# Adverse Drug Reactions and Pharmacovigilance for NEET PG Pharmacology: Types A–F, Pharmacogenetics, PvPI, WHO-UMC Causality, Special Populations Source: https://tracknation.in/story/adverse-drug-reactions-and-pharmacovigilance-for-neet-pg-pharmacology-types-a-f-pharmacogenetics-pvpi-who-umc-causality-special-populations (TrackNation — free UPSC notes with PYQs) > NEET PG Pharmacology: what counts as an ADR and a serious ADR, the six types A to F with examples, pharmacogenetic reactions (acetylators, G6PD, HLA-B*1502, pseudocholinesterase, CYP2C19), how to report under India's PvPI and what happens next, WHO-UMC causality categories, rechallenge, and drug use in older adults, children and pregnancy, with hooks, MCQs and cards. ## Start Here 🎯 **Exam priority: High.** *Expect a one-liner on an ADR type, a genetic reaction (slow acetylator, G6PD, HLA-B*1502, succinylcholine apnoea), a PvPI reporting fact, or a WHO-UMC causality category from a short case.* CBME mapping: **PH 1.10** (geriatric, paediatric and special situations), **PH 1.11** (ADRs and their types), **PH 1.12** (pharmacovigilance and ADR reporting) and **PH 1.13** (drug interactions). ## What Counts as an ADR - An **adverse drug reaction** is an unintended effect of a medicine that is undesirable, unpleasant or harmful. Every medicine can cause one. "Side effect" is an imprecise term. - A reaction is **serious** if it causes death, is life-threatening, causes or prolongs hospitalisation, causes disability, or causes a congenital anomaly. - Severity is graded **mild, moderate, severe or lethal**. - Allergic (hypersensitivity) reactions are **not dose-related** and need **prior exposure**; they usually do not happen the first time a drug is ever taken. - Higher risk: **older adults, children, renal or hepatic impairment, genetic variants** (for example, the variant behind abacavir hypersensitivity), and polypharmacy. Fatal ADRs occur mainly after age 75. ## The Six Types: A to F | **Type** | **Name** | **Key feature** | **Example** | | A | Augmented (intrinsic) | Predictable from the drug's action; dose-related; common; reversible | Hypotension with antihypertensives | | B | Bizarre (idiosyncratic) | Unpredictable; not dose-related; uncommon | Hypersensitivity, Stevens-Johnson syndrome, malignant hyperthermia with anaesthetics | | C | Chronic | From prolonged use; related to cumulative dose | Adrenal suppression with long-term steroids; jaw osteonecrosis with bisphosphonates | | D | Delayed | Appears some time after use; usually dose-related | Teratogenesis, carcinogenesis | | E | End of use (withdrawal) | Soon after the drug is stopped | Opioid withdrawal | | F | Failure | Unexpected failure of therapy, often from an interaction | Oral contraceptive failure with rifampin | Type A reactions are a particular problem with drugs that have a narrow therapeutic index, such as bleeding with oral anticoagulants. ## Pharmacogenetic Reactions Drug elimination rates vary up to **40-fold** between people, mostly because of genes and age. | **Genetic variation** | **Consequence** | | Slow acetylator (N-acetyltransferase) | More adverse effects: isoniazid peripheral neuritis; hydralazine or procainamide lupus | | Fast acetylator | Needs higher or more frequent isoniazid doses | | G6PD deficiency | Haemolytic anaemia with oxidant drugs such as chloroquine and primaquine | | Pseudocholinesterase deficiency | Succinylcholine not inactivated: prolonged apnoea needing ventilation | | HLA-B*1502 | Serious skin reactions (Stevens-Johnson syndrome) with carbamazepine | | CYP2C19 variants | Clopidogrel poorly activated: less antiplatelet effect, more thrombosis | | CYP2C9 and VKORC1 variants | Greater warfarin effect, more bleeding | | Aldehyde dehydrogenase-2 deficiency | Flushing and tachycardia after alcohol (acetaldehyde builds up) | | TPMT genotype | Tested before azathioprine or 6-mercaptopurine to choose the starting dose | ## Pharmacovigilance in India (PvPI) - The **Pharmacovigilance Programme of India** was approved by MoHFW in **July 2010**. Its National Coordination Centre is the **Indian Pharmacopoeia Commission, Ghaziabad**, a WHO Collaborating Centre for pharmacovigilance since 30 October 2017. - **What to report** (form version 1.4): all suspected ADRs, non-serious or serious, known or unknown, frequent or rare, to **medicines, vaccines and herbal products**. Every serious ADR must be reported. - **Who reports**: any healthcare professional — clinicians, dentists, pharmacists, nurses. - **Where**: the nearest **ADR Monitoring Centre (AMC)**, or directly to the NCC; or by the toll-free helpline **1800-180-3024**. - **Then**: the AMC does the causality assessment on the **WHO-UMC scale** and forwards the report to the NCC through the ADR database. - The patient's identity is confidential, and a report has **no legal implication** for the reporter. Serious adverse events after immunization can also be reported on the AEFI form. ## Is the Drug to Blame? WHO-UMC Causality | **WHO-UMC category** | **Time link** | **Other explanation** | **Withdrawal / rechallenge** | | Certain | Plausible | Cannot be explained by disease or other drugs | Withdrawal response plausible; rechallenge satisfactory if needed | | Probable / likely | Reasonable | Unlikely to be disease or other drugs | Withdrawal response clinically reasonable; rechallenge not required | | Possible | Reasonable | Could also be disease or other drugs | Withdrawal information may be lacking or unclear | | Unlikely | Makes a link improbable (not impossible) | Disease or other drugs give plausible explanations | — | | Conditional / unclassified | — | — | More data needed or under examination | | Unassessable / unclassifiable | — | — | Information insufficient or contradictory; cannot be supplemented | - **Dechallenge** = stopping the drug and watching the response; **rechallenge** = giving it again. Rechallenge can prove the link, but is not done after a serious allergic reaction. - If the drug is essential despite an allergy, **desensitization** may be used, such as penicillin for syphilis in a pregnant woman who is allergic to penicillin. ## Older Adults - **Kidney**: after 40, GFR falls by an average of **8 mL/min/1.73 m² per decade**, yet serum creatinine often stays normal because muscle mass is lower — so estimate clearance rather than trust creatinine. - **Liver**: phase I metabolism is more likely to be prolonged; **phase II (conjugation) is largely unaffected**, so phase II drugs may be preferred. First-pass metabolism falls about **1% a year after 40**. - **Body composition**: more fat raises the volume of distribution of lipophilic drugs such as diazepam (longer half-life); less body water lowers it for water-soluble drugs such as digoxin and aminoglycosides (higher levels). - Higher stomach pH reduces calcium carbonate absorption; calcium citrate absorbs better. - Hospital admissions from adverse drug effects are **4 to 7 times** more common than in younger patients. The **Beers Criteria** flag risky drug-disease combinations, and a **prescribing cascade** is when a drug's adverse effect is mistaken for a new disease and treated with another drug. ## Children and Pregnancy - **Neonates**: less stomach acid raises the bioavailability of acid-labile penicillin and lowers that of weakly acidic phenobarbital. Thin skin increases transdermal absorption. Albumin is low until about 10–12 months, so free drug is higher. - Many drugs (phenytoin, barbiturates, analgesics, cardiac glycosides) have half-lives **2 to 3 times longer** in neonates. Younger children need **higher per-kg doses of water-soluble drugs** because more of their body weight is water. - **Pregnancy labelling**: the US Pregnancy and Lactation Labeling Rule (published 4 December 2014, effective 30 June 2015) **removed the letter categories A, B, C, D and X**. Labels now give a risk summary, the supporting data and advice for counselling, plus information on pregnancy testing, contraception and infertility for males and females of reproductive potential. Older questions may still use the letters. ## Traps the Examiner Sets - Type A = augmented and dose-related; Type B = bizarre and not dose-related. Allergy is Type B. - Pill failure with rifampin is Type F (failure), not Type B. - Slow acetylators get isoniazid neuropathy and hydralazine lupus; fast acetylators need more isoniazid. - Post-succinylcholine apnoea = pseudocholinesterase deficiency, not malignant hyperthermia. - PvPI: any healthcare professional can report; causality is assessed at the AMC using WHO-UMC. - "Rechallenge not required" belongs to *probable*; "rechallenge satisfactory, if necessary" to *certain*. - Normal creatinine in an 80-year-old does not mean normal renal function. ## Memory Hooks & Shortcuts *Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.* - 🧠 **A B C D E F = Augmented, Bizarre, Chronic, Delayed, End of use, Failure** — the six ADR types in order - 🧠 **Slow and Sick** — slow acetylators get isoniazid neuritis and hydralazine lupus - 🧠 **Sux stuck = Pseudo low** — prolonged succinylcholine apnoea = pseudocholinesterase deficiency - 🧠 **Carba-B-1502** — carbamazepine SJS with HLA-B*1502 - 🧠 **Certain needs a Comeback, Probable needs none** — rechallenge: satisfactory if necessary (certain); not required (probable) - 🧠 **Old fat holds Diazepam, old dry raises Digoxin** — more fat → bigger Vd for diazepam; less water → higher digoxin levels ## Rapid-Revision Cards - Unintended, undesirable or harmful effect of a medicine. - Death, life-threatening, hospitalisation, disability, congenital anomaly. - Augmented: dose-related, predictable (hypotension with antihypertensives). - Bizarre: not dose-related (allergy, SJS, malignant hyperthermia). - Chronic: cumulative dose (steroid adrenal suppression). - Delayed: teratogenesis, carcinogenesis. - End of use: withdrawal (opioids). - Failure: pill failure with rifampin. - INH neuritis; hydralazine/procainamide lupus. - Haemolysis with primaquine, chloroquine. - Pseudocholinesterase deficiency. - Carbamazepine SJS. - Clopidogrel less active. - Before azathioprine / 6-MP. - Approved July 2010; NCC at IPC Ghaziabad. - 1800-180-3024 (toll free). - Any healthcare professional. - At the AMC, WHO-UMC scale. - Plausible timing, no other cause, rechallenge satisfactory if needed. - Unlikely other cause; rechallenge not required. - Could also be disease or other drugs. - Falls about 8 mL/min/1.73 m² per decade. - Conjugation largely unaffected by age. - Removed from US labels by the 2015 PLLR. ## Sources *Facts in this article were checked against these documents.* - MSD Manual Professional Edition: Adverse Drug Reactions; Pharmacogenetics — Merck & Co. (MSD Manuals), 2025 (link) - MSD Manual Professional Edition: Drug-Related Problems in Older Adults; Pharmacokinetics in Older Adults; Pharmacokinetics in Children — Merck & Co. (MSD Manuals), 2025 (link) - Suspected Adverse Drug Reaction Reporting Form for Healthcare Professionals, Version 1.4 — Indian Pharmacopoeia Commission (NCC-PvPI), MoHFW, current (link) - Pharmacovigilance Programme of India — National Coordination Centre — Indian Pharmacopoeia Commission, accessed November 2026 - Causality Assessment: WHO-UMC Causality Categories for ADR Reporting (training page reproducing the WHO-UMC system table) — National TB Elimination Programme, MoHFW, accessed November 2026 (link) - Requirements for Pregnancy and Lactation Labeling — final rule (79 FR 72064) — US Food and Drug Administration, Federal Register, 2014 (link) - Competency Based Undergraduate Curriculum, Pharmacology (PH 1.10–1.13) — National Medical Commission, 2024 ## Test Yourself: Practice Questions Twenty-five questions in NEET PG style, including clinical vignettes. ## Practice Questions (NEET PG pattern) *Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.* **Q1.** Hypotension after starting an antihypertensive is which type of adverse drug reaction? - (a) Type C (chronic) - (b) Type A (augmented) - (c) Type B (bizarre) - (d) Type F (failure) **Answer: (b)** — Type A reactions follow from the drug's known action, are dose-related and common. **Q2.** Malignant hyperthermia during general anaesthesia is classified as - (a) Type B (idiosyncratic) - (b) Type D (delayed) - (c) Type A (augmented) - (d) Type E (withdrawal) **Answer: (a)** — Type B reactions are unpredictable and not dose-related: hypersensitivity, SJS, malignant hyperthermia. **Q3.** Adrenal suppression after long-term corticosteroid therapy is a - (a) Type F reaction - (b) Type B reaction - (c) Type E reaction - (d) Type C (chronic) reaction **Answer: (d)** — Type C reactions come from prolonged use and relate to cumulative dose. **Q4.** Oral contraceptive failure in a woman taking rifampin is which ADR type? - (a) Type A (augmented) - (b) Type D (delayed) - (c) Type B (bizarre) - (d) Type F (failure) **Answer: (d)** — Type F is unexpected failure of therapy, often due to an interaction (rifampin induces metabolism). **Q5.** Teratogenesis is an example of which ADR type? - (a) Type E (withdrawal) - (b) Type A (augmented) - (c) Type D (delayed) - (d) Type C (chronic) **Answer: (c)** — Type D reactions appear some time after use: teratogenic effects and carcinogenesis. **Q6.** Which feature is typical of an allergic (hypersensitivity) drug reaction? - (a) It occurs only with overdose - (b) It is not dose-related and needs prior exposure - (c) It occurs on the very first ever dose in most patients - (d) It is dose-related and predictable **Answer: (b)** — Hypersensitivity ADRs are not dose-related and require prior exposure. **Q7.** Isoniazid peripheral neuritis is more likely in - (a) fast acetylators - (b) G6PD-deficient patients - (c) people with pseudocholinesterase deficiency - (d) slow acetylators **Answer: (d)** — Slow acetylators inactivate isoniazid slowly; hydralazine and procainamide lupus is also more common in them. **Q8.** Drug-induced lupus with hydralazine is linked to - (a) fast acetylation - (b) HLA-B*1502 - (c) CYP2C19 variants - (d) slow acetylation **Answer: (d)** — Slow N-acetyltransferase activity raises the risk of hydralazine- or procainamide-induced lupus. **Q9.** Prolonged apnoea after a normal dose of succinylcholine suggests - (a) G6PD deficiency - (b) plasma pseudocholinesterase deficiency - (c) malignant hyperthermia - (d) slow acetylation **Answer: (b)** — Succinylcholine is not inactivated, giving prolonged respiratory paralysis that may need ventilation. **Q10.** Before starting carbamazepine, testing for which marker reduces the risk of Stevens-Johnson syndrome? - (a) G6PD - (b) HLA-B*1502 - (c) TPMT - (d) CYP2C19 **Answer: (b)** — HLA-B*1502 raises the risk of serious skin reactions to carbamazepine. **Q11.** Reduced antiplatelet effect of clopidogrel is associated with variants in - (a) VKORC1 - (b) N-acetyltransferase - (c) CYP2C19 - (d) CYP2D6 **Answer: (c)** — CYP2C19 variants reduce activation of the prodrug clopidogrel, increasing thrombosis risk. **Q12.** Primaquine can cause haemolytic anaemia in - (a) G6PD deficiency - (b) pseudocholinesterase deficiency - (c) slow acetylators - (d) HLA-B*1502 carriers **Answer: (a)** — Oxidant drugs such as chloroquine and primaquine cause haemolysis in G6PD deficiency. **Q13.** Under PvPI, who may report a suspected adverse drug reaction on the healthcare professional form? - (a) Only the drug manufacturer - (b) Any healthcare professional, including clinicians, dentists, pharmacists and nurses - (c) Only the hospital pharmacist - (d) Only the treating consultant **Answer: (b)** — All healthcare professionals can report ADRs (form version 1.4). **Q14.** The National Coordination Centre of the Pharmacovigilance Programme of India is located at - (a) the Indian Pharmacopoeia Commission, Ghaziabad - (b) NCDC, Delhi - (c) CDSCO headquarters, New Delhi - (d) AIIMS, New Delhi **Answer: (a)** — NCC-PvPI is at the Indian Pharmacopoeia Commission, Ghaziabad (programme approved in July 2010). **Q15.** Which reactions should be reported under PvPI? - (a) Only fatal reactions - (b) All suspected ADRs — serious or non-serious, known or unknown — to medicines, vaccines and herbal products - (c) Only reactions to newly approved drugs - (d) Only serious and unknown reactions to allopathic drugs **Answer: (b)** — The form asks for non-serious, known or unknown, frequent or rare ADRs, and every serious ADR. **Q16.** Under PvPI, causality assessment of a submitted report is done - (a) by the reporting doctor using the Naranjo scale - (b) by the manufacturer - (c) by the court - (d) at the ADR Monitoring Centre using the WHO-UMC scale **Answer: (d)** — The AMC assesses causality on the WHO-UMC scale and forwards the report to the NCC. **Q17.** A rash with a reasonable time link to a drug, unlikely to be due to disease or other drugs, improving on withdrawal, with no rechallenge, is - (a) possible - (b) unlikely - (c) certain - (d) probable / likely **Answer: (d)** — Probable: reasonable time relationship, unlikely other cause, clinically reasonable withdrawal response, rechallenge not required. **Q18.** In the WHO-UMC system, an event that could also be explained by disease or other drugs, with unclear withdrawal information, is - (a) certain - (b) probable - (c) unassessable - (d) possible **Answer: (d)** — Possible: reasonable time link but could also be explained by disease or other drugs. **Q19.** Why is serum creatinine misleading for drug dosing in an 80-year-old? - (a) It is unaffected by GFR - (b) It often stays normal despite reduced GFR because muscle mass is lower - (c) It measures liver function - (d) It rises falsely with age **Answer: (b)** — GFR falls about 8 mL/min/1.73 m² per decade after 40, but creatinine often stays in the normal range. **Q20.** In older adults, which drug's volume of distribution rises because body fat increases? - (a) Diazepam - (b) Lithium - (c) Digoxin - (d) Gentamicin **Answer: (a)** — More fat → larger Vd and longer half-life for lipophilic drugs (diazepam, chlordiazepoxide); less water → higher levels of digoxin and aminoglycosides. **Q21.** When a drug's adverse effect is mistaken for a new disease and treated with another drug, this is called - (a) therapeutic duplication - (b) a prescribing cascade - (c) a Type F reaction - (d) tachyphylaxis **Answer: (b)** — A prescribing cascade: the adverse effect is misread as a new disorder and treated, which can cause further adverse effects. **Q22.** The US Pregnancy and Lactation Labeling Rule (effective 2015) - (a) banned all drugs in the first trimester - (b) removed the pregnancy letter categories A, B, C, D and X - (c) added category X - (d) applies only to vaccines **Answer: (b)** — The final rule requires removal of pregnancy categories A, B, C, D and X from prescription drug labels. **Q23.** Compared with adults, neonates have - (a) lower transdermal absorption - (b) shorter half-lives of phenytoin - (c) higher bioavailability of acid-labile penicillin because of less gastric acid - (d) higher albumin levels **Answer: (c)** — Reduced gastric acid raises penicillin bioavailability; transdermal absorption is higher; albumin is lower; many half-lives are 2–3 times longer. **Q24.** An 84-year-old on digoxin becomes toxic at a dose that suited her at 60, although her serum creatinine is normal. Two age-related reasons are - (a) less body water raising digoxin concentration, and a lower GFR hidden by low muscle mass - (b) higher albumin and faster absorption - (c) more body fat and faster metabolism - (d) enzyme induction and more body water **Answer: (a)** — Less body water lowers the Vd of water-soluble drugs such as digoxin (higher levels); GFR falls with age while creatinine may stay normal. **Q25.** A potent steroid cream is applied over large areas of a 3-week-old baby's skin. The particular risk is - (a) no absorption at all - (b) increased systemic absorption through thin neonatal skin - (c) allergy only - (d) rapid first-pass metabolism **Answer: (b)** — Transdermal absorption is enhanced in neonates and young infants because the stratum corneum is thin. ### Active Recall From memory: define an ADR and a serious ADR; list types A to F with one example each; name five pharmacogenetic reactions and the drug involved; explain who reports to PvPI, where and how causality is assessed; give the WHO-UMC categories; and list the pharmacokinetic changes of old age.