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HKMLE HIGH-YIELD ANKI FLASHCARDS
Additional Pharmacology: Autacoids | Gonadal Hormones | Antineoplastics
Immunomodulators | Antivirals | Antiprotozoals/Anthelmintics
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SECTION 1: AUTACOIDS
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1A. H1 ANTIHISTAMINES
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[CARD 1 - Type 3: Mnemonic]
Q: What is the mnemonic for 1st vs 2nd generation antihistamines?
A: "1st Gen = Sedating, 2nd Gen = Safe" = 1st generation crosses BBB (sedating, anticholinergic); 2nd generation does not cross BBB (non-sedating, no anticholinergic effects)

[CARD 2 - Type 1]
Q: What is the mechanism of 1st generation antihistamines?
A: H1 receptor antagonist + anticholinergic + anti-alpha1 activity.
[Trap: common wrong answer is "pure H1 blocker" — 1st gen also has significant anticholinergic effects, which is why they cause dry mouth, urinary retention, and are avoided in the elderly]

[CARD 3 - Type 1]
Q: What is the mechanism of 2nd generation antihistamines (e.g. cetirizine, loratadine)?
A: H1 receptor antagonist ONLY — no significant anticholinergic effects, does not cross BBB.

[CARD 4 - Type 1]
Q: What are the key side effects of 1st generation antihistamines?
A: Sedation, dry mouth, urinary retention, blurred vision, constipation (all anticholinergic).

[CARD 5 - Type 1]
Q: What are the contraindications of 1st generation antihistamines?
A: Glaucoma, BPH, elderly patients (due to anticholinergic effects — Beers Criteria).

[CARD 6 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: An elderly patient is given diphenhydramine for allergic rhinitis. What is the concern?
A: Diphenhydramine is a 1st gen antihistamine with strong anticholinergic effects — avoid in elderly (Beers Criteria); causes confusion, urinary retention, constipation.
[Trap: common wrong answer is "it is safe because it is just an antihistamine" — diphenhydramine has significant anticholinergic toxicity]

[CARD 7 - Type 2: Cloze]
[c]Promethazine[/c] causes extrapyramidal effects in children because it has dopamine D2 receptor antagonist activity in addition to H1 blockade.
[Trap: common wrong answer is "sedation only" — promethazine is avoided in children <2 years due to extrapyramidal and respiratory depression risk]

[CARD 8 - Type 1]
Q: Which 2nd generation antihistamine is mildly sedating?
A: Cetirizine (loratadine and fexofenadine are essentially non-sedating).

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1B. H2 ANTIHISTAMINES
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[CARD 9 - Type 1]
Q: What is the mechanism of H2 antihistamines?
A: Competitive H2 receptor antagonist on gastric parietal cells → decreased acid secretion.

[CARD 10 - Type 1]
Q: What are the indications for H2 antihistamines?
A: Peptic ulcer disease, GERD, Zollinger-Ellison syndrome.

[CARD 11 - Type 2: Cloze]
[c]Cimetidine[/c] causes gynaecomastia and impotence because it has anti-androgen activity (blocks androgen receptors).

[CARD 12 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on cimetidine is also taking warfarin. What happens?
A: Cimetidine inhibits CYP450 → increases warfarin levels → increased bleeding risk; must monitor INR or switch to famotidine/ranitidine.
[Trap: common wrong answer is "no interaction" — cimetidine is one of the most tested CYP450 inhibitors in HKMLE]

[CARD 13 - Type 1]
Q: Which 3 drugs have dangerous interactions with cimetidine?
A: Warfarin, theophylline, and phenytoin — cimetidine inhibits CYP450 and raises levels of all three.

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1C. SEROTONIN PHARMACOLOGY
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[CARD 14 - Type 3: Mnemonic]
Q: What is the mnemonic for serotonin receptor subtypes and drugs?
A: "5-HT3 = Nausea; 5-HT1 = Migraine; SSRIs block reuptake" = ondansetron (5-HT3 antagonist), sumatriptan (5-HT1B/1D agonist), SSRIs (block 5-HT transporter)

[CARD 15 - Type 1]
Q: What is the mechanism of ondansetron?
A: 5-HT3 receptor antagonist → prevents chemotherapy- and surgery-induced nausea/vomiting.

[CARD 16 - Type 1]
Q: What is the key cardiac side effect of ondansetron?
A: QT prolongation — avoid with other QT-prolonging drugs.

[CARD 17 - Type 1]
Q: What is the mechanism of sumatriptan?
A: 5-HT1B/1D agonist → causes vasoconstriction of cranial blood vessels → aborts acute migraine.

[CARD 18 - Type 2: Cloze]
[c]Sumatriptan[/c] is contraindicated in ischaemic heart disease because it causes coronary vasoconstriction via 5-HT1B/1D agonism.
[Trap: common wrong answer is "sumatriptan only affects brain vessels" — it constricts coronary arteries too, so it is absolutely contraindicated in IHD and uncontrolled hypertension]

[CARD 19 - Type 1]
Q: What is the mechanism of metoclopramide?
A: D2 + 5-HT3 antagonist; 5-HT4 agonist → prokinetic + antiemetic.

[CARD 20 - Type 1]
Q: What are the key side effects of metoclopramide?
A: Extrapyramidal effects (akathisia, acute dystonia) and tardive dyskinesia with prolonged use.

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1D. PROSTAGLANDINS & LEUKOTRIENES
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[CARD 21 - Type 1]
Q: What is the mechanism of misoprostol?
A: PGE1 analogue → binds prostaglandin receptors → reduces gastric acid secretion + protects gastric mucosa; also stimulates uterine contractions.

[CARD 22 - Type 1]
Q: What are the indications for misoprostol?
A: Peptic ulcer prophylaxis with NSAIDs; cervical ripening; postpartum haemorrhage.

[CARD 23 - Type 2: Cloze]
[c]Misoprostol[/c] is contraindicated in pregnancy (when used for peptic ulcer prophylaxis) because it causes uterine contractions and can induce abortion.
[Trap: common wrong answer is "misoprostol is safe since it is a gastric protectant" — in a pregnant patient on NSAIDs, it is absolutely contraindicated as it is abortifacient]

[CARD 24 - Type 1]
Q: What is the mechanism and indication of latanoprost?
A: PGF2α analogue → increases aqueous humour outflow → reduces IOP → used for glaucoma.

[CARD 25 - Type 1]
Q: What are the cosmetic side effects of latanoprost?
A: Darkening/browning of iris, increased eyelash growth (hypertrichosis).

[CARD 26 - Type 1]
Q: What is the indication of alprostadil (PGE1)?
A: Erectile dysfunction (intracavernosal injection) + maintaining patent ductus arteriosus in neonates with duct-dependent cardiac lesions.

[CARD 27 - Type 1]
Q: What is the mechanism of montelukast?
A: LTD4 (CysLT1) receptor antagonist → reduces bronchoconstriction and mucus secretion.

[CARD 28 - Type 1]
Q: What are the indications for montelukast?
A: Asthma (especially aspirin-sensitive asthma), allergic rhinitis.

[CARD 29 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What serious FDA black box warning is associated with montelukast?
A: Neuropsychiatric effects including depression, suicidal ideation — must counsel patients.

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SECTION 2: GONADAL HORMONES & CONTRACEPTIVES
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2A. COMBINED OCP
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[CARD 30 - Type 3: Mnemonic]
Q: What is the mnemonic for combined OCP uses?
A: "COPE" = Contraception, acne, Ovarian cyst prevention, Period regulation/dysmenorrhoea, Endometriosis

[CARD 31 - Type 1]
Q: What is the mechanism of the combined oral contraceptive pill?
A: Oestrogen + progestogen → suppresses LH and FSH via negative feedback on hypothalamus/pituitary → inhibits ovulation.

[CARD 32 - Type 1]
Q: What are the key side effects of the combined OCP?
A: VTE (increased clotting factors), hypertension, nausea, breast tenderness, breakthrough bleeding, chloasma, cholestasis.

[CARD 33 - Type 1]
Q: What are the absolute contraindications to the combined OCP?
A: VTE/DVT history, migraine with aura, age >35 + smoking, breast cancer, active liver disease, uncontrolled hypertension.

[CARD 34 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on the combined OCP is prescribed rifampicin for TB. What should you do?
A: Rifampicin is a CYP450 inducer → reduces OCP levels → risk of unintended pregnancy; advise additional contraception.
[Trap: common wrong answer is "rifampicin has no effect on the OCP" — CYP induction reducing OCP efficacy is a classic HKMLE drug interaction]

[CARD 35 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A 28-year-old woman has migraine with aura and wants contraception. Can she take the combined OCP?
A: No — migraine with aura is an ABSOLUTE contraindication to the combined OCP due to the significantly increased risk of ischaemic stroke.
[Trap: common wrong answer is "OCP is fine, just monitor" — this is one of the strongest absolute contraindications regardless of age or other risk factors]

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2B. PROGESTOGEN-ONLY PILL (POP) / DEPOT
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[CARD 36 - Type 1]
Q: What is the mechanism of the progestogen-only pill?
A: Low-dose POP thickens cervical mucus; higher dose depot/implant also inhibits ovulation.

[CARD 37 - Type 1]
Q: When is the progestogen-only pill preferred over the combined OCP?
A: When oestrogen is contraindicated — post-DVT, migraine with aura, breastfeeding, smokers over age 35.

[CARD 38 - Type 1]
Q: What are the side effects of the progestogen-only pill?
A: Irregular bleeding, amenorrhoea, weight gain, acne.

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2C. SERMs & ANTI-OESTROGENS
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[CARD 39 - Type 3: Mnemonic]
Q: What is the mnemonic for tamoxifen vs clomiphene?
A: "Tamoxifen Treats, Clomiphene Causes (ovulation)" = tamoxifen treats breast cancer; clomiphene causes ovulation induction

[CARD 40 - Type 1]
Q: What is the mechanism of tamoxifen?
A: SERM — oestrogen antagonist in breast tissue; oestrogen agonist in uterus and bone.

[CARD 41 - Type 1]
Q: What are the indications for tamoxifen?
A: ER+ breast cancer treatment and prevention.

[CARD 42 - Type 2: Cloze]
[c]Tamoxifen[/c] causes endometrial cancer because it acts as an oestrogen AGONIST in the uterus despite being an oestrogen antagonist in the breast.
[Trap: common wrong answer is "tamoxifen blocks all oestrogen receptors" — it is tissue-selective; it stimulates the endometrium, increasing cancer risk]

[CARD 43 - Type 1]
Q: What are the other key side effects of tamoxifen?
A: VTE, hot flushes, menstrual irregularity.

[CARD 44 - Type 1]
Q: What is the mechanism of clomiphene?
A: SERM — blocks oestrogen receptors in the hypothalamus → removes negative feedback → increased FSH/LH release → stimulates ovulation.

[CARD 45 - Type 1]
Q: What are the side effects of clomiphene?
A: Ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, hot flushes.

[CARD 46 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: How does raloxifene differ from tamoxifen in terms of uterine effects?
A: Raloxifene is an oestrogen antagonist in BOTH breast AND uterus — NO endometrial cancer risk (unlike tamoxifen which is a uterine agonist).
[Trap: common wrong answer is "both SERMs carry the same endometrial cancer risk" — raloxifene does NOT stimulate the endometrium]

[CARD 47 - Type 1]
Q: What are the indications for raloxifene?
A: Post-menopausal osteoporosis; breast cancer prevention.

[CARD 48 - Type 1]
Q: What is the mechanism and key limitation of aromatase inhibitors (letrozole, anastrozole)?
A: Block peripheral conversion of androgens to oestrogen → used in post-menopausal ER+ breast cancer ONLY — ineffective pre-menopausally because ovaries still produce oestrogen directly.
[Trap: common wrong answer is "aromatase inhibitors can be used in pre-menopausal women" — ovarian oestrogen synthesis bypasses the aromatase block]

[CARD 49 - Type 1]
Q: What are the side effects of aromatase inhibitors?
A: Bone loss (osteoporosis), joint pain, hot flushes.

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2D. ANTI-ANDROGENS
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[CARD 50 - Type 1]
Q: What is the mechanism of finasteride?
A: 5α-reductase inhibitor → reduces conversion of testosterone to dihydrotestosterone (DHT).

[CARD 51 - Type 1]
Q: What are the indications for finasteride?
A: BPH, male pattern baldness.

[CARD 52 - Type 2: Cloze]
[c]Finasteride[/c] is teratogenic to male foetuses because DHT is required for normal development of male external genitalia.
[Trap: common wrong answer is "finasteride is a topical drug only and not teratogenic" — pregnant women must not even handle crushed tablets as it is absorbed through skin]

[CARD 53 - Type 1]
Q: What are the side effects of finasteride?
A: Sexual dysfunction (decreased libido, erectile dysfunction), gynaecomastia.

[CARD 54 - Type 1]
Q: What is the mechanism of spironolactone relevant to anti-androgen use?
A: Aldosterone receptor antagonist + androgen receptor antagonist → used for hirsutism, PCOS, heart failure.

[CARD 55 - Type 1]
Q: What are the side effects of spironolactone?
A: Hyperkalaemia, gynaecomastia, menstrual irregularity.

[CARD 56 - Type 1]
Q: What is the main concern with cyproterone and flutamide?
A: Hepatotoxicity — monitor liver function tests.

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SECTION 3: ANTINEOPLASTIC DRUGS
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[CARD 57 - Type 3: Mnemonic]
Q: What is the mnemonic for antineoplastic drug classes?
A: "CAMPD" = Cyclophosphamide/alkylating agents | Antimetabolites | Microtubule/plant alkaloids | Platinum compounds | Doxorubicin/anthracyclines

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3A. ALKYLATING AGENTS
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[CARD 58 - Type 1]
Q: What is the mechanism of alkylating agents?
A: Form covalent cross-links in DNA → prevent DNA replication — cell cycle NON-specific.

[CARD 59 - Type 1]
Q: What are the class-wide side effects of alkylating agents?
A: Myelosuppression, nausea/vomiting, infertility (gonadal toxicity), secondary malignancy (AML).

[CARD 60 - Type 2: Cloze]
[c]Cyclophosphamide[/c] causes haemorrhagic cystitis because its metabolite acrolein is directly toxic to the bladder epithelium.
[Trap: common wrong answer is "haemorrhagic cystitis is due to myelosuppression" — it is a direct chemical toxicity from acrolein, not thrombocytopaenia]

[CARD 61 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: How do you prevent cyclophosphamide-induced haemorrhagic cystitis?
A: Give mesna (mercaptoethane sulfonate) — binds and inactivates acrolein in the bladder + ensure adequate IV hydration.

[CARD 62 - Type 2: Cloze]
[c]Busulfan[/c] uniquely causes pulmonary fibrosis and hyperpigmentation in addition to standard alkylating agent toxicities.
[Trap: common wrong answer is "all alkylating agents cause pulmonary fibrosis" — busulfan is the classic alkylating agent associated with pulmonary fibrosis; cyclophosphamide is associated with cystitis]

[CARD 63 - Type 1]
Q: What additional toxicity does busulfan cause at high doses?
A: Seizures (prophylactic anticonvulsants are given with high-dose busulfan conditioning regimens).

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3B. ANTIMETABOLITES
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[CARD 64 - Type 3: Mnemonic]
Q: What is the mnemonic for the key antimetabolite trio?
A: "MTX-5FU-6MP" = Methotrexate | 5-Fluorouracil | 6-Mercaptopurine

[CARD 65 - Type 1]
Q: What is the mechanism of methotrexate (MTX)?
A: Dihydrofolate reductase (DHFR) inhibitor → blocks folate synthesis → inhibits DNA/RNA synthesis.

[CARD 66 - Type 1]
Q: What are the indications for methotrexate?
A: ALL, NHL, breast cancer, choriocarcinoma, RA, psoriasis.

[CARD 67 - Type 1]
Q: What are the key side effects of methotrexate?
A: Myelosuppression, mucositis, hepatotoxicity, pulmonary fibrosis.

[CARD 68 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient has methotrexate toxicity. What is the antidote?
A: Folinic acid (leucovorin/calcium folinate) — bypasses the DHFR block; NOT folic acid.
[Trap: common wrong answer is "give folic acid" — folic acid cannot be converted to its active form because DHFR is blocked; only folinic acid (already reduced) works]

[CARD 69 - Type 1]
Q: What is the mechanism of 5-fluorouracil (5-FU)?
A: Thymidylate synthase inhibitor → depletes thymidine → prevents DNA synthesis.

[CARD 70 - Type 1]
Q: What are the indications for 5-FU?
A: Colorectal, breast, and gastric cancer.

[CARD 71 - Type 1]
Q: What is the unique side effect of 5-FU (high dose)?
A: Hand-foot syndrome (palmar-plantar erythrodysaesthesia), cerebellar ataxia at high doses.

[CARD 72 - Type 1]
Q: What is the mechanism of 6-mercaptopurine (6-MP)?
A: Purine analogue → inhibits purine synthesis → blocks DNA/RNA synthesis.

[CARD 73 - Type 2: Cloze]
[c]6-Mercaptopurine[/c] is severely toxic when combined with allopurinol because allopurinol inhibits xanthine oxidase, the enzyme that metabolises 6-MP — drug levels rise to toxic levels.
[Trap: common wrong answer is "allopurinol is safe to add to any chemotherapy" — if 6-MP or azathioprine is being used, the 6-MP dose must be reduced by 75% if allopurinol must be given]

[CARD 74 - Type 1]
Q: What is the mechanism and indication of hydroxyurea?
A: Ribonucleotide reductase inhibitor → reduces DNA synthesis; used in CML, sickle cell disease (raises HbF), essential thrombocythaemia.

[CARD 75 - Type 1]
Q: What is the unique benefit of hydroxyurea in sickle cell disease?
A: Increases fetal haemoglobin (HbF) production → reduces sickling episodes.

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3C. PLANT ALKALOIDS & MICROTUBULE AGENTS
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[CARD 76 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Vincristine vs vinblastine — which causes neuropathy and which causes myelosuppression?
A: Vincristine = peripheral neuropathy (dose-limiting), minimal myelosuppression. Vinblastine = myelosuppression (dose-limiting), less neuropathy.
[Trap: common wrong answer is "both vinca alkaloids are equally myelosuppressive" — vincristine is the classic neuropathy drug; vinblastine is the classic myelosuppressive vinca]

[CARD 77 - Type 2: Cloze]
[c]Vincristine[/c] causes SIADH in addition to peripheral neuropathy, while [c]vinblastine[/c] causes myelosuppression as its dose-limiting toxicity.

[CARD 78 - Type 1]
Q: What is the mechanism of vinca alkaloids (vincristine, vinblastine)?
A: Bind tubulin → inhibit microtubule polymerisation → arrest mitosis at metaphase.

[CARD 79 - Type 1]
Q: What is the mechanism of paclitaxel/docetaxel?
A: Stabilise microtubules → prevent depolymerisation → arrest mitosis (opposite mechanism to vinca alkaloids).

[CARD 80 - Type 1]
Q: What are the key side effects of paclitaxel?
A: Peripheral neuropathy, myelosuppression, hypersensitivity reactions, alopecia.

[CARD 81 - Type 1]
Q: What is the mechanism and side effect of etoposide?
A: Topoisomerase II inhibitor; key side effect is secondary AML (therapy-related myeloid neoplasm).

[CARD 82 - Type 1]
Q: What is the mechanism and key side effect of irinotecan?
A: Topoisomerase I inhibitor; key side effect is delayed diarrhoea (treated with loperamide).

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3D. PLATINUM COMPOUNDS
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[CARD 83 - Type 1]
Q: What is the mechanism of platinum compounds (cisplatin, carboplatin, oxaliplatin)?
A: Form platinum-DNA adducts → cross-link DNA → inhibit replication.

[CARD 84 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Cisplatin vs carboplatin vs oxaliplatin — what is each drug's dose-limiting toxicity?
A: Cisplatin = nephrotoxicity + ototoxicity. Carboplatin = myelosuppression. Oxaliplatin = cold-triggered peripheral neuropathy.
[Trap: common wrong answer is "all platinum compounds cause the same toxicity" — these distinctions are directly tested in HKMLE]

[CARD 85 - Type 2: Cloze]
[c]Cisplatin[/c] causes nephrotoxicity, ototoxicity (high-frequency hearing loss), severe nausea/vomiting, and hypomagnesaemia because platinum compounds accumulate in the proximal tubule and inner ear.

[CARD 86 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: How do you prevent cisplatin-induced nephrotoxicity?
A: Aggressive IV hydration with normal saline + mannitol diuresis before and after cisplatin administration.

[CARD 87 - Type 2: Cloze]
[c]Oxaliplatin[/c] causes a unique sensory peripheral neuropathy that is acutely worsened by exposure to cold (touching cold objects, cold drinks).

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3E. ANTHRACYCLINES (DOXORUBICIN)
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[CARD 88 - Type 1]
Q: What is the mechanism of doxorubicin?
A: Intercalates DNA + inhibits topoisomerase II + generates free radicals → multiple mechanisms of DNA damage.

[CARD 89 - Type 1]
Q: What are the indications for doxorubicin?
A: Breast cancer, leukaemias, lymphomas, sarcomas.

[CARD 90 - Type 2: Cloze]
[c]Doxorubicin[/c] causes dilated cardiomyopathy because free radical damage to cardiomyocytes is cumulative and dose-dependent — exceeding the lifetime cumulative dose is irreversible.
[Trap: common wrong answer is "cardiotoxicity is reversible with dose reduction" — once cardiomyopathy develops, it is generally irreversible; prevention (monitoring LVEF, using dexrazoxane) is key]

[CARD 91 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: How do you protect against doxorubicin-induced cardiomyopathy?
A: Dexrazoxane (iron chelator) — chelates iron, reducing free radical generation in the heart; also monitor LVEF before each cycle and do not exceed lifetime cumulative dose.

[CARD 92 - Type 1]
Q: What harmless but alarming side effect do anthracyclines cause?
A: Red/orange urine (due to drug metabolite excretion — not haematuria).

[CARD 93 - Type 1]
Q: What is the contraindication to anthracyclines?
A: Pre-existing cardiomyopathy; do not exceed the lifetime cumulative dose.

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SECTION 4: IMMUNOMODULATORS
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[CARD 94 - Type 3: Mnemonic]
Q: What is the mnemonic for immunosuppressant classes?
A: "CaT SiMply" = Calcineurin inhibitors (Cyclosporine, Tacrolimus) | Sirolimus (mTOR inhibitor) | Mycophenolate mofetil

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4A. CALCINEURIN INHIBITORS
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[CARD 95 - Type 1]
Q: What is the mechanism of cyclosporine?
A: Binds cyclophilin → inhibits calcineurin → reduces IL-2 transcription → inhibits T-cell proliferation.

[CARD 96 - Type 1]
Q: What is the mechanism of tacrolimus (FK506)?
A: Binds FKBP-12 → inhibits calcineurin → reduces IL-2 transcription → inhibits T-cell proliferation. (Same endpoint as cyclosporine but 100x more potent.)

[CARD 97 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Cyclosporine vs tacrolimus — which causes more diabetes, and which causes more gingival hyperplasia/hirsutism?
A: Tacrolimus = more diabetes. Cyclosporine = more gingival hyperplasia and hirsutism.
[Trap: common wrong answer is "both CNIs have identical side effect profiles" — these specific differences are regularly tested]

[CARD 98 - Type 2: Cloze]
Both [c]cyclosporine[/c] and [c]tacrolimus[/c] cause nephrotoxicity (dose-limiting) because calcineurin inhibitors cause afferent arteriolar vasoconstriction in the kidney — trough level monitoring is essential.
[Trap: common wrong answer is "sirolimus is also nephrotoxic" — sirolimus/rapamycin does NOT cause nephrotoxicity (it is actually used when CNI nephrotoxicity limits therapy)]

[CARD 99 - Type 1]
Q: What is the therapeutic drug monitoring parameter for cyclosporine and tacrolimus?
A: Trough plasma levels (drawn just before next dose); also monitor CrCl/eGFR for nephrotoxicity.

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4B. mTOR INHIBITOR (SIROLIMUS)
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[CARD 100 - Type 1]
Q: What is the mechanism of sirolimus (rapamycin)?
A: Binds FKBP-12 → inhibits mTOR → blocks IL-2 signalling → stops cell proliferation.

[CARD 101 - Type 1]
Q: How does sirolimus differ from tacrolimus if both bind FKBP-12?
A: Both bind FKBP-12, but sirolimus-FKBP12 complex inhibits mTOR (not calcineurin) — so sirolimus does NOT inhibit IL-2 production; it blocks the response to IL-2.

[CARD 102 - Type 1]
Q: What are the key side effects of sirolimus?
A: Hyperlipidaemia, thrombocytopenia, impaired wound healing, interstitial pneumonitis — NOT nephrotoxic.

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4C. AZATHIOPRINE & MYCOPHENOLATE
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[CARD 103 - Type 1]
Q: What is the mechanism of azathioprine?
A: Prodrug → converted to 6-MP → inhibits purine synthesis → reduces lymphocyte proliferation.

[CARD 104 - Type 2: Cloze]
[c]Azathioprine[/c] + allopurinol = life-threatening toxicity because allopurinol inhibits xanthine oxidase (same enzyme that metabolises azathioprine's active metabolite 6-MP), causing toxic drug accumulation.
[Trap: common wrong answer is "allopurinol only interacts with 6-MP directly" — azathioprine converts TO 6-MP in vivo, so azathioprine is equally affected]

[CARD 105 - Type 1]
Q: What is the mechanism of mycophenolate mofetil (MMF)?
A: Inhibits IMPDH (inosine monophosphate dehydrogenase) → blocks de novo purine synthesis → selectively suppresses lymphocyte proliferation (lymphocytes lack the salvage pathway).

[CARD 106 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which immunosuppressant does NOT require therapeutic drug monitoring (TDM)?
A: Mycophenolate mofetil (MMF) — unlike cyclosporine, tacrolimus, and sirolimus which all require trough level monitoring.
[Trap: common wrong answer is "all immunosuppressants require TDM" — MMF is the exception; it is monitored clinically, not by drug levels]

[CARD 107 - Type 1]
Q: What are the side effects of mycophenolate mofetil?
A: GI toxicity (diarrhoea, nausea), myelosuppression, increased infection/malignancy risk, teratogenic.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: ANTIVIRAL DRUGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 108 - Type 3: Mnemonic]
Q: What is the mnemonic for antiviral drug-virus matching?
A: "ACE GOaR" = Acyclovir (HSV/VZV) | CMV/Ganciclovir | Ebola/Oseltamivir/Remdesivir | (H)IV/Ribavirin

──────────────────────────────────────
5A. ANTI-HERPES DRUGS
──────────────────────────────────────

[CARD 109 - Type 1]
Q: What is the mechanism of acyclovir?
A: Viral thymidine kinase (in HSV/VZV-infected cells) phosphorylates acyclovir → active form inhibits viral DNA polymerase — selective to infected cells only.

[CARD 110 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Why is acyclovir selectively toxic to herpes-infected cells and not normal cells?
A: Acyclovir is only phosphorylated (activated) by viral thymidine kinase, which is only present in HSV/VZV-infected cells — this is the basis of its safety profile.

[CARD 111 - Type 1]
Q: What are the indications for acyclovir?
A: HSV-1/2 (genital/oral herpes), VZV (chickenpox, shingles), HSV encephalitis (IV).

[CARD 112 - Type 1]
Q: What are the side effects of IV acyclovir?
A: Crystalluria/nephrotoxicity (crystallises in renal tubules — prevent with adequate IV hydration), neurotoxicity.

[CARD 113 - Type 1]
Q: What is the mechanism of ganciclovir?
A: Similar to acyclovir — activated by viral kinase (UL97 kinase in CMV) → inhibits CMV DNA polymerase.

[CARD 114 - Type 1]
Q: What is ganciclovir used for?
A: CMV retinitis, CMV colitis (NOT first-line for HSV — use acyclovir for HSV).
[Trap: common wrong answer is "ganciclovir can replace acyclovir for HSV" — acyclovir remains preferred for HSV; ganciclovir is the CMV drug]

[CARD 115 - Type 2: Cloze]
[c]Ganciclovir[/c] causes myelosuppression (dose-limiting) whereas [c]acyclovir[/c] has minimal side effects because ganciclovir is less selective and inhibits cellular DNA polymerases to a greater degree.

[CARD 116 - Type 1]
Q: What is foscarnet used for and what is its mechanism?
A: Resistant HSV and CMV — directly inhibits viral DNA polymerase WITHOUT requiring kinase activation (used when resistance due to TK mutation occurs).
[Trap: common wrong answer is "foscarnet requires viral thymidine kinase like acyclovir" — foscarnet's key advantage is that it bypasses the need for viral kinase; it acts directly on the polymerase]

[CARD 117 - Type 1]
Q: What are the major side effects of foscarnet?
A: Nephrotoxicity, hypocalcaemia (chelates calcium), hypomagnesaemia, penile/vulval ulcers.

──────────────────────────────────────
5B. ANTI-INFLUENZA
──────────────────────────────────────

[CARD 118 - Type 1]
Q: What is the mechanism of oseltamivir (Tamiflu)?
A: Neuraminidase inhibitor → prevents viral release from host cells (neuraminidase cleaves sialic acid to release new virions).

[CARD 119 - Type 1]
Q: What are the indications for oseltamivir?
A: Influenza A and B treatment (started within 48 hours of symptom onset); prophylaxis.

[CARD 120 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: When must oseltamivir be started to be effective?
A: Within 48 hours of influenza symptom onset — after this window, clinical benefit is minimal.
[Trap: common wrong answer is "oseltamivir can be started at any time" — timing is critical and is directly tested]

[CARD 121 - Type 1]
Q: What are the side effects of oseltamivir?
A: Nausea, vomiting; rare neuropsychiatric effects (mainly in paediatric patients).

[CARD 122 - Type 1]
Q: What is zanamivir and when is it preferred?
A: Inhaled neuraminidase inhibitor (same mechanism as oseltamivir) — used for oseltamivir-resistant strains; AVOID in asthma/COPD (causes bronchospasm).

[CARD 123 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Do neuraminidase inhibitors cover both influenza A and B?
A: Yes — oseltamivir and zanamivir cover both A and B, unlike the older amantadine which only covers influenza A.

──────────────────────────────────────
5C. BROAD-SPECTRUM ANTIVIRALS
──────────────────────────────────────

[CARD 124 - Type 1]
Q: What is the mechanism of ribavirin?
A: Guanosine analogue → inhibits viral RNA polymerase + mRNA capping → broad antiviral effect.

[CARD 125 - Type 1]
Q: What are the indications for ribavirin?
A: HCV (with pegylated interferon), RSV (inhaled in children), Lassa fever.

[CARD 126 - Type 2: Cloze]
[c]Ribavirin[/c] is teratogenic and causes haemolytic anaemia (dose-limiting), and is absolutely contraindicated in pregnancy.

[CARD 127 - Type 1]
Q: What is the mechanism of remdesivir?
A: Adenosine nucleotide analogue → inhibits viral RNA polymerase → causes RNA chain termination.

[CARD 128 - Type 1]
Q: What are the indications and side effects of remdesivir?
A: COVID-19 (hospitalised patients), studied in Ebola; side effects include bradycardia, elevated LFTs, nausea.

──────────────────────────────────────
5D. ANTIRETROVIRALS (HIV)
──────────────────────────────────────

[CARD 129 - Type 3: Mnemonic]
Q: What is the mnemonic for HIV drug classes?
A: "NRRTI-PI-II" = NRTIs (Nucleoside RTIs) | NNRTIs (Non-nucleoside RTIs) | PIs (Protease inhibitors) | Integrase inhibitors

[CARD 130 - Type 1]
Q: What is the mechanism of NRTIs?
A: Incorporate into viral DNA as chain terminators (lacking 3'-OH) → halt reverse transcription.

[CARD 131 - Type 2: Cloze]
[c]Zidovudine (AZT)[/c] causes anaemia and myelosuppression; [c]tenofovir[/c] causes nephrotoxicity and bone loss; the class side effects of NRTIs include lactic acidosis and lipoatrophy.

[CARD 132 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which NRTI is used in prevention of mother-to-child HIV transmission (PMTCT)?
A: Zidovudine (AZT) — given to HIV-positive mothers during labour and to neonates after birth to reduce vertical transmission.

[CARD 133 - Type 1]
Q: What is the mechanism of NNRTIs?
A: Bind reverse transcriptase allosterically → cause conformational change → block RT activity (NOT incorporated into DNA).

[CARD 134 - Type 2: Cloze]
[c]Efavirenz[/c] causes vivid dreams, dizziness and CNS effects, and is teratogenic (neural tube defects) — do NOT use in the first trimester of pregnancy.
[Trap: common wrong answer is "efavirenz is safe in pregnancy because it is an NNRTI" — it is specifically associated with neural tube defects in the first trimester]

[CARD 135 - Type 1]
Q: What serious side effect is associated with nevirapine?
A: Severe hepatotoxicity and Stevens-Johnson syndrome.

[CARD 136 - Type 1]
Q: What is the mechanism of HIV protease inhibitors (PIs)?
A: Block HIV protease → immature, non-infectious virions are produced.

[CARD 137 - Type 1]
Q: What are the class side effects of HIV protease inhibitors?
A: Hyperlipidaemia, insulin resistance/diabetes, lipodystrophy, GI side effects.

[CARD 138 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is ritonavir primarily used for in modern HIV regimens?
A: As a pharmacokinetic "booster" — it inhibits CYP3A4, raising levels of co-administered PIs (e.g. lopinavir/ritonavir), NOT primarily as an antiviral alone.
[Trap: common wrong answer is "ritonavir is used as the main antiretroviral agent" — ritonavir's main role in current regimens is CYP3A4 inhibition to boost levels of other drugs]

[CARD 139 - Type 1]
Q: What is the mechanism of integrase inhibitors (raltegravir, dolutegravir)?
A: Block HIV integrase → prevent integration of viral cDNA into host genome.

[CARD 140 - Type 1]
Q: What are the side effects of integrase inhibitors?
A: Generally well tolerated; insomnia, headache.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 6: ANTIPROTOZOALS & ANTHELMINTICS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 141 - Type 3: Mnemonic]
Q: What is the mnemonic for antiparasitic drugs?
A: "CAMP MAPping" = Chloroquine | Artemisinins | Metronidazole | Primaquine | Mebendazole/Albendazole | Praziquantel

──────────────────────────────────────
6A. ANTIMALARIALS
──────────────────────────────────────

[CARD 142 - Type 1]
Q: What is the mechanism of chloroquine?
A: Concentrates in parasite food vacuole → inhibits haem polymerisation → toxic haem accumulates → kills parasite.

[CARD 143 - Type 1]
Q: What are the indications for chloroquine?
A: Malaria treatment/prophylaxis (sensitive strains); RA; SLE (antimalarial/anti-inflammatory).

[CARD 144 - Type 1]
Q: What are the key side effects of chloroquine?
A: Retinopathy with prolonged use (visual field defects — requires regular eye monitoring), pruritus in dark-skinned patients, QT prolongation.

[CARD 145 - Type 1]
Q: What is the mechanism of primaquine?
A: Disrupts mitochondrial function in parasites (generates reactive oxygen species).

[CARD 146 - Type 1]
Q: What is the specific indication for primaquine that no other antimalarial covers?
A: Radical cure of P. vivax and P. ovale — eliminates liver hypnozoites to prevent relapse.

[CARD 147 - Type 2: Cloze]
[c]Primaquine[/c] causes haemolytic anaemia in G6PD-deficient patients because G6PD-deficient red cells cannot neutralise the reactive oxygen species generated by the drug.
[Trap: common wrong answer is "G6PD status only matters for dapsone" — primaquine is THE classic HKMLE G6PD haemolysis question; always test G6PD before giving primaquine]

[CARD 148 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What must you check before prescribing primaquine?
A: G6PD (glucose-6-phosphate dehydrogenase) status — primaquine causes severe haemolytic anaemia in G6PD deficiency.

[CARD 149 - Type 1]
Q: What are the serious neuropsychiatric side effects of mefloquine?
A: Anxiety, vivid dreams, psychosis, seizures — contraindicated in patients with psychiatric history.

[CARD 150 - Type 1]
Q: What is the mechanism of artemisinin derivatives (artesunate, artemether)?
A: Generate free radicals that damage parasite proteins and membranes — used for severe/multi-drug-resistant malaria.

[CARD 151 - Type 1]
Q: What is the combination antimalarial used for prophylaxis and P. falciparum treatment?
A: Atovaquone + proguanil (Malarone) — inhibits mitochondrial electron transport + folate synthesis.

──────────────────────────────────────
6B. METRONIDAZOLE
──────────────────────────────────────

[CARD 152 - Type 1]
Q: What is the mechanism of metronidazole?
A: Nitroimidazole → forms cytotoxic free radicals (after reduction in anaerobic/microaerophilic organisms) → causes DNA strand breaks.

[CARD 153 - Type 1]
Q: What are the indications for metronidazole?
A: Giardiasis, amoebiasis (intestinal + hepatic abscess), trichomoniasis, C. difficile, anaerobic bacterial infections, H. pylori (triple therapy).

[CARD 154 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What drug covers giardiasis AND amoebiasis AND trichomoniasis all with one agent?
A: Metronidazole — the only drug used for all three protozoal infections.

[CARD 155 - Type 2: Cloze]
[c]Metronidazole[/c] + alcohol causes a disulfiram-like reaction (flushing, palpitations, severe nausea) because metronidazole inhibits aldehyde dehydrogenase → acetaldehyde accumulates.
[Trap: common wrong answer is "a small amount of alcohol is safe with metronidazole" — even small amounts of alcohol cause this reaction; patients must abstain completely during and for 48 hours after treatment]

[CARD 156 - Type 1]
Q: What is the contraindication of metronidazole in pregnancy?
A: Contraindicated in the 1st trimester (teratogenicity concern).

[CARD 157 - Type 1]
Q: What side effect does prolonged metronidazole use cause?
A: Peripheral neuropathy.

──────────────────────────────────────
6C. ANTHELMINTICS
──────────────────────────────────────

[CARD 158 - Type 1]
Q: What is the mechanism of mebendazole?
A: Inhibits microtubule polymerisation in worms → impairs glucose uptake → kills the worm.

[CARD 159 - Type 1]
Q: What are the indications for mebendazole?
A: GI nematodes — roundworm (Ascaris), hookworm, whipworm (Trichuris), threadworm (Enterobius); stays in the gut (minimal systemic absorption).

[CARD 160 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Mebendazole vs albendazole — which treats systemic parasitic infections?
A: Albendazole — better absorbed than mebendazole, crosses the BBB, and treats systemic infections including neurocysticercosis and hydatid cyst (echinococcosis); mebendazole stays in the gut.
[Trap: common wrong answer is "mebendazole and albendazole are interchangeable" — for CNS/systemic worm infections, only albendazole has adequate tissue penetration]

[CARD 161 - Type 2: Cloze]
[c]Albendazole[/c] treats neurocysticercosis and hydatid cyst disease because it is well absorbed and crosses the blood-brain barrier, unlike mebendazole.

[CARD 162 - Type 1]
Q: What are the side effects of albendazole?
A: Hepatotoxicity, bone marrow suppression with prolonged use, teratogenic.

[CARD 163 - Type 1]
Q: What is the mechanism of praziquantel?
A: Increases membrane permeability to Ca2+ → spastic paralysis of the worm → worm dies and is expelled.

[CARD 164 - Type 1]
Q: What are the indications for praziquantel?
A: Schistosomiasis, tapeworms (Taenia), liver flukes.

[CARD 165 - Type 1]
Q: What is the mechanism of ivermectin?
A: Binds glutamate-gated Cl- channels in invertebrates → hyperpolarisation → paralysis of worm.

[CARD 166 - Type 1]
Q: What are the indications for ivermectin?
A: Onchocerciasis (river blindness), strongyloides, scabies, head lice.

[CARD 167 - Type 1]
Q: What is the Mazzotti reaction?
A: Inflammatory reaction (fever, rash, pruritus) caused by dying microfilariae after ivermectin treatment for onchocerciasis — not a drug allergy.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: MNEMONICS CHEAT SHEET (RAPID REVIEW)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 168 - Type 3: Mnemonic]
Q: What is the mnemonic for combined OCP indications?
A: "COPE" = Contraception | acne | Ovarian cyst prevention | Period regulation/dysmenorrhoea + Endometriosis

[CARD 169 - Type 3: Mnemonic]
Q: What is the mnemonic for antineoplastic drug classes?
A: "CAMPD" = Cyclophosphamide (alkylating) | Antimetabolites | Microtubule agents/plant alkaloids | Platinum compounds | Doxorubicin/anthracyclines

[CARD 170 - Type 3: Mnemonic]
Q: What is the mnemonic for the antimetabolite trio?
A: "MTX-5FU-6MP" = Methotrexate (DHFR inhibitor) | 5-Fluorouracil (thymidylate synthase inhibitor) | 6-Mercaptopurine (purine analogue)

[CARD 171 - Type 3: Mnemonic]
Q: What is the mnemonic for immunosuppressant classes?
A: "CaT SiMply" = Calcineurin inhibitors (Cyclosporine, Tacrolimus) | Sirolimus (mTOR) | Mycophenolate

[CARD 172 - Type 3: Mnemonic]
Q: What is the mnemonic for HIV drug classes?
A: "NRRTI-PI-II" = NRTIs | NNRTIs | Protease inhibitors | Integrase inhibitors

[CARD 173 - Type 3: Mnemonic]
Q: What is the mnemonic for antiparasitic agents?
A: "CAMP MAPping" = Chloroquine | Artemisinins | Metronidazole | Primaquine | Mebendazole/Albendazole | Praziquantel

[CARD 174 - Type 3: Mnemonic]
Q: What is the mnemonic for TB drug toxicities?
A: "RIP PE" = Rifampicin (orange urine/secretions, CYP inducer) | INH/Isoniazid (peripheral neuropathy — give pyridoxine) | Pyrazinamide (hyperuricaemia/gout) | Pyridoxine (B6, given with INH) | Ethambutol (Eyes — optic neuritis)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
RAPID-FIRE TRAP SUMMARY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 175 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the rescue agent for methotrexate toxicity, and what is commonly given by mistake?
A: Folinic acid (leucovorin) rescues — NOT folic acid (folic acid cannot be used because DHFR is blocked).

[CARD 176 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which two drug pairs cause severe toxicity due to shared xanthine oxidase metabolism?
A: 6-Mercaptopurine + allopurinol; and Azathioprine + allopurinol — reduce 6-MP/azathioprine dose by 75% if allopurinol must be used.

[CARD 177 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which immunosuppressant is NOT nephrotoxic among CNIs and mTOR inhibitors?
A: Sirolimus (mTOR inhibitor) — cyclosporine and tacrolimus are both nephrotoxic.

[CARD 178 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Name two SERM drugs and state the key difference in their uterine effects.
A: Tamoxifen = uterine AGONIST (increases endometrial cancer risk). Raloxifene = uterine ANTAGONIST (no endometrial cancer risk).

[CARD 179 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: When is foscarnet used instead of acyclovir/ganciclovir?
A: When resistance has developed (e.g. acyclovir-resistant HSV, ganciclovir-resistant CMV) — foscarnet does not require viral thymidine kinase activation.

[CARD 180 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the single most important pre-treatment check before prescribing primaquine?
A: G6PD status — G6PD deficiency causes severe haemolytic anaemia with primaquine.

[CARD 181 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient needs malaria prophylaxis but has a history of depression. Which drug is contraindicated?
A: Mefloquine — causes neuropsychiatric effects (anxiety, vivid dreams, psychosis, seizures); avoid in any psychiatric history.

[CARD 182 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Vincristine vs vinblastine dose-limiting toxicity?
A: Vincristine = peripheral neuropathy (dose-limiting). Vinblastine = myelosuppression (dose-limiting).

[CARD 183 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which anti-androgen is teratogenic and must not be handled by pregnant women?
A: Finasteride — inhibits DHT formation; male foetuses exposed in utero develop genital abnormalities; women must not handle crushed tablets.

[CARD 184 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Cisplatin vs carboplatin — what electrolyte does cisplatin classically deplete?
A: Magnesium — cisplatin causes hypomagnesaemia (also hypocalcaemia and hypokalaemia) via tubular damage.

[CARD 185 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which antiviral is used in ALL of the following — giardiasis, amoebiasis, trichomoniasis, C. difficile, and anaerobic infections?
A: Metronidazole.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
END OF DECK — 185 CARDS TOTAL
Topics: Autacoids | Gonadal Hormones | Antineoplastics | Immunomodulators
         Antivirals | Antiprotozoals/Anthelmintics
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

========================================================
HKMLE HIGH-YIELD ANKI FLASHCARDS
Haematology Pharmacology
Topics: Warfarin | Heparin/LMWH | DTIs | DOACs | Antiplatelets |
Thrombolytics | Antifibrinolytics | Haematinics | Growth Factors | Reversal Agents
========================================================

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
MASTER MAP MNEMONIC
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 1 - Type 3: Mnemonic]
Q: What is the master mnemonic for haematology pharmacology topics?
A: "WATCH A GRIP" = Warfarin | Anticoagulants | DOACs (Xa + IIa) | Thrombolytics (tPA) | Clot stabilisers (TXA) | Heparin (UFH + LMWH) + DTIs | Antiplatelets | Growth factors | Reversal agents | Iron/B12/Folate (haematinics) | Platelets/coagulation cascade

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: WARFARIN
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 2 - Type 3: Mnemonic]
Q: What is the mnemonic for warfarin-blocked factors?
A: "WEPT" = Warfarin: Extended PT, inhibits factors II, VII, IX, X + Proteins C and S (the vitamin K-dependent clotting factors)

[CARD 3 - Type 1]
Q: What is the mechanism of warfarin?
A: Inhibits vitamin K epoxide reductase → blocks activation of vitamin K-dependent clotting factors II, VII, IX, X and anticoagulant proteins C and S.

[CARD 4 - Type 1]
Q: Why does warfarin have a delayed onset of 3-5 days?
A: Existing activated clotting factors must be cleared first; factor VII (shortest half-life ~6h) falls first, raising INR, but full anticoagulation requires depletion of all factors (II has the longest half-life).
[Trap: common wrong answer is "INR rising means the patient is fully anticoagulated" - early INR rise reflects only factor VII depletion; the patient is NOT fully anticoagulated until all factors, especially factor II, are depleted]

[CARD 5 - Type 1]
Q: What test monitors warfarin therapy?
A: INR (measures the extrinsic pathway - factors VII, X, II, V, fibrinogen).

[CARD 6 - Type 1]
Q: What is the target INR for AF and DVT/PE?
A: 2.0 - 3.0.

[CARD 7 - Type 1]
Q: What is the target INR for a mechanical mitral valve?
A: 2.5 - 3.5.
[Trap: common wrong answer is "2.0-3.0 for all mechanical valves" - mitral valves require a higher target (2.5-3.5) due to higher thromboembolism risk; some guidelines also use 2.5-3.5 for aortic valves]

[CARD 8 - Type 1]
Q: What is the target INR for recurrent PE or antiphospholipid syndrome?
A: 2.5 - 3.5.

[CARD 9 - Type 2: Cloze]
[c]Warfarin[/c] causes skin necrosis early in therapy because it reduces Protein C and S (which have short half-lives) before full anticoagulation is achieved, creating a transient procoagulant state - especially dangerous in Protein C/S deficiency.
[Trap: common wrong answer is "start warfarin alone in acute DVT" - warfarin MUST always be bridged with heparin/LMWH when starting in acute thrombosis to prevent the procoagulant window]

[CARD 10 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Why must heparin always be started alongside warfarin in acute thrombosis?
A: Warfarin first depletes Protein C and S (short half-lives) before reducing procoagulant factors II, IX, X - this transient procoagulant state can cause warfarin-induced skin necrosis or worsening thrombosis.

[CARD 11 - Type 1]
Q: Is warfarin safe in pregnancy?
A: No - warfarin is Category X (teratogen); warfarin embryopathy (nasal hypoplasia, stippled epiphyses) occurs weeks 6-12; fetal haemorrhage risk in T3; LMWH is the only safe anticoagulant in pregnancy.
[Trap: common wrong answer is "DOACs are safe alternatives in pregnancy" - DOACs are also contraindicated; LMWH is the ONLY safe option]

──────────────────────────────────────
Warfarin Drug Interactions
──────────────────────────────────────

[CARD 12 - Type 3: Mnemonic]
Q: What is the mnemonic for drugs that INCREASE warfarin INR?
A: "CAFE MIX" = Clarithromycin/Ciprofloxacin | Amiodarone | Fluconazole | Erythromycin | Metronidazole | Isoniazid | eXcretion inhibitors/statins (inhibit CYP2C9 → reduce warfarin metabolism → raise levels)

[CARD 13 - Type 3: Mnemonic]
Q: What is the mnemonic for drugs that DECREASE warfarin INR?
A: "PRICARS" = Phenytoin | Rifampicin | Isoniazid (high dose) | Carbamazepine | Alcohol (chronic) | St John's Wort (induce CYP2C9 → increase warfarin metabolism → lower levels)

[CARD 14 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on warfarin is started on amiodarone. What happens to their INR?
A: INR rises (increased bleeding risk) - amiodarone inhibits CYP2C9, reducing warfarin metabolism; warfarin dose must be reduced and INR monitored closely.

[CARD 15 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on warfarin is started on rifampicin. What happens?
A: INR falls (decreased anticoagulation efficacy) - rifampicin induces CYP2C9, increasing warfarin metabolism; the warfarin dose must be increased and INR monitored.

[CARD 16 - Type 1]
Q: Do NSAIDs change the INR in a patient on warfarin?
A: No - NSAIDs do not directly change INR, but they increase bleeding risk by inhibiting platelet function and damaging GI mucosa; the INR remains variable.

──────────────────────────────────────
Warfarin Reversal
──────────────────────────────────────

[CARD 17 - Type 1]
Q: What do you do for INR 3-5 with no bleeding in a patient on warfarin?
A: Reduce or omit the dose, recheck INR in 1-2 days.

[CARD 18 - Type 1]
Q: What do you do for INR 5-8 with no significant bleeding?
A: Stop warfarin, give low-dose oral vitamin K 1-2 mg.

[CARD 19 - Type 1]
Q: What do you do for INR >8 with no or minor bleeding?
A: Stop warfarin, give oral vitamin K 5 mg (repeat at 24h if INR still high).

[CARD 20 - Type 1]
Q: What do you do for any INR with MAJOR bleeding on warfarin?
A: Stop warfarin + IV vitamin K 5-10 mg + 4-factor Prothrombin Complex Concentrate (PCC) immediately.
[Trap: common wrong answer is "give FFP instead of PCC" - PCC is preferred over FFP (faster reversal, lower volume, less transfusion risk)]

[CARD 21 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Why is 4-factor PCC preferred over FFP for urgent warfarin reversal?
A: PCC reverses anticoagulation faster, requires lower volume, and avoids the risks of large-volume blood product transfusion.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: HEPARIN (UFH & LMWH)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 22 - Type 3: Mnemonic]
Q: What is the mnemonic for heparin monitoring?
A: "HEPARIN = Helps Every Patient And Requires INR-free monitoring (UFH monitored by aPTT, not INR)"

[CARD 23 - Type 1]
Q: What is the mechanism of UFH?
A: Binds antithrombin III → inhibits thrombin (IIa) and factor Xa (and IXa, XIa, XIIa).

[CARD 24 - Type 1]
Q: What is the mechanism of LMWH (e.g. enoxaparin)?
A: Binds antithrombin III → preferentially inhibits factor Xa only (short chain cannot bridge thrombin).
[Trap: common wrong answer is "LMWH inhibits thrombin like UFH" - LMWH mainly inhibits Xa; it lacks the long chain required to simultaneously bind antithrombin and thrombin]

[CARD 25 - Type 1]
Q: How is UFH monitored?
A: aPTT (target 1.5-2.5x normal).

[CARD 26 - Type 1]
Q: How is LMWH monitored?
A: Usually NOT required routinely; anti-Xa level if obese, pregnant, or in renal impairment.

[CARD 27 - Type 1]
Q: What is the reversal agent for UFH?
A: Protamine sulfate 1 mg per 100 units UFH (given IV slowly).
[Trap: common wrong answer is "protamine fully reverses LMWH" - protamine only ~60% reverses LMWH (partial neutralisation)]

[CARD 28 - Type 1]
Q: Is LMWH safe in pregnancy?
A: Yes - LMWH does not cross the placenta and is the anticoagulant of choice in pregnancy.

[CARD 29 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: When should you avoid or reduce LMWH in a patient with renal impairment?
A: LMWH accumulates in renal failure - reduce dose or avoid if eGFR <30 mL/min; use UFH instead (renally cleared via reticuloendothelial system).
[Trap: common wrong answer is "LMWH is safer than UFH in all patients" - in renal failure, LMWH accumulates dangerously; UFH is preferred]

[CARD 30 - Type 1]
Q: What are the risk factors for side effects with protamine sulfate?
A: Fish allergy and prior vasectomy - associated with increased risk of hypotension, bradycardia, anaphylaxis.

──────────────────────────────────────
Heparin-Induced Thrombocytopenia (HIT)
──────────────────────────────────────

[CARD 31 - Type 3: Mnemonic]
Q: What is the mnemonic for HIT management?
A: "Stop Heparin, Start Argatroban/Fondaparinux, NO platelets, NO warfarin yet" (the 4 rules of HIT management)

[CARD 32 - Type 1]
Q: What is Type I HIT?
A: Mild non-immune platelet fall (>100) within 1-2 days of heparin - benign; can continue heparin.

[CARD 33 - Type 1]
Q: What is Type II HIT?
A: Immune-mediated (IgG antibodies against heparin-PF4 complex) → platelet activation → paradoxical THROMBOSIS; platelet count falls >50% from baseline, typically days 5-10 of heparin use.
[Trap: common wrong answer is "HIT causes bleeding because platelets are low" - HIT is THROMBOTIC (not just thrombocytopenic); the paradox is that low platelets coexist with increased clot formation]

[CARD 34 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on heparin develops a 50% drop in platelets on day 7 with a new DVT. What is the diagnosis and immediate management?
A: Type II HIT - immediately stop ALL heparin (UFH and LMWH), start argatroban or fondaparinux; do NOT give platelets; do NOT start warfarin yet.

[CARD 35 - Type 1]
Q: What scoring system is used to diagnose HIT?
A: The 4Ts score - Thrombocytopenia severity, Timing (day 5-10), Thrombosis, other causes of Thrombocytopenia excluded.

[CARD 36 - Type 1]
Q: What confirmatory test is used for HIT?
A: Anti-PF4/heparin ELISA or serotonin release assay.

[CARD 37 - Type 2: Cloze]
[c]Platelet transfusion[/c] is contraindicated in HIT because transfused platelets fuel further platelet activation and thrombosis via the heparin-PF4-IgG complex.
[Trap: common wrong answer is "give platelets because the platelet count is low" - platelet transfusion in HIT is dangerous and worsens thrombosis]

[CARD 38 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Why should warfarin NOT be started immediately in HIT?
A: Warfarin depletes Protein C (short half-life) before adequate anticoagulation is achieved, causing a procoagulant state that can lead to venous limb gangrene - wait until platelets >150 before introducing warfarin.

[CARD 39 - Type 1]
Q: What anticoagulants should be used instead of heparin in a patient with a history of HIT?
A: Fondaparinux or a DOAC - both UFH and LMWH are contraindicated in prior HIT.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: DIRECT THROMBIN INHIBITORS (DTIs)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 40 - Type 1]
Q: What is the mechanism of direct thrombin inhibitors (DTIs)?
A: Directly inhibit thrombin (factor IIa) → block fibrin formation and thrombin-mediated platelet activation - act independently of antithrombin (unlike heparin).

[CARD 41 - Type 1]
Q: What are the IV DTIs and their main uses?
A: Argatroban (HIT in renal failure - hepatic elimination) and bivalirudin (PCI alternative to heparin - renal elimination).

[CARD 42 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which DTI is preferred in HIT complicated by renal failure, and why?
A: Argatroban - it is eliminated hepatically, so renal failure does not affect its clearance (unlike most anticoagulants which are renally cleared).

[CARD 43 - Type 1]
Q: Is there a reversal agent for argatroban or bivalirudin?
A: No specific reversal agent - stop the infusion (both have very short half-lives: argatroban ~50 min, bivalirudin ~25 min).

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: DIRECT ORAL ANTICOAGULANTS (DOACs)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 44 - Type 3: Mnemonic]
Q: What is the mnemonic for DOACs by target?
A: "3 Xas + 1 IIa" = Rivaroxaban, Apixaban, Edoxaban (all factor Xa inhibitors) + Dabigatran (factor IIa/thrombin inhibitor)

[CARD 45 - Type 1]
Q: What are the indications common to all DOACs?
A: Non-valvular AF (stroke prevention), DVT/PE treatment and prevention, post-surgical VTE prophylaxis.

[CARD 46 - Type 1]
Q: What are the contraindications common to all DOACs?
A: Pregnancy (teratogenic), mechanical heart valves (warfarin is superior - RE-ALIGN trial), triple-positive antiphospholipid syndrome (warfarin preferred), severe renal impairment.

[CARD 47 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Can DOACs be used in patients with mechanical heart valves?
A: No - DOACs are contraindicated in mechanical heart valves; warfarin is the only anticoagulant proven safe and effective in this setting (RE-ALIGN trial showed dabigatran was inferior).
[Trap: common wrong answer is "DOACs are suitable for any patient with AF including those with mechanical valves" - mechanical valves are an absolute contraindication to DOACs]

[CARD 48 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Which DOAC has the highest renal clearance and must be avoided in renal failure?
A: Dabigatran - 80% renally cleared; avoid if CrCl <30 mL/min.
[Trap: common wrong answer is "all DOACs are equally risky in renal failure" - dabigatran is the most renally dependent; apixaban is the safest DOAC in CKD (~27% renal clearance)]

[CARD 49 - Type 1]
Q: Which DOAC is safest in chronic kidney disease (CKD)?
A: Apixaban - lowest renal clearance (~27%); dose reduce if 2 of: age ≥80, weight ≤60 kg, creatinine ≥133 µmol/L.

[CARD 50 - Type 1]
Q: What drugs reduce the efficacy of ALL DOACs?
A: St John's Wort, rifampicin, carbamazepine, phenytoin - all are P-gp/CYP3A4 inducers that increase DOAC metabolism.

[CARD 51 - Type 3: Mnemonic]
Q: What is the mnemonic for DOAC reversal agents?
A: "I-DAR for IIa (dabigatran), AND-exanet for Xa" = Idarucizumab reverses dabigatran (IIa); Andexanet alfa reverses Xa inhibitors (rivaroxaban, apixaban, edoxaban)

[CARD 52 - Type 1]
Q: What is idarucizumab and what does it reverse?
A: Monoclonal antibody Fab fragment (Praxbind) 5 g IV - reverses dabigatran within minutes; specific for dabigatran only.

[CARD 53 - Type 1]
Q: What is andexanet alfa and what does it reverse?
A: Recombinant factor Xa decoy - binds and sequesters Xa inhibitors (rivaroxaban, apixaban, edoxaban); if unavailable, use 4F-PCC 25-50 units/kg.
[Trap: common wrong answer is "idarucizumab reverses all DOACs" - idarucizumab is ONLY for dabigatran; Xa inhibitors require andexanet alfa or PCC]

[CARD 54 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on rivaroxaban has a major bleed. What is the reversal agent?
A: Andexanet alfa (recombinant Xa decoy); if unavailable, 4-factor PCC 25-50 units/kg.

[CARD 55 - Type 1]
Q: What are the key advantages of DOACs over warfarin?
A: No routine monitoring, fewer drug interactions, predictable dosing, faster onset/offset, lower risk of intracranial haemorrhage.

[CARD 56 - Type 1]
Q: What is the key GI bleeding concern with DOACs vs warfarin?
A: GI bleeding is higher with dabigatran and rivaroxaban compared to warfarin.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: ANTIPLATELETS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 57 - Type 1]
Q: What is the mechanism of aspirin as an antiplatelet?
A: Irreversibly inhibits COX-1 → reduces thromboxane A2 (TXA2) production → decreases platelet aggregation for the lifetime of the platelet (7-10 days).

[CARD 58 - Type 1]
Q: What are the indications for low-dose aspirin?
A: Secondary prevention of ACS, post-PCI, secondary stroke prevention, PAD.

[CARD 59 - Type 2: Cloze]
[c]Aspirin[/c] should never be given to children under 12 because it causes Reye's syndrome (hepatic encephalopathy) in children with viral illness.

[CARD 60 - Type 1]
Q: What is the mechanism of clopidogrel?
A: Irreversibly blocks the P2Y12 ADP receptor on platelets → prevents ADP-mediated platelet aggregation; prodrug requiring CYP2C19 activation.

[CARD 61 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient on clopidogrel is found to be a CYP2C19 poor metaboliser. What is the clinical consequence?
A: Reduced efficacy of clopidogrel (insufficient conversion of prodrug to active metabolite); consider switching to ticagrelor (not a prodrug) or prasugrel.
[Trap: common wrong answer is "clopidogrel dose can simply be increased" - pharmacogenomics limits the response regardless of dose in poor metabolisers]

[CARD 62 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Do PPIs reduce clopidogrel efficacy?
A: Yes - PPIs (especially omeprazole) compete for CYP2C19 → reduce clopidogrel activation → reduced antiplatelet effect; use pantoprazole if a PPI is needed.

[CARD 63 - Type 1]
Q: What is the mechanism of ticagrelor?
A: Reversibly blocks the P2Y12 receptor - NOT a prodrug (no CYP2C19 activation needed), faster and more consistent onset.

[CARD 64 - Type 2: Cloze]
[c]Ticagrelor[/c] causes dyspnoea because it inhibits adenosine reuptake → elevated adenosine levels → adenosine-mediated breathlessness - this is NOT bronchospasm and does not indicate lung disease.
[Trap: common wrong answer is "ticagrelor-associated dyspnoea = bronchospasm requiring drug switch" - adenosine-mediated dyspnoea is common (~15%), usually mild, and is NOT bronchospasm; do not discontinue without good reason]

[CARD 65 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient is on ticagrelor post-ACS. Can they take high-dose aspirin?
A: No - high-dose aspirin (>100 mg/day) reduces ticagrelor efficacy; always use low-dose aspirin (75-100 mg) with ticagrelor.

[CARD 66 - Type 1]
Q: What is the mechanism of prasugrel?
A: Irreversibly blocks P2Y12; prodrug with more efficient activation than clopidogrel → more potent and faster platelet inhibition.

[CARD 67 - Type 2: Cloze]
[c]Prasugrel[/c] is contraindicated in patients with a history of TIA or stroke because the combination of potent platelet inhibition and prior cerebrovascular disease confers an unacceptably high risk of intracranial haemorrhage.
[Trap: common wrong answer is "prasugrel is safe after TIA since it is just an antiplatelet" - prasugrel is the MOST potent P2Y12 blocker; prior TIA/stroke is an absolute contraindication]

[CARD 68 - Type 1]
Q: What other patients should NOT receive prasugrel?
A: Age >75 and weight <60 kg (excessive bleeding risk outweighs benefit).

[CARD 69 - Type 1]
Q: What is DAPT and how long is it prescribed after ACS/PCI?
A: Dual antiplatelet therapy = aspirin + P2Y12 inhibitor (clopidogrel/ticagrelor/prasugrel); standard duration is 12 months post-ACS or post-PCI.

[CARD 70 - Type 1]
Q: What is the mechanism of dipyridamole?
A: Inhibits phosphodiesterase → increases cAMP → decreases platelet aggregation; also blocks adenosine reuptake → vasodilation.

[CARD 71 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the clinical use of dipyridamole in cardiac imaging?
A: Dipyridamole (adenosine analogue effect) is used as a pharmacological stress agent in cardiac stress tests - it dilates coronary arteries, revealing areas of ischaemia.

[CARD 72 - Type 1]
Q: How long before elective surgery should antiplatelets be stopped?
A: Clopidogrel/prasugrel/ticagrelor: 5-7 days (7-10 days by platelet lifespan); aspirin may often be continued for most elective procedures.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 6: THROMBOLYTICS (FIBRINOLYTICS)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 73 - Type 3: Mnemonic]
Q: What is the mnemonic for thrombolytic mechanism?
A: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots"

[CARD 74 - Type 1]
Q: What is the class mechanism of thrombolytics?
A: Activate plasminogen → plasmin → plasmin cleaves fibrin → dissolves existing thrombus.

[CARD 75 - Type 1]
Q: What is alteplase (tPA) and what are its indications?
A: Recombinant tissue plasminogen activator - used for ischaemic stroke (≤4.5h), massive PE, and STEMI (if no PCI available); short half-life (~5 min) given as IV infusion.

[CARD 76 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What must be done BEFORE giving alteplase for ischaemic stroke?
A: CT head first to exclude haemorrhagic stroke - alteplase must NOT be given if there is intracranial haemorrhage; also control BP to <185/110 mmHg and treat within 4.5 hours.
[Trap: common wrong answer is "give tPA urgently without imaging" - a CT head is mandatory before thrombolysis to exclude haemorrhage]

[CARD 77 - Type 1]
Q: What is tenecteplase (TNK-tPA)?
A: Modified tPA with longer half-life - given as single IV bolus (more convenient than alteplase infusion for STEMI); increasingly used in ischaemic stroke.

[CARD 78 - Type 2: Cloze]
[c]Streptokinase[/c] can only be used ONCE because it is a bacterial protein (from Streptococcus) - administration induces antibodies that make repeat use within 5 years ineffective and can cause anaphylaxis.
[Trap: common wrong answer is "streptokinase can be given again after a waiting period of a few weeks" - antibodies persist for up to 5 years; streptokinase is a one-time use drug]

[CARD 79 - Type 1]
Q: What is the blood pressure limit before giving alteplase for ischaemic stroke?
A: BP must be controlled to <185/110 mmHg before administering thrombolysis.

[CARD 80 - Type 3: Mnemonic]
Q: What is the mnemonic for absolute contraindications to thrombolytics?
A: "BRAIN HURTS" = Bleeding (active internal) | Recent surgery/trauma (<3 months) | Aortic dissection (suspected) | Intracranial history (prior ICH) | Neurosurgery (recent) | Haemorrhagic stroke (any prior) | Uncontrolled BP (SBP >180) | Recent head injury (<3 months) | Time window exceeded | Severe bleeding disorder

[CARD 81 - Type 1]
Q: What is the time window for alteplase in ischaemic stroke?
A: ≤4.5 hours from symptom onset; door-to-needle time target <60 minutes.

[CARD 82 - Type 1]
Q: Is thrombolysis indicated for submassive PE (RV strain, no haemodynamic compromise)?
A: No - anticoagulation is first-line for submassive PE; thrombolysis is reserved for massive PE with haemodynamic compromise.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: ANTIFIBRINOLYTICS (TRANEXAMIC ACID)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

[CARD 83 - Type 3: Mnemonic]
Q: What is the mnemonic for tranexamic acid mechanism?
A: "TXA = Tranexamic acid eXActs its effect by Blocking plasmin (and plasminogen binding)"

[CARD 84 - Type 1]
Q: What is the mechanism of tranexamic acid (TXA)?
A: Synthetic lysine analogue → competitively inhibits plasminogen activation (blocks lysine-binding sites) → prevents fibrin clot breakdown → preserves haemostasis.

[CARD 85 - Type 1]
Q: What are the key indications for TXA?
A: Trauma haemorrhage (CRASH-2 trial), postpartum haemorrhage (WOMAN trial), heavy menstrual bleeding, elective surgery (cardiac, orthopaedic - reduces transfusion), hereditary angioedema (prophylaxis).

[CARD 86 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What does the CRASH-2 trial tell us about TXA in trauma?
A: TXA given within 3 hours of injury reduces all-cause mortality (NNT ~67); given after 3 hours - no mortality benefit (and possibly harmful); time-critical administration is essential.
[Trap: common wrong answer is "TXA can be given at any time in trauma as long as the patient is bleeding" - after 3 hours, the CRASH-2 data shows no benefit]

[CARD 87 - Type 3: Mnemonic]
Q: What is the TXA timing rule mnemonic?
A: "3 hours or bust" = TXA must be given within 3 hours of trauma to reduce mortality (CRASH-2)

[CARD 88 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What does the WOMAN trial show about TXA in postpartum haemorrhage?
A: TXA given early in PPH reduces death from bleeding - now WHO recommended as part of PPH management.

[CARD 89 - Type 1]
Q: What are the contraindications to TXA?
A: Active thromboembolic disease (DVT, PE, stroke), DIC with consumption (blocking fibrinolysis worsens DIC), haematuria from upper urinary tract (blood clots may obstruct the ureter).

[CARD 90 - Type 1]
Q: What are the side effects of TXA?
A: Nausea/vomiting (GI), VTE risk, colour vision changes (rare), seizures at high doses.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: HAEMATINICS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

──────────────────────────────────────
8A. IRON
──────────────────────────────────────

[CARD 91 - Type 3: Mnemonic]
Q: What is the mnemonic for iron pharmacology?
A: "FERRIC" = Ferrous is absorbed | Ferritin stores it | Restores Hb | Iron deficiency - Check cause | Constipation = key side effect

[CARD 92 - Type 1]
Q: Which form of iron is better absorbed orally - ferrous (Fe2+) or ferric (Fe3+)?
A: Ferrous (Fe2+) is better absorbed from the GI tract.
[Trap: common wrong answer is "ferric supplements are equally well absorbed" - ferric Fe3+ must be reduced to ferrous Fe2+ before absorption; ferrous sulphate is the first-line oral preparation]

[CARD 93 - Type 3: Mnemonic]
Q: What is the mnemonic for iron absorption?
A: "Vitamin C = ↑ (reduces Fe3+ to Fe2+); Tea/antacids/PPIs = ↓ (chelate iron); Ferrous > Ferric (better absorbed)"

[CARD 94 - Type 1]
Q: What is the expected Hb response to iron replacement therapy?
A: Hb rises by approximately 10-20 g/L per 3 weeks; reticulocyte count rises at ~1 week (reticulocyte crisis = earliest marker of response).

[CARD 95 - Type 1]
Q: What are the side effects of oral iron?
A: Nausea, epigastric pain, constipation (most common), diarrhoea, dark stools (harmless).

[CARD 96 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: When is IV iron indicated over oral iron?
A: Oral failure/intolerance, IBD (impaired absorption), CKD on dialysis, severe deficiency in pregnancy, post-bariatric surgery.

[CARD 97 - Type 2: Cloze]
[c]Ferric carboxymaltose[/c] (IV iron) can cause transient hypophosphataemia because it stimulates FGF-23, increasing phosphate excretion in the kidney.

[CARD 98 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the most important thing to do after diagnosing iron deficiency anaemia?
A: Always identify and treat the underlying cause (GI cancer? Menorrhagia? Malabsorption?) - treating the anaemia without finding the cause is insufficient.

──────────────────────────────────────
8B. VITAMIN B12
──────────────────────────────────────

[CARD 99 - Type 3: Mnemonic]
Q: What is the mnemonic for vitamin B12?
A: "B12 = Big red cells (macrocytic), Bad nerves (subacute combined degeneration of spinal cord), Bypass stomach (intrinsic factor needed for absorption)"

[CARD 100 - Type 1]
Q: What are the two main functions of vitamin B12?
A: (1) Methylcobalamin: cofactor for methionine synthesis (DNA synthesis); (2) Adenosylcobalamin: cofactor for succinyl-CoA production (myelin formation).

[CARD 101 - Type 1]
Q: What are the causes of vitamin B12 deficiency?
A: Pernicious anaemia (absent intrinsic factor), dietary deficiency (strict vegans), post-gastrectomy, terminal ileum disease (Crohn's, resection - site of B12 absorption), malabsorption.

[CARD 102 - Type 1]
Q: What are the neurological features of B12 deficiency?
A: Subacute combined degeneration of the spinal cord (posterior columns + lateral corticospinal tracts) - bilateral paraesthesiae, ataxia, spasticity, extensor plantar responses.

[CARD 103 - Type 1]
Q: What is pernicious anaemia?
A: Autoimmune destruction of gastric parietal cells → absent intrinsic factor → failure to absorb dietary B12; antibodies: anti-intrinsic factor (most specific) and anti-parietal cell.

[CARD 104 - Type 1]
Q: What is the treatment for pernicious anaemia?
A: IM hydroxocobalamin 1 mg alternate days for 2 weeks, then every 3 months lifelong - oral B12 is NOT sufficient for pernicious anaemia (intrinsic factor is absent).
[Trap: common wrong answer is "oral B12 supplements are adequate for pernicious anaemia" - oral B12 requires intrinsic factor for absorption; IM injection bypasses this requirement]

[CARD 105 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: A patient with suspected B12 deficiency is given folic acid alone. What is the danger?
A: Folic acid corrects the blood picture (macrocytic anaemia) but unmasks and accelerates subacute combined degeneration of the spinal cord (neurological deterioration) - always rule out B12 deficiency before giving folate alone.
[Trap: common wrong answer is "folic acid is safe to give empirically for macrocytic anaemia" - giving folate without correcting B12 deficiency can cause irreversible neurological damage]

[CARD 106 - Type 1]
Q: What electrolyte abnormality can occur when starting B12 treatment?
A: Hypokalaemia - B12 stimulates rapid RBC production → increased cellular K+ uptake → serum K+ falls.

──────────────────────────────────────
8C. FOLATE (FOLIC ACID)
──────────────────────────────────────

[CARD 107 - Type 3: Mnemonic]
Q: What is the mnemonic for folate?
A: "FOLATE" = First trimester supplement | Only treats blood (not neuro) | Looks same as B12 anaemia (macrocytic) | Avoid giving alone in B12 deficiency | Treatment is oral

[CARD 108 - Type 1]
Q: What is the standard folate dose for preconception and first trimester pregnancy?
A: 400 mcg (0.4 mg) daily - to prevent neural tube defects.

[CARD 109 - Type 1]
Q: What is the high-risk folate dose in pregnancy and who requires it?
A: 5 mg daily - for women with previous NTD, diabetes, obesity, or taking antiepileptics (phenytoin/valproate).

[CARD 110 - Type 1]
Q: What folate dose is given alongside methotrexate?
A: 5 mg once weekly (given 1-2 days after MTX to reduce toxicity without reducing MTX efficacy).

[CARD 111 - Type 1]
Q: What are the common causes of folate deficiency?
A: Poor diet, pregnancy (increased demand), alcohol (most common cause in HK/Western clinical practice), malabsorption (coeliac), methotrexate (DHFR inhibition), trimethoprim, phenytoin.

[CARD 112 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: How do you differentiate B12 deficiency anaemia from folate deficiency anaemia clinically?
A: Both cause macrocytic anaemia with hypersegmented neutrophils - B12 deficiency causes neurological symptoms (subacute combined degeneration); folate deficiency does NOT cause neurological features.

[CARD 113 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the most common cause of folate deficiency in clinical practice?
A: Alcoholism.

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SECTION 9: HAEMATOPOIETIC GROWTH FACTORS
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9A. ERYTHROPOIETIN (EPO) / ESAs
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[CARD 114 - Type 3: Mnemonic]
Q: What is the mnemonic for EPO use?
A: "EPO = Every Patient On dialysis needs this" (primary indication = anaemia of CKD)

[CARD 115 - Type 1]
Q: What is the mechanism of erythropoiesis-stimulating agents (ESAs)?
A: Recombinant EPO (epoetin alfa/darbepoetin alfa) binds EPO receptor on erythroid progenitors in bone marrow → stimulates RBC production.

[CARD 116 - Type 1]
Q: What are the indications for ESAs?
A: Anaemia of CKD (primary use), chemotherapy-induced anaemia, myelodysplastic syndrome (low-risk), autologous blood donation pre-surgery.

[CARD 117 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the target Hb when using EPO in CKD, and why should normal Hb NOT be targeted?
A: Target Hb 100-120 g/L in CKD - targeting normal Hb (>130 g/L) increases VTE and cardiovascular mortality (shown in CHOIR and CREATE trials).
[Trap: common wrong answer is "correct the Hb to normal range with EPO" - overcorrection is actively harmful in CKD patients on EPO]

[CARD 118 - Type 1]
Q: What must be checked before starting EPO and why?
A: Iron stores (ferritin and TSAT) - iron deficiency makes EPO ineffective (iron is required for haem synthesis); iron deficiency must be corrected first.

[CARD 119 - Type 2: Cloze]
[c]EPO[/c] causes hypertension (most common side effect) because increased haemoglobin raises blood viscosity and increases peripheral vascular resistance.

[CARD 120 - Type 1]
Q: What is pure red cell aplasia (PRCA) in the context of EPO therapy?
A: Rare complication - anti-EPO antibodies develop → sudden worsening anaemia after initial response; treat by stopping EPO and giving immunosuppression.

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9B. G-CSF (FILGRASTIM / PEGFILGRASTIM)
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[CARD 121 - Type 3: Mnemonic]
Q: What is the mnemonic for G-CSF?
A: "G-CSF = Grows White cells (neutrophils)" - stimulates neutrophil proliferation and release from bone marrow

[CARD 122 - Type 1]
Q: What is the mechanism of G-CSF?
A: Binds G-CSF receptor → stimulates proliferation, differentiation, and survival of neutrophil precursors → increases mature neutrophil release from bone marrow.

[CARD 123 - Type 1]
Q: What are the indications for G-CSF?
A: Prevention and treatment of chemotherapy-induced febrile neutropaenia, congenital/drug-induced neutropaenia, stem cell mobilisation before harvest for transplant.

[CARD 124 - Type 1]
Q: What is the most common side effect of G-CSF?
A: Bone pain (due to medullary expansion of bone marrow) - treated with paracetamol ± ibuprofen.

[CARD 125 - Type 1]
Q: What is a rare but serious side effect of G-CSF?
A: Splenic rupture (splenomegaly due to increased splenic workload; rare but potentially fatal).

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9C. THROMBOPOIETIN RECEPTOR AGONISTS (TPO-RAs)
──────────────────────────────────────

[CARD 126 - Type 1]
Q: What is the mechanism of romiplostim and eltrombopag?
A: Bind and activate the thrombopoietin receptor (Mpl) → stimulate megakaryocyte proliferation → increase platelet production.

[CARD 127 - Type 1]
Q: What are the indications for TPO receptor agonists?
A: Immune thrombocytopenia (ITP) second-line after steroids; aplastic anaemia (eltrombopag); thrombocytopenia in HCV/chronic liver disease (eltrombopag).

[CARD 128 - Type 1]
Q: What are the key side effects of TPO-RAs?
A: Bone marrow reticulin fibrosis (with prolonged use), thrombosis (increased platelet count → VTE risk), headache.

[CARD 129 - Type 1]
Q: What is a key drug interaction for eltrombopag?
A: Must be taken without food and away from polyvalent cations (Ca2+, Mg2+, Fe3+, Al3+) as chelation dramatically reduces absorption; also monitor LFTs (hepatotoxicity).

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SECTION 10: REVERSAL AGENTS SUMMARY
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[CARD 130 - Type 3: Mnemonic]
Q: What is the mnemonic for reversal agents?
A: "4Ps + 2Is + 1A" = Protamine (heparin) | Phytomenadione/Vitamin K (warfarin) | PCC (warfarin/Xa) | Platelets (only if truly indicated) | Idarucizumab (dabigatran) | bIn/Andexanet alfa (Xa inhibitors) | Aminocaproic/TXA (fibrinolytics)

[CARD 131 - Type 1]
Q: What reverses UFH?
A: Protamine sulfate 1 mg per 100 units UFH - given IV slowly (risk of hypotension, bradycardia, anaphylaxis, especially in fish allergy or prior vasectomy).

[CARD 132 - Type 1]
Q: What reverses LMWH?
A: Protamine sulfate - only ~60% neutralisation (partial reversal).

[CARD 133 - Type 1]
Q: What is the difference in onset between oral and IV vitamin K for warfarin reversal?
A: Oral vitamin K: onset 6-12 hours; IV vitamin K: onset 1-2 hours (faster); IV is associated with rare anaphylaxis risk.

[CARD 134 - Type 1]
Q: What reverses fibrinolytic/thrombolytic agents?
A: No specific antidote - supportive care + TXA (antifibrinolytic) + FFP/cryoprecipitate (replace clotting factors and fibrinogen).

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RAPID-FIRE TRAP SUMMARY (HKMLE HIGH-RISK MCQs)
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[CARD 135 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Mechanical heart valves - what is the ONLY safe anticoagulant?
A: Warfarin only - DOACs are contraindicated (RE-ALIGN trial); LMWH is used only as short-term bridging.

[CARD 136 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Pregnancy - what is the ONLY safe anticoagulant?
A: LMWH - warfarin is teratogenic (Category X); DOACs are also contraindicated.

[CARD 137 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: HIT - what THREE things should you NOT do?
A: (1) Do NOT continue any heparin (UFH or LMWH), (2) Do NOT give platelets, (3) Do NOT start warfarin until platelets >150.

[CARD 138 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Folate given alone when B12 is deficient - what is the risk?
A: Corrects blood picture but unmasks/accelerates subacute combined degeneration of the spinal cord - irreversible neurological damage.

[CARD 139 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: EPO in CKD - what happens if you target a normal Hb?
A: Increased VTE and cardiovascular mortality (CHOIR and CREATE trials) - target Hb 100-120 g/L, NOT normal.

[CARD 140 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Alteplase for stroke - what must you do FIRST?
A: CT head to exclude haemorrhagic stroke + confirm time of onset ≤4.5h + BP <185/110 mmHg.

[CARD 141 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Streptokinase - can it be given twice?
A: No - antibodies form after first use; repeat use within 5 years is ineffective and risks anaphylaxis.

[CARD 142 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: INR pathway - which clotting factor rises first when starting warfarin?
A: Factor VII (shortest half-life ~6h) - INR rises first, but patient is NOT fully anticoagulated until all factors (especially factor II) are depleted (3-5 days).

[CARD 143 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Prasugrel contraindications?
A: Prior TIA or stroke, age >75, weight <60 kg - mnemonic: "Prior TIA/stroke = Prasugrel is PRASUREly dangerous."

[CARD 144 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: What is the B12 vs folate differentiating clinical feature?
A: B12 deficiency = neurological symptoms (subacute combined degeneration); folate deficiency = no neurological features - mnemonic: "B12 = Bad nerves; Folate = Fine nerves."

[CARD 145 - Type 4: HKMLE Pearl]
Q: HKMLE Pearl: Pernicious anaemia - why does oral B12 not work?
A: Pernicious anaemia destroys gastric parietal cells → no intrinsic factor → oral B12 cannot be absorbed; IM injection is required.

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QUICK MNEMONICS CHEAT SHEET (ALL IN ONE)
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[CARD 146 - Type 3]
Q: What is the mnemonic for drugs that INCREASE warfarin INR (CYP2C9 inhibitors)?
A: "CAFE MIX" = Clarithromycin/Ciprofloxacin | Amiodarone | Fluconazole | Erythromycin | Metronidazole | Isoniazid | eXcretion inhibitors (statins)

[CARD 147 - Type 3]
Q: What is the mnemonic for drugs that DECREASE warfarin INR (CYP2C9 inducers)?
A: "PRICARS" = Phenytoin | Rifampicin | Isoniazid (high dose) | Carbamazepine | Alcohol (chronic) | St John's Wort

[CARD 148 - Type 3]
Q: What is the mnemonic for absolute contraindications to thrombolytics?
A: "BRAIN HURTS" = Bleeding | Recent surgery/trauma | Aortic dissection | Intracranial history | Neurosurgery | Haemorrhagic stroke | Uncontrolled BP | Recent head injury | Time exceeded | Severe coagulopathy

[CARD 149 - Type 3]
Q: What is the mnemonic for EPO target in CKD?
A: "100-120 g/L, NOT normal" = overcorrecting Hb with EPO above 130 g/L increases VTE and CV events

[CARD 150 - Type 3]
Q: What is the mnemonic for DOAC reversal?
A: "I-DAR for IIa (dabigatran) = Idarucizumab; AND-exanet for Xa = Andexanet alfa"

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END OF DECK — 150 CARDS TOTAL
Topics: Warfarin | Heparin/LMWH/HIT | DTIs | DOACs | Antiplatelets |
Thrombolytics | TXA | Iron/B12/Folate | EPO/G-CSF/TPO-RAs | Reversal Agents
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