NIPER JEE cheat sheet

Recombinant DNA workflow: restriction digestion → ligation into vector → transformation → selection → screening → expression; selectable markers (ampR, kanR) allow only transformants to grow.

PCR cycle: denaturation ~94-95 °C, primer annealing ~50-65 °C (≈Tm minus 5 °C), extension ~72 °C for Taq; 30-40 cycles give ~2^n amplification.

Monoclonal antibodies come from a single B-cell clone fused with myeloma cells (hybridoma); polyclonal antisera contain many epitope-specificities.

Western blot detects protein (antibody probe after SDS-PAGE transfer); Southern detects DNA; Northern detects RNA; ELISA quantifies antigen in solution.

Restriction enzymes: Type II cut within palindromic recognition sites producing sticky or blunt ends; ligase joins 5'-phosphate to 3'-OH.

Bacterial growth phases: lag → log (exponential) → stationary → death; specific growth rate µ = ln2/generation time.

CRISPR-Cas9 requires a guide RNA complementary to the target and a PAM adjacent to the protospacer; Cas9 creates a double-strand break repaired by NHEJ or HDR.

Plasmid vector essentials: origin of replication, selectable marker, multiple cloning site, and promoter for expression constructs.

Lipinski rule of five: MW ≤ 500, logP ≤ 5, H-bond donors ≤ 5, H-bond acceptors ≤ 10; violation of two or more predicts poor oral absorption.

Hansch equation: log(1/C) = k1·logP + k2·(logP)² + k3·σ + k4·Es + k5; parabolic logP terms model optimal lipophilicity.

Bioisosteres replace groups with similar size/electronics: -H↔-F, -OH↔-NH2, -COOH↔tetrazole, -O-↔-S-, -CH2-↔-NH-.

Prodrug design masks polar groups to improve absorption; ester prodrugs are hydrolyzed by carboxylesterases to release the active acid.

Michaelis-Menten: v = Vmax[S]/(Km+[S]); competitive inhibitors raise apparent Km at unchanged Vmax; non-competitive lowers Vmax.

CYP450 inhibition causes drug-drug interactions; mechanism-based (suicide) inhibitors like erythromycin form metabolic-intermediate complexes.

Chirality matters: only the (S)-enantiomer of omeprazole (esomeprazole) carries most proton-pump activity; enantiomers differ in potency and PK.

Structure-activity relationship strategy: scaffold hopping, homologation, ring contraction/expansion, and substituent scanning to map pharmacophore.

Alkaloids are basic nitrogen heterocycles: morphine (phenanthrene), quinine (quinoline), atropine (tropane), vincristine (indole dimer), caffeine (xanthine).

Glycosides: cardiac glycosides (digoxin) act on Na+/K+-ATPase; cyanogenic glycosides release HCN on hydrolysis; saponins foam in water.

Terpenes follow the isoprene (C5) rule: monoterpene C10, sesquiterpene C15, diterpene C20, triterpene C30, tetraterpene C40 (carotenoids).

Shikimic acid pathway yields phenylpropanoids, coumarins, lignans, and flavonoids; acetate-malonate pathway yields polyketides and fatty acids.

Mevolonate pathway supplies sterols and triterpenoids; statins (lovastatin, compactin) are fungal polyketide-triterpenoid hybrids inhibiting HMG-CoA reductase.

Extraction sequence for plant material: defatting with petroleum ether → alcohol extraction → partitioning between solvents of increasing polarity.

Identification tests: Dragendorff for alkaloids, Molisch for carbohydrates, Fehling/Benedict for reducing sugars, Liebermann-Burchard for sterols/triterpenes.

Artemisinin (sesquiterpene lactone endoperoxide from Artemisia annua) requires the peroxide bridge for antimalarial activity; semisynthetic derivatives include artesunate.

Beer-Lambert law: A = εbc; absorbance is linear with concentration only in the dilute range, so calibration curves must be validated.

UV λmax depends on chromophores: C=C ~190 nm, C=O ~280 nm, conjugated dienes shift to longer wavelengths (bathochromic shift).

HPLC resolution: Rs = 2(t2-t1)/(w1+w2); baseline separation needs Rs ≥ 1.5. Plate count N = 16(tR/w)².

Retention factor k = (tR - t0)/t0; selectivity α = k2/k1; capacity factor should typically fall between 1 and 10.

Validation parameters per ICH Q2: accuracy, precision, specificity, linearity, range, detection limit, quantitation limit, robustness.

LOD = 3.3σ/S and LOQ = 10σ/S where σ is the standard deviation of the response and S the slope of the calibration curve.

Titration: at equivalence of a weak acid with strong base, pH ≈ 7 + ½(pKa + log C); phenolphthalein (pH 8.2-10) suits weak-acid titrations.

Mass spectrometry: ESI favors polar/labile molecules producing multiply charged ions; EI gives hard fragmentation useful for library matching.

Drug price control in India: NLEM-scheduled formulations are capped by ceiling price = average price to retailer of all brands with ≥1% market share plus 16% retailer margin.

Patent types: product patent (composition of matter) vs process patent; TRIPS requires 20-year term from filing date; compulsory licences under Section 84 require a three-year wait.

Schedule M of the Drugs and Cosmetics Rules prescribes GMP requirements for premises and plant; Schedule Y covers clinical trial and new drug approval.

Pharmacoeconomic analyses: cost-minimization (equal outcomes), cost-effectiveness (cost per natural unit), cost-utility (cost per QALY), cost-benefit (monetary outcome).

Inventory control: EOQ = √(2DS/H); ABC analysis classifies items by annual consumption value; VED classifies by criticality.

Break-even quantity = fixed cost / (selling price − variable cost per unit); contribution margin drives product-line decisions.

Pharmacovigilance reporting in India: serious adverse events reported to CDSCO within 24 hours and in writing within 15 days; PvPI coordinates collection.

Good distribution practices require temperature mapping, validated cold chain (2-8 °C), and batch traceability from manufacturer to patient.

Tablet compression stages: die filling → metering → compression → ejection; force-displacement profiles detect capping and lamination.

Granulation methods: wet (binder + solvent, then drying), dry (slugging/roller compaction), and direct compression for free-flowing, compressible excipients.

Fluidized bed granulation combines mixing, granulation, and drying in one unit; top-spray is typical for granulation, bottom-spray for pellet coating.

Hard gelatin capsule sizes 000 (largest) to 5 (smallest); capsule filling requires powders with good flow and low hygroscopicity.

Sterilization: moist heat 121 °C/15 min/15 psi; dry heat 160 °C/2 h; ethylene oxide for heat-labile plastics; filtration 0.22 µm for solutions.

Sustained-release systems: matrix (Higuchi release, Q ∝ √t), reservoir/membrane (zero-order), and osmotic pump (zero-order via osmotic pressure).

Coating defects: picking (sticking to punch), sticking, capping (top separation), lamination (horizontal split), mottling (uneven color).

Lyophilization stages: freezing → primary drying (sublimation below collapse temperature) → secondary drying (desorption of bound water).

Receptor families: GPCRs (7TM, second messengers), ligand-gated ion channels (fast, ms), kinase-linked receptors (insulin), nuclear receptors (slow, gene transcription).

Dose-response: EC50 is concentration at half-maximal effect; potency compares EC50, efficacy compares Emax; partial agonists have lower Emax than full agonists.

Autonomic mapping: α1 → vasoconstriction, β1 → cardiac stimulation, β2 → bronchodilation, M2 → bradycardia, M3 → secretion and smooth-muscle contraction.

Pharmacokinetics: Vd = dose/C0; CL = k·Vd; t½ = 0.693·Vd/CL; steady state reached in ~4-5 half-lives.

First-pass metabolism reduces oral bioavailability; F = (AUCoral/AUCiv) × (Doseiv/Doseoral).

Cyclooxygenase inhibitors: aspirin irreversibly acetylates COX-1/COX-2; selective COX-2 inhibitors spare gastric protection but increase cardiovascular risk.

Toxicology: LD50 is the median lethal dose; therapeutic index = TD50/ED50; chronic exposure uses NOAEL and LOAEL to set reference doses.

Antidotes: N-acetylcysteine for paracetamol, naloxone for opioids, atropine plus pralidoxime for organophosphates, deferoxamine for iron, dimercaprol for arsenic.

Routes and barriers: oral absorption depends on solubility, permeability, and first-pass effect; BCS Class I (high/high) is best absorbed.

Stokes' law: sedimentation velocity v = d²(ρp−ρl)g/18η; smaller particles and higher viscosity slow settling in suspensions.

Emulsion type determined by phase volume and emulsifier: Bancroft rule places the emulsifier in the continuous phase; HLB 3-6 favors w/o, 8-18 favors o/w.

Ointment bases: hydrocarbon (occlusive), absorption (wool fat), water-removable (emulsion), water-soluble (PEG); choose by drug solubility and site.

Suppository displacement value = weight of drug displacing 1 g base; theobroma oil melts at 30-36 °C.

Micromeritics: Carr's index = (ρtapped−ρbulk)/ρtapped × 100; <15% indicates good flow; Hausner ratio <1.25 indicates good flow.

Particle-size analysis: laser diffraction gives volume distribution; sieve analysis gives mass distribution; BET measures surface area.

Osmotic pump delivery is independent of gastrointestinal pH and motility, giving zero-order release over 12-24 hours.

Clinical trial phases: I (safety/PK, 20-80 subjects), II (efficacy/dose finding, 100-300), III (comparative efficacy, 1000+), IV (post-marketing surveillance).

Randomization methods: simple, block, stratified; allocation concealment prevents selection bias; blinding levels are open-label, single, double, triple.

Informed consent requires voluntariness, capacity, disclosure of risks/benefits/alternatives, and documentation; assent applies to minors.

ICH-GCP principles: ethics committee approval, protocol adherence, source document verification, investigator qualifications, and safety reporting.

Pharmacovigilance causality tools: Naranjo scale and WHO-UMC categories (certain, probable, possible, unlikely); WHO-ART codes adverse events.

Therapeutic drug monitoring is indicated for narrow-index drugs (digoxin, phenytoin, lithium, vancomycin, cyclosporine); trough sampling before next dose.

Pharmaceutical care process: collect patient data → identify drug-related problems → develop care plan → implement → monitor and follow up.

Sample size for two-proportion comparison: n per arm ≈ 2(zα+zβ)²p(1−p)/Δ²; power of 80% uses zβ = 0.84.

Molecular descriptors: 1D (formula, MW), 2D (topological indices, fingerprints), 3D (shape, pharmacophore); Lipinski and Veber rules filter libraries.

Similarity metrics: Tanimoto coefficient = c/(a+b−c) on binary fingerprints; values above 0.85 suggest similar bioactivity.

Docking score ≠ binding free energy; rescoring with MM-GBSA or empirical scoring improves ranking; redocking RMSD < 2 Å validates the protocol.

QSAR workflow: dataset curation → descriptor calculation → feature selection → model training (PLS, random forest) → external validation (R², Q², RMSE).

Pharmacophore modeling captures essential features: H-bond donor/acceptor, hydrophobic, aromatic, positive/negative ionizable centers with distance constraints.

ADMET prediction tools estimate Caco-2 permeability, hERG blockade, CYP inhibition, and plasma protein binding; hERG risk correlates with lipophilicity and basic amines.

Databases: PubChem (compounds/bioassays), ChEMBL (bioactivity), PDB (structures), DrugBank (approved drugs and targets), UniProt (protein sequences).

Sequence alignment: BLAST heuristic search; scoring uses substitution matrices (BLOSUM62) with gap penalties; E-value < 1e-5 indicates significant homology.

Device classification in India (Medical Devices Rules 2017) uses risk classes A (low), B (low-moderate), C (moderate-high), D (high), with licensing via CDSCO/state authorities.

Sterility assurance level (SAL) of 10⁻⁶ is required for sterile devices; validation uses biological indicators with known D-values.

ISO 10993 governs biological evaluation: cytotoxicity (ISO 10993-5), sensitization/irritation (10), systemic toxicity (11), implantation (6).

ISO 13485 specifies quality management for device manufacturers; ISO 14971 covers risk management (hazard identification, risk estimation, control).

Drug-device combination products require both drug and device regulatory pathways; a metered-dose inhaler is regulated as a drug-device combination.

In vitro diagnostics need analytical validation (accuracy, precision, LoD, interference) and clinical validation (sensitivity, specificity, PPV, NPV).

Medical device vigilance: manufacturer reports serious incidents to the competent authority within statutory timelines; trend reporting covers non-serious increases.

Biomaterials: biocompatibility depends on surface chemistry, degradation products, and host response; biodegradable polymers include PLGA and PCL.