Pharmacology
MBBS Pharmacology — high-yield long questions and short notes from K.D. Tripathi, covering general pharmacology, autonomic and cardiovascular drugs, CNS, autacoids, chemotherapy, endocrine and more, written to the marks with mechanisms, classification, clinical uses, adverse effects and pearls.
12chapters144questions99High-Yield
Definition
Haematinics are substances required for normal red-cell formation, used to treat the different types of anaemia.
Main Haematinics
- Iron — for iron-deficiency (microcytic) anaemia
- Vitamin B12 — megaloblastic anaemia, pernicious anaemia
- Folic acid — megaloblastic anaemia, pregnancy
- Erythropoietin — anaemia of chronic kidney disease
Principles of Use
- Identify the type of anaemia before treating
- Oral iron preferred; parenteral if intolerant
- Continue iron 3 months after haemoglobin normalises (refill stores)
- Never give folate alone in B12 deficiency (worsens neuropathy)
Correct diagnosis of the deficiency guides which haematinic to give. Anaemia Haematinic Microcytic Iron Megaloblastic B12 / folate Renal Erythropoietin Applied
- Reticulocyte rise confirms response
- Vitamin C ↑ iron absorption
🔑KEY POINTS TO REMEMBER- Haematinics: iron, vitamin B12, folic acid, erythropoietin.
- Type of anaemia determines the choice.
- Never give folate alone in B12 deficiency.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Anticoagulants prevent formation and extension of blood clots by inhibiting the coagulation cascade.
Parenteral Anticoagulants
- Heparin — activates antithrombin III (immediate)
- Low-molecular-weight heparin — enoxaparin (anti-Xa)
- Fondaparinux; direct thrombin inhibitors
Oral Anticoagulants
- Warfarin — vitamin K antagonist (slow onset)
- DOACs — dabigatran (thrombin), rivaroxaban/apixaban (factor Xa)
- DOACs need no routine monitoring
Uses
- Deep vein thrombosis and pulmonary embolism
- Atrial fibrillation (stroke prevention)
- Prosthetic valves (warfarin), acute coronary syndrome
Heparin covers the immediate period until oral anticoagulation takes effect. Drug Monitoring Antidote Heparin aPTT Protamine Warfarin INR Vitamin K DOAC None routine Specific agents Applied
- Bleeding is the main adverse effect
- Warfarin contraindicated in pregnancy (heparin is safe)
🔑KEY POINTS TO REMEMBER- Heparin acts immediately (antithrombin III); warfarin is slow (vitamin K antagonist).
- Monitoring: aPTT for heparin, INR for warfarin; DOACs need none.
- Antidotes: protamine (heparin), vitamin K (warfarin).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Antiplatelet drugs prevent platelet aggregation, while fibrinolytics dissolve a clot that has already formed.
Antiplatelet Drugs
- Aspirin — irreversible COX-1 inhibition (↓ thromboxane A2)
- Clopidogrel, ticagrelor — block ADP (P2Y12) receptors
- Abciximab, tirofiban — GP IIb/IIIa inhibitors
- Dipyridamole
Fibrinolytics (thrombolytics)
- Streptokinase, urokinase — activate plasminogen
- Alteplase, tenecteplase — tissue plasminogen activators (clot-selective)
- Convert plasminogen → plasmin → lyse fibrin
One stops clots forming; the other breaks down clots already present. Drug Use Aspirin Prevention (MI, stroke) Clopidogrel With aspirin after stenting Alteplase Acute MI, ischaemic stroke Applied
- Thrombolysis is most effective within the first hours
- Main risk: haemorrhage (especially intracranial)
🔑KEY POINTS TO REMEMBER- Antiplatelets: aspirin (COX-1), clopidogrel (P2Y12), GP IIb/IIIa inhibitors.
- Fibrinolytics convert plasminogen to plasmin → lyse fibrin.
- Bleeding, especially intracranial, is the main risk.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Anticancer (antineoplastic) drugs kill or inhibit rapidly dividing malignant cells, mostly by damaging DNA or blocking its synthesis.
Classification
- Alkylating agents — cyclophosphamide, cisplatin
- Antimetabolites — methotrexate, 5-fluorouracil, 6-mercaptopurine
- Plant alkaloids — vincristine, paclitaxel
- Antibiotics — doxorubicin, bleomycin
- Targeted / hormonal — imatinib, tamoxifen, monoclonal antibodies
Common Toxicities
- Bone-marrow suppression (dose-limiting for most)
- Nausea, vomiting, alopecia, mucositis
- Specific: cardiotoxicity (doxorubicin), pulmonary fibrosis (bleomycin), neuropathy (vincristine)
- Nephrotoxicity (cisplatin), haemorrhagic cystitis (cyclophosphamide)
The drugs cannot fully distinguish tumour from normal dividing cells. Drug Specific toxicity Doxorubicin Cardiotoxicity Bleomycin Pulmonary fibrosis Vincristine Neuropathy Cisplatin Nephrotoxicity Applied
- Combination chemotherapy → better response, less resistance
- Mesna prevents cyclophosphamide cystitis
🔑KEY POINTS TO REMEMBER- Classes: alkylating agents, antimetabolites, plant alkaloids, antibiotics, targeted drugs.
- Bone-marrow suppression is the common dose-limiting toxicity.
- Organ-specific toxicities: doxorubicin (heart), bleomycin (lung), vincristine (nerve).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Immunosuppressants suppress the immune response, used in transplantation and autoimmune disease.
Classes
- Calcineurin inhibitors — ciclosporin, tacrolimus (↓ interleukin-2)
- Corticosteroids — prednisolone
- Antiproliferative — azathioprine, mycophenolate mofetil
- mTOR inhibitors — sirolimus
- Biologics — basiliximab, antithymocyte globulin
Uses & Risks
- Organ transplant rejection (prevention and treatment)
- Autoimmune disease — rheumatoid arthritis, lupus, nephrotic syndrome
- Risks: infection, malignancy (lymphoma), organ-specific toxicity
- Ciclosporin — nephrotoxicity, gum hypertrophy, hypertension
Damping T-cell responses protects the graft but lowers host defence. Drug Mechanism Ciclosporin ↓ Interleukin-2 Azathioprine ↓ Purine synthesis Sirolimus mTOR inhibition Applied
- Triple therapy after transplant (steroid + calcineurin inhibitor + antiproliferative)
- Monitor drug levels and screen for infection
🔑KEY POINTS TO REMEMBER- Classes: calcineurin inhibitors, steroids, antiproliferatives, mTOR inhibitors, biologics.
- Used in transplantation and autoimmune disease.
- Main risks: infection and malignancy; ciclosporin is nephrotoxic.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Heparin is a parenteral anticoagulant with immediate onset, acting through antithrombin III.
Mechanism
- Binds and activates antithrombin III (1000-fold)
- Inactivates thrombin (IIa) and factor Xa
- Acts immediately, in vivo and in vitro
- LMWH acts mainly on factor Xa
Uses & Adverse Effects
- Deep vein thrombosis, pulmonary embolism, acute coronary syndrome
- Safe in pregnancy (does not cross the placenta)
- Monitored by aPTT
- Adverse: bleeding, heparin-induced thrombocytopenia, osteoporosis
Heparin supercharges antithrombin III to shut down the cascade at once. Feature Detail Onset Immediate Monitoring aPTT Antidote Protamine sulphate Applied
- LMWH: predictable, no routine monitoring, once daily
- Anticoagulant of choice in pregnancy
🔑KEY POINTS TO REMEMBER- Heparin activates antithrombin III → inactivates thrombin and factor Xa.
- Immediate action; monitored by aPTT; antidote protamine.
- Safe in pregnancy; can cause heparin-induced thrombocytopenia.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Warfarin is an oral anticoagulant that acts as a vitamin K antagonist, with slow onset and a narrow therapeutic index.
Mechanism
- Inhibits vitamin K epoxide reductase
- ↓ γ-carboxylation of factors II, VII, IX, X (and protein C, S)
- Acts only in vivo; onset delayed 3–5 days
- Monitored by INR (target usually 2–3)
Uses & Cautions
- Atrial fibrillation, deep vein thrombosis, prosthetic heart valves
- Adverse: bleeding, skin necrosis, teratogenic
- Contraindicated in pregnancy
- Many interactions (enzyme inducers/inhibitors, protein binding)
Blocking vitamin K recycling gradually depletes clotting factors. Feature Detail Monitoring INR (2–3) Antidote Vitamin K, FFP Pregnancy Contraindicated Applied
- Overlap with heparin for the first 5 days
- Advise consistent dietary vitamin K intake
🔑KEY POINTS TO REMEMBER- Warfarin inhibits vitamin K epoxide reductase → ↓ factors II, VII, IX, X.
- Slow onset; monitored by INR; antidote vitamin K.
- Teratogenic — contraindicated in pregnancy.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Iron therapy replaces body iron stores in iron-deficiency anaemia, the commonest anaemia worldwide.
Oral Iron
- Ferrous sulphate (preferred), fumarate, gluconate
- Ferrous (Fe²⁺) form better absorbed than ferric
- Absorption ↑ by vitamin C, ↓ by antacids, tea, calcium
- Adverse: nausea, constipation, black stools
Parenteral Iron
- Iron sucrose, ferric carboxymaltose (IV)
- Indications: intolerance, malabsorption, non-compliance, chronic kidney disease
- Risk of anaphylaxis (test dose historically)
Treatment continues beyond correction of haemoglobin to replenish stores. Route Indication Oral Standard therapy Parenteral Intolerance, malabsorption Applied
- Reticulocytosis at 5–10 days confirms response
- Investigate the cause of iron deficiency (e.g. GI bleeding)
🔑KEY POINTS TO REMEMBER- Ferrous sulphate is the standard oral iron preparation.
- Vitamin C ↑ absorption; antacids and tea ↓ it.
- Continue for 3 months after haemoglobin normalises.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Clopidogrel is an antiplatelet drug that irreversibly blocks the platelet ADP (P2Y12) receptor.
Mechanism
- Prodrug activated by hepatic CYP2C19
- Irreversibly blocks P2Y12 ADP receptors
- ↓ Expression of GP IIb/IIIa → ↓ platelet aggregation
- Effect lasts the platelet lifespan (7–10 days)
Uses & Adverse Effects
- Acute coronary syndrome (with aspirin — dual antiplatelet therapy)
- After coronary stenting
- Ischaemic stroke, peripheral arterial disease
- Alternative when aspirin is not tolerated
- Adverse: bleeding, rash, rarely TTP
Irreversible receptor blockade disables platelets for their entire lifespan. Feature Detail Target P2Y12 ADP receptor Duration 7–10 days Interaction Omeprazole (CYP2C19) Applied
- Stop 5–7 days before major surgery
- Pantoprazole preferred over omeprazole with clopidogrel
🔑KEY POINTS TO REMEMBER- Clopidogrel irreversibly blocks the platelet P2Y12 ADP receptor.
- Used with aspirin after stenting and in acute coronary syndrome.
- Prodrug — omeprazole reduces its activation.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Fibrinolytics (thrombolytics) dissolve formed thrombi by converting plasminogen into plasmin, which digests fibrin.
Drugs
- Streptokinase — from streptococci; antigenic, non-clot-selective
- Alteplase (tPA), tenecteplase — clot-selective, non-antigenic
- Urokinase, reteplase
Uses & Risks
- Acute myocardial infarction (ST-elevation)
- Acute ischaemic stroke (within window), massive pulmonary embolism
- Adverse: bleeding, hypotension, allergy (streptokinase)
- Contraindicated: recent surgery, active bleeding, haemorrhagic stroke, severe hypertension
Generating plasmin breaks the fibrin mesh and reopens the vessel. Drug Feature Streptokinase Antigenic, cheap Alteplase Clot-selective Applied
- ‘Time is muscle’ — give as early as possible
- Streptokinase cannot be repeated (antibodies)
🔑KEY POINTS TO REMEMBER- Fibrinolytics convert plasminogen to plasmin → lyse fibrin.
- Streptokinase is antigenic; alteplase is clot-selective.
- Main risk is bleeding; earliest administration gives best benefit.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, used in cancer and autoimmune disease.
Mechanism
- Inhibits dihydrofolate reductase
- ↓ Tetrahydrofolate → ↓ purine and thymidylate synthesis
- ↓ DNA synthesis (S-phase specific)
- Also anti-inflammatory at low dose
Uses & Toxicity
- Cancers — leukaemia, lymphoma, choriocarcinoma
- Rheumatoid arthritis, psoriasis (low weekly dose)
- Ectopic pregnancy, medical abortion
- Toxicity: marrow suppression, mucositis, hepatotoxicity, pulmonary fibrosis
- Teratogenic — contraindicated in pregnancy
Folate blockade starves dividing cells of DNA building blocks. Feature Detail Target Dihydrofolate reductase Rescue Folinic acid (leucovorin) Dosing (RA) Weekly Applied
- Folinic acid rescue limits toxicity after high doses
- Weekly (not daily) dosing in rheumatoid arthritis — fatal errors occur
🔑KEY POINTS TO REMEMBER- Methotrexate inhibits dihydrofolate reductase → ↓ DNA synthesis.
- Used in cancers and, in low weekly dose, rheumatoid arthritis and psoriasis.
- Folinic acid rescue; teratogenic and hepatotoxic.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Vitamin B12 and folic acid are haematinics essential for DNA synthesis; deficiency of either causes megaloblastic anaemia.
Vitamin B12 (cobalamin)
- Needs intrinsic factor for absorption (terminal ileum)
- Deficiency: pernicious anaemia, vegan diet, ileal disease
- Causes anaemia plus neurological damage (subacute combined degeneration)
- Given parenterally (hydroxocobalamin)
Folic Acid
- Absorbed in the jejunum
- Deficiency: poor diet, pregnancy, alcohol, methotrexate, phenytoin
- Causes anaemia without neurological damage
- Prophylaxis in pregnancy prevents neural tube defects
Both cause megaloblastic anaemia; only B12 deficiency damages nerves. Feature B12 Folate Absorption Ileum (IF) Jejunum Neuropathy Yes No Stores Years Months Applied
- Always exclude B12 deficiency before giving folate
- 5 mg folic acid preconception in high-risk pregnancy
🔑KEY POINTS TO REMEMBER- Both cause megaloblastic anaemia; B12 also causes neuropathy.
- B12 needs intrinsic factor; folate is absorbed in the jejunum.
- Folate alone in B12 deficiency worsens neurological damage.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.