyclophosphamide.
86
L-asparaginase is used in: Most Probable
AAcute lymphoblastic
BBreast cancer
CLung cancer
DProstate cancer
π Explanation
β Correct β A: L-asparaginase (Erwinase from Erwinia / E. coli enzyme / PEG-asparaginase) β pediatric ALL induction + intensification. Unique mechanism β antimetabolite-like but depletes extracellular amino acid. ADR: hypersensitivity (β switch formulation); pancreatitis (acute β stop drug permanently in some protocols); coagulopathy (β antithrombin III, fibrinogen, factors) β thrombosis or bleeding; hyperglycaemia; CNS symptoms (hyperammonaemia). PEG-asparaginase (pegaspargase/Oncaspar/Asparlas) β longer half-life, less immunogenic.
β B/C/D wrong: Not indications.
87
Thalidomide & lenalidomide in multiple myeloma act as: Most Probable
AAlkylators
BImmunomodulatory drugs
CAntimetabolites
DMicrotubule inhibitors
π Explanation
β Correct β B: IMiDs era (thalidomide β lenalidomide β pomalidomide β iberdomide/CC-220). MM regimens: VRd (bortezomib-lenalidomide-dex), DVd (daratumumab-velcade-dex), KRd (carfilzomib-lenalidomide-dex), IXAZOMIB-Rd, ISA-Kd. ADR: thromboembolism (pretreat with aspirin / LMWH); neutropenia (lenalidomide more than thalidomide); rash, fatigue, peripheral neuropathy (thalidomide ββ), teratogenicity. Revlimid REMS + registries. Proteasome inhibitors: bortezomib (reversible), carfilzomib, ixazomib (oral) β also used in MM.
β A/C/D wrong: Not IMiD mechanism.
88
Interferon-Ξ± in cancer is mainly used for: Most Probable
β Correct β A: BCG = live attenuated M. bovis. Approved use: (1) TB vaccination (intradermal, neonatal in high-TB countries); (2) intravesical for NMIBC (high-grade Ta/T1, CIS) β induction 6 weekly + maintenance; standard of care after TURBT. Mechanism involves activation of macrophages, T cells, NK cells in bladder mucosa. Contraindications: active TB, immunosuppression, HIV, traumatic catheterisation (risk of BCG sepsis). Global shortage periodically. Chemotherapy alternatives: mitomycin C, gemcitabine intravesical.
β B/C/D wrong: Other cancers.
90
CAR-T cell therapy targets in B-cell ALL & DLBCL: Practice Question